AiPD: Autoinhibited Protein Database

O60260

Gene name	PRKN (PARK2)
Protein name	E3 ubiquitin-protein ligase parkin
Names	Parkin, Parkin RBR E3 ubiquitin-protein ligase, Parkinson juvenile disease protein 2, Parkinson disease protein 2
Species	Homo sapiens (Human)
KEGG Pathway	hsa:5071
EC number	2.3.2.31: Aminoacyltransferases
Protein Class	RBR FAMILY RING FINGER AND IBR DOMAIN-CONTAINING (PTHR11685)

Descriptions

Parkin belongs to the RBR subfamily of E3 ubiquitin ligases that function by transferring Ub from an E2-conjugating enzyme to a substrate through an E3-Ub intermediate. Parkin contains an N-terminal ubiquitin-like (UbL) domain connected through a linker to four zinc-coordinating domains consisting of RING0, following by the RBR (RING1, In-Between-RING (IBR), RING2) module common to other E3 Ub ligases. RING1 contains an E2 binding site and RING2 contains a catalytic cysteine that is an acceptor for an ubiquitin from RING1-bound E2~Ub forming an intermediate (E3~Ub) that leads to substrate or autoubiquitination.
Structural studies revealed that Parkin, in its basal state, adopts an autoinhibited conformation with several distinct sites of inhibition. First, the UbL domain is bound to RING1 such that Ser65 is poorly accessible for phosphorylation by PINK1. Second, the Repressor Element of Parkin (REP) blocks the site of E2 Ub-conjugating enzyme binding on RING1. Finally, the RING0 domain binds to RING2, where it occludes the Cys431 Ub acceptor site. PINK1 stimulates parkin activity through phosphorylation of both Ub and parkin's UbL domain at an equivalent serine 65 position in sequence and structure. The phosphorylation of both the UbL domain and Ub are required to activate parkin by releasing the UbL domain, forming an extended structure needed to facilitate E2-Ub binding.

Autoinhibitory domains (AIDs)

Target domain	228-318 (RING1 domain)
Relief mechanism	PTM, Ligand binding
Assay	Deletion assay, Split protein assay, Structural analysis, Mutagenesis experiment

AID

1-72 (Ubiquitin-like domain, UbL)

Target domain

228-318 (RING1 domain)

Relief mechanism

PTM (Phosphorylation of UbL domain by PINK1), Ligand binding (Phosphoubiquitin binding to helix H3 of RING1 domain)

Assay

Deletion assay, Split protein assay, Structural analysis, Mutagenesis experiment

Target domain	228-318 (RING1 domain); 409-463 (RING2 domain)
Relief mechanism	PTM
Assay	Mutagenesis experiment, Structural analysis

AID

378-410 (REP linker)

Target domain

228-318 (RING1 domain); 409-463 (RING2 domain)

Relief mechanism

PTM (Phosphorylation of UbL domain)

Assay

Mutagenesis experiment, Structural analysis

Target domain	409-463 (RING2 domain)
Relief mechanism
Assay	Deletion assay, Mutagenesis experiment, Structural analysis

AID

141-225 (RING0 domain)

Target domain

409-463 (RING2 domain)

Relief mechanism

Assay

Deletion assay, Mutagenesis experiment, Structural analysis

Accessory elements

No accessory elements

References

Aguirre JD et al. (2017) "Structure of phosphorylated UBL domain and insights into PINK1-orchestrated parkin activation", Proceedings of the National Academy of Sciences of the United States of America, 114, 298-303

Kumar A et al. (2015) "Disruption of the autoinhibited state primes the E3 ligase parkin for activation and catalysis", The EMBO journal, 34, 2506-21

Tang MY et al. (2017) "Structure-guided mutagenesis reveals a hierarchical mechanism of Parkin activation", Nature communications, 8, 14697

Seirafi M et al. (2015) "Parkin structure and function", The FEBS journal, 282, 2076-88

Byrd RA et al. (2013) "Compact Parkin only: insights into the structure of an autoinhibited ubiquitin ligase", The EMBO journal, 32, 2087-9

Gladkova C et al. (2018) "Mechanism of parkin activation by PINK1", Nature, 559, 410-414

Autoinhibited structure

Activated structure

15 structures for O60260

Entry ID	Method	Resolution	Chain	Position	Source
1IYF	NMR	-	A	1-76	PDB
2JMO	NMR	-	A	308-384	PDB
4BM9	X-ray	225 A	A	137-465	PDB
4I1F	X-ray	158 A	A	141-465	PDB
4I1H	X-ray	200 A	A	141-465	PDB
5C1Z	X-ray	179 A	A/B	1-465	PDB
5C23	X-ray	237 A	A/B	1-465	PDB
5C9V	X-ray	235 A	A	137-465	PDB
5N2W	X-ray	268 A	A	1-465	PDB
5N38	X-ray	260 A	A	1-465	PDB
5TR5	NMR	-	A	1-76	PDB
6GLC	X-ray	180 A	A	1-382	PDB
6HUE	X-ray	285 A	A/B	1-465	PDB
6N13	NMR	-	B	144-465	PDB
AF-O60260-F1	Predicted				AlphaFoldDB

599 variants for O60260

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
rs772786691 RCV001449634 RCV000585185	1	M>?	Variant assessed as Somatic; HIGH impact. Young-onset Parkinson disease [NCI-TCGA, ClinVar]	Yes	ClinVar NCI-TCGA dbSNP
RCV001784521 rs771586218 RCV000992706	1	M>T	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinVar dbSNP
rs532703934 VAR_019733 CA4090529	15	V>M	PARK2 [UniProt]	Yes	ClinGen UniProt 1000Genomes ExAC TOPMed dbSNP gnomAD
CA4090515 rs147757966 RCV001090784 RCV002477613 VAR_019734	33	R>Q	Autosomal recessive juvenile Parkinson disease 2 PARK2 [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ESP ExAC TOPMed dbSNP gnomAD
RCV001449626 RCV001782974 RCV000488202 rs55777503	34	Q>missing	Autosomal recessive juvenile Parkinson disease 2 Young-onset Parkinson disease [ClinVar]	Yes	ClinVar dbSNP
RCV001030787 rs748142049	34	Q>missing	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinVar dbSNP
RCV001662570 RCV000537921 CA4090514 RCV001507187 rs148851677	34	Q>R	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
VAR_019735 RCV001154507 rs148990138 RCV001090783 CA4090511	37	P>L	Autosomal recessive juvenile Parkinson disease 2 PARK2 [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
RCV001319468 RCV000474986 rs368134308 CA4090504	42	R>H	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs368134308 CA4090505 VAR_019736 RCV000797973	42	R>P	PARK2 and PARK; induces a conformational change in the PSMD4-binding site of Ubl resulting in impaired proteasomal binding; decreases ubiquitination and degradation; increased aggregation; impairs the ability to ubiquitinate and degrade SYT11 [UniProt]	Yes	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
VAR_019737	46	A>P	PARK2 [UniProt]	Yes	UniProt
RCV000534302 RCV002497154 rs75860381 CA4090502 RCV001154506	46	A>T	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
RCV000644912 RCV002477430 rs754809877 RCV001034683	52	N>missing	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinVar dbSNP
RCV001369417 VAR_070078 CA254085 rs137853059 RCV000007463	56	V>E	Autosomal recessive juvenile Parkinson disease 2 PARK2 [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ExAC TOPMed dbSNP gnomAD
RCV001809895 RCV001009157 rs746646126	74	W>missing	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinVar dbSNP
RCV000455485 RCV000007454 CA254080 rs55774500 RCV000762444 VAR_019738	82	A>E	Autosomal recessive juvenile Parkinson disease 2 PARK2 [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
RCV002497571 rs141825163 CA4090440 RCV002032396 RCV001151479	83	T>A	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
VAR_019739 CA4090428 rs566229879 COSM1242616	92	A>V	oesophagus PARK2 [Cosmic, UniProt]	Yes	ClinGen cosmic curated UniProt 1000Genomes ExAC dbSNP gnomAD
RCV003130142 rs769099303 CA4090420 RCV001063120	104	R>W	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV002479309 rs771529549 RCV001050394 RCV001809967	113	P>missing	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinVar dbSNP
RCV001217964 RCV002484184 rs144001694 CA4090412	118	G>A	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
CA4090357 rs55654276 RCV000551517 RCV000987812 RCV002497155	153	P>R	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
RCV000007459 VAR_019741 rs137853057 CA254083	161	K>N	Autosomal recessive juvenile Parkinson disease 2 PARK2; severely compromises the mitochondrial localization; fails to stabilize BCL2; decreased binding to the TP53 promoter; abolishes TP53 transcriptional repression [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV000034122 VAR_019742 RCV000252261 RCV001516809 RCV002490453 rs1801474 CA344227	167	S>N	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
VAR_019743 CA4090308 CA4090309 RCV000712860 rs9456735 VAR_054107 RCV001080145 RCV000732668	192	M>L	Autosomal recessive juvenile Parkinson disease 2 PARK2; unknown pathological significance [ClinVar, UniProt]	Yes	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD ClinVar UniProt dbSNP
VAR_019743 rs9456735	192	M>V	PARK2; unknown pathological significance [UniProt]	Yes	UniProt dbSNP
CA4090302 rs200985148 RCV002558369 RCV001156909	205	S>N	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
COSM741234 RCV000007467 CA254087 COSM4859986 rs137853060 RCV001851722 VAR_019744	211	K>N	lung Autosomal recessive juvenile Parkinson disease 2 Variant assessed as Somatic; MODERATE impact. PARK2; severely compromises the mitochondrial localization; fails to stabilize BCL2 [Cosmic, ClinVar, NCI-TCGA, UniProt]	Yes	ClinGen cosmic curated ClinVar UniProt ExAC TOPMed dbSNP gnomAD NCI-TCGA Cosmic
RCV000007462 CA254084 rs137853058 VAR_019746 RCV001034684	212	C>Y	Autosomal recessive juvenile Parkinson disease 2 PARK2 [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt 1000Genomes ExAC dbSNP gnomAD
rs886061238 RCV000330219 CA10623398	236	I>V	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP
RCV000419390 RCV000625845 VAR_019747 RCV001449638 COSM3722940 rs137853054 RCV000007470 CA254089 COSM98176	240	T>M	upper_aerodigestive_tract Autosomal recessive juvenile Parkinson disease 2 Young-onset Parkinson disease Neoplasm of ovary PARK2 [Cosmic, ClinVar, UniProt]	Yes	ClinGen cosmic curated ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs137853054 CA254077 RCV000007452 VAR_019748	240	T>R	Autosomal recessive juvenile Parkinson disease 2 PARK2; impairs the ability to ubiquitinate SNCAIP and BCL2; loss of UBE2L3 binding; severely compromises the mitochondrial localization [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs146173584 RCV002289704 CA4090262 RCV001049281 RCV000517145	243	D>N	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA4090237 RCV000995593 VAR_019749 rs747427602 RCV000799872	253	C>Y	Autosomal recessive juvenile Parkinson disease 2 PARK; late onset [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ExAC TOPMed dbSNP gnomAD
RCV001304995 RCV000469518 rs139600787 CA4090236	254	N>S	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
RCV001155245 CA4090232 VAR_019750 RCV000696926 rs150562946	256	R>C	Autosomal recessive juvenile Parkinson disease 2 PARK2 and PARK; at heterozygosity it is associated with late onset Parkinson disease; impairs the ability to ubiquitinate SNCAIP and ZNF746; decreased binding to the TP53 promoter; abolishes TP53 transcriptional repression [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs114696251 RCV001344970 CA4090223 RCV002477847	267	Y>H	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
RCV002032431 CA4090215 rs141366047 RCV001155244	272	L>I	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
RCV000612317 RCV000007466 COSM1722445 rs34424986 CA254086 RCV000514660 VAR_019752 RCV001197176 COSM1722444 RCV000763143	275	R>W	Autosomal recessive juvenile Parkinson disease 2 NS Leprosy, susceptibility to, 2 Young-onset Parkinson disease PARK2 and PARK; at heterozygosity it is associated with late onset Parkinson disease; impairs the ability to ubiquitinate SNCAIP; abolishes p53/TP53 transcriptional repression; impairs the ability to ubiquitinate and degrade SYT11 [ClinVar, Cosmic, UniProt]	Yes	ClinGen cosmic curated ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
RCV001861915 CA4090206 VAR_019753 RCV000702268 rs72480422	280	D>N	Autosomal recessive juvenile Parkinson disease 2 PARK; does not affect PINK-1 dependent localization to depolarized mitochondria [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ExAC TOPMed dbSNP gnomAD
RCV003313956 CA4090202 RCV000460040 rs751037529 RCV003326436 VAR_019754	284	G>R	Autosomal recessive juvenile Parkinson disease 2 Autism spectrum disorder PARK2 [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ExAC TOPMed dbSNP gnomAD
VAR_019755 CA151534315 rs55961220	289	C>G	PARK2; increased aggregation; fails to ubiquitinate SYT11; loses ability to bind SYT11; impaired relocalization to damaged mitochondria; loss of function in mitophagy [UniProt]	Yes	ClinGen UniProt Ensembl dbSNP
rs1273010274 CA366459551 COSM3860249 COSM3860250 RCV001155243	298	I>F	Autosomal recessive juvenile Parkinson disease 2 Variant assessed as Somatic; MODERATE impact. [ClinVar, NCI-TCGA]	Yes	ClinGen NCI-TCGA Cosmic ClinVar NCI-TCGA TOPMed dbSNP
RCV001224682 CA4090116 RCV002272421 rs755749488	302	H>Y	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV000699717 rs72480423 CA4090111 RCV001343109 RCV002477601	310	E>D	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
CA254078 RCV000007453 rs137853055	311	Q>*	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
VAR_019756	328	G>E	PARK2; does not affect PINK-1 dependent localization to depolarized mitochondria [UniProt]	Yes	UniProt
rs199657839 RCV000514167 CA4090080 RCV001079680 VAR_019757 RCV000289814	334	R>C	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinGen ClinVar UniProt 1000Genomes ExAC TOPMed dbSNP gnomAD
rs746215864 RCV001347074 CA4090079 RCV002497153	334	R>H	Autosomal recessive juvenile Parkinson disease 2 Variant assessed as Somatic; MODERATE impact. [ClinVar, NCI-TCGA]	Yes	ClinGen ClinVar ExAC NCI-TCGA TOPMed dbSNP gnomAD
VAR_019759 CA366460357 rs1554274861	351	T>P	PARK2; impairs folding of IBR domain [UniProt]	Yes	ClinGen UniProt Ensembl dbSNP
rs56092260 CA344223 VAR_019760 RCV000858940 RCV000034119	366	R>W	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
RCV000173805 RCV000034120 RCV002496510 VAR_019761 RCV001513673 CA200721 rs1801582	380	V>L	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
RCV000244341 rs1801334 RCV000034121 RCV002504863 RCV001080144 CA344225 VAR_019762	394	D>N	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
RCV001154407 rs1784919731	398	A>V	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinVar dbSNP
VAR_070079 rs55830907 CA4089979 RCV000487928 RCV001154406	402	R>C	Autosomal recessive juvenile Parkinson disease 2 PARK2 [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
RCV001151374 RCV002557264 CA4089978 rs766915327	402	R>H	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV000361836 CA10621744 rs886061237	405	A>T	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
CA4089972 RCV000712859 rs778125254 VAR_019763	415	T>N	PARK2; impairs the ability to ubiquitinate SNCAIP; does not affect turnover of CDCRE1; impairs PINK1-dependent localization to dysfunctional depolarized mitochondria [UniProt]	Yes	ClinGen ClinVar UniProt ExAC dbSNP gnomAD
CA366456463 VAR_070080 rs1554252200	418	C>R	PARK2; decreased binding to the TP53 promoter; abolishes TP53 transcriptional repression; fails to ubiquitinate SYT11 but does not loose ability to bind SYT11 [UniProt]	Yes	ClinGen UniProt Ensembl dbSNP
rs191486604 RCV000992705 CA4089945 RCV002480234 RCV000269607 VAR_019764	430	G>D	Autosomal recessive juvenile Parkinson disease 2 PARK2; impairs PINK1-dependent localization to dysfunctional depolarized mitochondria; impaired E3 ubiquitin-protein ligase toward ZNF746 [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ESP ExAC TOPMed dbSNP gnomAD
rs397514694 VAR_019765 CA263212 RCV000043509	431	C>F	Autosomal recessive juvenile Parkinson disease 2 PARK2; impaired E3 ubiquitin-protein ligase toward ZNF746 and BCL2 [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
CA151429477 RCV001332482 rs949479970	434	M>I	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV000999646 CA366456342 rs1582953433	434	M>T	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV000336291 rs149953814 RCV001151373 CA4089939 VAR_019766	437	P>L	Autosomal recessive juvenile Parkinson disease 2 PARK2; impaired E3 ubiquitin-protein ligase toward BCL2 [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
VAR_019767 RCV001237187 CA4089936 rs778305273 RCV001780174	441	C>R	Autosomal recessive juvenile Parkinson disease 2 PARK2; decreased binding to the TP53 promoter; abolishes TP53 transcriptional repression [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ExAC TOPMed dbSNP gnomAD
rs137853056 RCV000762443 CA254081 RCV000007458	453	W>*	Variant assessed as Somatic; HIGH impact. Autosomal recessive juvenile Parkinson disease 2 [NCI-TCGA, ClinVar]	Yes	ClinGen ClinVar Ensembl NCI-TCGA dbSNP
CA4089931 rs748955949 RCV001302417 RCV000304835	455	R>H	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
rs755627153 RCV001858989 CA4089929 RCV001151372	456	V>I	Autosomal recessive juvenile Parkinson disease 2 [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
rs1462649580 CA366477855	2	I>M		No	ClinGen TOPMed gnomAD
CA4090562 rs747682986 RCV001313653	2	I>V		No	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
CA4090535 CA4090534 rs758661420	6	R>S		No	ClinGen ExAC gnomAD
CA4090531 rs748110477	8	N>I		No	ClinGen ExAC TOPMed gnomAD
rs1427758458 CA366477482	8	N>K		No	ClinGen TOPMed
rs748110477 CA4090532	8	N>S		No	ClinGen ExAC TOPMed gnomAD
rs748110477 CA4090530	8	N>T		No	ClinGen ExAC TOPMed gnomAD
COSM461856 CA366477481 rs111356273 COSM4821710	9	S>A	cervix Variant assessed as Somatic; MODERATE impact. [Cosmic, NCI-TCGA]	No	ClinGen NCI-TCGA Cosmic cosmic curated NCI-TCGA gnomAD
CA366477478 rs1399415195	9	S>C		No	ClinGen TOPMed
CA151293024 rs111356273	9	S>P		No	ClinGen gnomAD
rs1554325735 CA366477473	10	S>N		No	ClinGen Ensembl
TCGA novel	12	G>D	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
COSM4869019 COSM1075805	13	F>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
CA366477444 rs1159057404	14	P>S		No	ClinGen TOPMed
rs532703934 CA4090528	15	V>L		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA151293004 rs199841689	16	E>A		No	ClinGen TOPMed
CA366477423 rs146288080	18	D>H		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA4090524 rs146288080	18	D>N		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1438259227 CA366477419	18	D>V		No	ClinGen gnomAD
TCGA novel	19	S>Y	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
CA366477398 rs530092788	21	T>I		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA4090523 rs530092788	21	T>N		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs768213475 CA4090522	22	S>G		No	ClinGen ExAC gnomAD
COSM4872400 COSM1075804	22	S>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs768213475 CA151292973	22	S>R		No	ClinGen ExAC gnomAD
CA366477388 rs199859147 RCV000819694	23	I>N		No	ClinGen ClinVar 1000Genomes ExAC dbSNP gnomAD
CA4090521 rs199859147	23	I>T		No	ClinGen 1000Genomes ExAC gnomAD
rs1283476623 CA366477378	24	F>L		No	ClinGen TOPMed
rs1221959433 CA366477384	24	F>L		No	ClinGen TOPMed
rs1440010564 CA366477375	25	Q>*		No	ClinGen gnomAD
CA366477374 rs1562768862	25	Q>P		No	ClinGen Ensembl
CA366477360 rs1562768845	27	K>R		No	ClinGen Ensembl
rs200805156 CA4090519	28	E>G		No	ClinGen 1000Genomes ExAC gnomAD
CA366477344 rs1583580793	29	V>G		No	ClinGen Ensembl
rs745697155 CA4090518	30	V>D		No	ClinGen ExAC gnomAD
rs1285335787 CA366477334	31	A>D		No	ClinGen gnomAD
rs781111288 CA4090517	32	K>T		No	ClinGen ExAC TOPMed gnomAD
RCV001058075 rs770591350 CA4090516	33	R>*		No	ClinGen ClinVar ExAC dbSNP gnomAD
rs147757966 CA366477322	33	R>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA366477323 rs147757966	33	R>P		No	ClinGen ESP ExAC TOPMed gnomAD
rs1468779980 CA366477306	36	V>I		No	ClinGen gnomAD
rs1008851822 CA151292935	37	P>T		No	ClinGen TOPMed
rs1433385523 CA366477292	38	A>V		No	ClinGen TOPMed gnomAD
rs756595206 CA4090508	39	D>E		No	ClinGen ExAC gnomAD
CA4090509 rs780581295	39	D>G		No	ClinGen ExAC
rs1554325684 CA366477283	40	Q>*		No	ClinGen Ensembl
rs750884521 CA4090507	41	L>F		No	ClinGen ExAC TOPMed gnomAD
rs577232474 CA4090506	42	R>C		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA366477269 rs368134308	42	R>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA366477262 rs1210977280 COSM207532	44	I>L	large_intestine [Cosmic]	No	ClinGen cosmic curated gnomAD
CA366477246 rs75860381 RCV001231427	46	A>S		No	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA366477243 rs1373931707	46	A>V		No	ClinGen TOPMed
rs1242294277 CA366477242	47	G>R		No	ClinGen TOPMed
RCV001090782 rs1790151629	48	K>missing		No	ClinVar dbSNP
rs199762783 RCV001060078	49	E>D		No	ClinVar dbSNP
CA366477220 rs1378857360	50	L>V		No	ClinGen gnomAD
rs1005880478 CA151292892	51	R>T		No	ClinGen Ensembl
rs765314868 CA4090500	51	R>W		No	ClinGen ExAC
rs759577251 CA4090499	52	N>H		No	ClinGen ExAC gnomAD
CA366477206 rs1292308780	52	N>K		No	ClinGen TOPMed
CA4090498 rs776644079	52	N>S		No	ClinGen ExAC gnomAD
rs770775415 CA4090496	53	D>E		No	ClinGen ExAC gnomAD
CA151292871 rs952977187	53	D>N		No	ClinGen Ensembl
CA366477195 rs1344168940	54	W>*		No	ClinGen gnomAD
CA366477196 rs1554325654	54	W>R		No	ClinGen Ensembl
TCGA novel	56	V>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
CA4090495 rs145942836	56	V>M		No	ClinGen ESP ExAC TOPMed
COSM4811580 COSM1311801 rs1554325642	57	Q>=	Variant assessed as Somatic; LOW impact. [NCI-TCGA]	No	NCI-TCGA Cosmic NCI-TCGA
CA366477178 rs1421197461	57	Q>E		No	ClinGen gnomAD
CA366476216 rs1428787131	59	C>F		No	ClinGen gnomAD
CA366476211 rs1197520335	60	D>N		No	ClinGen gnomAD
CA366476190 rs1435195836	63	Q>*		No	ClinGen gnomAD
CA366476188 rs1269160083	63	Q>R		No	ClinGen gnomAD
CA4090455 rs373204115	64	Q>P		No	ClinGen ESP ExAC TOPMed gnomAD
CA4090454 rs754604402	65	S>N		No	ClinGen ExAC TOPMed gnomAD
CA366476161 rs1406898777	67	V>F	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ClinGen NCI-TCGA TOPMed
CA151118946 rs994961460	68	H>P		No	ClinGen Ensembl
CA366476147 rs1410734761	69	I>T		No	ClinGen TOPMed
rs766391627 CA4090452 RCV001235576	69	I>V		No	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
CA4090451 rs760555216	70	V>G		No	ClinGen ExAC gnomAD
CA366476143 rs899299169	70	V>L		No	ClinGen Ensembl
rs899299169 CA151118933	70	V>M		No	ClinGen Ensembl
rs767216170 CA4090449	72	R>*		No	ClinGen ExAC gnomAD
TCGA novel	72	R>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
CA4090447 rs775743629	73	P>L		No	ClinGen ExAC TOPMed gnomAD
CA366476124 rs775743629	73	P>Q		No	ClinGen ExAC TOPMed gnomAD
CA366476123 rs775743629	73	P>R		No	ClinGen ExAC TOPMed gnomAD
rs761534755 CA4090448	73	P>T		No	ClinGen ExAC TOPMed gnomAD
rs759650233 CA4090444	75	R>K		No	ClinGen ExAC TOPMed gnomAD
rs1050736954 CA151118876	78	Q>P		No	ClinGen gnomAD
rs770994041 CA366476085	79	E>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
rs770994041 CA366476086	79	E>K		No	ClinGen ExAC TOPMed gnomAD
CA4090442 rs770994041	79	E>Q		No	ClinGen ExAC TOPMed gnomAD
CA366476082 rs1440224564	79	E>V		No	ClinGen TOPMed
rs1378447280 CA366476073	80	M>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
CA366476062 rs1186161188	82	A>T		No	ClinGen TOPMed
CA4090441 rs55774500	82	A>V		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA151118843 rs1042122187	85	G>C	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ClinGen NCI-TCGA TOPMed
COSM4992657 CA151118834 COSM4992658 rs747891099	86	D>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ClinGen NCI-TCGA Cosmic NCI-TCGA TOPMed gnomAD
CA366476041 rs747891099	86	D>Y		No	ClinGen TOPMed gnomAD
rs754657726 CA4090437	87	D>N		No	ClinGen ExAC gnomAD
CA4090435 COSM134154 rs779465584	88	P>L	skin [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA366476026 rs779465584	88	P>R		No	ClinGen ExAC gnomAD
rs753483597 CA4090436	88	P>S		No	ClinGen ExAC gnomAD
CA366476024 rs755588390	89	R>G		No	ClinGen ExAC gnomAD
CA366476021 rs1238707850	89	R>K		No	ClinGen gnomAD
rs750337199 CA4090433	89	R>S		No	ClinGen ExAC gnomAD
TCGA novel	90	N>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
CA366476009 rs552077922	91	A>S		No	ClinGen 1000Genomes ExAC gnomAD
CA4090431 rs552077922	91	A>T		No	ClinGen 1000Genomes ExAC gnomAD
COSM3782026 CA4090430 COSM3782025 rs528661586	91	A>V	pancreas [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
TCGA novel	92	A>R	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
CA366476001 rs1158228651	93	G>R		No	ClinGen gnomAD
rs770930242 CA4090426	94	G>C		No	ClinGen ExAC TOPMed gnomAD
CA151118764 rs770930242	94	G>S		No	ClinGen ExAC TOPMed gnomAD
rs899118511 CA151118757	95	C>Y		No	ClinGen TOPMed gnomAD
rs377591051 CA4090425	96	E>K		No	ClinGen ESP ExAC TOPMed
rs369634041 CA366475975	97	R>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA4090422 rs369634041	97	R>Q		No	ClinGen ESP ExAC TOPMed gnomAD
rs373593750 CA4090423	97	R>W		No	ClinGen ESP ExAC TOPMed gnomAD
CA366475963 rs1443653639	99	P>H		No	ClinGen gnomAD
RCV001325205 VAR_019740 rs1256316516 CA366475954	100	Q>H		No	ClinGen ClinVar UniProt dbSNP gnomAD
TCGA novel	101	S>R	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
CA151118692 rs748892763	104	R>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
rs748892763 COSM3024429 COSM3024428 CA4090419	104	R>Q	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ClinGen NCI-TCGA Cosmic ExAC NCI-TCGA gnomAD
rs1583283886 CA366475924	105	V>G		No	ClinGen Ensembl
CA151118690 rs1026282132	106	D>E		No	ClinGen Ensembl
RCV001299911 rs1288568218	106	D>G		No	ClinVar dbSNP
CA366475918 rs1288568218	106	D>V		No	ClinGen gnomAD
rs779702970 CA4090418	107	L>V		No	ClinGen ExAC gnomAD
CA151118666 rs948332278	108	S>C		No	ClinGen TOPMed gnomAD
CA366475910 rs948332278	108	S>R		No	ClinGen TOPMed gnomAD
rs755641313 CA4090417	108	S>T		No	ClinGen ExAC TOPMed gnomAD
CA366475902 rs1450232889	109	S>N		No	ClinGen gnomAD
CA366475887 rs1465787705	111	V>A		No	ClinGen TOPMed
rs1404458540 CA366475875	113	P>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ClinGen NCI-TCGA TOPMed
COSM4861152 COSM741230	113	P>S	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs148252233 CA151118663	113	P>T		No	ClinGen Ensembl
CA4090416 rs529360617	115	D>N		No	ClinGen 1000Genomes ExAC gnomAD
rs757166995 CA4090414	117	V>L		No	ClinGen ExAC
rs1562622877 CA366475849	118	G>R		No	ClinGen Ensembl
rs376992611 CA4090411	119	L>M		No	ClinGen ESP ExAC TOPMed gnomAD
rs1420113868 CA366475825	122	I>N		No	ClinGen gnomAD
TCGA novel	122	I>S	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1562622812 CA366475801	126	D>H		No	ClinGen Ensembl
CA151118645 rs373443322	127	S>N		No	ClinGen ESP TOPMed
CA151118638 rs200239028	128	R>K		No	ClinGen Ensembl
CA366475781 rs1554292420	129	K>*		No	ClinGen Ensembl
CA366475773 rs1206232844	130	D>N		No	ClinGen TOPMed
RCV000998736 rs747624684	133	P>missing		No	ClinVar dbSNP
rs1487073927 CA366475748	133	P>L		No	ClinGen gnomAD
CA4090405 rs760707405	134	A>V		No	ClinGen ExAC gnomAD
CA4090404 rs201052724	135	G>R		No	ClinGen 1000Genomes ExAC gnomAD
CA366475730 rs1190424416	136	S>R		No	ClinGen TOPMed
COSM6172938 COSM6172939	138	A>P	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1321208493 CA366475661	139	G>S		No	ClinGen TOPMed
rs1583190025 CA366475655	140	R>G		No	ClinGen Ensembl
CA4090367 rs772022432	140	R>S		No	ClinGen ExAC TOPMed gnomAD
CA4090366 rs747984930	142	I>M		No	ClinGen ExAC TOPMed gnomAD
CA151069270 rs745400855	143	Y>*		No	ClinGen Ensembl
rs778798543 CA4090365	143	Y>C		No	ClinGen ExAC gnomAD
COSM3622678 CA366475620 rs1554283774 COSM3622679	145	S>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ClinGen NCI-TCGA Cosmic Ensembl NCI-TCGA
CA151069267 rs371890659	145	S>R		No	ClinGen ESP gnomAD
RCV000811453 rs149379304 CA151069250	147	Y>F		No	ClinGen ClinVar ESP TOPMed dbSNP
CA4090363 rs537030286	147	Y>H		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
RCV001304862 rs1060502319 CA16611895	148	V>E		No	ClinGen ClinVar dbSNP gnomAD
COSM3777299 COSM3777300 CA366475600 rs1259302587	148	V>L	Variant assessed as Somatic; MODERATE impact. urinary_tract [NCI-TCGA, Cosmic]	No	ClinGen NCI-TCGA Cosmic cosmic curated NCI-TCGA TOPMed
rs781548251 CA4090362	149	Y>H		No	ClinGen ExAC gnomAD
CA366475589 rs1371337373	150	C>R		No	ClinGen gnomAD
CA4090361 rs757483787	150	C>Y		No	ClinGen ExAC gnomAD
rs55654276 CA366475565	153	P>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1554283761 CA4090355	156	R>T		No	ClinGen Ensembl
CA366475538 rs1211085218	157	V>A		No	ClinGen gnomAD
CA366475542 rs1239344143	157	V>M	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
COSM6172941 COSM6172940	158	Q>H	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs367631227 CA4090353	158	Q>K		No	ClinGen ESP ExAC TOPMed gnomAD
rs1026034251 CA151069199	158	Q>R		No	ClinGen TOPMed
rs562500530 CA4090352	159	P>L		No	ClinGen ExAC TOPMed gnomAD
COSM3622674 COSM3622675	160	G>E	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1309896026 CA366475514	161	K>I		No	ClinGen gnomAD
CA366475515 rs1309896026	161	K>R		No	ClinGen gnomAD
rs760226358 CA4090350	162	L>F		No	ClinGen ExAC gnomAD
rs772798796 CA4090349	163	R>K		No	ClinGen ExAC gnomAD
CA151069169 rs772798796	163	R>T		No	ClinGen ExAC gnomAD
rs1304117265 CA366475502	164	V>I		No	ClinGen TOPMed gnomAD
rs1359518704 CA366475491	165	Q>H		No	ClinGen gnomAD
CA4090348 rs374988995	165	Q>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA4090347 rs748118673	166	C>R		No	ClinGen ExAC gnomAD
rs1554283741 CA366475487	166	C>Y		No	ClinGen Ensembl
rs1381410710 CA366475470	168	T>I		No	ClinGen gnomAD
CA4090346 rs768625409	169	C>S		No	ClinGen ExAC
rs1007797597 CA151069154	170	R>K		No	ClinGen TOPMed gnomAD
rs1367746077 CA366475453	171	Q>P		No	ClinGen TOPMed
CA4090345 rs749094429 RCV001318619	173	T>A		No	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
COSM3622673 COSM3622672 CA4090344 rs781608005	173	T>M	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ClinGen NCI-TCGA Cosmic ExAC NCI-TCGA TOPMed gnomAD
CA366475442 rs749094429	173	T>P		No	ClinGen ExAC TOPMed gnomAD
CA366475436 rs1485637704	174	L>F	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
rs777942244 CA4090341	175	T>I		No	ClinGen ExAC
rs371512669 CA4090340	176	L>F		No	ClinGen ESP ExAC TOPMed gnomAD
rs1246047894 CA366475420	177	T>A		No	ClinGen gnomAD
rs765648938 CA4090339	177	T>I		No	ClinGen ExAC gnomAD
CA4090338 rs765648938	177	T>N		No	ClinGen ExAC gnomAD
TCGA novel	178	Q>=	Variant assessed as Somatic; LOW impact. [NCI-TCGA]	No	NCI-TCGA
rs912896883 CA151069118	178	Q>R		No	ClinGen TOPMed gnomAD
rs370479735 CA366475394	179	G>A		No	ClinGen ESP ExAC TOPMed gnomAD
CA4090320 rs370479735 RCV001207440	179	G>D		No	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
rs56274447 CA150936488	179	G>S		No	ClinGen Ensembl
rs370479735 CA366475393	179	G>V		No	ClinGen ESP ExAC TOPMed gnomAD
CA4090319 rs755495887	181	S>P		No	ClinGen ExAC gnomAD
rs1465616743 CA366475381	182	C>R		No	ClinGen gnomAD
RCV000821393 rs1582962161 CA366475365	183	W>C		No	ClinGen ClinVar Ensembl dbSNP
rs142383136 CA4090318	184	D>V		No	ClinGen ESP ExAC TOPMed gnomAD
CA4090316 rs756411170	185	D>A		No	ClinGen ExAC gnomAD
CA4090314 rs377344238	185	D>E		No	ClinGen ESP ExAC TOPMed gnomAD
CA4090317 rs766731978	185	D>Y		No	ClinGen ExAC gnomAD
COSM741232 COSM4859145	186	V>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1562485799 CA366475342 RCV000706097	187	L>*		No	ClinGen ClinVar Ensembl dbSNP
CA150936395 rs199810018	188	I>V		No	ClinGen 1000Genomes
rs761430731 CA4090313	189	P>S		No	ClinGen ExAC TOPMed gnomAD
CA4090312 rs149060668	190	N>D		No	ClinGen ESP ExAC TOPMed gnomAD
rs530632014 CA4090310	191	R>Q		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs763650901 CA4090311	191	R>W		No	ClinGen ExAC TOPMed gnomAD
rs1377008518 CA366475315	192	M>R		No	ClinGen TOPMed
rs1018598457 CA150936347	193	S>N		No	ClinGen TOPMed
rs773550500 CA4090306	194	G>D		No	ClinGen ExAC gnomAD
rs748352072 CA4090304	199	P>L		No	ClinGen ExAC gnomAD
TCGA novel	199	P>Q	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
COSM741233 COSM4862611	200	H>P	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
CA150936312 rs72480421	200	H>Q		No	ClinGen gnomAD
CA150936310 rs888068912	201	C>*		No	ClinGen gnomAD
rs1231455463 CA571732449	201	C>*		No	ClinGen gnomAD
rs778993899 CA4090303	204	T>S	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
CA4090300 rs1554264900	206	A>V		No	ClinGen Ensembl
rs1583425504 CA366467027	207	E>A		No	ClinGen Ensembl
COSM3622668 COSM3622669	207	E>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
CA4090282 rs768779161	207	E>Q		No	ClinGen ExAC gnomAD
CA151579788 rs938983242	208	F>C		No	ClinGen Ensembl
TCGA novel	208	F>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
COSM1219291	209	F>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
CA366466999 rs1160371736	211	K>E		No	ClinGen gnomAD
CA366466997 RCV000804548 rs1583425462	211	K>I		No	ClinGen ClinVar Ensembl dbSNP
CA366466991 rs1388911686	212	C>G		No	ClinGen TOPMed
CA366466992 rs1388911686	212	C>R		No	ClinGen TOPMed
RCV001316760 rs1780901583	212	C>W		No	ClinVar dbSNP
COSM6105654 COSM6105653	213	G>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1562430382 CA366466977 COSM246366	214	A>E	prostate [Cosmic]	No	ClinGen cosmic curated Ensembl
rs1425142690 CA366466978	214	A>T		No	ClinGen gnomAD
rs1780900959 RCV001306888	215	H>P		No	ClinVar dbSNP
rs746340817 CA4090280	215	H>Q		No	ClinGen ExAC TOPMed gnomAD
rs1168709615 CA366466966	216	P>A		No	ClinGen TOPMed
CA4090279 rs781443859	218	S>C		No	ClinGen ExAC gnomAD
TCGA novel	220	K>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs757579280 CA4090278	220	K>R		No	ClinGen ExAC gnomAD
COSM1442090 rs1206205875 CA366466923	222	T>K	Variant assessed as Somatic; MODERATE impact. large_intestine [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated NCI-TCGA gnomAD
rs539815495 CA4090276	224	V>A		No	ClinGen 1000Genomes ExAC gnomAD
CA151579785 rs202212928	225	A>S		No	ClinGen TOPMed gnomAD
CA366466906 rs1356263061	225	A>V		No	ClinGen gnomAD
COSM741235 COSM1672964	229	I>F	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1562430302 CA366466880 RCV001348801	229	I>T		No	ClinGen ClinVar Ensembl dbSNP
rs571490973 CA366466875 RCV000584910	230	A>E		No	ClinGen ClinVar 1000Genomes ExAC dbSNP gnomAD
COSM1075797 COSM3024374 CA366466878 rs1554256339	230	A>T	Variant assessed as Somatic; MODERATE impact. endometrium [NCI-TCGA, Cosmic]	No	ClinGen NCI-TCGA Cosmic cosmic curated Ensembl NCI-TCGA
RCV001312630 rs571490973 CA4090274	230	A>V		No	ClinGen ClinVar 1000Genomes ExAC dbSNP gnomAD
CA151579784 rs764754559	231	T>K		No	ClinGen ExAC TOPMed gnomAD
CA4090273 rs764754559	231	T>R		No	ClinGen ExAC TOPMed gnomAD
TCGA novel	232	N>H	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
CA366466853 rs373822092	234	R>G		No	ClinGen ESP ExAC TOPMed gnomAD
rs144032774 CA4090270 RCV001036207	234	R>Q		No	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
rs373822092 CA4090271	234	R>W		No	ClinGen ESP ExAC TOPMed gnomAD
COSM3860256 COSM3860255	237	T>A	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1473499076 CA366466836	237	T>P		No	ClinGen gnomAD
CA366466832 rs1418016570	237	T>S		No	ClinGen gnomAD
CA4090268 rs114974496	238	C>W		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs768832012 CA4090266	239	I>S		No	ClinGen ExAC gnomAD
rs1476658565 CA366466822	239	I>V		No	ClinGen TOPMed gnomAD
CA4090265 rs137853054	240	T>K		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1194371893 CA366466815	240	T>S		No	ClinGen gnomAD
rs1405650185 CA366466812	241	C>S		No	ClinGen gnomAD
rs746368282 CA4090263	242	T>I		No	ClinGen ExAC gnomAD
CA366466791 rs1403011922	244	V>A		No	ClinGen TOPMed gnomAD
RCV001865695 rs771259513 CA4090261	244	V>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ClinGen ClinVar ExAC NCI-TCGA TOPMed dbSNP gnomAD
CA366466787 rs1217001446	245	R>M		No	ClinGen gnomAD
CA4090241 rs1300606784	246	S>R		No	ClinGen Ensembl
RCV001288687 rs1790398941	248	V>missing		No	ClinVar dbSNP
RCV000952107 rs777074432 CA4090239	248	V>I		No	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
CA366465713 rs777074432	248	V>L		No	ClinGen ExAC TOPMed gnomAD
RCV001042659 rs1790398298	252	Q>L		No	ClinVar dbSNP
CA366465678 rs747427602	253	C>F		No	ClinGen ExAC TOPMed gnomAD
rs1413623928 CA366465682	253	C>G		No	ClinGen gnomAD
rs1174733303 CA366465676	253	C>W		No	ClinGen gnomAD
CA366465664 rs1479824956	255	S>C		No	ClinGen TOPMed gnomAD
CA366465659 rs1233588284	256	R>H	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ClinGen NCI-TCGA TOPMed gnomAD
COSM3860253 COSM3860254	256	R>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs748797721 CA366465650 RCV000817068	257	H>Q		No	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
CA4090229 rs756064095	258	V>L		No	ClinGen ExAC TOPMed gnomAD
CA4090230 rs756064095	258	V>M	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
rs750325162 RCV000705221 CA4090228	259	I>V		No	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
rs1214145439 CA366465635	260	C>S		No	ClinGen TOPMed
TCGA novel	261	L>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs9456711 CA366465626	261	L>F		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1348418442 CA366465612	263	C>S		No	ClinGen gnomAD
rs930004731 CA151534353	264	F>L		No	ClinGen Ensembl
TCGA novel	265	H>Q	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs752922983 CA4090225	265	H>R		No	ClinGen ExAC TOPMed gnomAD
CA4090226 rs148453342	265	H>Y		No	ClinGen ESP ExAC TOPMed gnomAD
rs765494290 CA4090224	266	L>S		No	ClinGen ExAC gnomAD
rs377554392 RCV000992707 CA4090220	268	C>*		No	ClinGen ClinVar ESP ExAC dbSNP gnomAD
rs1315134059 CA366465581	268	C>R		No	ClinGen TOPMed gnomAD
rs1315134059 CA366465582	268	C>S		No	ClinGen TOPMed gnomAD
CA4090221 rs200720727	268	C>Y		No	ClinGen ExAC gnomAD
rs1396188392 CA366465576	269	V>M		No	ClinGen TOPMed
CA4090218 rs773794753	271	R>K		No	ClinGen ExAC TOPMed gnomAD
rs772622421 VAR_019751 CA366465559	271	R>S		No	ClinGen UniProt ExAC TOPMed dbSNP gnomAD
rs141366047 CA366465558	272	L>F		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA4090216 rs141366047	272	L>V		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1212684133 CA366465554	273	N>H		No	ClinGen gnomAD
CA4090213 rs373750972 COSM4916586 COSM4916587	273	N>S	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ClinGen NCI-TCGA Cosmic ESP ExAC NCI-TCGA gnomAD
CA151534337 rs538358438	274	D>G		No	ClinGen TOPMed gnomAD
CA366465545 rs1285127997	274	D>N		No	ClinGen TOPMed gnomAD
COSM6172944 COSM6172943	275	R>P	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs769230602 CA4090212 RCV001198059	275	R>Q	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ClinGen ClinVar ExAC NCI-TCGA TOPMed dbSNP gnomAD
CA4090210 rs147028059	279	H>P		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs149433924 CA366465512	279	H>Q		No	ClinGen ESP ExAC TOPMed gnomAD
rs147028059 CA4090209	279	H>R		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs573316115 CA4090211	279	H>Y		No	ClinGen 1000Genomes ExAC gnomAD
rs1316563336 CA366465508	280	D>G		No	ClinGen TOPMed
CA4090207 rs72480422	280	D>Y		No	ClinGen ExAC TOPMed gnomAD
CA4090204 rs766578225	281	P>R		No	ClinGen ExAC TOPMed gnomAD
rs1554305870 CA366465496	282	Q>R		No	ClinGen Ensembl
RCV001326080 rs56154308 CA4090203	283	L>P		No	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
rs768102678 CA4090201	286	S>C		No	ClinGen ExAC TOPMed gnomAD
CA366465469 rs768102678	286	S>F		No	ClinGen ExAC TOPMed gnomAD
CA366465470 rs768102678	286	S>Y		No	ClinGen ExAC TOPMed gnomAD
rs762130249 CA4090200	287	L>V		No	ClinGen ExAC gnomAD
CA366465462 rs1477642410	288	P>H		No	ClinGen gnomAD
rs887280483 CA151534317	288	P>S		No	ClinGen Ensembl
CA366465451 rs1254254151	290	V>L		No	ClinGen TOPMed
rs1262180713 CA366465444	291	A>S		No	ClinGen TOPMed gnomAD
rs1262180713 CA366465446	291	A>T		No	ClinGen TOPMed gnomAD
TCGA novel	291	A>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
COSM4871209 COSM1075795	292	G>D	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
TCGA novel	292	G>R	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
CA366459613 rs1483319717	292	G>S		No	ClinGen Ensembl
CA366459597 rs1251166929	293	C>W		No	ClinGen gnomAD
CA4090121 rs748669247	293	C>Y		No	ClinGen ExAC gnomAD
COSM3622665 COSM3622664	294	P>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
COSM3024365 COSM1567935	295	N>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1006331297 CA151484415	295	N>S		No	ClinGen TOPMed gnomAD
rs1006331297 CA366459579	295	N>T		No	ClinGen TOPMed gnomAD
rs951351663 CA151484414	296	S>T		No	ClinGen TOPMed
rs1257682809 CA366459571	296	S>Y		No	ClinGen gnomAD
rs1362268565 CA366459553	297	L>F		No	ClinGen gnomAD
rs1562531584 CA366459562	297	L>V		No	ClinGen Ensembl
CA366459545 rs1273010274	298	I>L		No	ClinGen TOPMed
rs1483766444 CA366459539	298	I>M		No	ClinGen TOPMed
rs755374874 CA4090119	298	I>S		No	ClinGen ExAC gnomAD
rs755374874 CA366459541	298	I>T		No	ClinGen ExAC gnomAD
COSM741236 COSM4858895	300	E>G	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs867108423 CA151484413	300	E>K		No	ClinGen gnomAD
rs867108423 CA366459524	300	E>Q		No	ClinGen gnomAD
CA366459513 rs780417025	301	L>H		No	ClinGen ExAC gnomAD
CA4090118 rs780417025	301	L>P		No	ClinGen ExAC gnomAD
rs780417025 CA4090117	301	L>R		No	ClinGen ExAC gnomAD
rs750022000 CA4090115	302	H>R		No	ClinGen ExAC TOPMed gnomAD
CA4090114 rs766948045	303	H>Y		No	ClinGen ExAC TOPMed gnomAD
CA366459454 rs1394653511	306	I>L		No	ClinGen gnomAD
rs1330260959 CA366459448	306	I>M		No	ClinGen TOPMed gnomAD
CA366459427 rs1168877682	309	E>*		No	ClinGen TOPMed gnomAD
rs977176475 CA151484412	309	E>D		No	ClinGen TOPMed
rs1583239627 CA366459418	310	E>G		No	ClinGen Ensembl
CA366459409 rs1554277715	311	Q>H		No	ClinGen Ensembl
VAR_062672	311	Q>R	a patient with Parkinson disease; unknown pathological significance [UniProt]	No	UniProt
CA4090095 rs756869892	312	Y>C		No	ClinGen ExAC gnomAD
rs1583215669 RCV000792687 CA366460598	313	N>D		No	ClinGen ClinVar Ensembl dbSNP
CA366460595 rs1421841956	313	N>S		No	ClinGen TOPMed gnomAD
CA4090093 rs763652747	314	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA4090094 rs751095098	314	R>W		No	ClinGen ExAC gnomAD
rs764955994 CA4090090	316	Q>P		No	ClinGen ExAC gnomAD
CA366460561 rs1212919365	318	Y>C		No	ClinGen gnomAD
rs759364763 CA4090089	319	G>S		No	ClinGen ExAC gnomAD
CA366460551 rs1583215602	320	A>T		No	ClinGen Ensembl
rs767703008 CA4090087	321	E>D		No	ClinGen ExAC gnomAD
COSM6172946 COSM6172945	322	E>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1427755256 CA366460524	323	C>W		No	ClinGen TOPMed
rs1375002872 CA366460518	324	V>A		No	ClinGen TOPMed gnomAD
COSM4813018 COSM450872	324	V>F	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
CA366460522 rs1583215588	324	V>L		No	ClinGen Ensembl
COSM4879198 COSM1131982	326	Q>H	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
CA366460497 rs1562519353	327	M>I		No	ClinGen Ensembl
rs141061596 CA151481902	327	M>T		No	ClinGen ESP TOPMed
CA151481901 rs894633561	329	G>C		No	ClinGen TOPMed gnomAD
CA4090085 rs774445597	329	G>D		No	ClinGen ExAC gnomAD
COSM1637981 rs894633561 COSM1637980 CA151481900	329	G>S	bone [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
CA366460486 rs749768565	330	V>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
RCV001861912 COSM5005235 CA4090082 rs749768565 COSM5005236	330	V>M	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ClinGen NCI-TCGA Cosmic ClinVar ExAC NCI-TCGA TOPMed dbSNP gnomAD
COSM1442088 COSM5173598 rs745647746	330	V>R	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic NCI-TCGA
rs1583215504 RCV001008550	331	L>missing		No	ClinVar dbSNP
COSM3860247 COSM3860248	331	L>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs776048801 CA4090081	333	P>L		No	ClinGen ExAC TOPMed gnomAD
COSM3622662 COSM3622663	335	P>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
CA366460458 rs1255066400	335	P>T		No	ClinGen gnomAD
rs756996581 CA4090077	337	C>Y		No	ClinGen ExAC gnomAD
CA366460431 VAR_019758 rs1554274880	339	A>S		No	ClinGen UniProt Ensembl dbSNP
rs746620234 CA4090076	339	A>V		No	ClinGen ExAC TOPMed gnomAD
rs1318163167 CA366460425 RCV001367078	340	G>E		No	ClinGen ClinVar dbSNP gnomAD
CA4090072 COSM3622660 COSM3622661 rs529808032	343	P>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ClinGen NCI-TCGA Cosmic 1000Genomes ExAC NCI-TCGA TOPMed gnomAD
COSM6105656 COSM6105655	343	P>Q	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1320439103 CA366460398	345	P>A		No	ClinGen TOPMed gnomAD
CA366460395 rs1309668672	345	P>R		No	ClinGen gnomAD
rs1320439103 CA366460399	345	P>T		No	ClinGen TOPMed gnomAD
rs1361762771 CA366460390	346	D>A		No	ClinGen gnomAD
COSM4814588 COSM450871 COSM3024354 COSM741239	347	Q>H	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
TCGA novel	347	Q>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs919970556 CA151481899	348	R>K		No	ClinGen Ensembl
CA366460345 rs780996466	352	C>*		No	ClinGen TOPMed gnomAD
CA366460344 rs780996466	352	C>W		No	ClinGen TOPMed gnomAD
COSM6172947 COSM6172948	353	E>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1460011098 CA366460343	353	E>K		No	ClinGen TOPMed gnomAD
CA4090068 rs146599326	354	G>E		No	ClinGen ESP ExAC TOPMed gnomAD
COSM6105658 COSM6105657	354	G>R	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs146599326 CA366460331	354	G>V		No	ClinGen ESP ExAC TOPMed gnomAD
CA366460328 rs1166764231	355	G>C		No	ClinGen gnomAD
rs1018001612 CA151481897	355	G>D		No	ClinGen TOPMed
TCGA novel	355	G>R	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
CA366460322 rs1156249065	356	N>S		No	ClinGen TOPMed
TCGA novel	357	G>C	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
CA4090067 rs764212924	357	G>V		No	ClinGen ExAC gnomAD
CA366460310 rs1418575994	358	L>P		No	ClinGen gnomAD
CA4090065 rs201300874	359	G>D		No	ClinGen 1000Genomes ExAC gnomAD
CA4090066 rs763082278	359	G>S		No	ClinGen ExAC gnomAD
CA366460300 rs1242128610	360	C>Y		No	ClinGen gnomAD
CA366456832 rs759676993	363	A>D		No	ClinGen ExAC TOPMed gnomAD
CA366456835 rs1172606856	363	A>T		No	ClinGen gnomAD
CA4090028 rs759676993	363	A>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
rs754463648 CA4090027	364	F>C		No	ClinGen ExAC gnomAD
rs761213043 CA4090026	366	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs773654456 CA4090025	367	E>G		No	ClinGen ExAC gnomAD
VAR_062673 COSM3622659	371	A>T	Variant assessed as Somatic; MODERATE impact. a patient with Parkinson disease; unknown pathological significance [NCI-TCGA, UniProt]	No	NCI-TCGA Cosmic UniProt
COSM207507 CA4090024 rs375036403	371	A>V	large_intestine [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
RCV001343392 CA366456768 rs1240306663	373	H>N		No	ClinGen ClinVar TOPMed dbSNP
CA4090021 rs370271614	375	G>E		No	ClinGen ESP ExAC TOPMed gnomAD
rs1348629802 CA366456750	375	G>W		No	ClinGen gnomAD
CA366456736 rs1583005052	377	C>S		No	ClinGen Ensembl
COSM3622658 rs748763421 CA4090020	378	S>G	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ClinGen NCI-TCGA Cosmic ExAC NCI-TCGA gnomAD
COSM4625718	379	A>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
CA4090018 rs1801582	380	V>I		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
TCGA novel	381	F>C	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1328846265 CA366456695	383	A>D		No	ClinGen gnomAD
rs781046528 CA4090017	386	T>A		No	ClinGen ExAC gnomAD
CA4090015 rs753025419	387	T>A		No	ClinGen ExAC gnomAD
rs948581056 CA151433685	388	T>A		No	ClinGen TOPMed
rs547404732 CA4090014	388	T>I		No	ClinGen 1000Genomes ExAC gnomAD
rs751005126 CA4089992	390	A>D		No	ClinGen ExAC gnomAD
rs777708182 RCV001338467	390	A>S		No	ClinVar dbSNP
rs777708182 CA151430588	390	A>T		No	ClinGen Ensembl
CA366456635 rs767878841	391	Y>D		No	ClinGen ExAC gnomAD
rs767878841 CA4089991	391	Y>H		No	ClinGen ExAC gnomAD
rs539790024 CA151430587	392	R>K		No	ClinGen Ensembl
CA366456623 rs1464839870	393	V>I		No	ClinGen gnomAD
rs1435831243 CA366456614	394	D>G		No	ClinGen gnomAD
CA366456610 rs1554252239	395	E>*		No	ClinGen Ensembl
CA366456606 rs1205719126	395	E>G		No	ClinGen gnomAD
COSM450870	395	E>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
CA4089987 rs539917500	396	R>G		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA151430586 rs904536848	396	R>K		No	ClinGen Ensembl
COSM1075794	397	A>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
CA4089984 rs571092914	398	A>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA4089985 COSM1219288 rs571092914	398	A>T	large_intestine [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
rs746922936 CA4089982	399	E>K		No	ClinGen ExAC TOPMed gnomAD
CA4089980 rs771931085	401	A>G		No	ClinGen ExAC gnomAD
rs773142133 CA4089981	401	A>T		No	ClinGen ExAC gnomAD
rs766915327 CA366456566	402	R>L		No	ClinGen ExAC TOPMed gnomAD
CA366456557 rs1374200676	403	W>C		No	ClinGen gnomAD
rs1582967625 CA366456551	404	E>G		No	ClinGen Ensembl
rs1434366429 CA366456554	404	E>Q		No	ClinGen gnomAD
COSM741240	405	A>P	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
TCGA novel	405	A>S	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
COSM1442087	407	S>C	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
COSM4900163 rs1178259895 CA366456535	407	S>P	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ClinGen NCI-TCGA Cosmic NCI-TCGA gnomAD
CA4089977 rs562362828	408	K>R		No	ClinGen 1000Genomes ExAC gnomAD
rs1554252213 CA366456521	409	E>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	ClinGen Ensembl NCI-TCGA
rs1582967596 CA366456510	410	T>I		No	ClinGen Ensembl
CA4089976 rs745912659	411	I>N		No	ClinGen ExAC gnomAD
CA366456492 rs1294618455	413	K>T		No	ClinGen TOPMed
CA4089974 rs757738248	414	T>I		No	ClinGen ExAC TOPMed
CA366456458 rs1338515311	418	C>F		No	ClinGen gnomAD
rs1338515311 CA366456460	418	C>Y		No	ClinGen gnomAD
COSM6172951	419	P>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
CA366456452 rs1255292721	419	P>R		No	ClinGen gnomAD
rs752418689 CA4089970	419	P>S	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
COSM1442086 CA4089969 rs145135117	420	R>C	Variant assessed as Somatic; MODERATE impact. large_intestine [NCI-TCGA, Cosmic]	No	ClinGen NCI-TCGA Cosmic cosmic curated ESP ExAC NCI-TCGA TOPMed gnomAD
COSM1672963 RCV001044242 CA151430584 rs531247345	420	R>H	large_intestine [Cosmic]	No	ClinGen cosmic curated ClinVar 1000Genomes dbSNP gnomAD
CA151430583 rs868336390	421	C>S		No	ClinGen Ensembl
CA4089968 rs759137723	422	H>R		No	ClinGen ExAC TOPMed gnomAD
CA366456417 rs1233077263	425	V>A		No	ClinGen gnomAD
rs1354004837 CA366456398	428	N>H		No	ClinGen gnomAD
rs758718482	428	N>K	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
CA4089946 rs760223151	429	G>E		No	ClinGen ExAC TOPMed gnomAD
rs1226997153 CA366456371	430	G>S		No	ClinGen gnomAD
rs761791697 CA4089943	432	M>R		No	ClinGen ExAC gnomAD
rs767539742 CA4089944	432	M>V		No	ClinGen ExAC gnomAD
rs1410059451 CA366456350	433	H>P		No	ClinGen TOPMed
rs774317638 CA4089942	434	M>V		No	ClinGen ExAC TOPMed gnomAD
rs917999795 CA151429476	435	K>T		No	ClinGen gnomAD
CA4089941 rs759692468	437	P>A		No	ClinGen ExAC gnomAD
CA4089940 rs759692468	437	P>T		No	ClinGen ExAC gnomAD
rs1370041903 CA366456320	438	Q>*		No	ClinGen gnomAD
CA4089937 rs747064211	440	Q>R		No	ClinGen ExAC gnomAD
CA366456287 rs1166635083	442	R>S		No	ClinGen TOPMed gnomAD
CA366456278 rs772592654	444	E>*		No	ClinGen ExAC TOPMed gnomAD
RCV001308693 CA4089935 rs772592654	444	E>Q	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ClinGen ClinVar ExAC NCI-TCGA TOPMed dbSNP gnomAD
rs1554250662 CA366456266	445	W>*		No	ClinGen Ensembl
CA151429475 rs961239925	445	W>*		No	ClinGen TOPMed
rs544295360 CA151429474	447	W>R		No	ClinGen 1000Genomes gnomAD
rs908339150 CA151429473	449	C>S		No	ClinGen Ensembl
CA366456233 rs1268998803	450	G>S		No	ClinGen gnomAD
CA366456226 rs1191453704	451	C>R		No	ClinGen TOPMed gnomAD
rs755354082 CA4089933	452	E>K		No	ClinGen ExAC gnomAD
rs755354082 CA4089932	452	E>Q		No	ClinGen ExAC gnomAD
CA366456204 rs1231586290	454	N>D		No	ClinGen gnomAD
rs1582953250 CA366456202	454	N>T		No	ClinGen Ensembl
rs1490851246 CA366456195	455	R>C		No	ClinGen TOPMed
CA4089926 CA366456174 rs757263675	458	M>I		No	ClinGen ExAC TOPMed gnomAD
RCV000998734 CA4089927 rs182893847	458	M>L		No	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA4089928 rs182893847	458	M>V		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs751485437 CA366456169	459	G>A		No	ClinGen ExAC gnomAD
rs751485437 CA4089925	459	G>E	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
CA366456158 rs1305965991	461	H>Y		No	ClinGen gnomAD
CA366456142 rs1374007271	463	F>L		No	ClinGen TOPMed
COSM3410769	464	D>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
CA4089923 rs763854303	465	V>G		No	ClinGen ExAC gnomAD
CA151429471 rs997369852	466	V>Q		No	ClinGen Ensembl

3 associated diseases with O60260

[MIM: 168600]: Parkinson disease (PARK)

A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features. . Note=Disease susceptibility may be associated with variants affecting the gene represented in this entry. Heterozygous mutations act as susceptibility alleles for late-onset Parkinson disease (PubMed:12730996, PubMed:12629236).

[MIM: 600116]: Parkinson disease 2 (PARK2)

A neurodegenerative disorder characterized by bradykinesia, rigidity, postural instability, tremor, and onset usually before 40. It differs from classic Parkinson disease by early DOPA-induced dyskinesia, diurnal fluctuation of the symptoms, sleep benefit, dystonia and hyper-reflexia. Dementia is absent. Pathologically, patients show loss of dopaminergic neurons in the substantia nigra, similar to that seen in Parkinson disease; however, Lewy bodies (intraneuronal accumulations of aggregated proteins) are absent. . Note=The disease is caused by variants affecting the gene represented in this entry.

Without disease ID

A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features. . Note=Disease susceptibility may be associated with variants affecting the gene represented in this entry. Heterozygous mutations act as susceptibility alleles for late-onset Parkinson disease (PubMed:12730996, PubMed:12629236).
A neurodegenerative disorder characterized by bradykinesia, rigidity, postural instability, tremor, and onset usually before 40. It differs from classic Parkinson disease by early DOPA-induced dyskinesia, diurnal fluctuation of the symptoms, sleep benefit, dystonia and hyper-reflexia. Dementia is absent. Pathologically, patients show loss of dopaminergic neurons in the substantia nigra, similar to that seen in Parkinson disease; however, Lewy bodies (intraneuronal accumulations of aggregated proteins) are absent. . Note=The disease is caused by variants affecting the gene represented in this entry.

8 regional properties for O60260

Type	Name	Position	InterPro Accession
domain	Protein kinase domain	275 - 528	IPR000719
domain	SH2 domain	154 - 253	IPR000980
domain	Serine-threonine/tyrosine-protein kinase, catalytic domain	276 - 524	IPR001245
domain	SH3 domain	89 - 150	IPR001452
active_site	Tyrosine-protein kinase, active site	390 - 402	IPR008266
binding_site	Protein kinase, ATP binding site	281 - 303	IPR017441
domain	Tyrosine-protein kinase, catalytic domain	275 - 524	IPR020635
domain	Tyrosine-protein kinase Yes, SH3 domain	92 - 149	IPR035751

Functions

		Description
EC Number	2.3.2.31	Aminoacyltransferases
Subcellular Localization	Cytoplasm, cytosol Nucleus Endoplasmic reticulum Mitochondrion Mitochondrion outer membrane Cell projection, neuron projection Postsynaptic density Presynapse	Mainly localizes in the cytosol (PubMed:19029340, PubMed:19229105) Co-localizes with SYT11 in neutrites (PubMed:12925569) Co-localizes with SNCAIP in brainstem Lewy bodies (PubMed:10319893, PubMed:11431533) Translocates to dysfunctional mitochondria that have lost the mitochondrial membrane potential; recruitment to mitochondria is PINK1-dependent (PubMed:18957282, PubMed:19966284, PubMed:23620051, PubMed:24898855) Mitochondrial localization also gradually increases with cellular growth (PubMed:22082830)
PANTHER Family	PTHR11685	RBR FAMILY RING FINGER AND IBR DOMAIN-CONTAINING
PANTHER Subfamily	PTHR11685:SF471	E3 UBIQUITIN-PROTEIN LIGASE PARKIN
PANTHER Protein Class	ubiquitin-protein ligase protein modifying enzyme
PANTHER Pathway Category	Parkinson disease Parkin

17 GO annotations of cellular component

Name	Definition
aggresome	An inclusion body formed by dynein-dependent retrograde transport of an aggregated protein on microtubules.
cytoplasm	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
dopaminergic synapse	A synapse that uses dopamine as a neurotransmitter.
endoplasmic reticulum	The irregular network of unit membranes, visible only by electron microscopy, that occurs in the cytoplasm of many eukaryotic cells. The membranes form a complex meshwork of tubular channels, which are often expanded into slitlike cavities called cisternae. The ER takes two forms, rough (or granular), with ribosomes adhering to the outer surface, and smooth (with no ribosomes attached).
Golgi apparatus	A membrane-bound cytoplasmic organelle of the endomembrane system that further processes the core oligosaccharides (e.g. N-glycans) added to proteins in the endoplasmic reticulum and packages them into membrane-bound vesicles. The Golgi apparatus operates at the intersection of the secretory, lysosomal, and endocytic pathways.
Lewy body	Cytoplasmic, spherical inclusion commonly found in damaged neurons, and composed of abnormally phosphorylated, neurofilament proteins aggregated with ubiquitin and alpha-synuclein.
mitochondrial outer membrane	The outer, i.e. cytoplasm-facing, lipid bilayer of the mitochondrial envelope.
mitochondrion	A semiautonomous, self replicating organelle that occurs in varying numbers, shapes, and sizes in the cytoplasm of virtually all eukaryotic cells. It is notably the site of tissue respiration.
neuron projection	A prolongation or process extending from a nerve cell, e.g. an axon or dendrite.
nuclear speck	A discrete extra-nucleolar subnuclear domain, 20-50 in number, in which splicing factors are seen to be localized by immunofluorescence microscopy.
nucleus	A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
Parkin-FBXW7-Cul1 ubiquitin ligase complex	A ubiquitin ligase complex containing Parkin (PARK2), the F-box protein FBXW7 (also called SEL-10) and a cullin from the Cul1 subfamily; substrate specificity is conferred by the F-box protein.
perinuclear region of cytoplasm	Cytoplasm situated near, or occurring around, the nucleus.
postsynaptic density	An electron dense network of proteins within and adjacent to the postsynaptic membrane of an asymmetric, neuron-neuron synapse. Its major components include neurotransmitter receptors and the proteins that spatially and functionally organize them such as anchoring and scaffolding molecules, signaling enzymes and cytoskeletal components.
presynapse	The part of a synapse that is part of the presynaptic cell.
ubiquitin ligase complex	A protein complex that includes a ubiquitin-protein ligase and enables ubiquitin protein ligase activity. The complex also contains other proteins that may confer substrate specificity on the complex.

26 GO annotations of molecular function

Name	Definition
actin binding	Binding to monomeric or multimeric forms of actin, including actin filaments.
beta-catenin binding	Binding to a catenin beta subunit.
cullin family protein binding	Binding to a member of the cullin family, hydrophobic proteins that act as scaffolds for ubiquitin ligases (E3).
enzyme binding	Binding to an enzyme, a protein with catalytic activity.
F-box domain binding	Binding to an F-box domain of a protein.
G protein-coupled receptor binding	Binding to a G protein-coupled receptor.
heat shock protein binding	Binding to a heat shock protein, a protein synthesized or activated in response to heat shock.
histone deacetylase binding	Binding to histone deacetylase.
Hsp70 protein binding	Binding to a Hsp70 protein, heat shock proteins around 70kDa in size.
identical protein binding	Binding to an identical protein or proteins.
kinase binding	Binding to a kinase, any enzyme that catalyzes the transfer of a phosphate group.
PDZ domain binding	Binding to a PDZ domain of a protein, a domain found in diverse signaling proteins.
phospholipase binding	Binding to a phospholipase.
protein kinase binding	Binding to a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate.
protein-containing complex binding	Binding to a macromolecular complex.
protein-folding chaperone binding	Binding to a chaperone protein, a class of proteins that bind to nascent or unfolded polypeptides and ensure correct folding or transport.
SH3 domain binding	Binding to a SH3 domain (Src homology 3) of a protein, small protein modules containing approximately 50 amino acid residues found in a great variety of intracellular or membrane-associated proteins.
transcription corepressor activity	A transcription coregulator activity that represses or decreases the transcription of specific gene sets via binding to a DNA-bound DNA-binding transcription factor, either on its own or as part of a complex. Corepressors often act by altering chromatin structure and modifications. For example, one class of transcription corepressors modifies chromatin structure through covalent modification of histones. A second class remodels the conformation of chromatin in an ATP-dependent fashion. A third class modulates interactions of DNA-bound DNA-binding transcription factors with other transcription coregulators.
tubulin binding	Binding to monomeric or multimeric forms of tubulin, including microtubules.
ubiquitin binding	Binding to ubiquitin, a protein that when covalently bound to other cellular proteins marks them for proteolytic degradation.
ubiquitin conjugating enzyme binding	Binding to a ubiquitin conjugating enzyme, any of the E2 proteins.
ubiquitin protein ligase activity	Catalysis of the transfer of ubiquitin to a substrate protein via the reaction X-ubiquitin + S -> X + S-ubiquitin, where X is either an E2 or E3 enzyme, the X-ubiquitin linkage is a thioester bond, and the S-ubiquitin linkage is an amide bond
ubiquitin protein ligase binding	Binding to a ubiquitin protein ligase enzyme, any of the E3 proteins.
ubiquitin-protein transferase activity	Catalysis of the transfer of ubiquitin from one protein to another via the reaction X-Ub + Y --> Y-Ub + X, where both X-Ub and Y-Ub are covalent linkages.
ubiquitin-specific protease binding	Binding to a ubiquitin-specific protease.
zinc ion binding	Binding to a zinc ion (Zn).

101 GO annotations of biological process

Name	Definition
adult locomotory behavior	Locomotory behavior in a fully developed and mature organism.
aggresome assembly	The aggregation, arrangement and bonding together of a set of components to form an aggresome; requires the microtubule cytoskeleton and dynein.
amyloid fibril formation	The generation of amyloid fibrils, insoluble fibrous protein aggregates exhibiting beta sheet structure, from proteins.
autophagy of mitochondrion	The autophagic process in which mitochondria are delivered to a type of vacuole and degraded in response to changing cellular conditions.
cellular response to dopamine	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a dopamine stimulus.
cellular response to manganese ion	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a manganese ion stimulus.
cellular response to oxidative stress	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of oxidative stress, a state often resulting from exposure to high levels of reactive oxygen species, e.g. superoxide anions, hydrogen peroxide (H2O2), and hydroxyl radicals.
cellular response to toxic substance	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a toxic stimulus.
cellular response to unfolded protein	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an unfolded protein stimulus.
central nervous system development	The process whose specific outcome is the progression of the central nervous system over time, from its formation to the mature structure. The central nervous system is the core nervous system that serves an integrating and coordinating function. In vertebrates it consists of the brain and spinal cord. In those invertebrates with a central nervous system it typically consists of a brain, cerebral ganglia and a nerve cord.
dopamine metabolic process	The chemical reactions and pathways involving dopamine, a catecholamine neurotransmitter and a metabolic precursor of noradrenaline and adrenaline.
dopamine uptake involved in synaptic transmission	The directed movement of dopamine into a presynaptic neuron or glial cell. In this context, dopamine is a catecholamine neurotransmitter and a metabolic precursor of noradrenaline and adrenaline.
ERAD pathway	The protein catabolic pathway which targets endoplasmic reticulum (ER)-resident proteins for degradation by the cytoplasmic proteasome. It begins with recognition of the ER-resident protein, includes retrotranslocation (dislocation) of the protein from the ER to the cytosol, protein modifications necessary for correct substrate transfer (e.g. ubiquitination), transport of the protein to the proteasome, and ends with degradation of the protein by the cytoplasmic proteasome.
free ubiquitin chain polymerization	The process of creating free ubiquitin chains, compounds composed of a large number of ubiquitin monomers. These chains are not conjugated to a protein.
learning	Any process in an organism in which a relatively long-lasting adaptive behavioral change occurs as the result of experience.
macroautophagy	The major inducible pathway for the general turnover of cytoplasmic constituents in eukaryotic cells, it is also responsible for the degradation of active cytoplasmic enzymes and organelles during nutrient starvation. Macroautophagy involves the formation of double-membrane-bounded autophagosomes which enclose the cytoplasmic constituent targeted for degradation in a membrane-bounded structure. Autophagosomes then fuse with a lysosome (or vacuole) releasing single-membrane-bounded autophagic bodies that are then degraded within the lysosome (or vacuole). Some types of macroautophagy, e.g. pexophagy, mitophagy, involve selective targeting of the targets to be degraded.
mitochondrial fission	The division of a mitochondrion within a cell to form two or more separate mitochondrial compartments.
mitochondrion organization	A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of a mitochondrion; includes mitochondrial morphogenesis and distribution, and replication of the mitochondrial genome as well as synthesis of new mitochondrial components.
mitochondrion to lysosome transport	Transport from the mitochondrion to the lysosome, mediated by mitochondrion-derived vesicles.
mitophagy	The selective autophagy process in which a mitochondrion is degraded by macroautophagy.
negative regulation by host of viral genome replication	A process in which a host organism stops, prevents or reduces the frequency, rate or extent of viral genome replication.
negative regulation of actin filament bundle assembly	Any process that stops, prevents, or reduces the frequency, rate or extent of the assembly of actin filament bundles.
negative regulation of canonical Wnt signaling pathway	Any process that decreases the rate, frequency, or extent of the Wnt signaling pathway through beta-catenin, the series of molecular signals initiated by binding of a Wnt protein to a frizzled family receptor on the surface of the target cell, followed by propagation of the signal via beta-catenin, and ending with a change in transcription of target genes.
negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	Any process that stops, prevents or reduces the frequency, rate or extent of an endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway.
negative regulation of endoplasmic reticulum stress-induced neuron intrinsic apoptotic signaling pathway	Any process that stops, prevents or reduces the frequency, rate or extent of an endoplasmic reticulum stress-induced neuron intrinsic apoptotic signaling pathway.
negative regulation of exosomal secretion	Any process that stops, prevents or reduces the frequency, rate or extent of exosomal secretion.
negative regulation of gene expression	Any process that decreases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
negative regulation of glucokinase activity	Any process that stops, prevents, or reduces the frequency, rate or extent of glucokinase activity, the catalysis of the transfer of a phosphate group, usually from ATP, to a glucose molecule.
negative regulation of insulin secretion	Any process that stops, prevents, or reduces the frequency, rate or extent of the regulated release of insulin.
negative regulation of intralumenal vesicle formation	Any process that stops, prevents or reduces the frequency, rate or extent of intralumenal vesicle formation.
negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator	Any process that stops, prevents or reduces the frequency, rate or extent of intrinsic apoptotic signaling pathway by p53 class mediator.
negative regulation of JNK cascade	Any process that stops, prevents, or reduces the frequency, rate or extent of signal transduction mediated by the JNK cascade.
negative regulation of mitochondrial fusion	Any process that decreases the frequency, rate or extent of merging of two or more mitochondria within a cell to form a single compartment.
negative regulation of neuron apoptotic process	Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process in neurons.
negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway	Any process that stops, prevents or reduces the frequency, rate or extent of oxidative stress-induced neuron intrinsic apoptotic signaling pathway.
negative regulation of primary amine oxidase activity	Any process that stops, prevents or reduces the frequency, rate or extent of primary amine oxidase activity.
negative regulation of protein phosphorylation	Any process that stops, prevents or reduces the rate of addition of phosphate groups to amino acids within a protein.
negative regulation of reactive oxygen species metabolic process	Any process that stops, prevents or reduces the frequency, rate or extent of reactive oxygen species metabolic process.
negative regulation of release of cytochrome c from mitochondria	Any process that decreases the rate, frequency or extent of release of cytochrome c from mitochondria, the process in which cytochrome c is enabled to move from the mitochondrial intermembrane space into the cytosol, which is an early step in apoptosis and leads to caspase activation.
negative regulation of spontaneous neurotransmitter secretion	Any process that stops, prevents or reduces the frequency, rate or extent of spontaneous neurotransmitter secretion.
negative regulation of transcription by RNA polymerase II	Any process that stops, prevents, or reduces the frequency, rate or extent of transcription mediated by RNA polymerase II.
neuron cellular homeostasis	The cellular homeostatic process that preserves a neuron in a stable, differentiated functional and structural state.
norepinephrine metabolic process	The chemical reactions and pathways involving norepinephrine, a hormone secreted by the adrenal medulla, and a neurotransmitter in the sympathetic peripheral nervous system and in some tracts in the central nervous system. It is also the demethylated biosynthetic precursor of epinephrine.
parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization	A positive regulation of the macromitophagy pathway that is triggered by mitochondrial depolarization and requires the function of a parkin-family molecule.
positive regulation of autophagy of mitochondrion	Any process that activates or increases the frequency, rate or extent of mitochondrion degradation by autophagy.
positive regulation of dendrite extension	Any process that activates or increases the frequency, rate or extent of dendrite extension.
positive regulation of DNA binding	Any process that increases the frequency, rate or extent of DNA binding. DNA binding is any process in which a gene product interacts selectively with DNA (deoxyribonucleic acid).
positive regulation of gene expression	Any process that increases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
positive regulation of I-kappaB kinase/NF-kappaB signaling	Any process that activates or increases the frequency, rate or extent of I-kappaB kinase/NF-kappaB signaling.
positive regulation of mitochondrial fission	Any process that increases the rate, frequency or extent of mitochondrial fission. Mitochondrial fission is the division of a mitochondrion within a cell to form two or more separate mitochondrial compartments.
positive regulation of mitochondrial fusion	Any process that increases the frequency, rate or extent of merging of two or more mitochondria within a cell to form a single compartment.
positive regulation of mitophagy in response to mitochondrial depolarization	Any process that activates or increases the frequency, rate or extent of mitophagy in response to mitochondrial depolarization.
positive regulation of neurotransmitter uptake	Any process that activates or increases the frequency, rate or extent of the directed movement of a neurotransmitter into a neuron or glial cell.
positive regulation of proteasomal protein catabolic process	Any process that activates or increases the frequency, rate or extent of proteasomal protein catabolic process.
positive regulation of proteasomal ubiquitin-dependent protein catabolic process	Any process that activates or increases the frequency, rate or extent of the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of ubiquitin, and mediated by the proteasome.
positive regulation of protein binding	Any process that activates or increases the frequency, rate or extent of protein binding.
positive regulation of protein catabolic process	Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the breakdown of a protein by the destruction of the native, active configuration, with or without the hydrolysis of peptide bonds.
positive regulation of protein linear polyubiquitination	Any process that activates or increases the frequency, rate or extent of protein linear polyubiquitination.
positive regulation of protein localization to membrane	Any process that activates or increases the frequency, rate or extent of protein localization to membrane.
positive regulation of retrograde transport, endosome to Golgi	Any process that activates or increases the frequency, rate or extent of retrograde transport, endosome to Golgi.
positive regulation of transcription by RNA polymerase II	Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter.
positive regulation of tumor necrosis factor-mediated signaling pathway	Any process that activates or increases the frequency, rate or extent of tumor necrosis factor-mediated signaling pathway.
proteasomal protein catabolic process	The chemical reactions and pathways resulting in the breakdown of a protein or peptide by hydrolysis of its peptide bonds that is mediated by the proteasome.
proteasome-mediated ubiquitin-dependent protein catabolic process	The chemical reactions and pathways resulting in the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of ubiquitin, and mediated by the proteasome.
protein autoubiquitination	The ubiquitination by a protein of one or more of its own amino acid residues, or residues on an identical protein. Ubiquitination occurs on the lysine residue by formation of an isopeptide crosslink.
protein destabilization	Any process that decreases the stability of a protein, making it more vulnerable to degradative processes or aggregation.
protein deubiquitination	The removal of one or more ubiquitin groups from a protein.
protein K11-linked ubiquitination	A protein ubiquitination process in which ubiquitin monomers are attached to a protein, and then ubiquitin polymers are formed by linkages between lysine residues at position 11 of the ubiquitin monomers. K11-linked polyubiquitination targets the substrate protein for degradation. The anaphase-promoting complex promotes the degradation of mitotic regulators by assembling K11-linked polyubiquitin chains.
protein K27-linked ubiquitination	A protein ubiquitination process in which a polymer of ubiquitin, formed by linkages between lysine residues at position 27 of the ubiquitin monomers, is added to a protein.
protein K29-linked ubiquitination	A protein ubiquitination process in which a polymer of ubiquitin, formed by linkages between lysine residues at position 29 of the ubiquitin monomers, is added to a protein. K29-linked ubiquitination targets the substrate protein for degradation.
protein K48-linked ubiquitination	A protein ubiquitination process in which a polymer of ubiquitin, formed by linkages between lysine residues at position 48 of the ubiquitin monomers, is added to a protein. K48-linked ubiquitination targets the substrate protein for degradation.
protein K6-linked ubiquitination	A protein ubiquitination process in which a polymer of ubiquitin, formed by linkages between lysine residues at position 6 of the ubiquitin monomers, is added to a protein. K6-linked ubiquitination is involved in DNA repair.
protein K63-linked ubiquitination	A protein ubiquitination process in which a polymer of ubiquitin, formed by linkages between lysine residues at position 63 of the ubiquitin monomers, is added to a protein. K63-linked ubiquitination does not target the substrate protein for degradation, but is involved in several pathways, notably as a signal to promote error-free DNA postreplication repair.
protein localization to mitochondrion	A process in which a protein is transported to, or maintained in, a location within the mitochondrion.
protein monoubiquitination	Addition of a single ubiquitin group to a protein.
protein polyubiquitination	Addition of multiple ubiquitin groups to a protein, forming a ubiquitin chain.
protein stabilization	Any process involved in maintaining the structure and integrity of a protein and preventing it from degradation or aggregation.
protein ubiquitination	The process in which one or more ubiquitin groups are added to a protein.
regulation of apoptotic process	Any process that modulates the occurrence or rate of cell death by apoptotic process.
regulation of autophagy	Any process that modulates the frequency, rate or extent of autophagy. Autophagy is the process in which cells digest parts of their own cytoplasm.
regulation of canonical Wnt signaling pathway	Any process that modulates the rate, frequency, or extent of the Wnt signaling pathway through beta-catenin, the series of molecular signals initiated by binding of a Wnt protein to a frizzled family receptor on the surface of the target cell, followed by propagation of the signal via beta-catenin, and ending with a change in transcription of target genes.
regulation of cellular response to oxidative stress	Any process that modulates the frequency, rate or extent of cellular response to oxidative stress.
regulation of dopamine metabolic process	Any process that modulates the frequency, rate or extent of the chemical reactions and pathways involving dopamine.
regulation of dopamine secretion	Any process that modulates the frequency, rate or extent of the regulated release of dopamine.
regulation of glucose metabolic process	Any process that modulates the rate, frequency or extent of glucose metabolism. Glucose metabolic processes are the chemical reactions and pathways involving glucose, the aldohexose gluco-hexose.
regulation of lipid transport	Any process that modulates the frequency, rate or extent of the directed movement of lipids into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
regulation of mitochondrial membrane potential	Any process that modulates the establishment or extent of the mitochondrial membrane potential, the electric potential existing across the mitochondrial membrane arising from charges in the membrane itself and from the charges present in the media on either side of the membrane.
regulation of mitochondrion organization	Any process that modulates the frequency, rate or extent of a process involved in the formation, arrangement of constituent parts, or disassembly of a mitochondrion.
regulation of necroptotic process	Any process that modulates the rate, frequency or extent of a necroptotic process, a necrotic cell death process that results from the activation of endogenous cellular processes, such as signaling involving death domain receptors or Toll-like receptors.
regulation of protein stability	Any process that affects the structure and integrity of a protein, altering the likelihood of its degradation or aggregation.
regulation of protein targeting to mitochondrion	Any process that modulates the frequency, rate or extent of protein targeting to mitochondrion.
regulation of protein ubiquitination	Any process that modulates the frequency, rate or extent of the addition of ubiquitin groups to a protein.
regulation of reactive oxygen species metabolic process	Any process that modulates the frequency, rate or extent of reactive oxygen species metabolic process.
regulation of synaptic vesicle endocytosis	Any process that modulates the frequency, rate or extent of synaptic vesicle endocytosis.
regulation of synaptic vesicle transport	Any process that modulates the frequency, rate or extent of synaptic vesicle transport.
regulation protein catabolic process at presynapse	Any process that modulates the frequency, rate or extent of the chemical reactions and pathways resulting in the breakdown of a protein at the presynapse.
response to endoplasmic reticulum stress	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stress acting at the endoplasmic reticulum. ER stress usually results from the accumulation of unfolded or misfolded proteins in the ER lumen.
response to oxidative stress	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of oxidative stress, a state often resulting from exposure to high levels of reactive oxygen species, e.g. superoxide anions, hydrogen peroxide (H2O2), and hydroxyl radicals.
startle response	An action or movement due to the application of a sudden unexpected stimulus.
synaptic transmission, glutamatergic	The vesicular release of glutamate from a presynapse, across a chemical synapse, the subsequent activation of glutamate receptors at the postsynapse of a target cell (neuron, muscle, or secretory cell) and the effects of this activation on the postsynaptic membrane potential and ionic composition of the postsynaptic cytosol. This process encompasses both spontaneous and evoked release of neurotransmitter and all parts of synaptic vesicle exocytosis. Evoked transmission starts with the arrival of an action potential at the presynapse.
ubiquitin-dependent protein catabolic process	The chemical reactions and pathways resulting in the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of a ubiquitin group, or multiple ubiquitin groups, to the protein.

5 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q7KTX7	park	E3 ubiquitin-protein ligase parkin	Drosophila melanogaster (Fruit fly)	SS
O95376	ARIH2	E3 ubiquitin-protein ligase ARIH2	Homo sapiens (Human)	EV
Q9Y4X5	ARIH1	E3 ubiquitin-protein ligase ARIH1	Homo sapiens (Human)	EV
Q9WVS6	Prkn	E3 ubiquitin-protein ligase parkin	Mus musculus (Mouse)	EV SS
Q9JK66	Prkn	E3 ubiquitin-protein ligase parkin	Rattus norvegicus (Rat)	EV SS

10	20	30	40	50	60
MIVFVRFNSS	HGFPVEVDSD	TSIFQLKEVV	AKRQGVPADQ	LRVIFAGKEL	RNDWTVQNCD
70	80	90	100	110	120
LDQQSIVHIV	QRPWRKGQEM	NATGGDDPRN	AAGGCEREPQ	SLTRVDLSSS	VLPGDSVGLA
130	140	150	160	170	180
VILHTDSRKD	SPPAGSPAGR	SIYNSFYVYC	KGPCQRVQPG	KLRVQCSTCR	QATLTLTQGP
190	200	210	220	230	240
SCWDDVLIPN	RMSGECQSPH	CPGTSAEFFF	KCGAHPTSDK	ETSVALHLIA	TNSRNITCIT
250	260	270	280	290	300
CTDVRSPVLV	FQCNSRHVIC	LDCFHLYCVT	RLNDRQFVHD	PQLGYSLPCV	AGCPNSLIKE
310	320	330	340	350	360
LHHFRILGEE	QYNRYQQYGA	EECVLQMGGV	LCPRPGCGAG	LLPEPDQRKV	TCEGGNGLGC
370	380	390	400	410	420
GFAFCRECKE	AYHEGECSAV	FEASGTTTQA	YRVDERAAEQ	ARWEAASKET	IKKTTKPCPR
430	440	450	460
CHVPVEKNGG	CMHMKCPQPQ	CRLEWCWNCG	CEWNRVCMGD	HWFDV