AiPD: Autoinhibited Protein Database

P30613

Gene name	PKLR (PK1, PKL)
Protein name	Pyruvate kinase PKLR
Names	EC 2.7.1.40 , Pyruvate kinase 1 , Pyruvate kinase isozymes L/R , R-type/L-type pyruvate kinase , Red cell/liver pyruvate kinase
Species	Homo sapiens (Human)
KEGG Pathway	hsa:5313
EC number	2.7.1.40: Phosphotransferases with an alcohol group as acceptor
Protein Class

Descriptions

Pyruvate kinase M2 (PKM2) plays a vital role in glycolysis, and it catalyzes the conversion of phosphoenolpyruvate to pyruvate with the production of ATP in the final reaction of glycolysis. PKM2 provides an in vivo growth advantage in cancer cells. Pyruvate Kinase isozymes type PKM1, PKL, and PKR exist in unstable and high-activity tetramer forms, whereas PKM2 is found in both a highly active tetramer form and a low-activity dimer form. The switch between dimer and tetramer is allosterically modulated by the binding of ligands such as amino acids and metabolic intermediates to the regulatory C-terminal domain. Post-translational modifications at specific residues relieve this inhibition, allowing metabolic flux.

Autoinhibitory domains (AIDs)

432-574 (C-terminal domain) SS

Target domain	86-418 (Pyruvate kinase)
Relief mechanism	PTM, Partner binding
Assay

AID

432-574 (C-terminal domain)

Target domain

86-418 (Pyruvate kinase)

Relief mechanism

PTM (de-glycosylation of residues in the regulatory domain facilitates tetramer formation. Other diverse modifications are involved in the activity regulation), Partner binding (Mucin-1 to the C-terminal domain increases PKM2 activity, while JMJD5 and HSP40 reduce the activity.),

Assay

Accessory elements

No accessory elements

References

Zhang Z et al. (2019) "PKM2, function and expression and regulation", Cell & bioscience, 9, 52

Zahra K et al. (2020) "Pyruvate Kinase M2 and Cancer: The Role of PKM2 in Promoting Tumorigenesis", Frontiers in oncology, 10, 159

Autoinhibited structure

Activated structure

50 structures for P30613

Entry ID	Method	Resolution	Chain	Position	Source
2VGB	X-ray	273 A	A/B/C/D	47-574	PDB
2VGF	X-ray	275 A	A/B/C/D	47-574	PDB
2VGG	X-ray	274 A	A/B/C/D	47-574	PDB
2VGI	X-ray	287 A	A/B/C/D	47-574	PDB
4IMA	X-ray	195 A	A/B/C/D	34-574	PDB
4IP7	X-ray	180 A	A/B/C/D	34-574	PDB
5SC8	X-ray	177 A			PDB
5SC9	X-ray	169 A			PDB
5SCA	X-ray	192 A			PDB
5SCB	X-ray	180 A			PDB
5SCC	X-ray	189 A			PDB
5SCD	X-ray	204 A			PDB
5SCE	X-ray	215 A			PDB
5SCF	X-ray	219 A			PDB
5SCG	X-ray	194 A			PDB
5SCH	X-ray	209 A			PDB
5SCI	X-ray	215 A			PDB
5SCJ	X-ray	235 A			PDB
5SCK	X-ray	172 A			PDB
5SCL	X-ray	213 A			PDB
5SDT	X-ray	194 A			PDB
6NN4	X-ray	215 A	A/B/C/D	34-574	PDB
6NN5	X-ray	226 A	A/B/C/D	34-574	PDB
6NN7	X-ray	232 A	A/B/C/D/E/F/G/H	34-574	PDB
6NN8	X-ray	242 A	A/B/C/D/E/F/G/H	34-574	PDB
7FRV	X-ray	200 A			PDB
7FRW	X-ray	174 A			PDB
7FRX	X-ray	185 A			PDB
7FRY	X-ray	196 A			PDB
7FRZ	X-ray	208 A			PDB
7FS0	X-ray	241 A			PDB
7FS1	X-ray	186 A			PDB
7FS2	X-ray	237 A			PDB
7FS3	X-ray	166 A			PDB
7FS4	X-ray	219 A			PDB
7FS5	X-ray	218 A			PDB
7FS6	X-ray	224 A			PDB
7FS7	X-ray	277 A			PDB
7FS8	X-ray	210 A			PDB
7FS9	X-ray	172 A			PDB
7FSA	X-ray	191 A			PDB
7FSB	X-ray	250 A			PDB
7FSC	X-ray	185 A			PDB
7FSD	X-ray	177 A			PDB
7QDN	X-ray	170 A	A/B/C/D/E/F/G/H	30-574	PDB
7QZU	X-ray	196 A	A/B/C/D/E/F/G/H	30-574	PDB
8TBS	X-ray	235 A	A/B/C/D/E/F/G/H	50-574	PDB
8TBT	X-ray	234 A	A/B/C/D	50-574	PDB
8TBU	X-ray	235 A	A/B/C/D/E/F/G/H	50-574	PDB
AF-P30613-F1	Predicted				AlphaFoldDB

756 variants for P30613

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
rs150077703 RCV001508890 RCV001096025	31	A>V	Pyruvate kinase deficiency of red cells [ClinVar]	Yes	ClinVar ESP ExAC TOPMed dbSNP gnomAD
rs118204087 CA115036 VAR_011435 RCV000001576	37	G>E	Pyruvate kinase hyperactivity PKHYP [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ExAC dbSNP gnomAD
rs1484388413 VAR_058467	40	R>W	PKRD [UniProt]	Yes	UniProt dbSNP gnomAD
RCV001101483 rs374805791	41	R>Q	Pyruvate kinase deficiency of red cells [ClinVar]	Yes	ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
RCV003137904 CA1144441 rs375189218 RCV000283593	41	R>W	Pyruvate kinase deficiency of red cells [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
VAR_058468	48	T>del	PKRD [UniProt]	Yes	UniProt
CA10608274 RCV000342304 RCV003133211 rs886045353	63	A>G	Pyruvate kinase deficiency of red cells [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
VAR_058469 rs140571200	73	L>P	PKRD [UniProt]	Yes	ESP TOPMed gnomAD UniProt
rs2148218886 RCV001729977	75	L>P	Pyruvate kinase deficiency of red cells [ClinVar]	Yes	ClinVar Ensembl dbSNP
VAR_011436	80	S>P	PKRD [UniProt]	Yes	UniProt
VAR_011437	86	R>P	PKRD [UniProt]	Yes	UniProt
rs1647900493 VAR_011438	90	I>N	PKRD [UniProt]	Yes	TOPMed UniProt
rs750857114 VAR_011439	95	G>R	PKRD [UniProt]	Yes	ExAC TOPMed gnomAD UniProt dbSNP
RCV001508887 RCV001732191 rs1433205059	103	R>missing	Pyruvate kinase deficiency of red cells [ClinVar]	Yes	ClinVar dbSNP
VAR_004028	107	M>T	PKRD [UniProt]	Yes	UniProt
RCV000625798 RCV003488737 CA30904892 rs918627824 VAR_011440	111	G>R	Pyruvate kinase deficiency of red cells PKRD [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt TOPMed dbSNP gnomAD
VAR_011441	115	A>P	PKRD; Val de Marne [UniProt]	Yes	UniProt
VAR_011442	120	S>F	PKRD; Beaujon [UniProt]	Yes	UniProt
VAR_011443 rs118204089 CA215081 RCV000001578	130	S>Y	Pyruvate kinase deficiency of red cells PKRD; Conakry [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt TOPMed dbSNP
RCV002487303 RCV000371504 rs886045351 RCV003137903 CA10608268	131	I>missing	Pyruvate kinase deficiency of red cells Pyruvate kinase hyperactivity [ClinVar]	Yes	ClinGen ClinVar dbSNP
VAR_004029	131	I>del	PKRD [UniProt]	Yes	UniProt
VAR_004030 rs574051756 RCV001702985	134	V>D	PKRD [UniProt]	Yes	ClinVar UniProt ExAC TOPMed dbSNP gnomAD
VAR_011474	153	I>T	PKRD [UniProt]	Yes	UniProt
VAR_058470 rs780192373	154	A>T	Variant assessed as Somatic; MODERATE impact. PKRD [NCI-TCGA, UniProt]	Yes	UniProt ExAC NCI-TCGA TOPMed dbSNP gnomAD
VAR_004031	155	L>P	PKRD [UniProt]	Yes	UniProt
RCV001782642 VAR_011444 rs1239029841	159	G>V	PKRD [UniProt]	Yes	ClinVar UniProt dbSNP gnomAD
CA215073 RCV000001571 rs118204083 RCV002512653 VAR_004033	163	R>C	Pyruvate kinase deficiency of red cells PKRD; Linz [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
VAR_058471	163	R>L	PKRD [UniProt]	Yes	UniProt
RCV001099492 rs1220156417	164	T>N	Pyruvate kinase deficiency of red cells [ClinVar]	Yes	ClinVar dbSNP gnomAD
rs1647527499 VAR_058472	165	G>V	PKRD [UniProt]	Yes	Ensembl UniProt
RCV001099491 RCV001811652 RCV002558004 rs199824528	169	G>W	Pyruvate kinase deficiency of red cells Inborn genetic diseases [ClinVar]	Yes	ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs757359024 VAR_004032	172	E>Q	PKRD; Sassari [UniProt]	Yes	UniProt ExAC TOPMed dbSNP gnomAD
VAR_011475 rs200572803	219	I>T	PKRD [UniProt]	Yes	UniProt ESP ExAC TOPMed dbSNP gnomAD
VAR_004034	221	D>DD	PKRD [UniProt]	Yes	UniProt
VAR_011445	222	G>A	PKRD; Katsushika [UniProt]	Yes	UniProt
RCV000762858 RCV000295664 RCV000261579 CA1144229 rs201953584	241	E>*	Pyruvate kinase deficiency of red cells Pyruvate kinase hyperactivity [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV000374958 rs745797890 CA1144226	243	G>S	Pyruvate kinase deficiency of red cells [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
rs774192277 RCV001099489	244	G>D	Pyruvate kinase deficiency of red cells [ClinVar]	Yes	ClinVar ExAC TOPMed dbSNP gnomAD
rs1253386414 VAR_011447 COSM3689036	263	G>R	Variant assessed as Somatic; MODERATE impact. large_intestine PKRD [NCI-TCGA, Cosmic, UniProt]	Yes	NCI-TCGA Cosmic cosmic curated UniProt Ensembl NCI-TCGA dbSNP
VAR_011448	263	G>W	PKRD [UniProt]	Yes	UniProt
RCV001099488 rs200695047 RCV002556015	269	V>F	Pyruvate kinase deficiency of red cells [ClinVar]	Yes	ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
VAR_058473 RCV001812322 rs147659527 RCV001334373	272	L>V	Pyruvate kinase deficiency of red cells PKRD [ClinVar, UniProt]	Yes	ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs747549978 VAR_004035	275	G>R	PKRD [UniProt]	Yes	UniProt ExAC TOPMed dbSNP gnomAD
rs754939638 RCV002295341 RCV003416372 RCV001508885	276	V>missing	Pyruvate kinase deficiency of red cells PKLR-related condition [ClinVar]	Yes	ClinVar dbSNP
RCV001097711 rs147689373 RCV000946502	277	E>K	Pyruvate kinase deficiency of red cells [ClinVar]	Yes	ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
COSM1720029 rs1647439571 VAR_004036	281	D>N	NS PKRD [Cosmic, UniProt]	Yes	cosmic curated Ensembl UniProt
VAR_004037	287	F>V	PKRD [UniProt]	Yes	UniProt
VAR_011449	288	V>L	PKRD; Moriguchi [UniProt]	Yes	UniProt
rs1352610988 VAR_011446	293	D>N	PKRD [UniProt]	Yes	UniProt dbSNP gnomAD
rs766353400 VAR_011450	295	A>V	PKRD [UniProt]	Yes	UniProt ExAC TOPMed dbSNP gnomAD
RCV003480579 rs141571402 CA1144178 RCV000369340	306	H>Q	Pyruvate kinase deficiency of red cells [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
VAR_011451	310	I>N	PKRD; Dordrecht [UniProt]	Yes	UniProt
VAR_004038 rs981505482	314	I>T	PKRD; Hong Kong [UniProt]	Yes	UniProt TOPMed dbSNP gnomAD
rs2148204818 RCV002251280	315	E>D	Pyruvate kinase deficiency of red cells [ClinVar]	Yes	ClinVar Ensembl dbSNP
rs1557959063 VAR_011452 RCV000778187	315	E>K	Pyruvate kinase deficiency of red cells PKRD [ClinVar, UniProt]	Yes	ClinVar Ensembl dbSNP UniProt
rs549295725 VAR_058474	320	V>L	PKRD [UniProt]	Yes	UniProt 1000Genomes ExAC TOPMed dbSNP gnomAD
RCV001097709 rs763964110	322	R>S	Pyruvate kinase deficiency of red cells [ClinVar]	Yes	ExAC TOPMed gnomAD ClinVar dbSNP
VAR_004039 RCV001508883 rs138476691	331	D>E	PKRD; Parma [UniProt]	Yes	ClinVar UniProt ESP ExAC TOPMed dbSNP gnomAD
rs773893686 VAR_011453	331	D>N	PKRD [UniProt]	Yes	UniProt ExAC TOPMed dbSNP gnomAD
rs773626254 VAR_004040 RCV000757661	332	G>S	Variant assessed as Somatic; MODERATE impact. PKRD; loss of catalytical activity [NCI-TCGA, UniProt]	Yes	ClinVar UniProt ExAC NCI-TCGA TOPMed dbSNP gnomAD
VAR_011476	335	V>M	PKRD [UniProt]	Yes	UniProt
VAR_004041	336	A>S	PKRD [UniProt]	Yes	UniProt
VAR_004042	337	R>P	PKRD [UniProt]	Yes	UniProt
VAR_004043 rs1167329263	337	R>Q	PKRD [UniProt]	Yes	UniProt dbSNP gnomAD
rs1193689718 RCV002251079	339	D>missing	Pyruvate kinase deficiency of red cells [ClinVar]	Yes	ClinVar dbSNP
VAR_004044 rs747097960	339	D>H	PKRD [UniProt]	Yes	UniProt ExAC TOPMed dbSNP gnomAD
RCV002019914 rs747097960 RCV002250798	339	D>N	Pyruvate kinase deficiency of red cells [ClinVar]	Yes	ClinVar ExAC TOPMed dbSNP gnomAD
rs1227427396 VAR_004045	341	G>A	PKRD [UniProt]	Yes	UniProt TOPMed dbSNP gnomAD
VAR_011454 rs1227427396	341	G>D	PKRD [UniProt]	Yes	TOPMed gnomAD UniProt
VAR_011455	342	I>F	PKRD [UniProt]	Yes	UniProt
VAR_011456	348	K>N	PKRD; Kamata [UniProt]	Yes	UniProt
VAR_011457	348	K>del	PKRD; Brescia [UniProt]	Yes	UniProt
rs1240481888 VAR_011477	352	A>D	PKRD [UniProt]	Yes	UniProt Ensembl dbSNP
rs2148204121 RCV002251296	354	K>R	Pyruvate kinase deficiency of red cells [ClinVar]	Yes	ClinVar Ensembl dbSNP
VAR_004046	354	K>del	PKRD [UniProt]	Yes	UniProt
rs752423472 RCV000768418	356	M>R	Pyruvate kinase deficiency of red cells [ClinVar]	Yes	ClinVar ExAC TOPMed dbSNP gnomAD
rs779152555 VAR_004047	357	I>T	PKRD [UniProt]	Yes	UniProt ExAC TOPMed dbSNP gnomAD
VAR_058475	358	G>E	PKRD [UniProt]	Yes	UniProt
RCV002550747 VAR_004048 RCV001001091 rs138871700	359	R>C	PKRD; Aomori [UniProt]	Yes	ClinVar UniProt ESP ExAC TOPMed dbSNP gnomAD
COSM3385236 rs1376070580 VAR_004049	359	R>H	Variant assessed as Somatic; MODERATE impact. pancreas PKRD [NCI-TCGA, Cosmic, UniProt]	Yes	NCI-TCGA Cosmic cosmic curated UniProt NCI-TCGA TOPMed dbSNP gnomAD
RCV003489862 rs765903674 VAR_004050 RCV000778186	361	N>D	Pyruvate kinase deficiency of red cells PKRD [ClinVar, UniProt]	Yes	ClinVar UniProt ExAC dbSNP gnomAD
RCV001007616 RCV001811621 rs1358047518	361	N>T	Pyruvate kinase deficiency of red cells [ClinVar]	Yes	ClinVar TOPMed dbSNP gnomAD
rs763466930 RCV001097707	363	A>E	Pyruvate kinase deficiency of red cells [ClinVar]	Yes	ClinVar ExAC TOPMed dbSNP gnomAD
RCV001947013 VAR_011458 rs981579065	364	G>D	PKRD; Tjaereborg; unstability of the protein and decrease in catalytic activity [UniProt]	Yes	ClinVar UniProt TOPMed dbSNP gnomAD
VAR_004051	368	V>F	PKRD; Osaka [UniProt]	Yes	UniProt
VAR_058476	374	L>P	PKRD [UniProt]	Yes	UniProt
VAR_011459	376	S>I	PKRD [UniProt]	Yes	UniProt
CA215075 rs74315362 VAR_004052 COSM675768 RCV000001572	384	T>M	lung Pyruvate kinase deficiency of red cells Variant assessed as Somatic; MODERATE impact. endometrium PKRD; Tokyo/Beirut; no conformational change [Cosmic, ClinVar, NCI-TCGA, UniProt]	Yes	ClinGen NCI-TCGA Cosmic cosmic curated ClinVar UniProt NCI-TCGA TOPMed dbSNP gnomAD
VAR_011478	385	R>W	PKRD [UniProt]	Yes	UniProt
VAR_011460	387	E>G	PKRD [UniProt]	Yes	UniProt
VAR_011461 rs147034239 RCV001961352	390	D>N	PKRD; Mantova; almost complete inactivation [UniProt]	Yes	ClinVar UniProt ESP TOPMed dbSNP
VAR_004053 rs1403323591 RCV001508881	392	A>T	PKRD [UniProt]	Yes	ClinVar UniProt dbSNP gnomAD
VAR_004054 rs1168490341	393	N>K	PKRD [UniProt]	Yes	UniProt TOPMed dbSNP gnomAD
rs776594413 RCV002246424 VAR_004055 RCV002250766 RCV001546580	393	N>S	Pyruvate kinase deficiency of red cells Pyruvate kinase hyperactivity PKRD; Paris [ClinVar, UniProt]	Yes	ClinVar UniProt ExAC TOPMed dbSNP gnomAD
rs1035640530 VAR_011462	394	A>D	PKRD [UniProt]	Yes	UniProt Ensembl dbSNP
VAR_011463	394	A>V	PKRD [UniProt]	Yes	UniProt
VAR_004056	401	C>CS	PKRD [UniProt]	Yes	UniProt
rs779817999 RCV002251136	406	G>E	Pyruvate kinase deficiency of red cells [ClinVar]	Yes	ClinVar ExAC TOPMed dbSNP gnomAD
VAR_011464	408	T>A	PKRD; Hirosaki [UniProt]	Yes	UniProt
VAR_004057 rs1647348099	408	T>I	PKRD [UniProt]	Yes	TOPMed UniProt
COSM1287177 RCV000268968 CA1144063 rs756549612	417	A>V	Pyruvate kinase deficiency of red cells Variant assessed as Somatic; MODERATE impact. autonomic_ganglia [ClinVar, NCI-TCGA, Cosmic]	Yes	ClinGen NCI-TCGA Cosmic cosmic curated ClinVar ExAC NCI-TCGA TOPMed dbSNP gnomAD
rs118204084 CA215077 RCV000001573 VAR_004058	421	Q>K	Pyruvate kinase deficiency of red cells PKRD; Fukushima/Maebashi/Sendai [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV003318511 VAR_004059 rs768002493 RCV002211108	426	R>Q	Pyruvate kinase deficiency of red cells Variant assessed as Somatic; MODERATE impact. PKRD; Sapporo [ClinVar, NCI-TCGA, UniProt]	Yes	ClinVar UniProt ExAC NCI-TCGA TOPMed dbSNP gnomAD
VAR_004060 rs1023689443	426	R>W	Variant assessed as Somatic; MODERATE impact. PKRD; Naniwa [NCI-TCGA, UniProt]	Yes	UniProt NCI-TCGA TOPMed dbSNP gnomAD
VAR_011465	427	E>A	PKRD [UniProt]	Yes	UniProt
VAR_011466	427	E>D	PKRD [UniProt]	Yes	UniProt
RCV002549224 VAR_004061 RCV001003791 rs762591322	431	A>T	Hemolytic anemia Variant assessed as Somatic; MODERATE impact. PKRD [ClinVar, NCI-TCGA, UniProt]	Yes	ClinVar UniProt ExAC NCI-TCGA TOPMed dbSNP gnomAD
rs142238268 COSM1716443 RCV001095925 RCV003480954	435	R>W	lung Pyruvate kinase deficiency of red cells [Cosmic, ClinVar]	Yes	cosmic curated ClinVar ESP ExAC TOPMed dbSNP gnomAD
RCV000001580 RCV001851554 rs771145576	440	E>*	Pyruvate kinase deficiency of red cells [ClinVar]	Yes	ClinVar ExAC dbSNP gnomAD
RCV001507461 rs755522396 RCV001729927 VAR_004062	458	G>D	Pyruvate kinase deficiency of red cells PKRD [ClinVar, UniProt]	Yes	ClinVar UniProt ExAC TOPMed dbSNP gnomAD
COSM4022995 VAR_004063	459	A>V	Variant assessed as Somatic; MODERATE impact. PKRD [NCI-TCGA, UniProt]	Yes	NCI-TCGA Cosmic UniProt
CA1144023 RCV002478762 RCV001507460 RCV000490506 rs149946271	460	V>A	Pyruvate kinase deficiency of red cells Pyruvate kinase hyperactivity [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
rs752034960 RCV001811616 VAR_004064	460	V>M	PKRD [UniProt]	Yes	ClinVar UniProt ExAC TOPMed dbSNP gnomAD
rs750540943 VAR_011479	468	A>G	PKRD [UniProt]	Yes	UniProt ExAC TOPMed dbSNP gnomAD
VAR_004065	468	A>V	PKRD; Hadano [UniProt]	Yes	UniProt
rs759466273 VAR_011467	477	T>A	PKRD [UniProt]	Yes	UniProt ExAC dbSNP
VAR_011480 RCV000001574 RCV001781165 CA215078 rs118204085	479	R>H	Pyruvate kinase deficiency of red cells PKRD; Amish; no conformational change [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ESP ExAC TOPMed dbSNP gnomAD
VAR_011468	485	S>F	PKRD [UniProt]	Yes	UniProt
rs768210809 RCV003490065 COSM3965867 RCV001095924	486	R>Q	Pyruvate kinase deficiency of red cells Variant assessed as Somatic; MODERATE impact. [ClinVar, NCI-TCGA]	Yes	NCI-TCGA Cosmic ClinVar ExAC NCI-TCGA TOPMed dbSNP gnomAD
RCV000001577 VAR_004066 rs116100695 RCV000762857 RCV002251854 RCV000991156 CA215080 RCV000724015	486	R>W	Pyruvate kinase deficiency of red cells Pyruvate kinase hyperactivity PKRD; no conformational change [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
RCV000508434 VAR_011469 rs369183199 CA1143990 RCV003133292	488	R>Q	PKRD [UniProt]	Yes	ClinGen ClinVar UniProt ESP ExAC TOPMed dbSNP gnomAD
RCV001331143 rs746257586	490	R>Q	Pyruvate kinase hyperactivity [ClinVar]	Yes	ClinVar ExAC TOPMed dbSNP gnomAD
VAR_004067 rs200133000 RCV000309349 CA1143989 RCV002227119	490	R>W	Pyruvate kinase deficiency of red cells PKRD [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt 1000Genomes ExAC TOPMed dbSNP gnomAD
VAR_011470	495	A>T	PKRD [UniProt]	Yes	UniProt
rs141560532 VAR_004068	495	A>V	PKRD [UniProt]	Yes	UniProt ESP ExAC TOPMed dbSNP gnomAD
RCV001782643 rs551883218 VAR_004069	498	R>C	PKRD [UniProt]	Yes	ClinVar UniProt 1000Genomes ExAC TOPMed dbSNP gnomAD
VAR_004070 rs758327704 RCV001782644	498	R>H	PKRD [UniProt]	Yes	ClinVar UniProt ExAC TOPMed dbSNP gnomAD
RCV000714615 rs185753709	504	R>H	Pyruvate kinase deficiency of red cells Variant assessed as Somatic; MODERATE impact. [ClinVar, NCI-TCGA]	Yes	ClinVar 1000Genomes ExAC NCI-TCGA TOPMed dbSNP
VAR_011471 rs185753709	504	R>L	PKRD; instability of the protein [UniProt]	Yes	UniProt 1000Genomes ExAC TOPMed dbSNP
RCV000224042 rs8177988 RCV001095923 CA1143975 VAR_018848 RCV000764981	506	V>I	Pyruvate kinase deficiency of red cells Pyruvate kinase hyperactivity [ClinVar]	Yes	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
VAR_004071 RCV000001575 rs113403872 RCV000224660 COSM675770 CA215079 RCV003421893	510	R>Q	lung Pyruvate kinase deficiency of red cells PKLR-related condition PKRD [Cosmic, ClinVar, UniProt]	Yes	ClinGen cosmic curated ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs1647233974 VAR_011472	511	G>R	PKRD [UniProt]	Yes	gnomAD UniProt
rs139002629 RCV001095922 RCV002557974	518	R>C	Pyruvate kinase deficiency of red cells [ClinVar]	Yes	ClinVar ESP ExAC TOPMed dbSNP gnomAD
rs2148198897 RCV002251217	525	W>*	Pyruvate kinase deficiency of red cells [ClinVar]	Yes	ClinVar Ensembl dbSNP
rs1674554041 VAR_011473 COSM896870	531	R>C	Variant assessed as Somatic; MODERATE impact. endometrium PKRD [NCI-TCGA, Cosmic, UniProt]	Yes	NCI-TCGA Cosmic cosmic curated Ensembl UniProt
rs1674554041 RCV001534615	531	R>S	Pyruvate kinase deficiency of red cells [ClinVar]	Yes	ClinVar Ensembl dbSNP
RCV001782641 rs758278200 VAR_004072	532	R>Q	PKRD [UniProt]	Yes	ClinVar UniProt ExAC TOPMed dbSNP gnomAD
rs201255024 VAR_004073 RCV001262945 RCV003405471 RCV003135903	532	R>W	Pyruvate kinase deficiency of red cells PKLR-related condition PKRD; Complete loss in the responsiveness to fructose 1,6-bisphosphate, FBP [ClinVar, UniProt]	Yes	ClinVar UniProt ExAC dbSNP gnomAD
RCV000522980 CA1143959 RCV000764980 rs201217064	538	E>D	Pyruvate kinase hyperactivity [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
VAR_004074 RCV002261875 rs370316462	552	V>M	PKRD [UniProt]	Yes	ClinVar UniProt ESP dbSNP
VAR_011481 RCV001810610 rs1674489086	557	G>A	PKRD [UniProt]	Yes	ClinVar Ensembl dbSNP UniProt
VAR_004075	559	R>G	PKRD [UniProt]	Yes	UniProt
VAR_004076	566	N>K	PKRD [UniProt]	Yes	UniProt
rs61755431 RCV001811654 VAR_011482 RCV003323797 RCV001101366	569	R>Q	Pyruvate kinase deficiency of red cells PKRD [ClinVar, UniProt]	Yes	ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs774176341	2	S>*		No	ExAC TOPMed gnomAD
COSM896877 rs774176341	2	S>L	Variant assessed as Somatic; MODERATE impact. endometrium [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated ExAC TOPMed gnomAD
rs774176341	2	S>W		No	ExAC TOPMed gnomAD
rs758112712	4	Q>H		No	Ensembl
rs762490269	7	I>K		No	ExAC gnomAD
rs762490269	7	I>T		No	ExAC gnomAD
TCGA novel	8	S>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs1647981030	8	S>P		No	TOPMed gnomAD
rs1647980781	12	L>V		No	Ensembl
rs769174570	13	R>Q		No	ExAC TOPMed gnomAD
rs772818969	13	R>W		No	ExAC TOPMed gnomAD
rs750812851	15	W>*		No	Ensembl
rs748703432	15	W>R		No	ExAC TOPMed gnomAD
rs1442131020	17	S>C		No	TOPMed gnomAD
rs1442131020 COSM163518	17	S>F	Variant assessed as Somatic; MODERATE impact. breast [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated NCI-TCGA TOPMed gnomAD
rs1442131020	17	S>Y		No	TOPMed gnomAD
rs781610938	18	K>E		No	ExAC gnomAD
rs769038526	19	S>C		No	ExAC gnomAD
rs769038526	19	S>Y		No	ExAC gnomAD
rs200357340	20	Q>R		No	TOPMed gnomAD
rs1278895712	21	R>K		No	TOPMed gnomAD
rs1201759277	22	D>N		No	gnomAD
rs1647979024	22	D>V		No	Ensembl
rs1553231692	23	L>I		No	TOPMed
COSM6121467	24	A>E	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs754783713	24	A>T		No	TOPMed
rs1394682499	24	A>V		No	TOPMed gnomAD
rs1647978536	25	K>E		No	TOPMed
rs747323509	26	S>C		No	ExAC gnomAD
rs1647978191	27	I>V		No	Ensembl
rs780370877	28	L>P		No	ExAC gnomAD
rs142735355 RCV001813036	29	I>T		No	ClinVar ESP ExAC TOPMed dbSNP gnomAD
rs1647977935	29	I>V		No	Ensembl
rs771523060	30	G>E		No	Ensembl
rs150077703	31	A>D		No	ESP ExAC TOPMed gnomAD
rs1446138836	31	A>P		No	TOPMed gnomAD
rs1446138836	31	A>T		No	TOPMed gnomAD
rs1647977007	33	G>R		No	TOPMed gnomAD
rs1173752341	35	P>S		No	gnomAD
rs770019694	36	A>G		No	ExAC TOPMed gnomAD
rs770019694	36	A>V		No	ExAC TOPMed gnomAD
rs118204087	37	G>V		No	ExAC gnomAD
rs745811076	40	R>L		No	ExAC TOPMed gnomAD
rs745811076	40	R>P		No	ExAC TOPMed gnomAD
rs745811076	40	R>Q		No	ExAC TOPMed gnomAD
rs374805791	41	R>L		No	1000Genomes ExAC TOPMed gnomAD
rs1553231550	42	A>G		No	Ensembl
COSM4818974	43	S>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs753415917	44	V>E		No	Ensembl
rs924210755	44	V>M		No	gnomAD
rs1305717947	46	Q>K		No	gnomAD
rs1380918810	49	Q>*		No	gnomAD
rs1647912559	49	Q>H		No	TOPMed
COSM529302 rs752199380	50	E>K	lung [Cosmic]	No	cosmic curated ExAC gnomAD
rs1185596611	51	L>P		No	TOPMed
rs760029571	52	G>C		No	ExAC gnomAD
rs752093404	52	G>D		No	ExAC gnomAD
rs760443294	53	T>S		No	Ensembl
rs1553231530	53	T>S		No	Ensembl
rs753089348	54	A>T		No	Ensembl
rs1374868491	54	A>V		No	Ensembl
rs746308116	56	F>Y		No	Ensembl
rs772567442 RCV001000991	57	Q>*		No	ClinVar TOPMed dbSNP
RCV002261901 rs1165604977	63	A>T		No	ClinVar TOPMed dbSNP gnomAD
rs773589949	65	M>L		No	ExAC TOPMed gnomAD
rs1187424402	65	M>T		No	TOPMed gnomAD
rs773589949	65	M>V		No	ExAC TOPMed gnomAD
rs1647908455	68	T>N		No	TOPMed
rs754696137	71	E>V		No	Ensembl
rs200791251 RCV001508889	73	L>F		No	ClinVar ExAC dbSNP gnomAD
rs140571200	73	L>H		No	ESP TOPMed gnomAD
rs1394809863	74	C>S		No	TOPMed gnomAD
rs1331269086	76	L>P	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	Ensembl NCI-TCGA
rs766051969	80	S>T		No	Ensembl
rs139707114	81	E>K		No	ESP ExAC TOPMed gnomAD
rs151005140	82	P>A		No	ESP ExAC TOPMed gnomAD
rs1291071651	82	P>L		No	gnomAD
rs754785851	83	V>A		No	Ensembl
rs368492204	83	V>M		No	ESP ExAC TOPMed gnomAD
rs1273516896	85	A>T		No	gnomAD
rs752391774	86	R>C		No	ExAC TOPMed gnomAD
rs752391774 RCV001508888	86	R>G		No	ClinVar ExAC TOPMed dbSNP gnomAD
rs375471342	86	R>H		No	ESP ExAC TOPMed gnomAD
rs754454017	87	S>C		No	ExAC TOPMed gnomAD
rs754454017	87	S>G		No	ExAC TOPMed gnomAD
rs1553231499	88	T>S		No	Ensembl
rs752037743 RCV002005495	91	I>T		No	ClinVar ExAC dbSNP gnomAD
rs750857114	95	G>W		No	ExAC TOPMed gnomAD
rs1474390898	96	P>S	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA TOPMed gnomAD
RCV002003104 rs1302535902	98	S>T		No	ClinVar TOPMed dbSNP gnomAD
rs148636159	99	R>C		No	ESP ExAC gnomAD
rs534895384	99	R>H		No	1000Genomes ExAC gnomAD
rs762661462	100	S>T		No	ExAC gnomAD
RCV001001145 rs1572057758	101	V>A		No	ClinVar Ensembl dbSNP
rs143984223	101	V>L		No	ESP ExAC TOPMed gnomAD
rs143984223	101	V>M		No	ESP ExAC TOPMed gnomAD
rs1647552348	102	E>G		No	TOPMed
TCGA novel	102	E>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs779765565 COSM347143	103	R>C	lung [Cosmic]	No	cosmic curated ExAC TOPMed gnomAD
rs779765565	103	R>G		No	ExAC TOPMed gnomAD
rs371471086	103	R>H		No	ESP
COSM3976195 rs779765565	103	R>S	lung [Cosmic]	No	cosmic curated ExAC TOPMed gnomAD
rs1647551634	105	K>R		No	TOPMed
rs1647551316	106	E>Q		No	gnomAD
rs1647550981	107	M>I		No	TOPMed gnomAD
rs1647550818	108	I>V		No	TOPMed gnomAD
rs1159724535	109	K>E		No	gnomAD
rs1553230926	110	A>D		No	Ensembl
TCGA novel	110	A>P	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs1557960823	110	A>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	Ensembl NCI-TCGA
COSM3418118	110	A>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1325130058	111	G>E		No	TOPMed gnomAD
COSM3474939 rs1553230922	112	M>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic Ensembl NCI-TCGA
rs746377052	112	M>L		No	ExAC TOPMed gnomAD
rs746377052	112	M>V		No	ExAC TOPMed gnomAD
rs1347580980	113	N>S		No	TOPMed
RCV001813027 rs779517988	114	I>T		No	ClinVar ExAC dbSNP gnomAD
rs971962553 COSM1334629	116	R>*	Variant assessed as Somatic; HIGH impact. large_intestine [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated NCI-TCGA TOPMed
rs754441130	116	R>L		No	ExAC gnomAD
rs754441130	116	R>Q		No	ExAC gnomAD
rs754282523	117	L>R		No	ExAC gnomAD
rs1489078045	118	N>S		No	TOPMed
rs1553230917	119	F>V		No	Ensembl
rs1572057652	121	H>Q		No	Ensembl
rs1647545745	122	G>S		No	TOPMed
rs756428691	123	S>C		No	ExAC gnomAD
rs1240858486	124	H>Q		No	TOPMed gnomAD
rs767598564	125	E>A		No	ExAC TOPMed gnomAD
rs1260433542	125	E>D		No	TOPMed
rs752905261	125	E>Q		No	ExAC gnomAD
TCGA novel	126	Y>C	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1572057427 RCV001002644	127	H>D		No	ClinVar Ensembl dbSNP
rs1572057410 RCV001002382	127	H>R		No	ClinVar Ensembl dbSNP
rs773981429	129	E>K		No	ExAC TOPMed gnomAD
rs1647536192	132	A>T		No	gnomAD
rs770337533	133	N>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA gnomAD
rs749817706	133	N>K		No	ExAC TOPMed gnomAD
rs770175821	135	R>W		No	ExAC TOPMed gnomAD
rs1452107518	137	A>T		No	gnomAD
rs1275173660	137	A>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA gnomAD
rs1647534720	138	V>L		No	TOPMed
rs748560715	139	E>K		No	ExAC TOPMed gnomAD
rs757997111	139	E>V		No	Ensembl
rs781504670	140	S>R		No	ExAC gnomAD
rs1553230882	141	F>L		No	Ensembl
rs1647533800	141	F>S		No	Ensembl
rs1647533662	142	A>P		No	Ensembl
rs2148207982	143	G>R		No	Ensembl
rs1647533510	144	S>C		No	TOPMed
rs1553230879	145	P>L		No	Ensembl
rs1360239034	147	S>C		No	gnomAD
rs1269961789	147	S>T		No	gnomAD
rs757378318	149	R>Q		No	Ensembl
rs1437892556	149	R>W		No	gnomAD
rs1327358866	150	P>S		No	TOPMed gnomAD
rs1393285415	151	V>L		No	gnomAD
rs1393285415	151	V>M		No	gnomAD
rs751716279	152	A>G		No	ExAC gnomAD
rs1417213156	153	I>V		No	gnomAD
rs780192373	154	A>P		No	ExAC TOPMed gnomAD
rs1647530315	156	D>G		No	gnomAD
rs1647530478	156	D>H		No	Ensembl
rs1647530478	156	D>Y		No	Ensembl
rs753840260	157	T>A		No	ExAC TOPMed gnomAD
rs753840260	157	T>P		No	ExAC TOPMed gnomAD
COSM3802107	158	K>Q	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1009060425	158	K>R		No	Ensembl
COSM4023001 rs1206958691	160	P>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic NCI-TCGA TOPMed gnomAD
COSM3802106 rs1272792336	161	E>D	breast Variant assessed as Somatic; MODERATE impact. [Cosmic, NCI-TCGA]	No	cosmic curated gnomAD NCI-TCGA Cosmic
rs2148207813	162	I>F		No	Ensembl
rs1647528158	162	I>M		No	Ensembl
rs1553230854	162	I>N		No	Ensembl
rs1553230854	162	I>T		No	Ensembl
COSM1334627 rs1220156417	164	T>I	Variant assessed as Somatic; MODERATE impact. large_intestine [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated NCI-TCGA gnomAD
rs929087559	166	I>T		No	Ensembl
rs759323460	167	L>P		No	ExAC gnomAD
rs1647526577	168	Q>E		No	Ensembl
rs762330662	169	G>A		No	ExAC TOPMed gnomAD
rs762330662	169	G>E		No	ExAC TOPMed gnomAD
rs199824528	169	G>R		No	1000Genomes ESP ExAC TOPMed gnomAD
rs779196057	170	G>S	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA TOPMed gnomAD
rs956505039	172	E>G		No	TOPMed gnomAD
rs757359024	172	E>K		No	ExAC TOPMed gnomAD
rs2148207268	174	E>D		No	Ensembl
rs781236222	175	V>A		No	ExAC gnomAD
rs370513342	175	V>M		No	ESP ExAC TOPMed gnomAD
rs138482544	177	L>M		No	ESP ExAC TOPMed gnomAD
COSM3862914	178	V>G	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs751361992	178	V>M		No	ExAC gnomAD
rs1362487132	180	G>D	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA TOPMed gnomAD
rs1362487132	180	G>V		No	TOPMed gnomAD
rs1553230808	181	S>P		No	Ensembl
rs993639560	182	Q>H		No	TOPMed gnomAD
rs1647505031	183	V>A		No	TOPMed
rs1478312403	185	V>L		No	TOPMed gnomAD
rs1478312403	185	V>M		No	TOPMed gnomAD
rs370932346	187	V>A		No	ESP ExAC TOPMed gnomAD
rs1264493201	187	V>M		No	gnomAD
rs758042780	188	D>N		No	ExAC TOPMed gnomAD
rs758042780	188	D>Y		No	ExAC TOPMed gnomAD
rs577247981	189	P>A		No	1000Genomes ExAC TOPMed gnomAD
rs1213745985	190	A>P		No	gnomAD
rs1336522710	190	A>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA gnomAD
COSM1334626	191	F>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1217960562	191	F>Y		No	TOPMed
rs1485617455	192	R>Q	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA TOPMed gnomAD
rs1242775292	192	R>W		No	TOPMed gnomAD
COSM4023000 rs1270838814	193	T>M	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic NCI-TCGA gnomAD
rs552916457	194	R>L		No	1000Genomes ExAC gnomAD
COSM4714799	194	R>W	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs781165565	196	N>D		No	Ensembl
rs764631858	196	N>K		No	ExAC TOPMed gnomAD
TCGA novel	196	N>T	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs761210207	197	A>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA gnomAD
rs775787566	198	N>K		No	ExAC TOPMed gnomAD
rs898938497	198	N>S		No	Ensembl
rs1463112401	199	T>N		No	gnomAD
TCGA novel	200	V>M	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs772473652	201	W>*		No	ExAC TOPMed gnomAD
rs1647499374	201	W>C		No	TOPMed
rs772473652	201	W>L		No	ExAC TOPMed gnomAD
COSM4022999	202	V>M	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1647498854	205	P>R		No	TOPMed
rs1216054637	205	P>S		No	gnomAD
rs759694655	206	N>S		No	ExAC gnomAD
rs780259014	207	I>S		No	Ensembl
rs1647497802	208	V>L		No	Ensembl
rs200480300	209	R>Q		No	1000Genomes ExAC TOPMed gnomAD
TCGA novel	209	R>W	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs777980472	211	V>L		No	ExAC TOPMed gnomAD
rs777980472	211	V>M		No	ExAC TOPMed gnomAD
rs777667459	212	P>L		No	ExAC gnomAD
rs768541145	212	P>S		No	ExAC TOPMed gnomAD
rs200979497 RCV001508886	213	V>A		No	ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
rs1303985650	214	G>R		No	gnomAD
COSM2210460	215	G>A	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1052308239	215	G>A		No	TOPMed gnomAD
rs1647494546	215	G>C		No	gnomAD
rs1052308239	215	G>D		No	TOPMed gnomAD
COSM4022998	216	R>H	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs926099988	216	R>L		No	Ensembl
rs756878847	217	I>L		No	ExAC gnomAD
rs1325293184	218	Y>H		No	gnomAD
rs753384013	219	I>F		No	ExAC gnomAD
rs753384013	219	I>V		No	ExAC gnomAD
rs1316380783	221	D>H		No	TOPMed gnomAD
rs1647492142	222	G>R		No	TOPMed
rs1396216541	222	G>V		No	gnomAD
rs768657605	224	I>N		No	Ensembl
rs768657605	224	I>T		No	Ensembl
rs767781894	225	S>F		No	ExAC TOPMed gnomAD
COSM1334624	226	L>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs774736844	227	V>E		No	ExAC gnomAD
rs771329959	228	V>I		No	ExAC gnomAD
rs1647485350	229	Q>E		No	Ensembl
rs763237413	229	Q>R		No	ExAC gnomAD
rs1647484906	231	I>T		No	Ensembl
rs764375399	231	I>V		No	Ensembl
rs750606318	232	G>C		No	TOPMed gnomAD
rs1402934561	232	G>D		No	gnomAD
rs1175303714	233	P>L		No	TOPMed gnomAD
rs1386589533	233	P>S		No	TOPMed gnomAD
rs1386589533	233	P>T		No	TOPMed gnomAD
rs892370971	235	G>E		No	gnomAD
rs892370971	235	G>V		No	gnomAD
rs769475930	236	L>P		No	Ensembl
TCGA novel	237	V>A	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1647459349	237	V>M		No	TOPMed
rs1301549572	238	T>P		No	gnomAD
rs776546824	241	E>V		No	ExAC TOPMed gnomAD
rs1193894766	242	N>T		No	gnomAD
rs1208131291	243	G>D		No	gnomAD
rs1208131291	243	G>V		No	gnomAD
rs759517847	244	G>S		No	TOPMed gnomAD
rs555712170	245	V>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	1000Genomes ExAC NCI-TCGA TOPMed gnomAD
rs1443489252	247	G>D		No	TOPMed
rs1433553552	247	G>S		No	gnomAD
rs368830326	249	R>Q		No	ESP ExAC TOPMed gnomAD
rs748947397	249	R>W	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA TOPMed gnomAD
rs267598065	251	G>C		No	gnomAD
COSM36782 rs267598065	251	G>S	skin [Cosmic]	No	cosmic curated gnomAD
rs1647454047	252	V>M		No	Ensembl
rs1647453746	253	N>Y		No	TOPMed
rs943436402 RCV001810820	254	L>F		No	ClinVar Ensembl dbSNP
rs1647453288	255	P>Q		No	Ensembl
rs1647452916	256	G>E		No	Ensembl
TCGA novel	257	A>P	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs752053420	257	A>S		No	ExAC TOPMed gnomAD
rs752053420	257	A>T		No	ExAC TOPMed gnomAD
rs766853199	257	A>V		No	ExAC TOPMed gnomAD
rs750161685	259	V>L		No	gnomAD
rs750161685	259	V>M		No	gnomAD
rs765541284	260	D>E		No	ExAC gnomAD
rs140575553	260	D>H		No	1000Genomes ESP ExAC TOPMed gnomAD
COSM3474938 rs140575553	260	D>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic 1000Genomes ESP ExAC NCI-TCGA TOPMed gnomAD
COSM3979868 rs761905811	261	L>F	ovary [Cosmic]	No	cosmic curated ExAC TOPMed gnomAD
rs1186641890	261	L>W		No	gnomAD
rs1463495893	262	P>L		No	TOPMed gnomAD
rs867384868	263	G>A		No	gnomAD
rs867384868 COSM3474937	263	G>E	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic NCI-TCGA gnomAD
rs769783555	265	S>C		No	Ensembl
rs1438320407	266	E>G		No	gnomAD
rs1196986764	266	E>Q		No	TOPMed gnomAD
rs764143249 RCV000994123	267	Q>*		No	ClinVar ExAC dbSNP gnomAD
rs764143249	267	Q>K		No	ExAC gnomAD
rs576755609	268	D>E		No	1000Genomes ExAC TOPMed gnomAD
rs770747923	269	V>A	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA TOPMed gnomAD
rs770747923	269	V>D		No	ExAC TOPMed gnomAD
COSM2154835	269	V>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs772860949	270	R>*		No	ExAC TOPMed gnomAD
rs772860949	270	R>G		No	ExAC TOPMed gnomAD
rs1647446710	270	R>L		No	Ensembl
RCV001776810 rs1454650109	271	D>Y		No	ClinVar dbSNP gnomAD
rs1647446208	272	L>P		No	gnomAD
rs747753310	273	R>C		No	ExAC gnomAD
rs141393570	273	R>H		No	1000Genomes ESP ExAC TOPMed gnomAD
rs141393570	273	R>P		No	1000Genomes ESP ExAC TOPMed gnomAD
COSM6058329	275	G>A	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1553230589	276	V>E		No	Ensembl
rs780659178	276	V>M		No	ExAC TOPMed gnomAD
rs1298683548	278	H>R		No	TOPMed gnomAD
rs1350652440	278	H>Y	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA gnomAD
rs758560647	279	G>E		No	ExAC TOPMed gnomAD
rs1337184181	279	G>R		No	TOPMed gnomAD
rs758560647	279	G>V		No	ExAC TOPMed gnomAD
rs1647439746	280	V>G		No	TOPMed
rs1647439956	280	V>M		No	TOPMed
TCGA novel	280	V>W	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs972319705	282	I>M		No	TOPMed
rs1647438800	283	V>D		No	gnomAD
rs1557959233	283	V>L		No	Ensembl
COSM72194	289	R>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs749666187 COSM1334622	289	R>Q	large_intestine [Cosmic]	No	cosmic curated ExAC gnomAD
TCGA novel	289	R>W	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs780875123	290	K>R		No	Ensembl
TCGA novel	291	A>P	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs749573131	292	S>C		No	TOPMed
rs749573131	292	S>G		No	TOPMed
rs2148205075	292	S>N		No	Ensembl
rs1215189514	292	S>R		No	TOPMed gnomAD
rs1352610988	293	D>H		No	gnomAD
rs760709075	294	V>L		No	ExAC TOPMed gnomAD
rs751524706	295	A>T		No	ExAC TOPMed gnomAD
rs1171887541	296	A>D		No	gnomAD
COSM896874 rs148435198	297	V>I	Variant assessed as Somatic; MODERATE impact. large_intestine endometrium [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated ESP ExAC NCI-TCGA TOPMed gnomAD
rs148435198	297	V>L		No	ESP ExAC TOPMed gnomAD
rs769464933	299	A>D		No	ExAC TOPMed gnomAD
COSM6121469	301	L>P	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1468795405	301	L>V		No	TOPMed gnomAD
rs1273785008	302	G>A		No	TOPMed gnomAD
rs201979697	303	P>A		No	1000Genomes ExAC TOPMed gnomAD
rs746566827	303	P>L		No	ExAC TOPMed gnomAD
rs746566827	303	P>Q		No	ExAC TOPMed gnomAD
rs201979697	303	P>S		No	1000Genomes ExAC TOPMed gnomAD
rs2148204914	305	G>A		No	Ensembl
rs2148204914 COSM3474936	305	G>E	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic Ensembl
TCGA novel rs2148204923	305	G>R	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Ensembl
rs1647433617	306	H>R		No	TOPMed
rs373990660	307	G>R		No	ESP ExAC TOPMed gnomAD
rs373990660	307	G>S		No	ESP ExAC TOPMed gnomAD
RCV002003743 rs754124936	307	G>V		No	ClinVar ExAC dbSNP gnomAD
rs1647432625	310	I>M		No	TOPMed gnomAD
rs1557959092	312	S>G		No	Ensembl
rs1460894843	312	S>R		No	gnomAD
rs777926506	313	K>Q		No	ExAC gnomAD
rs1348220831	313	K>R		No	gnomAD
rs1647431022	316	N>D		No	TOPMed gnomAD
rs745663677	317	H>Q		No	ExAC gnomAD
rs767580478	318	E>G		No	ExAC gnomAD
COSM3474935	318	E>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
RCV001508884 rs2148204773	319	G>*		No	ClinVar dbSNP
rs763006858	319	G>D		No	ExAC gnomAD
rs1171765666	319	G>S		No	gnomAD
rs1399195622	322	R>M		No	gnomAD
rs8177974	324	D>E		No	1000Genomes ExAC TOPMed gnomAD
rs760413736	324	D>G		No	ExAC TOPMed gnomAD
COSM6121470	324	D>H	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
COSM414003	324	D>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1557958902	326	I>N		No	Ensembl
rs758924903	327	L>P		No	ExAC gnomAD
rs758924903	327	L>Q		No	ExAC gnomAD
rs767088632	327	L>V		No	ExAC TOPMed gnomAD
rs2148204412	328	E>Q		No	Ensembl
rs1443439423	331	D>G		No	gnomAD
rs773626254	332	G>C		No	ExAC TOPMed gnomAD
COSM3474934	332	G>D	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1647418569	333	I>V		No	TOPMed
rs756339496	334	M>I		No	Ensembl
rs1462758901	334	M>T		No	gnomAD
COSM896873	336	A>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs748376799	337	R>G		No	ExAC
rs748376799	337	R>W		No	ExAC
COSM1334620	339	D>T	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
RCV002211109 rs747097960	339	D>Y		No	ClinVar ExAC TOPMed dbSNP gnomAD
rs781715321	343	E>K		No	gnomAD
rs781715321	343	E>Q		No	gnomAD
TCGA novel	344	I>S	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1647415148	346	A>P		No	Ensembl
rs1647415148	346	A>T		No	Ensembl
rs2148204187	347	E>V		No	Ensembl
rs1647414487	349	V>I		No	Ensembl
RCV001812972 rs755934816	350	F>S		No	ClinVar ExAC TOPMed dbSNP
rs755934816	350	F>Y		No	ExAC TOPMed
rs1553230470	351	L>Q		No	Ensembl
rs1341339479	351	L>V		No	TOPMed gnomAD
COSM675767	353	Q>H	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1482347822	355	M>V		No	TOPMed gnomAD
rs752423472	356	M>T		No	ExAC TOPMed gnomAD
rs779152555	357	I>N		No	ExAC TOPMed gnomAD
rs1557958688	357	I>V		No	Ensembl
rs1647411252	358	G>R		No	Ensembl
rs1572054918	360	C>G		No	Ensembl
rs773803500	360	C>S		No	ExAC TOPMed gnomAD
rs773803500 RCV001091727	360	C>Y		No	ClinVar ExAC TOPMed dbSNP gnomAD
rs763466930	363	A>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA TOPMed gnomAD
RCV001867837 rs1434008042	365	K>missing		No	ClinVar dbSNP
rs980930459	365	K>N		No	gnomAD
rs533316562	366	P>A		No	1000Genomes ExAC gnomAD
rs533316562	366	P>S		No	1000Genomes ExAC gnomAD
rs777020292	367	V>F		No	ExAC gnomAD
rs777020292	367	V>I		No	ExAC gnomAD
rs1482703790	372	Q>*		No	gnomAD
COSM3474930	375	E>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
COSM3474929	377	M>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs758011557	381	P>L		No	ExAC TOPMed gnomAD
rs1385862868	381	P>S		No	TOPMed
rs952129836	382	R>Q		No	TOPMed gnomAD
rs140964046	382	R>W		No	ESP ExAC TOPMed gnomAD
rs767333188	383	P>A		No	ExAC TOPMed gnomAD
rs767333188	383	P>S		No	ExAC TOPMed gnomAD
rs74315362	384	T>R		No	TOPMed gnomAD
rs1553230279	385	R>G		No	Ensembl
rs147089210 COSM109670	387	E>K	skin [Cosmic]	No	cosmic curated Ensembl
rs548802413	389	S>N		No	gnomAD
rs772465237	389	S>R		No	ExAC TOPMed gnomAD
rs759834904	390	D>G		No	ExAC gnomAD
rs771080781	391	V>A		No	ExAC gnomAD
rs1647353051	394	A>S		No	TOPMed
RCV001812548 rs1647353051	394	A>T		No	ClinVar TOPMed dbSNP
rs1451219602	395	V>M		No	gnomAD
rs1553230251	397	D>E		No	Ensembl
rs1647352222	398	G>E		No	TOPMed
rs1553230244	399	A>T		No	Ensembl
TCGA novel	401	C>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs1553230243	401	C>S		No	Ensembl
rs766913459	401	C>Y		No	Ensembl
TCGA novel	402	I>F	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1407665319	402	I>T		No	TOPMed gnomAD
rs902651473	402	I>V		No	TOPMed gnomAD
rs368784290	403	M>I		No	ESP ExAC TOPMed gnomAD
rs768361068	403	M>T		No	ExAC gnomAD
rs1647351264	403	M>V		No	TOPMed
rs779817999	406	G>A		No	ExAC TOPMed gnomAD
rs375456388	406	G>R		No	ESP TOPMed
rs375456388	406	G>W		No	ESP TOPMed
rs866472917 RCV001811789	407	E>K		No	ClinVar TOPMed dbSNP
rs866472917	407	E>Q		No	TOPMed
rs780985369	407	E>V		No	Ensembl
rs745461639	411	G>A		No	ExAC gnomAD
rs745461639	411	G>D		No	ExAC gnomAD
rs756750467	412	N>K		No	ExAC TOPMed gnomAD
rs774006353 RCV001508880	412	N>T		No	ClinVar ExAC TOPMed dbSNP gnomAD
rs1397695525	413	F>L		No	Ensembl
rs1647346476	414	P>R		No	TOPMed
rs1367875373	414	P>S	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA gnomAD
rs764713394	416	E>K		No	ExAC TOPMed gnomAD
rs759855502	418	V>M		No	ExAC TOPMed gnomAD
rs774652817	423	A>=	Variant assessed as Somatic; LOW impact. [NCI-TCGA]	No	NCI-TCGA
rs763528176	423	A>E		No	gnomAD
COSM896871 rs763528176	423	A>V	Variant assessed as Somatic; MODERATE impact. endometrium [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated NCI-TCGA gnomAD
RCV001810615 rs1647338688	424	I>M		No	ClinVar Ensembl dbSNP
rs753198136	425	A>D		No	ExAC gnomAD
rs756703156	425	A>S		No	ExAC TOPMed gnomAD
rs756703156	425	A>T		No	ExAC TOPMed gnomAD
rs753198136	425	A>V		No	ExAC gnomAD
rs1408937465	429	E>D		No	TOPMed gnomAD
rs2148202023	429	E>K		No	Ensembl
rs1557957612	430	A>T		No	Ensembl
rs1210938549	430	A>V		No	TOPMed
rs1553230166	432	V>A		No	Ensembl
rs1485686979	434	H>R		No	gnomAD
rs142238268	435	R>G		No	ESP ExAC TOPMed gnomAD
rs1189319617	435	R>P		No	TOPMed gnomAD
rs1189319617	435	R>Q		No	TOPMed gnomAD
rs778805401	436	Q>*		No	TOPMed gnomAD
rs778805401	436	Q>E		No	TOPMed gnomAD
rs758965704	436	Q>L		No	TOPMed
rs758965704	436	Q>R		No	TOPMed
TCGA novel	437	L>R	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs1416978773	437	L>V		No	TOPMed gnomAD
rs2148201893	439	E>*		No	Ensembl
rs771145576	440	E>K		No	ExAC gnomAD
rs1441486786	441	L>I		No	gnomAD
rs773396824	442	R>C		No	ExAC gnomAD
rs370554398	442	R>H		No	ESP ExAC TOPMed gnomAD
rs760606711	443	R>L		No	ExAC TOPMed gnomAD
rs760606711	443	R>Q		No	ExAC TOPMed gnomAD
rs1326895470	443	R>W		No	gnomAD
rs1647326651	444	A>G		No	TOPMed gnomAD
rs531294009	445	A>E		No	1000Genomes ExAC TOPMed gnomAD
rs531294009 COSM2210434	445	A>V	haematopoietic_and_lymphoid_tissue [Cosmic]	No	cosmic curated 1000Genomes ExAC TOPMed gnomAD
rs774102445	447	L>I		No	ExAC TOPMed gnomAD
rs1647326018	448	S>N		No	gnomAD
rs189360283	449	R>C		No	1000Genomes ExAC TOPMed gnomAD
rs149932430	449	R>H		No	ESP ExAC TOPMed gnomAD
rs149932430	449	R>L		No	ESP ExAC TOPMed gnomAD
rs769123407	453	E>A		No	ExAC TOPMed gnomAD
rs769123407	453	E>G		No	ExAC TOPMed gnomAD
rs748700869	455	T>A		No	ExAC
rs1220101882	455	T>I		No	Ensembl
rs756864028	456	A>T		No	TOPMed gnomAD
rs377022809	457	I>V		No	ESP TOPMed gnomAD
rs755522396	458	G>A		No	ExAC TOPMed gnomAD
COSM4022996 rs1647322395	459	A>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic Ensembl
rs752034960	460	V>L		No	ExAC TOPMed gnomAD
rs1385287371	463	A>S		No	TOPMed gnomAD
rs1385287371	463	A>T		No	TOPMed gnomAD
RCV001812947 rs1647321523	463	A>V		No	ClinVar Ensembl dbSNP
COSM4847288	464	F>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1210256362	465	K>M		No	gnomAD
rs1210256362	465	K>R		No	gnomAD
COSM1472713	467	C>W	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1267288023	468	A>S		No	gnomAD
rs765388322	470	A>S		No	ExAC gnomAD
rs1553230130	470	A>V		No	Ensembl
rs1422440206	472	I>M		No	TOPMed gnomAD
rs1433195419	476	T>K		No	gnomAD
rs1553230126	476	T>S		No	Ensembl
rs201406712 RCV002241661 RCV001813095	479	R>C		No	ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
rs118204085 RCV002041863	479	R>L		No	ClinVar ESP ExAC TOPMed dbSNP gnomAD
rs773040738	481	A>D		No	ExAC TOPMed gnomAD
rs773040738	481	A>V		No	ExAC TOPMed gnomAD
rs1202916217	483	L>F		No	gnomAD
rs902988637	488	R>*		No	TOPMed gnomAD
rs200133000	490	R>G		No	1000Genomes ExAC TOPMed gnomAD
rs746257586	490	R>L		No	ExAC TOPMed gnomAD
rs1461630879	492	A>E		No	TOPMed
rs1238958347	492	A>S		No	TOPMed gnomAD
rs749456521	493	V>D		No	ExAC gnomAD
rs1395197329	493	V>I		No	gnomAD
rs1467286964	494	I>T		No	gnomAD
rs1168559609	497	T>N		No	TOPMed gnomAD
rs1451331645	497	T>S		No	TOPMed gnomAD
rs551883218	498	R>S		No	1000Genomes ExAC TOPMed gnomAD
COSM225970	499	S>F	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1179972066	503	A>T		No	gnomAD
rs750255401 RCV002033426	503	A>V		No	ClinVar ExAC dbSNP gnomAD
TCGA novel	504	R>A	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs967010243	504	R>C		No	TOPMed gnomAD
rs1336765862	505	Q>R		No	TOPMed gnomAD
rs1647238293	506	V>G		No	TOPMed gnomAD
rs760152160	507	H>N		No	ExAC gnomAD
rs1572052047	509	C>*		No	Ensembl
rs760208078	509	C>R		No	Ensembl
RCV001507459 rs1331742633	510	R>*		No	ClinVar TOPMed dbSNP gnomAD
rs371489505	513	F>L		No	ESP ExAC TOPMed gnomAD
rs1553229902	513	F>L		No	Ensembl
rs1553229901	515	L>S		No	Ensembl
rs1341550191	516	L>F		No	gnomAD
TCGA novel	516	L>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs779681839	516	L>P		No	Ensembl
rs2148198978	517	Y>S		No	Ensembl
rs771218326	518	R>H	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA TOPMed gnomAD
RCV000733378 rs139002629	518	R>S		No	ClinVar ESP ExAC TOPMed dbSNP gnomAD
rs761819694	519	E>D		No	Ensembl
rs1674555327	519	E>Q		No	Ensembl
rs1335751664	520	P>L		No	TOPMed gnomAD
rs562318137	520	P>S		No	1000Genomes ExAC gnomAD
rs562318137	520	P>T		No	1000Genomes ExAC gnomAD
rs756341032	521	P>S		No	ExAC gnomAD
rs1674554905	522	E>K		No	gnomAD
rs1674554802	523	A>D		No	TOPMed
rs1674554701	524	I>T		No	Ensembl
rs748219831	527	D>N		No	ExAC gnomAD
COSM1334618	528	D>Y	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1469593621	529	V>I		No	gnomAD
rs974898528 COSM1472712	531	R>H	Variant assessed as Somatic; MODERATE impact. breast [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated NCI-TCGA TOPMed gnomAD
rs201255024	532	R>G		No	ExAC gnomAD
rs758278200 RCV001895024	532	R>P		No	ClinVar ExAC TOPMed dbSNP gnomAD
rs1674553211	535	F>I		No	TOPMed
rs754526647	535	F>S		No	Ensembl
rs1572051895 RCV000994122	536	G>V		No	ClinVar Ensembl dbSNP
rs1259480655	537	I>M		No	TOPMed gnomAD
rs1266658818	538	E>G		No	gnomAD
rs763878359	540	G>*		No	ExAC gnomAD
rs1169315216	541	K>N		No	TOPMed gnomAD
rs1553229729	542	L>F	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	Ensembl NCI-TCGA
rs1010136449	543	R>C		No	TOPMed gnomAD
rs752328700	543	R>H		No	ExAC TOPMed gnomAD
rs759039445	544	G>V		No	ExAC gnomAD
rs751050425	547	R>C		No	ExAC gnomAD
rs375525211	547	R>H		No	ESP ExAC TOPMed gnomAD
rs1340409753	549	G>E		No	TOPMed gnomAD
rs190966689	549	G>R		No	1000Genomes ExAC gnomAD
rs1674490071	551	L>R		No	gnomAD
rs773628430	552	V>A		No	ExAC TOPMed gnomAD
rs1674489561	554	V>A		No	Ensembl
rs770125793	555	V>L		No	ExAC gnomAD
rs1674489238	557	G>S		No	Ensembl
rs370938255	558	W>*		No	ESP ExAC gnomAD
rs532230312	559	R>*		No	1000Genomes ExAC TOPMed gnomAD
rs1456158956	559	R>Q	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA TOPMed gnomAD
rs997370208	563	G>C		No	TOPMed gnomAD
rs1185256935	563	G>D		No	TOPMed gnomAD
rs997370208 COSM1668031	563	G>S	haematopoietic_and_lymphoid_tissue [Cosmic]	No	cosmic curated TOPMed gnomAD
rs1221397220	565	T>S		No	TOPMed gnomAD
rs780275059	567	I>F		No	ExAC gnomAD
rs777435169	568	M>I		No	ExAC gnomAD
rs749179500	568	M>T		No	ExAC gnomAD
rs1052176	569	R>W		No	1000Genomes ESP ExAC TOPMed gnomAD
rs1427445604	570	V>L		No	gnomAD
rs1674485712	574	S>F		No	TOPMed

2 associated diseases with P30613

[MIM: 102900]: Pyruvate kinase hyperactivity (PKHYP)

Autosomal dominant phenotype characterized by increase of red blood cell ATP. . Note=The disease is caused by variants affecting the gene represented in this entry.

[MIM: 266200]: Pyruvate kinase deficiency of red cells (PKRD)

A frequent cause of hereditary non-spherocytic hemolytic anemia. Clinically, pyruvate kinase-deficient patients suffer from a highly variable degree of chronic hemolysis, ranging from severe neonatal jaundice and fatal anemia at birth, severe transfusion-dependent chronic hemolysis, moderate hemolysis with exacerbation during infection, to a fully compensated hemolysis without apparent anemia. . Note=The disease is caused by variants affecting the gene represented in this entry.

Without disease ID

Autosomal dominant phenotype characterized by increase of red blood cell ATP. . Note=The disease is caused by variants affecting the gene represented in this entry.
A frequent cause of hereditary non-spherocytic hemolytic anemia. Clinically, pyruvate kinase-deficient patients suffer from a highly variable degree of chronic hemolysis, ranging from severe neonatal jaundice and fatal anemia at birth, severe transfusion-dependent chronic hemolysis, moderate hemolysis with exacerbation during infection, to a fully compensated hemolysis without apparent anemia. . Note=The disease is caused by variants affecting the gene represented in this entry.

4 regional properties for P30613

Type	Name	Position	InterPro Accession
domain	Cyclic nucleotide-binding domain	595 - 708	IPR000595
domain	Ion transport domain	263 - 523	IPR005821
domain	Ion transport N-terminal	219 - 261	IPR013621
conserved_site	Cyclic nucleotide-binding, conserved site	622 - 638	IPR018488

Functions

		Description
EC Number	2.7.1.40	Phosphotransferases with an alcohol group as acceptor
Subcellular Localization
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

4 GO annotations of cellular component

Name	Definition
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.
extracellular exosome	A vesicle that is released into the extracellular region by fusion of the limiting endosomal membrane of a multivesicular body with the plasma membrane. Extracellular exosomes, also simply called exosomes, have a diameter of about 40-100 nm.
pyruvate kinase complex	A protein complex which is capable of pyruvate kinase activity.

6 GO annotations of molecular function

Name	Definition
ATP binding	Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
kinase activity	Catalysis of the transfer of a phosphate group, usually from ATP, to a substrate molecule.
magnesium ion binding	Binding to a magnesium (Mg) ion.
monosaccharide binding	Binding to a monosaccharide. Monosaccharides are the simplest carbohydrates; they are polyhydroxy aldehydes HnC(=O)H or polyhydroxy ketones HnC(=O)mH with three or more carbon atoms. They form the constitutional repeating units of oligo- and polysaccharides.
potassium ion binding	Binding to a potassium ion (K+).
pyruvate kinase activity	Catalysis of the reaction

11 GO annotations of biological process

Name	Definition
cellular response to epinephrine stimulus	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 epinephrine stimulus. Epinephrine is a catecholamine that has the formula C9H13NO3; it is secreted by the adrenal medulla to act as a hormone, and released by certain neurons to act as a neurotransmitter active in the central nervous system.
cellular response to insulin stimulus	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 insulin stimulus. Insulin is a polypeptide hormone produced by the islets of Langerhans of the pancreas in mammals, and by the homologous organs of other organisms.
glycolytic process	The chemical reactions and pathways resulting in the breakdown of a carbohydrate into pyruvate, with the concomitant production of a small amount of ATP and the reduction of NAD(P) to NAD(P)H. Glycolysis begins with the metabolism of a carbohydrate to generate products that can enter the pathway and ends with the production of pyruvate. Pyruvate may be converted to acetyl-coenzyme A, ethanol, lactate, or other small molecules.
phosphorylation	The process of introducing a phosphate group into a molecule, usually with the formation of a phosphoric ester, a phosphoric anhydride or a phosphoric amide.
pyruvate biosynthetic process	The chemical reactions and pathways resulting in the formation of pyruvate, 2-oxopropanoate.
response to ATP	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 an ATP (adenosine 5'-triphosphate) stimulus.
response to cAMP	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 a cAMP (cyclic AMP, adenosine 3',5'-cyclophosphate) stimulus.
response to glucose	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 a glucose stimulus.
response to hypoxia	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 a stimulus indicating lowered oxygen tension. Hypoxia, defined as a decline in O2 levels below normoxic levels of 20.8 - 20.95%, results in metabolic adaptation at both the cellular and organismal level.
response to metal ion	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 a metal ion stimulus.
response to nutrient	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 a nutrient stimulus.

12 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
P52489	PYK2	Pyruvate kinase 2	Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)	SS
P00549	CDC19	Pyruvate kinase 1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)	SS
P11979	PKM	Pyruvate kinase PKM	Felis catus (Cat) (Felis silvestris catus)	SS
P00548	PKM	Pyruvate kinase PKM	Gallus gallus (Chicken)	SS
Q29536	PKLR	Pyruvate kinase PKLR	Canis lupus familiaris (Dog) (Canis familiaris)	SS
O62619	PyK	Pyruvate kinase	Drosophila melanogaster (Fruit fly)	SS
P14618	PKM	Pyruvate kinase PKM	Homo sapiens (Human)	EV
P52480	Pkm	Pyruvate kinase PKM	Mus musculus (Mouse)	SS
P53657	Pklr	Pyruvate kinase PKLR	Mus musculus (Mouse)	SS
P11980	Pkm	Pyruvate kinase PKM	Rattus norvegicus (Rat)	SS
P12928	Pklr	Pyruvate kinase PKLR	Rattus norvegicus (Rat)	SS
Q9LIK0	PKP1	Plastidial pyruvate kinase 1, chloroplastic	Arabidopsis thaliana (Mouse-ear cress)	PR

10	20	30	40	50	60
MSIQENISSL	QLRSWVSKSQ	RDLAKSILIG	APGGPAGYLR	RASVAQLTQE	LGTAFFQQQQ
70	80	90	100	110	120
LPAAMADTFL	EHLCLLDIDS	EPVAARSTSI	IATIGPASRS	VERLKEMIKA	GMNIARLNFS
130	140	150	160	170	180
HGSHEYHAES	IANVREAVES	FAGSPLSYRP	VAIALDTKGP	EIRTGILQGG	PESEVELVKG
190	200	210	220	230	240
SQVLVTVDPA	FRTRGNANTV	WVDYPNIVRV	VPVGGRIYID	DGLISLVVQK	IGPEGLVTQV
250	260	270	280	290	300
ENGGVLGSRK	GVNLPGAQVD	LPGLSEQDVR	DLRFGVEHGV	DIVFASFVRK	ASDVAAVRAA
310	320	330	340	350	360
LGPEGHGIKI	ISKIENHEGV	KRFDEILEVS	DGIMVARGDL	GIEIPAEKVF	LAQKMMIGRC
370	380	390	400	410	420
NLAGKPVVCA	TQMLESMITK	PRPTRAETSD	VANAVLDGAD	CIMLSGETAK	GNFPVEAVKM
430	440	450	460	470	480
QHAIAREAEA	AVYHRQLFEE	LRRAAPLSRD	PTEVTAIGAV	EAAFKCCAAA	IIVLTTTGRS
490	500	510	520	530	540
AQLLSRYRPR	AAVIAVTRSA	QAARQVHLCR	GVFPLLYREP	PEAIWADDVD	RRVQFGIESG
550	560	570
KLRGFLRVGD	LVIVVTGWRP	GSGYTNIMRV	LSIS