AiPD: Autoinhibited Protein Database

P22681

Gene name	CBL (CBL2, RNF55)
Protein name	E3 ubiquitin-protein ligase CBL
Names	Casitas B-lineage lymphoma proto-oncogene, Proto-oncogene c-Cbl, RING finger protein 55, RING-type E3 ubiquitin transferase CBL, Signal transduction protein CBL
Species	Homo sapiens (Human)
KEGG Pathway	hsa:867
EC number	2.3.2.27: Aminoacyltransferases
Protein Class	CBL (PTHR23007)

Descriptions

Cbls are adaptor proteins with RING ubiquitin ligase activity, which function as a negative regulator of many signaling pathways. In human CBL, the phosphorylation of Y371 is essential in regulation of the E3 activity of CBL. When Y371 is unmodified, the RING domain is spatially restricted to regions distal from the TKBD substrate-binding site. Phosphorylation facilitates LHR (linker-loop1 (LL1), linker-helix (LH) and linker-loop2 (LL2)) conformational changes that enable the RING domain to approach the N-terminal tyrosine kinase-binding domain (TKBD) substrate-binding site, leading to an increased activity. Specifically, the absence of LH-TKBD contact enables dramatic movement of the RING domain, bringing E2 closer to the TKBD substrate-binding site. Restricting and freeing the RING domain may be a general mechanism for regulating other RING E3s.

Autoinhibitory domains (AIDs)

Target domain	47-353 (TKBD)
Relief mechanism	PTM
Assay	Mutagenesis experiment, Structural analysis

AID

364-375 (LH region)

Target domain

47-353 (TKBD)

Relief mechanism

PTM (Phosphorylation of Tyr371)

Assay

Mutagenesis experiment, Structural analysis

Accessory elements

No accessory elements

References

Dou H et al. (2012) "Structural basis for autoinhibition and phosphorylation-dependent activation of c-Cbl", Nature structural & molecular biology, 19, 184-92

Wybenga-Groot LE et al. (2021) "SLAP2 Adaptor Binding Disrupts c-CBL Autoinhibition to Activate Ubiquitin Ligase Function", Journal of molecular biology, 433, 166880

Autoinhibited structure

Activated structure

33 structures for P22681

Entry ID	Method	Resolution	Chain	Position	Source
1B47	X-ray	220 A	A/B/C	47-350	PDB
1FBV	X-ray	290 A	A	47-434	PDB
1YVH	X-ray	205 A	A	25-351	PDB
2CBL	X-ray	210 A	A	47-351	PDB
2JUJ	NMR	-	A	851-906	PDB
2K4D	NMR	-	A	358-437	PDB
2OO9	X-ray	210 A	A/B/C	856-895	PDB
2Y1M	X-ray	267 A	A/B/C/D/E/F	47-435	PDB
2Y1N	X-ray	200 A	A/C	47-435	PDB
3BUM	X-ray	200 A	B	25-351	PDB
3BUN	X-ray	200 A	B	25-351	PDB
3BUO	X-ray	260 A	B/D	25-351	PDB
3BUW	X-ray	145 A	B/D	25-351	PDB
3BUX	X-ray	135 A	B/D	25-351	PDB
3OB1	X-ray	220 A	B	25-351	PDB
3OB2	X-ray	210 A	B	25-351	PDB
3PLF	X-ray	192 A	B/D	25-351	PDB
4A49	X-ray	221 A	A	354-435	PDB
4A4B	X-ray	279 A	A	47-435	PDB
4A4C	X-ray	270 A	A	47-435	PDB
4GPL	X-ray	300 A	B	47-351	PDB
5HKW	X-ray	225 A	A/B/C	47-351	PDB
5HKX	X-ray	185 A	A	47-435	PDB
5HKY	X-ray	180 A	A	47-351	PDB
5HKZ	X-ray	180 A	A	47-351	PDB
5HL0	X-ray	220 A	A	47-351	PDB
5J3X	X-ray	282 A	A/B/C/D/E/F	47-435	PDB
5O76	X-ray	247 A	A/C	47-435	PDB
6O02	X-ray	295 A	A	47-353	PDB
6O03	X-ray	330 A	A/B	47-353	PDB
6XAR	X-ray	250 A	A/B	25-357	PDB
7SIY	X-ray	148 A	A	48-351	PDB
AF-P22681-F1	Predicted				AlphaFoldDB

745 variants for P22681

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
CA229653547 rs930860175 RCV000654938	8	S>N	RASopathy [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP gnomAD
rs868791422 CA10629967 RCV000375826	14	G>D	CBL-related disorder [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP
RCV000686788 CA382975764 rs1565851542	14	G>S	RASopathy [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
CA658797812 RCV000654928 rs1555225091	15	S>P	RASopathy [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs933058944 CA229653645 RCV000654969	27	G>V	RASopathy [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV001770529 RCV001860001 rs376679438 RCV000578005 CA6318224	31	D>E	RASopathy CBL-related disorder [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
rs373212940 RCV000502781 RCV001851404	40	H>missing	RASopathy [ClinVar]	Yes	ClinVar dbSNP
RCV000540192 rs373212940	41	H>missing	RASopathy [ClinVar]	Yes	ClinVar dbSNP
RCV000038350 rs373212940 RCV000278774 RCV000514229	42	H>missing	Noonan-like syndrome [ClinVar]	Yes	ClinVar dbSNP
RCV000555209 RCV000417822 rs730880433 CA295993	42	H>L	RASopathy [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
rs373212940 RCV001579695 RCV000157851	42	H>missing	RASopathy [ClinVar]	Yes	ClinVar dbSNP
rs1555225106 RCV000654952	43	L>missing	RASopathy [ClinVar]	Yes	ClinVar dbSNP
RCV000157854 rs730880429 CA295974 RCV000549374	68	R>W	RASopathy [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
RCV000704002 rs757898729 CA382894193	76	A>V	RASopathy [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
CA382894360 rs1555226659 RCV000654925	83	Y>C	RASopathy [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV000654935 CA382894498 rs1555226661	90	D>G	RASopathy [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV000543468 CA382894632 rs1415440583	98	I>V	RASopathy [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP
rs1949511665 RCV001105950	99	L>S	CBL-related disorder [ClinVar]	Yes	ClinVar dbSNP
rs397507489 RCV000984977 RCV000033348 CA282012	102	Y>*	CBL-related disorder [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
RCV000691445 rs1565859798 CA382894966	110	G>R	RASopathy [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
CA382895271 rs1490142046 RCV001873216 RCV001844236 RCV000788321	119	M>I	RASopathy [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
RCV001105951 rs1949512275	123	M>L	CBL-related disorder [ClinVar]	Yes	ClinVar dbSNP
RCV000415508 rs1057519030 CA16043920	135	E>D	CBL-related disorder [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV000654971 rs1555226684 CA382895872	140	M>R	RASopathy [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
CA229658291 rs199739868 RCV000698213 COSM168281	149	R>Q	RASopathy large_intestine [ClinVar, Cosmic]	Yes	ClinGen cosmic curated ClinVar TOPMed dbSNP gnomAD
rs1949850753 RCV001198819	154	L>P	CBL-related disorder [ClinVar]	Yes	ClinVar dbSNP
RCV000532294 rs1555229540 CA382907266	165	L>V	RASopathy [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs1565870421 CA382907295 RCV000687307	166	K>N	RASopathy [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs1949851157 RCV001197721	170	P>S	CBL-related disorder [ClinVar]	Yes	ClinVar dbSNP
RCV001854603 RCV000120468 COSM1283936 CA157878 rs587778162	187	A>V	RASopathy autonomic_ganglia [ClinVar, Cosmic]	Yes	ClinGen cosmic curated ClinVar TOPMed dbSNP gnomAD
CA6318321 rs767162260 RCV000379150 RCV000476171	209	L>V	RASopathy CBL-related disorder [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
rs1949868148 RCV001199018	227	T>S	CBL-related disorder [ClinVar]	Yes	ClinVar dbSNP
rs1414848678 RCV001270817 CA382909520	229	D>V	Noonan-like syndrome [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP
rs1949868655 RCV001327985	237	S>L	CBL-related disorder [ClinVar]	Yes	ClinVar dbSNP
rs1268100574 CA382909801 RCV000557437	243	I>T	RASopathy [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
rs372452974 RCV000853162 RCV002222191 CA229660492 RCV001869302	269	M>V	Cardiomyopathy, left ventricular noncompaction RASopathy CBL-related disorder [ClinVar]	Yes	ClinGen ClinVar ESP TOPMed dbSNP gnomAD
RCV001108180 RCV001855054 CA6318350 RCV000372964 rs145155035	280	R>Q	RASopathy CBL-related disorder [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
RCV000473617 CA16613530 rs1053471259	299	R>C	RASopathy [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP
CA6318412 RCV001919275 rs765471101	343	R>*	RASopathy [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV000551449 CA6318415 rs202095002	345	Q>E	RASopathy [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ExAC dbSNP gnomAD
rs397507490 RCV000033351	359	D>missing	RASopathy [ClinVar]	Yes	ClinVar dbSNP
rs756742202 CA6318418 RCV001850604 RCV000393886	365	Q>R	RASopathy CBL-related disorder [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
rs727504504 RCV001265817 RCV000155642 CA183197	367	Q>K	Noonan syndrome Inborn genetic diseases [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs267606704 RCV000014818 RCV000702464 RCV000033352 CA123484 VAR_064332	367	Q>P	NSLL RASopathy Fragile site 11b [UniProt, ClinVar]	Yes	ClinGen ClinVar UniProt ExAC TOPMed dbSNP gnomAD
rs1555230070 RCV000627092	367	Q>missing	CBL-related disorder [ClinVar]	Yes	ClinVar dbSNP
RCV000211127 CA128671 RCV000022700 rs387906666 RCV002223763 COSM34054	371	Y>C	Noonan syndrome-like disorder with juvenile myelomonocytic leukemia Juvenile myelomonocytic leukemia Juvenile myelomonocytic leukemia (jmml) haematopoietic_and_lymphoid_tissue [ClinVar, Ensembl, Cosmic]	Yes	ClinGen cosmic curated ClinVar Ensembl dbSNP
RCV000014822 rs267606706 CA123492 VAR_071042 RCV000441724 COSM34052 RCV000691502 RCV000437548	371	Y>H	Noonan syndrome-like disorder with juvenile myelomonocytic leukemia RASopathy Hematologic neoplasm found in patients with acute myeloid leukemia; unknown pathological significance; loss of the ability to negatively regulate signaling pathways; promotes cell cycle progression; decreases apoptosis haematopoietic_and_lymphoid_tissue [ClinVar, UniProt, Cosmic]	Yes	ClinGen cosmic curated ClinVar UniProt ExAC dbSNP gnomAD
RCV000856726 RCV000506397 rs267606706 CA296015 RCV001814073	371	Y>N	Noonan syndrome 1 CBL-related disorder [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
CA382912305 rs387906666 RCV000660642 COSM133823	371	Y>S	Juvenile myelomonocytic leukemia Juvenile myelomonocytic leukemia (jmml) haematopoietic_and_lymphoid_tissue [ClinVar, Ensembl, Cosmic]	Yes	ClinGen cosmic curated ClinVar Ensembl dbSNP
rs727502914 CA175402 RCV000150240 RCV001265818	377	T>A	Inborn genetic diseases [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
CA382912479 rs1377506801 RCV000525475 COSM34055	380	L>P	RASopathy haematopoietic_and_lymphoid_tissue [ClinVar, Cosmic]	Yes	ClinGen cosmic curated ClinVar dbSNP gnomAD
rs757874631 CA6318439 RCV000470469 COSM34056	381	C>R	RASopathy large_intestine haematopoietic_and_lymphoid_tissue [ClinVar, Cosmic]	Yes	ClinGen cosmic curated ClinVar ExAC dbSNP gnomAD
RCV001851859 RCV001268437 RCV000014819 COSM49107 rs267606705 VAR_064333 CA123486	382	K>E	NSLL; dominant-negative; impairs CBL-mediated ubiquitination, internalization and degradation of the EGF receptor/EGFR; decreases the ability to negatively regulate EGFR signaling RASopathy Fragile site 11b haematopoietic_and_lymphoid_tissue [UniProt, ClinVar, Cosmic]	Yes	ClinGen cosmic curated ClinVar UniProt Ensembl dbSNP
rs387906664 CA128665 RCV001857355 COSM34057 RCV001561040 RCV000420743 RCV000022698	384	C>R	Noonan syndrome-like disorder with juvenile myelomonocytic leukemia RASopathy skin Hematologic neoplasm haematopoietic_and_lymphoid_tissue [ClinVar, Cosmic]	Yes	ClinGen cosmic curated ClinVar Ensembl dbSNP
rs1060500676 CA16613479 RCV000457434	389	K>E	RASopathy [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs773598122 CA382912654 RCV000689730	389	K>N	RASopathy [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
CA6318445 RCV000680806 rs763058208 RCV001027992 RCV001868303	390	D>V	RASopathy CBL-related disorder [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
rs267606707 CA123488 RCV000014820 VAR_064334	390	D>Y	NSLL; dominant-negative; impairs CBL-mediated ubiquitination, internalization and degradation of the EGF receptor/EGFR; decreases the ability to negatively regulate EGFR signaling Fragile site 11b [UniProt, ClinVar]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV000022699 RCV000157860 rs387906665 CA128668 COSM34058	396	C>R	Noonan syndrome-like disorder with juvenile myelomonocytic leukemia large_intestine haematopoietic_and_lymphoid_tissue [ClinVar, Cosmic]	Yes	ClinGen cosmic curated ClinVar ExAC TOPMed dbSNP gnomAD
rs1303812580 RCV001108182 CA382912753	398	H>P	CBL-related disorder [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
COSM1234989 CA6318482 rs757456261 RCV001252955	416	C>S	haematopoietic_and_lymphoid_tissue CBL-related disorder [Cosmic, ClinVar]	Yes	ClinGen cosmic curated ClinVar ExAC TOPMed dbSNP gnomAD
CA123490 COSM34077 rs267606708 RCV000014821 VAR_064335 RCV000414703	420	R>Q	NSLL; dominant-negative; impairs CBL-mediated ubiquitination, internalization and degradation of the EGF receptor/EGFR; decreases the ability to negatively regulate EGFR signaling large_intestine Fragile site 11b central_nervous_system haematopoietic_and_lymphoid_tissue [UniProt, Cosmic, ClinVar]	Yes	ClinGen cosmic curated ClinVar UniProt ESP ExAC TOPMed dbSNP gnomAD
CA6318487 RCV000654967 rs769547118	426	T>I	RASopathy [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
RCV000684954 CA229662011 rs991981291	430	V>M	RASopathy [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP
CA295990 RCV000157862 rs140627020 RCV001813407 RCV001850196	433	P>L	Noonan syndrome and Noonan-related syndrome RASopathy [ClinVar]	Yes	ClinGen ClinVar ESP TOPMed dbSNP
rs200508558 RCV000532713 CA6318498	442	L>M	RASopathy [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
RCV000799853 rs1592401235	449	G>missing	RASopathy [ClinVar]	Yes	ClinVar dbSNP
RCV000370641 RCV001850605 rs371850672 RCV000593984 COSM34082 CA6318503	454	N>D	Noonan-like syndrome RASopathy haematopoietic_and_lymphoid_tissue [ClinVar, Cosmic]	Yes	ClinGen cosmic curated ClinVar ESP ExAC TOPMed dbSNP gnomAD
RCV000692032 rs1565872426 CA382914527	455	Y>C	RASopathy [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV000691279 rs397507494	460	D>missing	RASopathy [ClinVar]	Yes	ClinVar dbSNP
RCV000695338 rs770644035 CA6318506	465	D>V	RASopathy [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
RCV001102984 rs771673435 CA6318509	467	L>V	CBL-related disorder [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
rs764599897 RCV000542936 CA6318512	475	G>S	RASopathy [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
CA229641807 RCV000691587 rs995860476	487	M>T	RASopathy [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
RCV000553397 RCV000033360 CA282028 rs17848896	487	M>V	RASopathy [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
RCV000106326 rs377502790 RCV001813377 RCV000763710 CA150792 RCV001854518	488	A>V	Noonan syndrome and Noonan-related syndrome RASopathy Juvenile myelomonocytic leukemia CBL-related disorder [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
CA295996 rs730880434 RCV000707567 RCV000157864 RCV000622732	493	L>F	RASopathy Inborn genetic diseases [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
rs373989524 RCV000423118 RCV000680314 CA6318539 RCV001865325	495	P>L	RASopathy [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
rs778927765 RCV001257539 CA382918078	499	R>*	Rhabdomyosarcoma [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
rs1949969949 RCV001252854	500	L>F	Microcephaly [ClinVar]	Yes	ClinVar dbSNP
RCV000592226 CA6318541 RCV000227838 rs533554769	504	P>L	RASopathy [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
RCV000355691 RCV000654950 rs538054260 CA6318545	510	P>A	RASopathy CBL-related disorder [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
rs1949970576 RCV001873658 RCV001174990	513	A>V	RASopathy [ClinVar]	Yes	ClinVar dbSNP
rs377734587 RCV000654919 CA6318549	518	T>A	RASopathy [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
RCV001861884 CA6318550 rs371686364 RCV000680637	520	S>P	RASopathy [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP
RCV001260380 CA6318578 RCV001879990 rs751274314 COSM923816	546	P>L	RASopathy endometrium [ClinVar, Cosmic]	Yes	ClinGen cosmic curated ClinVar ExAC TOPMed dbSNP gnomAD
RCV000466595 CA184322 rs369030902 RCV000156176	549	D>E	RASopathy [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV000761157 CA382919594 rs143034856 RCV000596726	559	R>L	B lymphoblastic leukemia lymphoma with hyperdiploidy [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
COSM279594 rs143034856 RCV000684950 CA6318586	559	R>Q	RASopathy large_intestine [ClinVar, Cosmic]	Yes	ClinGen cosmic curated ClinVar ESP ExAC TOPMed dbSNP gnomAD
rs1246882963 RCV001331369	561	Q>*	CBL-related disorder [ClinVar]	Yes	ClinVar dbSNP
RCV000654931 CA382919693 rs1174693367	565	L>S	RASopathy [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
rs483352825 RCV000106327 CA150795 RCV001854519	571	D>N	RASopathy CBL-related disorder [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs374515645 RCV001852672 RCV001818206 RCV000033361 CA282031	575	R>G	RASopathy [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
RCV001238477 rs1949974996	578	L>missing	RASopathy [ClinVar]	Yes	ClinVar dbSNP
rs187952822 RCV000654963 COSM1193372 CA6318601	585	R>C	lung RASopathy [Cosmic, ClinVar]	Yes	ClinGen cosmic curated ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
CA295999 RCV000157865 rs727504640 RCV000546705	585	R>H	RASopathy [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
rs727504640 CA183762 RCV000492503 RCV000155901	585	R>L	CBL-related disorder [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
CA382920145 rs1555230612 RCV000556828	589	S>P	RASopathy [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
CA16613259 rs1060500679 RCV000459319	591	L>V	RASopathy [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs730880435 CA296002 RCV000157866 RCV001850197	593	R>Q	RASopathy [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV001192737 RCV001759779 CA229642422 RCV001050411 rs775675805	595	I>V	RASopathy [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP gnomAD
rs1060500675 RCV000458200 CA16613254	598	V>E	RASopathy [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs1340017837 RCV001106054 CA382920420 RCV001856425	599	P>A	RASopathy CBL-related disorder [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
rs1340017837 CA382920417 RCV000535435	599	P>T	RASopathy [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
RCV000545633 rs1555230616 CA382920497	604	S>G	RASopathy [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV001852673 RCV000033362 rs397507495 CA282034	608	P>H	RASopathy [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
RCV001873505 RCV001106055 CA6318612 rs763666786	608	P>T	RASopathy CBL-related disorder [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
rs730880427 RCV000157852 RCV000324245 CA295968	610	T>K	CBL-related disorder [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP
rs376094293 RCV000691788 CA6318616	616	N>T	RASopathy [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
RCV000654918 CA6318617 RCV000414250 rs780457588	617	R>L	RASopathy [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV000703955 CA229642460 rs780457588	617	R>Q	RASopathy [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV000033363 rs150550899 RCV000459030 CA282037	624	L>S	RASopathy [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
RCV000214364 rs552590011 RCV000199649 CA338766	631	R>G	RASopathy [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ExAC dbSNP gnomAD
RCV001879989 rs571045498 RCV001260379 CA382921004	642	S>I	RASopathy [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ExAC dbSNP gnomAD
rs769423231 CA6318646 RCV000464992 RCV000415487	649	M>V	RASopathy CBL-related disorder [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP
RCV000284244 CA10637377 rs886047770	656	G>D	CBL-related disorder [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV000534597 CA382922806 rs1439055502	673	I>V	RASopathy [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
RCV001682830 RCV000327543 RCV000120458 RCV000680340 CA157848 rs587778154	684	P>S	Juvenile myelomonocytic leukemia Juvenile myelomonocytic leukemia (jmml) CBL-related disorder [ClinVar, Ensembl]	Yes	ClinGen ClinVar TOPMed dbSNP gnomAD
rs146705974 RCV000287851 RCV000654929 CA296005	687	P>L	RASopathy CBL-related disorder [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
CA157854 RCV001854602 rs587778156 RCV000120460	693	E>K	RASopathy [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP gnomAD
rs143975631 CA10582878 RCV000231078	695	E>K	RASopathy [ClinVar]	Yes	ClinGen ClinVar ESP TOPMed dbSNP gnomAD
rs539217274 RCV001263314	696	E>Q	Global developmental delay [ClinVar]	Yes	ClinVar dbSNP
RCV000345485 rs866325598 CA10633643	699	E>G	CBL-related disorder [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP
RCV001108284 rs587778155 RCV000120459 CA157851	709	R>W	CBL-related disorder [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP
RCV000654940 rs144894769 CA6318687	718	R>Q	RASopathy [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
RCV001879991 RCV001260381 rs757126995 CA6318704	719	A>T	RASopathy [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV000548583 CA6318709 rs376848406	730	T>M	RASopathy [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
RCV000680285 rs2227986 RCV000296277 CA135715 RCV000038355	739	S>F	CBL-related disorder [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
rs763213265 CA6318712 RCV000706542 RCV000681187	741	A>V	RASopathy [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
rs199788586 RCV000552056 RCV000038356 CA135718	771	D>V	RASopathy [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
CA6318749 RCV000541862 rs774428573	772	D>E	RASopathy [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV000540794 CA382929526 rs1555027886	780	P>S	RASopathy [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV000467413 RCV000033370 rs140725852 CA282046	784	V>M	RASopathy [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
RCV000555815 rs143132980 RCV000154692 CA181178	787	R>C	RASopathy [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
RCV000473552 CA282049 RCV000033371 rs200220863	787	R>H	RASopathy [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
RCV000654975 CA6318768 rs747073805	797	S>T	RASopathy [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
CA382930119 RCV001856445 RCV001108286 rs1285510326	800	F>C	RASopathy CBL-related disorder [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP
rs777761446 RCV000300042 RCV000472107	806	D>V	Noonan-like syndrome RASopathy [ClinVar]	Yes	ClinVar dbSNP
rs1950085293 RCV001196736	815	E>A	CBL-related disorder [ClinVar]	Yes	ClinVar dbSNP
RCV000700970 rs1356499832 CA382931913	820	P>A	RASopathy [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP
CA6318792 RCV000701113 rs759358775	821	E>K	RASopathy [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
CA16042828 rs1057518072 RCV001861422 RCV000412957	835	R>Q	RASopathy [ClinVar]	Yes	ClinGen ClinVar dbSNP gnomAD
RCV001850198 CA296011 rs368696716 RCV000157869	835	R>W	RASopathy [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
rs144191570 RCV000529564 RCV000761809 RCV000500878 CA6318799	838	G>V	RASopathy [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA346243 RCV000157138 rs376536789	840	C>S	Noonan syndrome [ClinVar]	Yes	ClinGen ClinVar ESP ExAC dbSNP gnomAD
rs587778159 CA157866 RCV001103083 RCV000120464	844	S>R	CBL-related disorder [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP gnomAD
CA229652891 RCV000522715 RCV001851478 rs997859448	845	G>S	RASopathy [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP gnomAD
RCV000654974 rs771831548 CA6318807	846	P>L	RASopathy [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
CA282052 COSM41274 rs141710973 RCV000475436 RCV000033373	848	A>T	lung RASopathy [Cosmic, ClinVar]	Yes	ClinGen cosmic curated ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs201631570 RCV000338492 CA6318812	857	L>F	CBL-related disorder [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
rs146250423 CA135721 RCV000680287 RCV000540019 RCV000038357	863	N>S	RASopathy [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
CA6318821 RCV001047665 RCV000597829 RCV001823150 rs746795014	872	Q>K	RASopathy [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
rs1369884955 RCV000554761 CA382933899	889	K>R	RASopathy [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP gnomAD
rs1950088243 RCV001267510	892	L>missing	Inborn genetic diseases [ClinVar]	Yes	ClinVar dbSNP
CA282058 RCV000533281 RCV000033376 rs397507499	898	I>V	RASopathy [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs17122769 RCV000298937 RCV000120465 CA157869 RCV000514119 VAR_057213	904	V>I	CBL-related disorder [ClinVar]	Yes	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA382975567 rs1362763825	3	G>V		No	ClinGen TOPMed
CA382975575 rs1253368761	4	N>Y		No	ClinGen gnomAD
CA382975600 rs1453555739	5	V>G		No	ClinGen TOPMed
CA382975589 rs1222275357	5	V>M		No	ClinGen gnomAD
rs1481598770 CA382975627	6	K>N		No	ClinGen TOPMed gnomAD
CA6318209 rs746355406	6	K>Q		No	ClinGen ExAC gnomAD
rs930860175 CA382975665	8	S>T		No	ClinGen TOPMed gnomAD
CA382975678 rs772525018	9	S>C		No	ClinGen ExAC TOPMed gnomAD
CA6318212 rs772525018	9	S>F		No	ClinGen ExAC TOPMed gnomAD
rs1170501749 CA382975675	9	S>P		No	ClinGen gnomAD
rs1170501749 CA382975673	9	S>T		No	ClinGen gnomAD
rs772525018 CA6318213	9	S>Y		No	ClinGen ExAC TOPMed gnomAD
CA382975690 rs1423866481	10	G>A		No	ClinGen TOPMed
CA382975706 rs1302101624	11	A>D		No	ClinGen TOPMed gnomAD
CA382975709 rs1302101624	11	A>G		No	ClinGen TOPMed gnomAD
CA229653586 rs866844579	12	G>V		No	ClinGen Ensembl
CA229653580 rs866162034	12	G>W		No	ClinGen gnomAD
CA6318217 rs776906066	13	G>D		No	ClinGen ExAC gnomAD
rs1215282257 CA382975823	16	G>V		No	ClinGen gnomAD
rs1357308168 CA382975828	17	S>P		No	ClinGen gnomAD
rs1222060551 CA382975832	17	S>Y		No	ClinGen gnomAD
rs765337015 CA6318219	18	G>R		No	ClinGen ExAC gnomAD
rs1453694966 CA382975847	18	G>V		No	ClinGen gnomAD
CA382975849 rs1257650494	19	G>S		No	ClinGen TOPMed
CA6318220 rs750572996	20	S>L		No	ClinGen ExAC TOPMed gnomAD
rs1188757026 CA382975946	24	G>A		No	ClinGen TOPMed gnomAD
rs1486468563 CA382975934	24	G>S		No	ClinGen gnomAD
rs767515458 CA6318222	25	L>R		No	ClinGen ExAC gnomAD
CA382975967 rs1592364629	26	I>L		No	ClinGen Ensembl
rs1162552691 CA382976020	29	M>V		No	ClinGen TOPMed gnomAD
rs1406942749 CA382976110	33	F>I		No	ClinGen gnomAD
rs987225083 CA229653649	33	F>S		No	ClinGen Ensembl
CA6318227 rs777499142	36	H>P		No	ClinGen ExAC TOPMed gnomAD
CA382976209 rs748961080	36	H>Q		No	ClinGen ExAC TOPMed gnomAD
CA6318229 rs756913123	37	H>N		No	ClinGen ExAC gnomAD
RCV001192736 rs1949270382	40	H>D		No	ClinVar dbSNP
rs778655649 CA6318230	40	H>L		No	ClinGen ExAC gnomAD
RCV000484221 CA16619286 rs745328496	40	H>Q		No	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
CA6318233 rs368813067	42	H>Y		No	ClinGen ESP ExAC
CA382976304 rs1358704061	43	L>F		No	ClinGen gnomAD
rs1028757126 CA229653748	46	H>Y		No	ClinGen TOPMed
rs570719838 CA6318234	47	P>L		No	ClinGen 1000Genomes ExAC gnomAD
rs201291907 CA229653755	50	T>M		No	ClinGen 1000Genomes gnomAD
rs1565851611 CA382976469	53	K>R		No	ClinGen Ensembl
CA229653767 rs866496657	55	M>V		No	ClinGen Ensembl
CA382976698 rs1459635883	62	L>F		No	ClinGen gnomAD
rs1182439351 CA382976707	62	L>H		No	ClinGen TOPMed gnomAD
rs1320130914 CA382976714	63	M>L		No	ClinGen TOPMed
rs1565851628 RCV000681352 CA382976766	64	D>E		No	ClinGen ClinVar Ensembl dbSNP
CA6318246 rs757094442	66	V>M		No	ClinGen ExAC gnomAD
rs901321242 CA229635074	68	R>Q		No	ClinGen TOPMed
CA6318249 rs757898729	76	A>E		No	ClinGen ExAC TOPMed gnomAD
rs1483168332 CA382894186	76	A>T		No	ClinGen TOPMed gnomAD
CA382894240 rs1266550121	79	N>D		No	ClinGen gnomAD
CA382894309 rs1486391049	81	P>L		No	ClinGen TOPMed
CA382894340 rs1275935527	82	P>L		No	ClinGen TOPMed
CA6318250 rs779595064	84	I>T		No	ClinGen ExAC gnomAD
rs1379287344 CA16622061	84	I>V		No	ClinGen gnomAD
rs1038135199 CA229635105	86	D>E		No	ClinGen TOPMed gnomAD
CA157872 rs587778160 RCV000120466	91	T>A		No	ClinGen ClinVar ExAC dbSNP gnomAD
CA382894557 rs1252780472	93	Q>*		No	ClinGen TOPMed
COSM41270 rs1301481068 CA382894575	94	H>Y	lung [Cosmic]	No	ClinGen cosmic curated gnomAD
rs147438359 CA6318251	96	R>C		No	ClinGen ESP ExAC TOPMed gnomAD
rs781738309 CA6318252	96	R>H		No	ClinGen ExAC TOPMed gnomAD
rs1293881596 CA382894627	97	T>I		No	ClinGen TOPMed
rs1326179423 CA382894677	100	S>P		No	ClinGen gnomAD
rs139139107 CA229635125	101	R>G		No	ClinGen ESP
rs1224657938 CA382894837	105	K>R		No	ClinGen TOPMed gnomAD
rs1026372456 CA229635126	106	M>I		No	ClinGen TOPMed gnomAD
rs1414058182 CA382895058	113	E>K		No	ClinGen TOPMed
RCV001199951 rs748412298 RCV001760159 CA6318253	116	R>M		No	ClinGen ClinVar ExAC dbSNP gnomAD
CA382895250 rs1289071252	118	F>L		No	ClinGen TOPMed gnomAD
CA382895274 rs1490142046	119	M>I		No	ClinGen gnomAD
rs1173256276 CA382895253	119	M>V		No	ClinGen TOPMed
rs1193053038 CA382895340	122	L>M		No	ClinGen gnomAD
rs1210210972 CA382895396	123	M>T		No	ClinGen gnomAD
rs1269425522 CA382895446	124	K>N		No	ClinGen TOPMed gnomAD
rs868705826 CA229635127	128	Q>K		No	ClinGen Ensembl
rs770209522 CA6318254	129	T>A		No	ClinGen ExAC gnomAD
RCV000120467 CA157875 rs587778161	130	I>V		No	ClinGen ClinVar Ensembl dbSNP
CA382895670 rs1565859816	132	L>H		No	ClinGen Ensembl
CA382895665 rs1390898753	132	L>V		No	ClinGen gnomAD
rs1313093726 COSM428539 CA382895676	133	F>L	breast [Cosmic]	No	ClinGen cosmic curated Ensembl
CA6318259 rs774626378	139	R>G		No	ClinGen ExAC gnomAD
CA382895912 rs1295617809	141	Y>C		No	ClinGen gnomAD
rs1383200629 CA382896057	145	S>F		No	ClinGen gnomAD
CA229635154 rs755204320	146	Q>H		No	ClinGen gnomAD
CA6318260 rs760633685	146	Q>R		No	ClinGen ExAC gnomAD
rs1474071047 CA382896085	147	P>L		No	ClinGen TOPMed
CA6318277 RCV000413050 rs267602720	149	R>*		No	ClinGen ClinVar ExAC dbSNP
CA382907092 rs1262627997	155	S>F		No	ClinGen gnomAD
CA6318278 rs759473597	156	L>R		No	ClinGen ExAC gnomAD
RCV000157855 CA295977 rs730880430 RCV001192738	157	I>V		No	ClinGen ClinVar ExAC dbSNP gnomAD
rs776426602 CA6318279	161	M>L		No	ClinGen ExAC gnomAD
rs1445115422 CA382907230	162	L>P		No	ClinGen TOPMed
CA6318280 rs761864498	163	A>V		No	ClinGen ExAC gnomAD
CA382907263 rs1414902145	164	E>D		No	ClinGen gnomAD
CA6318282 rs750257998	166	K>R		No	ClinGen ExAC TOPMed gnomAD
CA382907393 rs1358074406	171	S>G		No	ClinGen gnomAD
rs1565870426 CA382907399	171	S>N		No	ClinGen Ensembl
rs1043878230 CA229658320	173	L>V		No	ClinGen Ensembl
CA382907501 rs727502912	174	F>L		No	ClinGen TOPMed gnomAD
rs751238837 CA6318284	175	Q>E		No	ClinGen ExAC gnomAD
rs754381153 CA6318285 RCV000479915	175	Q>H		No	ClinGen ClinVar ExAC dbSNP gnomAD
CA382907556 rs1352043598	176	G>V		No	ClinGen gnomAD
rs730880431 CA295980 RCV000157856	180	R>Q		No	ClinGen ClinVar dbSNP gnomAD
CA229658338 rs867847723	183	K>E		No	ClinGen Ensembl
CA6318287 rs753133509	184	A>V		No	ClinGen ExAC gnomAD
CA382907740 rs1212334952	187	A>T		No	ClinGen gnomAD
rs1480417498 CA382907791	191	R>G		No	ClinGen gnomAD
rs756736832 CA6318288	191	R>T		No	ClinGen ExAC gnomAD
CA6318289 rs778255715	193	A>P		No	ClinGen ExAC gnomAD
rs749633193 CA6318290	193	A>V		No	ClinGen ExAC gnomAD
CA6318291 rs757705359	196	E>K		No	ClinGen ExAC gnomAD
rs397517082 RCV000766699 CA135743 RCV000038365	199	I>V		No	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
CA229659713 rs926023115	201	P>A		No	ClinGen Ensembl
CA229659717 rs759082853	204	S>N		No	ClinGen ExAC TOPMed gnomAD
rs759082853 CA6318320	204	S>T		No	ClinGen ExAC TOPMed gnomAD
rs1228155346 CA382908974 COSM3415596	206	R>*	large_intestine [Cosmic]	No	ClinGen cosmic curated gnomAD
CA382909085 rs1247938307	210	H>Q		No	ClinGen gnomAD
CA6318322 rs775309469	212	V>M		No	ClinGen ExAC gnomAD
rs1249561626 CA382909173	213	H>R		No	ClinGen gnomAD
CA6318323 rs760192666	215	I>V		No	ClinGen ExAC TOPMed gnomAD
CA6318324 rs763760976	216	S>G		No	ClinGen ExAC TOPMed gnomAD
rs1411543318 CA382909248	216	S>I		No	ClinGen TOPMed
rs1414264462 CA382909268	217	S>C		No	ClinGen gnomAD
rs895664191 CA229659759	219	L>P		No	ClinGen TOPMed gnomAD
CA229659750 rs1052915853	219	L>V		No	ClinGen Ensembl
CA382909371 rs773611782	222	M>L		No	ClinGen TOPMed gnomAD
RCV000413220 rs1057518053 CA16042827	222	M>T		No	ClinGen ClinVar Ensembl dbSNP
CA229659778 rs773611782	222	M>V		No	ClinGen TOPMed gnomAD
rs1565870972 CA382909470	227	T>A		No	ClinGen Ensembl
rs1414848678 CA382909511	229	D>G		No	ClinGen TOPMed
rs1457872297 CA382909543	231	T>A		No	ClinGen TOPMed gnomAD
RCV000033349 RCV001818205 rs143276937 CA282015	233	N>S		No	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
rs757885273 CA6318325	234	D>N		No	ClinGen ExAC gnomAD
CA6318326 rs765486534	235	Y>C		No	ClinGen ExAC TOPMed gnomAD
rs1047761187 CA229659795	239	F>S		No	ClinGen TOPMed
rs1222422266 CA382909726	240	E>*		No	ClinGen gnomAD
rs375576063 CA6318328	245	T>I		No	ClinGen ESP ExAC gnomAD
rs1592398470 CA382909852	245	T>P		No	ClinGen Ensembl
CA6318329 rs376182596	246	R>*		No	ClinGen ESP ExAC TOPMed gnomAD
CA382909864 rs1253824253	246	R>Q		No	ClinGen gnomAD
CA382909872 rs1440134128	247	L>F		No	ClinGen gnomAD
rs776318077 CA6318342	251	W>*		No	ClinGen ExAC gnomAD
CA382910583 rs1477764968	252	S>C		No	ClinGen gnomAD
rs1427302571 CA382910721	260	S>N		No	ClinGen gnomAD
CA382910754 rs1477712322	263	V>I		No	ClinGen TOPMed
rs765725680 CA6318343	268	Y>N		No	ClinGen ExAC gnomAD
COSM923811 CA6318348 rs755244263	276	E>K	large_intestine endometrium [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs1439017220 CA382910980	277	V>L		No	ClinGen TOPMed
CA6318349 rs730880432	280	R>G		No	ClinGen ExAC TOPMed gnomAD
rs730880432 CA295983	280	R>W		No	ClinGen ExAC TOPMed gnomAD
CA6318351 rs778856115	284	F>S		No	ClinGen ExAC gnomAD
CA6318354 rs780039741	290	S>G		No	ClinGen ExAC gnomAD
CA6318382 rs771389825	292	I>S		No	ClinGen ExAC gnomAD
CA382911344 rs1455235474	294	R>Q		No	ClinGen TOPMed gnomAD
rs932287958 CA229661103	297	C>R		No	ClinGen TOPMed
CA6318383 rs200139643	297	C>Y		No	ClinGen 1000Genomes ExAC gnomAD
CA382911390 rs1365243839	299	R>P		No	ClinGen gnomAD
rs767877131 CA6318385	303	W>*		No	ClinGen ExAC gnomAD
CA6318386 rs775764308	305	I>V		No	ClinGen ExAC gnomAD
rs764199611 CA6318388	310	A>V		No	ClinGen ExAC gnomAD
CA382911479 rs1268883034	313	N>S		No	ClinGen gnomAD
rs1355888823 CA382911492	315	L>V		No	ClinGen TOPMed
CA6318390 rs757445363	319	P>H		No	ClinGen ExAC
rs730880436 RCV000157870	326	Q>missing		No	ClinVar dbSNP
rs1190026677 CA382911607	332	F>L		No	ClinGen gnomAD
CA382911629 rs1410157226	335	G>S		No	ClinGen gnomAD
CA382911793 rs1592400572	337	Y>H		No	ClinGen Ensembl
rs765471101 CA6318411	343	R>G		No	ClinGen ExAC TOPMed gnomAD
rs759585425 CA6318413	343	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs370489946 CA6318414	344	N>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs1592400595 CA382911916	348	D>G		No	ClinGen Ensembl
rs1300716485 CA382911933	350	T>S		No	ClinGen gnomAD
rs868373165 CA229661714	356	T>I		No	ClinGen Ensembl
CA382912036 rs1341984560	359	D>N		No	ClinGen gnomAD
rs933954615 CA229661723	360	H>Y		No	ClinGen TOPMed
CA382912065 rs1206278540	361	I>N		No	ClinGen gnomAD
rs1206278540 CA382912070	361	I>S		No	ClinGen gnomAD
rs753498708 CA6318417	361	I>V		No	ClinGen ExAC TOPMed
CA382912094 rs1592400621	363	V>G		No	ClinGen Ensembl
CA382912192 rs1245863855	366	E>K		No	ClinGen gnomAD
CA6318432 rs760326164	367	Q>H		No	ClinGen ExAC gnomAD
rs267606704 CA6318431 COSM87287	367	Q>R	haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs754168206 CA229661803	370	L>F		No	ClinGen Ensembl
CA382912355 rs571152174	373	E>D		No	ClinGen 1000Genomes ExAC gnomAD
rs756956596 CA6318434	374	M>I		No	ClinGen ExAC gnomAD
CA382912366 rs1350371301	374	M>L		No	ClinGen gnomAD
COSM34071 rs1387946965 CA382912407	376	S>F	haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
CA382912441 RCV000520043 rs749897878	378	F>L		No	ClinGen ClinVar ExAC dbSNP gnomAD
rs757874631 CA382912480	381	C>S		No	ClinGen ExAC gnomAD
rs768898787 CA6318440 COSM34073	381	C>Y	large_intestine haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA382912518 rs1265704711	383	I>L		No	ClinGen TOPMed gnomAD
CA382912520 rs1265704711	383	I>V		No	ClinGen TOPMed gnomAD
rs387906664 CA295987	384	C>G		No	ClinGen Ensembl
rs985412813 COSM34066 CA229661870	384	C>Y	large_intestine haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
CA382912571 rs1592400852	386	E>K		No	ClinGen Ensembl
CA382912594 rs1592400857	387	N>H		No	ClinGen Ensembl
CA382912613 rs911329155	388	D>N		No	ClinGen TOPMed gnomAD
CA229661880 rs911329155	388	D>Y		No	ClinGen TOPMed gnomAD
COSM132872 rs763058208 CA382912661	390	D>G	pancreas haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs538190997 COSM41272 CA6318446	391	V>I	lung [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC gnomAD
rs775272530 CA6318447	393	I>T		No	ClinGen ExAC gnomAD
CA382912715 rs387906665	396	C>S		No	ClinGen ExAC TOPMed gnomAD
CA6318449 rs776364583	397	G>E		No	ClinGen ExAC gnomAD
rs1320607569 CA382912730	397	G>R		No	ClinGen TOPMed gnomAD
CA229661898 COSM34075 rs946817829	398	H>Y	haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated TOPMed
CA382912765 rs878856172	400	M>L		No	ClinGen TOPMed
CA229661901 rs878856172	400	M>L		No	ClinGen TOPMed
RCV000033353 CA282021 COSM87285 rs397507491	400	M>R	haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated ClinVar Ensembl dbSNP
CA382912773 COSM1351843 rs397507491	400	M>T	large_intestine [Cosmic]	No	ClinGen cosmic curated Ensembl
CA382912797 rs1357686410 COSM1507168	401	C>F	lung [Cosmic]	No	ClinGen cosmic curated gnomAD
RCV000033354 rs397507492 CA282024 COSM1351844	401	C>R	large_intestine [Cosmic]	No	ClinGen cosmic curated ClinVar Ensembl dbSNP
COSM87284 rs1357686410 CA382912791	401	C>Y	haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated gnomAD
COSM34068 rs192712314 CA6318452	404	C>Y	haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
rs1223827888 CA382912876	405	L>H		No	ClinGen gnomAD
rs1223827888 CA382912880	405	L>R		No	ClinGen gnomAD
CA6318453 rs757834577	406	T>I		No	ClinGen ExAC gnomAD
COSM34060 rs755557498 CA382912908	408	W>R	haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
COSM34060 rs755557498 CA6318457	408	W>R	haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs1451625410 CA382912952	409	Q>H		No	ClinGen TOPMed
rs1257967691 CA382912951	409	Q>R		No	ClinGen gnomAD
CA229661987 rs371679886	413	G>C		No	ClinGen ESP
rs371679886 CA10603143 RCV000376659 COSM1507167	413	G>R	lung [Cosmic]	No	ClinGen cosmic curated ClinVar ESP dbSNP
rs1268484791 CA382913727	414	Q>E		No	ClinGen gnomAD
COSM133826 rs756530482 CA6318479	415	G>S	lung haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA382913754 COSM34061 rs1388592245	415	G>V	haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated TOPMed
rs1328906812 CA382913784 COSM133827	416	C>W	haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated gnomAD
CA382913768 COSM41789 rs757456261	416	C>Y	haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs779039234 CA6318483 COSM34081	417	P>L	large_intestine skin haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA229661993 COSM34069 rs867564832	417	P>S	haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated Ensembl
CA6318484 COSM34078 rs745896960	418	F>L	haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA6318485 rs772156285 COSM34070	418	F>S	large_intestine haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA382913796 rs745896960	418	F>V		No	ClinGen ExAC gnomAD
CA382913822 rs1225668816	419	C>Y		No	ClinGen gnomAD
COSM219132 CA6318486 rs200341293	420	R>*	large_intestine endometrium haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
rs1592401139 CA382913872	421	C>W		No	ClinGen Ensembl
rs868103494 CA229662003	423	I>N		No	ClinGen Ensembl
rs1023489315 CA229662005	425	G>S		No	ClinGen Ensembl
CA6318489 rs762677807	428	P>S		No	ClinGen ExAC TOPMed gnomAD
rs148368481 CA6318490	429	I>M		No	ClinGen ESP ExAC TOPMed gnomAD
CA229662013 rs917864680	430	V>A		No	ClinGen TOPMed
CA229662014 rs140627020	433	P>Q		No	ClinGen ESP TOPMed
CA6318492 rs767190596	434	F>V		No	ClinGen ExAC gnomAD
CA6318494 rs761300890	439	S>G		No	ClinGen ExAC gnomAD
rs754194646 CA6318496	440	G>S		No	ClinGen ExAC gnomAD
rs757570929 CA6318497	440	G>V		No	ClinGen ExAC gnomAD
rs1296401101 CA382914295	441	S>C		No	ClinGen TOPMed gnomAD
rs1296401101 CA382914290	441	S>R		No	ClinGen TOPMed gnomAD
CA382914315 rs1282405252	442	L>P		No	ClinGen gnomAD
rs1282405252 CA382914318	442	L>R		No	ClinGen gnomAD
rs867290095 CA229662032	447	A>T		No	ClinGen Ensembl
rs886041313 CA10603179 RCV000372415	451	P>A		No	ClinGen ClinVar Ensembl dbSNP
rs1214207578 CA382914463	451	P>L		No	ClinGen gnomAD
CA382914495 rs1262688624	453	P>L		No	ClinGen gnomAD
rs748055961 CA6318502	453	P>S		No	ClinGen ExAC TOPMed gnomAD
rs1167644498 CA382914555	456	D>E		No	ClinGen gnomAD
rs886041472 CA10603148 RCV000276444	456	D>Y		No	ClinGen ClinVar dbSNP gnomAD
rs886041425 RCV000386480 CA10603154 RCV001820803 COSM34079	462	R>*	haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated ClinVar dbSNP gnomAD
rs201762219 CA229662045	464	D>G		No	ClinGen 1000Genomes
CA6318507 rs770644035	465	D>G		No	ClinGen ExAC gnomAD
CA382914724 rs1385198964	467	L>P		No	ClinGen gnomAD
CA6318510 rs775186352	468	F>L		No	ClinGen ExAC gnomAD
rs138277394 CA6318511 COSM686897	469	M>I	lung urinary_tract [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
rs1339584269 CA382914748	469	M>L		No	ClinGen gnomAD
rs764599897 CA382914848	475	G>C		No	ClinGen ExAC TOPMed gnomAD
rs200054267 CA6318514	475	G>D		No	ClinGen ExAC TOPMed gnomAD
CA6318513 rs200054267	475	G>V		No	ClinGen ExAC TOPMed gnomAD
CA382914878 rs1243570781	477	K>T		No	ClinGen TOPMed
rs947855757 CA229641740	478	V>L		No	ClinGen TOPMed
CA229641772 rs1005648171	479	E>V		No	ClinGen TOPMed
rs369547447 CA6318534	485	F>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1368426444 CA382917911	490	Q>E		No	ClinGen TOPMed gnomAD
CA6318537 rs369656948	491	A>T		No	ClinGen ESP ExAC TOPMed gnomAD
rs767559244 CA6318538	494	P>S		No	ClinGen ExAC gnomAD
rs1385124529 CA382917996	495	P>S		No	ClinGen gnomAD
CA229641890 rs1018342862	500	L>P		No	ClinGen TOPMed gnomAD
rs1341830963 CA382918133	502	L>F		No	ClinGen gnomAD
rs1592405051 CA382918147	503	L>V		No	ClinGen Ensembl
CA382918234 rs886041500	506	R>*		No	ClinGen Ensembl
RCV000304245 CA10603155 rs886041500	506	R>G		No	ClinGen ClinVar Ensembl dbSNP
CA6318544 rs746728465	506	R>L		No	ClinGen ExAC gnomAD
rs1219382952 CA382918254	507	V>I		No	ClinGen TOPMed
rs1207525665 CA382918289	508	C>S		No	ClinGen gnomAD
rs1251778536 CA382918327	509	V>I		No	ClinGen gnomAD
CA6318546 rs776055321	510	P>R		No	ClinGen ExAC gnomAD
rs1281086600 CA382918368	511	S>T		No	ClinGen TOPMed
CA382918426 rs1427688105	512	S>G		No	ClinGen gnomAD
rs200442365 CA229641977	513	A>T		No	ClinGen 1000Genomes
CA382918504 rs1171133734	515	A>P		No	ClinGen gnomAD
rs770161679 CA6318548	517	G>V		No	ClinGen ExAC gnomAD
rs1341096551 CA382918575	518	T>I		No	ClinGen TOPMed
rs1344804418 CA382918830	526	S>F		No	ClinGen gnomAD
rs1592405167 CA382918867	527	L>P		No	ClinGen Ensembl
CA382918883 rs1592405174	528	H>P		No	ClinGen Ensembl
CA6318566 rs778239777	528	H>Y		No	ClinGen ExAC TOPMed gnomAD
rs749858627 CA6318567	529	K>E		No	ClinGen ExAC gnomAD
rs1359969684 CA382918962	531	K>I		No	ClinGen TOPMed
CA382919020 rs1288307546	532	P>L		No	ClinGen TOPMed
rs774743605 CA6318569 COSM923815	532	P>S	endometrium [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA382918983 rs774743605	532	P>T		No	ClinGen ExAC gnomAD
CA382919060 rs1281464618	534	P>A		No	ClinGen TOPMed gnomAD
rs1281464618 CA382919063	534	P>S		No	ClinGen TOPMed gnomAD
rs772140687 CA6318571	535	V>L		No	ClinGen ExAC gnomAD
rs144130138 CA6318572	536	P>S		No	ClinGen 1000Genomes ExAC gnomAD
CA6318573 rs760661205	537	P>R		No	ClinGen ExAC gnomAD
CA382919137 rs1482147657	537	P>S		No	ClinGen gnomAD
CA382919206 rs1565874210	539	L>P		No	ClinGen Ensembl
rs764340189 CA6318574	540	R>*		No	ClinGen ExAC gnomAD
CA382919216 COSM1475112 rs980503623	540	R>P	breast [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
rs980503623 CA229642211	540	R>Q		No	ClinGen TOPMed gnomAD
RCV000592557 CA6318575 rs147285276	541	D>V		No	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
CA382919279 rs1161480868	542	L>P		No	ClinGen gnomAD
rs1357842433 CA382919297	543	P>Q		No	ClinGen gnomAD
rs1314064262 CA382919329	544	P>S		No	ClinGen gnomAD
CA6318577 rs766442277	545	P>S		No	ClinGen ExAC gnomAD
rs1181978863 CA382919397	547	P>T		No	ClinGen TOPMed
rs17848897 CA6318580	548	P>L		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs202065722 CA6318581	550	R>W		No	ClinGen ExAC gnomAD
CA10604900 RCV000680317 rs200305176	551	P>S		No	ClinGen ClinVar TOPMed dbSNP gnomAD
rs771375289 CA382919585	558	S>C		No	ClinGen ExAC TOPMed
CA6318583 rs771375289	558	S>Y		No	ClinGen ExAC TOPMed
rs779425249 CA6318585	559	R>*		No	ClinGen ExAC gnomAD
CA6318584 rs779425249	559	R>G		No	ClinGen ExAC gnomAD
rs530189600 CA6318587	560	P>L		No	ClinGen 1000Genomes ExAC gnomAD
CA382919618 rs1246882963	561	Q>E		No	ClinGen TOPMed
rs761001752 CA6318588	561	Q>R		No	ClinGen ExAC gnomAD
CA6318589 rs768837912	563	R>C		No	ClinGen ExAC TOPMed gnomAD
CA382919660 rs1423287961	563	R>H		No	ClinGen TOPMed gnomAD
rs1397686173 CA382919682	564	P>L		No	ClinGen TOPMed
CA382919706 rs1428398685	566	P>R		No	ClinGen gnomAD
RCV000595298 rs762016318 CA6318591	568	T>I		No	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
rs766354351 CA6318592	569	P>A		No	ClinGen ExAC gnomAD
CA382919806 rs1249684522	573	P>H		No	ClinGen gnomAD
CA229642364 rs996627039	573	P>S		No	ClinGen gnomAD
CA382919820 rs1280982134	574	S>T		No	ClinGen gnomAD
CA6318594 rs767411521	577	K>E		No	ClinGen ExAC TOPMed gnomAD
CA382919883 rs1342845527	577	K>R		No	ClinGen Ensembl
CA229642371 rs776651600	578	L>P		No	ClinGen Ensembl
CA6318596 rs755812040	579	P>H		No	ClinGen ExAC gnomAD
CA382919914 rs755812040	579	P>L		No	ClinGen ExAC gnomAD
CA382919909 rs752260506 RCV000681049	579	P>S		No	ClinGen ClinVar ExAC dbSNP gnomAD
rs752260506 CA6318595	579	P>T		No	ClinGen ExAC gnomAD
rs753301731 CA6318598	580	P>L		No	ClinGen ExAC TOPMed gnomAD
CA6318597 rs763754559	580	P>S		No	ClinGen ExAC gnomAD
CA382920008 rs1251176334	584	S>G		No	ClinGen gnomAD
rs187952822 CA382920043	585	R>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA229642393 rs1029154785	586	L>P		No	ClinGen TOPMed gnomAD
CA6318602 rs747357424	588	D>Y		No	ClinGen ExAC TOPMed gnomAD
rs373623345 CA229642398	590	W>*		No	ClinGen ESP
CA382920182 rs373623345	590	W>C		No	ClinGen ESP
rs1412088799 CA382920233	592	P>A		No	ClinGen gnomAD
rs1412088799 CA382920232	592	P>S		No	ClinGen gnomAD
rs730880435 CA6318605	593	R>L		No	ClinGen ExAC TOPMed gnomAD
rs730880435 CA382920275	593	R>P		No	ClinGen ExAC TOPMed gnomAD
CA6318604 rs776999573	593	R>W		No	ClinGen ExAC TOPMed gnomAD
rs770056391 CA6318606	594	P>A		No	ClinGen ExAC
CA382920308 rs1439720739	594	P>L		No	ClinGen gnomAD
rs770056391 CA229642410	594	P>T		No	ClinGen ExAC
CA382920326 rs1373047959	595	I>N		No	ClinGen TOPMed
CA382920347 rs1304284873	596	P>S		No	ClinGen TOPMed
CA382920371 rs1363189852	597	K>R		No	ClinGen TOPMed
CA6318608 rs759558934	598	V>I		No	ClinGen ExAC gnomAD
CA382920443 rs1299267508	600	V>A		No	ClinGen gnomAD
rs775302733 CA6318610	601	S>C		No	ClinGen ExAC gnomAD
CA382920449 rs1271364778	601	S>T		No	ClinGen gnomAD
RCV000994740 rs1365230067 CA382920466	602	A>S		No	ClinGen ClinVar TOPMed dbSNP
CA6318611 rs760490210	606	S>R		No	ClinGen ExAC TOPMed gnomAD
CA382920571 rs397507495	608	P>R		No	ClinGen gnomAD
COSM35588 CA382920576 rs1031634822	609	W>*	central_nervous_system [Cosmic]	No	ClinGen cosmic curated gnomAD
rs1031634822 CA229642441	609	W>L		No	ClinGen gnomAD
rs764845853 CA6318614	612	R>G		No	ClinGen ExAC TOPMed gnomAD
CA382920603 rs1460460945	612	R>K		No	ClinGen gnomAD
CA6318615 rs750877214	615	T>S		No	ClinGen ExAC gnomAD
rs376094293 CA382920646	616	N>I		No	ClinGen ESP ExAC TOPMed gnomAD
CA382920645 rs376094293	616	N>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA382920652 rs538013681	617	R>G		No	ClinGen TOPMed gnomAD
CA229642447 rs538013681	617	R>W		No	ClinGen TOPMed gnomAD
rs1344210823 CA382920658	618	H>Y		No	ClinGen TOPMed
CA229642485 rs980388840	619	S>L		No	ClinGen TOPMed
CA135712 rs2227988 VAR_057211	620	L>F		No	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA229642486 rs2227988	620	L>V		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA6318618 rs755408968	621	P>A		No	ClinGen ExAC gnomAD
rs1334315007 CA382920702	621	P>L		No	ClinGen gnomAD
CA229642503 rs971746773	624	L>F		No	ClinGen TOPMed gnomAD
rs918766764 CA229642517	625	P>L		No	ClinGen TOPMed gnomAD
rs1186507278 CA382920871	630	P>R		No	ClinGen gnomAD
rs1449081255 CA382920867	630	P>S		No	ClinGen gnomAD
rs1429777415 CA382920891	632	P>L		No	ClinGen TOPMed
rs1474621886 CA382920906	634	V>M		No	ClinGen gnomAD
CA382920945 rs1268167047	637	L>H		No	ClinGen TOPMed
rs772002109 CA6318622	638	G>R		No	ClinGen ExAC TOPMed gnomAD
rs775290617 CA6318623	639	S>R		No	ClinGen ExAC
rs1263873227 CA382920980	640	T>M		No	ClinGen TOPMed
CA382920998 rs1157620085	642	S>G		No	ClinGen gnomAD
CA6318625 rs571045498	642	S>N		No	ClinGen 1000Genomes ExAC gnomAD
CA382921016 rs1311047726	643	L>P		No	ClinGen gnomAD
rs764823089 CA6318628	644	D>E		No	ClinGen ExAC gnomAD
CA6318629 rs749909542	647	M>V		No	ClinGen ExAC gnomAD
rs143264567 CA382922127	648	S>G		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
RCV000361702 CA6318645 rs143264567	648	S>R		No	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs762513702 CA6318648	649	M>I		No	ClinGen ExAC gnomAD
rs117204536 CA6318647	649	M>T		No	ClinGen 1000Genomes ExAC gnomAD
CA6318649 rs765873527	650	N>K		No	ClinGen ExAC gnomAD
CA229644422 rs1055456727	652	S>R		No	ClinGen Ensembl
CA382922259 rs1591265497	653	P>S		No	ClinGen Ensembl
rs1565874950 CA382922282	654	L>S		No	ClinGen Ensembl
CA382922365 rs1454548384	657	P>L		No	ClinGen gnomAD
COSM3721153 rs1565874960 CA382922375	658	E>Q	upper_aerodigestive_tract [Cosmic]	No	ClinGen cosmic curated Ensembl
rs1591265512 CA382922435	660	D>A		No	ClinGen Ensembl
rs1460903578 CA382922425	660	D>N		No	ClinGen gnomAD
COSM3808559 rs1591265521 CA382922462	661	H>P	breast [Cosmic]	No	ClinGen cosmic curated Ensembl
CA382922540 rs1371247214	663	K>R		No	ClinGen gnomAD
RCV000033364 CA282040 rs397507496	664	I>T		No	ClinGen ClinVar Ensembl dbSNP
CA382922605 rs1591265534	665	K>N		No	ClinGen Ensembl
rs1461378431 CA382922617	666	P>L		No	ClinGen TOPMed gnomAD
rs1333793793 CA382922670	668	S>P		No	ClinGen TOPMed
rs1402468252 CA382922771	671	N>K		No	ClinGen gnomAD
rs760168148 CA6318651	671	N>S		No	ClinGen ExAC TOPMed gnomAD
rs1352442106 CA382922786	672	A>D		No	ClinGen TOPMed
CA6318652 rs768160029	674	Y>C		No	ClinGen ExAC gnomAD
COSM144247 CA6318653 rs553979171	675	S>C	haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
rs553979171 CA229644466	675	S>F		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs768065878 CA6318671	680	P>H		No	ClinGen ExAC gnomAD
rs768065878 CA6318672	680	P>L		No	ClinGen ExAC gnomAD
rs374270823 CA382926388	681	L>H		No	ClinGen ESP TOPMed gnomAD
rs374270823 CA229649651	681	L>P		No	ClinGen ESP TOPMed gnomAD
CA6318674 rs578227001	681	L>V		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs764430929 CA6318676	682	P>A		No	ClinGen ExAC TOPMed
rs1485419246 CA382926460	684	P>L		No	ClinGen gnomAD
rs1555027603 CA382926467	685	K>E		No	ClinGen Ensembl
rs998810720 CA229649689	686	L>V		No	ClinGen TOPMed
rs754071882 CA6318677	687	P>S		No	ClinGen ExAC gnomAD
rs730880428 CA295971	688	P>S		No	ClinGen ExAC TOPMed gnomAD
rs756510511 CA229649706	692	C>Y		No	ClinGen Ensembl
CA229649711 rs946360086	693	E>V		No	ClinGen Ensembl
rs758486207 CA6318679	695	E>G		No	ClinGen ExAC gnomAD
CA382926839 rs1354142112	696	E>G		No	ClinGen TOPMed gnomAD
CA6318680 rs539217274	696	E>K		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA382926874 RCV000681179 rs1565272122	697	D>A		No	ClinGen ClinVar Ensembl dbSNP
rs1414663764 CA382926868	697	D>Y		No	ClinGen gnomAD
rs1565272125 CA382926899	698	T>K		No	ClinGen Ensembl
CA6318681 rs557613837	699	E>K		No	ClinGen 1000Genomes ExAC gnomAD
CA382926946 rs866325598	699	E>V		No	ClinGen TOPMed
rs368798262 COSM1704666 CA229649750	703	P>L	skin [Cosmic]	No	ClinGen cosmic curated ESP TOPMed
rs1229733932 CA382927089	703	P>S		No	ClinGen gnomAD
rs755908860 CA6318682	705	S>F		No	ClinGen ExAC gnomAD
rs576175174 CA6318684	707	P>L		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA382927239 rs576175174	707	P>R		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA382927247 rs1353164018	708	L>V		No	ClinGen TOPMed
rs770667508 CA382927271	709	R>L		No	ClinGen ExAC TOPMed gnomAD
CA6318686 rs770667508	709	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA382927314 rs1383138888	712	D>N		No	ClinGen TOPMed
CA382927334 rs1565272163	712	D>V		No	ClinGen Ensembl
rs867428849 CA229649811	714	S>F		No	ClinGen Ensembl
rs757126995 CA382927755	719	A>S		No	ClinGen ExAC TOPMed gnomAD
CA382927845 rs1330337934	722	C>G		No	ClinGen TOPMed
CA229650167 rs935006432	723	D>N		No	ClinGen Ensembl
CA6318707 rs771675288	727	D>G		No	ClinGen ExAC TOPMed gnomAD
rs1950071650 RCV001195481	729	C>R		No	ClinVar dbSNP
COSM319245 rs1212670088 CA382928196	731	Y>C	lung [Cosmic]	No	ClinGen cosmic curated gnomAD
CA382928234 rs1178824800	732	E>A		No	ClinGen TOPMed
CA382928281 rs1231247505	734	M>V		No	ClinGen TOPMed
CA282043 rs397507497 RCV000033365	736	N>D		No	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
CA382928395 rs1469059150	737	I>F		No	ClinGen TOPMed
rs770212268 CA6318711	738	Q>R		No	ClinGen ExAC gnomAD
rs1565272311 CA382928470	740	Q>*		No	ClinGen Ensembl
rs763213265 CA382928494	741	A>E		No	ClinGen ExAC TOPMed gnomAD
CA382928488 rs1468165055	741	A>T		No	ClinGen gnomAD
rs1254817781 CA382928532	742	P>L		No	ClinGen Ensembl
CA157857 rs587778157 RCV000120461	742	P>S		No	ClinGen ClinVar Ensembl dbSNP
rs759665371 CA6318715	743	S>P		No	ClinGen ExAC TOPMed gnomAD
rs1422371091 CA382928564	744	I>V		No	ClinGen TOPMed gnomAD
rs1465658550 CA382928579	745	T>A		No	ClinGen gnomAD
CA229650232 rs531007888	746	E>G		No	ClinGen Ensembl
CA6318717 rs369050822	746	E>K		No	ClinGen ESP ExAC TOPMed gnomAD
CA382928674 rs1323415711	749	T>P		No	ClinGen TOPMed
CA6318739 rs148139669	754	N>K		No	ClinGen ESP ExAC TOPMed gnomAD
CA382929004 rs146517083	757	A>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA157863 rs146517083 COSM3687124	757	A>T	large_intestine [Cosmic]	No	ClinGen cosmic curated 1000Genomes ESP ExAC TOPMed gnomAD
rs1489560722 CA382929007	757	A>V		No	ClinGen gnomAD
CA382929020 rs1209288584	758	A>V		No	ClinGen gnomAD
rs956529872 CA229650742	759	H>Q		No	ClinGen gnomAD
rs1254852132 CA382929043	759	H>R		No	ClinGen gnomAD
rs1187865266 CA382929105	761	N>S		No	ClinGen TOPMed gnomAD
CA6318741 rs779563820	762	T>P		No	ClinGen ExAC gnomAD
CA6318742 rs751292391	762	T>S		No	ClinGen ExAC TOPMed gnomAD
CA382929123 rs1454216416	763	G>S		No	ClinGen gnomAD
rs754415936 CA6318743	763	G>V		No	ClinGen ExAC gnomAD
rs373587039 CA6318745	765	E>K		No	ClinGen ESP ExAC TOPMed gnomAD
CA6318746 rs770244944	766	E>*		No	ClinGen ExAC gnomAD
rs749595774 CA6318748	770	E>K		No	ClinGen ExAC gnomAD
rs1241925405 CA382929387	773	G>E		No	ClinGen TOPMed
rs772021793 CA6318751	774	Y>H		No	ClinGen ExAC TOPMed gnomAD
CA382929470 rs1591270509	776	V>A		No	ClinGen Ensembl
CA6318752 rs775661028	777	P>A		No	ClinGen ExAC gnomAD
CA6318753 rs760842949	778	K>E		No	ClinGen ExAC gnomAD
CA6318754 rs765208946	779	P>L		No	ClinGen ExAC gnomAD
rs1401610037 CA382929541	780	P>L		No	ClinGen gnomAD
CA382929543 rs1343017768	781	V>L		No	ClinGen TOPMed gnomAD
CA382929544 rs1343017768	781	V>L		No	ClinGen TOPMed gnomAD
rs2229073 CA135724 VAR_057212	782	P>L		No	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
RCV001175063 rs1950077753	783	A>missing		No	ClinVar dbSNP
rs1171738358 CA382929637	786	A>P		No	ClinGen gnomAD
CA382929632 rs1171738358	786	A>S		No	ClinGen gnomAD
rs368326846 CA6318759	788	R>*		No	ClinGen ESP ExAC gnomAD
RCV001174978 rs1950077794	788	R>HTGPEESENEDDGYDVPKPPVPAVLAR		No	ClinVar dbSNP
rs150811339 COSM174890 RCV000157868 CA296008	788	R>Q	large_intestine [Cosmic]	No	ClinGen cosmic curated ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs757530036 CA6318761	789	T>I		No	ClinGen ExAC gnomAD
CA382929758 rs1313299985	792	D>N		No	ClinGen gnomAD
CA382929808 rs1235991942	793	I>V		No	ClinGen gnomAD
CA382929860 rs201620100	794	S>C		No	ClinGen ExAC TOPMed gnomAD
rs201620100 CA6318764	794	S>F		No	ClinGen ExAC TOPMed gnomAD
CA229650873 rs1046134200	794	S>T		No	ClinGen TOPMed gnomAD
rs138151048 CA6318765	797	S>G		No	ClinGen ESP ExAC gnomAD
rs747073805 CA229650904	797	S>N		No	ClinGen ExAC gnomAD
CA6318766 rs138151048	797	S>R		No	ClinGen ESP ExAC gnomAD
rs587778158 RCV000120462 CA157860	798	S>F		No	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
CA382930087 rs1433717520	799	S>C		No	ClinGen gnomAD
CA382930094 rs1433717520	799	S>F		No	ClinGen gnomAD
rs1465141746 CA382930161	801	G>C		No	ClinGen gnomAD
CA382930331 rs1402761195	804	S>F		No	ClinGen gnomAD
rs1293321507 CA382930404	807	G>V		No	ClinGen gnomAD
CA6318773 rs774158357	809	P>R		No	ClinGen ExAC gnomAD
rs1389098789 CA382930537	810	T>R		No	ClinGen gnomAD
rs749068285 CA6318774	811	T>I		No	ClinGen ExAC TOPMed gnomAD
CA229650977 rs907398440	812	N>D		No	ClinGen TOPMed
CA229652837 rs538228846	814	T>I		No	ClinGen 1000Genomes
rs1470726861 CA382931858	818	Q>E		No	ClinGen gnomAD
COSM923821 CA382931981 rs1487925103	822	R>G	endometrium [Cosmic]	No	ClinGen cosmic curated gnomAD
rs1241937644 CA382931986	822	R>K		No	ClinGen TOPMed
CA382932028 rs1331544915	823	P>L		No	ClinGen TOPMed
rs1591271119 CA382932065	825	K>Q		No	ClinGen Ensembl
rs763756632 CA6318796	828	P>L		No	ClinGen ExAC TOPMed gnomAD
rs371026706 CA6318795	828	P>S		No	ClinGen ESP ExAC TOPMed gnomAD
RCV000038360 CA135728 rs374672276	829	R>Q		No	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
CA6318797 rs761245258	829	R>W		No	ClinGen ExAC gnomAD
rs750959492 CA6318798	830	R>I		No	ClinGen ExAC gnomAD
rs1420899832 CA382932231	832	N>S		No	ClinGen gnomAD
rs1950086093 RCV001264606	837	A>T		No	ClinVar dbSNP
rs144191570 CA382932316	838	G>A		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA6318800 rs748936051	839	S>G		No	ClinGen ExAC TOPMed gnomAD
CA6318802 rs199771745	839	S>I		No	ClinGen ESP ExAC TOPMed gnomAD
CA6318801 rs199771745	839	S>T		No	ClinGen ESP ExAC TOPMed gnomAD
rs112330156 CA6318804	840	C>W		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs376536789 CA6318803	840	C>Y		No	ClinGen ESP ExAC gnomAD
CA229652889 rs139911109	843	G>D		No	ClinGen ESP TOPMed
CA382932401 rs587778159	844	S>G		No	ClinGen TOPMed gnomAD
rs1288047359 CA382932412	844	S>T		No	ClinGen gnomAD
CA229652893 rs201364447	845	G>V		No	ClinGen Ensembl
rs745842672 CA6318806	846	P>S		No	ClinGen ExAC gnomAD
CA6318808 rs141710973	848	A>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs768228850 CA6318809	851	A>S		No	ClinGen ExAC TOPMed gnomAD
rs1235336416 CA382932600	851	A>V		No	ClinGen gnomAD
rs1591271188 CA382932604	852	T>P		No	ClinGen Ensembl
CA382932630 rs1393832618	853	A>T		No	ClinGen TOPMed gnomAD
rs750919864 CA6318813	857	L>P		No	ClinGen ExAC gnomAD
CA6318815 rs767027008	859	S>N		No	ClinGen ExAC gnomAD
rs763510016 CA6318814	859	S>R		No	ClinGen ExAC gnomAD
rs540480725 CA6318817	861	I>V		No	ClinGen 1000Genomes ExAC gnomAD
rs397507498 CA282055 RCV000033374	862	E>K		No	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
CA135734 RCV000038362 rs397517081	863	N>K		No	ClinGen ClinVar ExAC dbSNP
CA382933096 rs1250041558	866	S>N		No	ClinGen gnomAD
CA382933147 rs1486469755	868	G>R		No	ClinGen gnomAD
rs1950087495 RCV001293470	868	G>V		No	ClinVar dbSNP
rs758291160 CA6318820	869	Y>C		No	ClinGen ExAC TOPMed gnomAD
CA6318819 rs758291160	869	Y>F		No	ClinGen ExAC TOPMed gnomAD
rs1159530524 CA382933203	869	Y>H		No	ClinGen TOPMed
CA382933298 rs1237783221	871	Y>C		No	ClinGen gnomAD
CA382933340 rs746795014	872	Q>E		No	ClinGen ExAC TOPMed gnomAD
CA382933371 rs1180934428	873	D>H		No	ClinGen TOPMed gnomAD
rs1484001715 CA382933497	875	Q>R		No	ClinGen Ensembl
CA382933550 rs1477997244	877	A>T		No	ClinGen gnomAD
CA6318823 rs776316491	879	V>F		No	ClinGen ExAC gnomAD
rs1425309639 CA382933689	881	A>S		No	ClinGen gnomAD
rs1415661404 CA382933694	882	Q>K		No	ClinGen gnomAD
rs1167857959 CA382933707	882	Q>P		No	ClinGen gnomAD
rs1465754964 CA382933755	884	N>D		No	ClinGen gnomAD
rs747804658 CA229653025	885	I>M		No	ClinGen ExAC TOPMed gnomAD
rs1435757249 CA382933838	886	E>K		No	ClinGen TOPMed gnomAD
CA382933855 rs1275341680	887	M>V		No	ClinGen gnomAD
CA229653055 rs12786651	892	L>H		No	ClinGen Ensembl
CA229653063 RCV000593423 rs751198294	893	R>Q		No	ClinGen ClinVar TOPMed dbSNP gnomAD
rs368138875 CA6318826 RCV000412750	893	R>W		No	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
rs1318882408 CA382934056	894	E>Q		No	ClinGen gnomAD
rs1451360238 CA382934364	900	S>F		No	ClinGen gnomAD
CA382934423 rs1420218812	903	H>N		No	ClinGen TOPMed gnomAD
rs1248988094 CA382934467	905	A>V		No	ClinGen gnomAD

1 associated diseases with P22681

[MIM: 613563]: Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL)

A syndrome characterized by a phenotype reminiscent of Noonan syndrome. Clinical features are highly variable, including facial dysmorphism, short neck, developmental delay, hyperextensible joints and thorax abnormalities with widely spaced nipples. The facial features consist of triangular face with hypertelorism, large low-set ears, ptosis, and flat nasal bridge. Some patients manifest cardiac defects. Some have an increased risk for certain malignancies, particularly juvenile myelomonocytic leukemia. {ECO:0000269|PubMed:20619386, ECO:0000269|PubMed:25178484}. Note=The disease is caused by variants affecting the gene represented in this entry.

Without disease ID

A syndrome characterized by a phenotype reminiscent of Noonan syndrome. Clinical features are highly variable, including facial dysmorphism, short neck, developmental delay, hyperextensible joints and thorax abnormalities with widely spaced nipples. The facial features consist of triangular face with hypertelorism, large low-set ears, ptosis, and flat nasal bridge. Some patients manifest cardiac defects. Some have an increased risk for certain malignancies, particularly juvenile myelomonocytic leukemia. {ECO:0000269|PubMed:20619386, ECO:0000269|PubMed:25178484}. Note=The disease is caused by variants affecting the gene represented in this entry.

7 regional properties for P22681

Type	Name	Position	InterPro Accession
domain	Zinc finger, RING-type	381 - 420	IPR001841
domain	Adaptor protein Cbl, N-terminal helical	52 - 175	IPR003153
domain	Adaptor protein Cbl, EF hand-like	179 - 262	IPR014741
domain	Adaptor protein Cbl, SH2-like domain	256 - 352	IPR014742
domain	Ubiquitin-associated domain	856 - 895	IPR015940
conserved_site	Zinc finger, RING-type, conserved site	396 - 405	IPR017907
domain	Adaptor protein Cbl, PTB domain	47 - 351	IPR024159

Functions

		Description
EC Number	2.3.2.27	Aminoacyltransferases
Subcellular Localization	Cytoplasm Cell membrane Cell projection, cilium Golgi apparatus	Colocalizes with FGFR2 in lipid rafts at the cell membrane
PANTHER Family	PTHR23007	CBL
PANTHER Subfamily	PTHR23007:SF5	E3 UBIQUITIN-PROTEIN LIGASE CBL
PANTHER Protein Class	ligase metabolite interconversion enzyme
PANTHER Pathway Category	EGF receptor signaling pathway c-Cbl

9 GO annotations of cellular component

Name	Definition
cilium	A specialized eukaryotic organelle that consists of a filiform extrusion of the cell surface and of some cytoplasmic parts. Each cilium is largely bounded by an extrusion of the cytoplasmic (plasma) membrane, and contains a regular longitudinal array of microtubules, anchored to a basal body.
cytosol	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
flotillin complex	A protein complex that contains flotillin-1 and flotillin-2, and may contain associated proteins. Flotillins associate into membrane microdomains resembling caveolae.
focal adhesion	A cell-substrate junction that anchors the cell to the extracellular matrix and that forms a point of termination of actin filaments. In insects focal adhesion has also been referred to as hemi-adherens junction (HAJ).
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.
growth cone	The migrating motile tip of a growing neuron projection, where actin accumulates, and the actin cytoskeleton is the most dynamic.
membrane raft	Any of the small (10-200 nm), heterogeneous, highly dynamic, sterol- and sphingolipid-enriched membrane domains that compartmentalize cellular processes. Small rafts can sometimes be stabilized to form larger platforms through protein-protein and protein-lipid interactions.
perinuclear region of cytoplasm	Cytoplasm situated near, or occurring around, the nucleus.
plasma membrane	The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.

9 GO annotations of molecular function

Name	Definition
cadherin binding	Binding to cadherin, a type I membrane protein involved in cell adhesion.
calcium ion binding	Binding to a calcium ion (Ca2+).
ephrin receptor binding	Binding to an ephrin receptor.
phosphatidylinositol 3-kinase regulatory subunit binding	Binding to a regulatory subunit of phosphatidylinositol 3-kinase. The regulatory subunit associates with the catalytic subunit to regulate both its activity and subcellular location.
phosphotyrosine residue binding	Binding to a phosphorylated tyrosine residue within a protein.
receptor tyrosine kinase binding	Binding to a receptor that possesses protein tyrosine kinase activity.
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.
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: an isopeptide bond between the C-terminal glycine of ubiquitin and the epsilon-amino group of lysine residues in the substrate or, in the linear extension of ubiquitin chains, a peptide bond the between the C-terminal glycine and N-terminal methionine of ubiquitin residues.
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.

32 GO annotations of biological process

Name	Definition
cell surface receptor signaling pathway	The series of molecular signals initiated by activation of a receptor on the surface of a cell. The pathway begins with binding of an extracellular ligand to a cell surface receptor, or for receptors that signal in the absence of a ligand, by ligand-withdrawal or the activity of a constitutively active receptor. The pathway ends with regulation of a downstream cellular process, e.g. transcription.
cellular response to DNA damage 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 a stimulus indicating damage to its DNA from environmental insults or errors during metabolism.
cellular response to nerve growth factor stimulus	A 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 nerve growth factor stimulus.
cellular response to oxygen-glucose deprivation	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 the deprivation of oxygen and glucose.
cellular response to platelet-derived growth factor 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 a platelet-derived growth factor stimulus.
cytokine-mediated signaling pathway	The series of molecular signals initiated by the binding of a cytokine to a receptor on the surface of a cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
entry of bacterium into host cell	The process in which a bacterium enters a host cell. The host is defined as the larger of the organisms involved in a symbiotic interaction.
epidermal growth factor receptor signaling pathway	The series of molecular signals initiated by binding of a ligand to the tyrosine kinase receptor EGFR (ERBB1) on the surface of a cell. The pathway ends with regulation of a downstream cellular process, e.g. transcription.
male gonad development	The process whose specific outcome is the progression of the male gonad over time, from its formation to the mature structure.
mast cell degranulation	The regulated exocytosis of secretory granules containing preformed mediators such as histamine, serotonin, and neutral proteases by a mast cell.
negative regulation of apoptotic process	Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process.
negative regulation of epidermal growth factor receptor signaling pathway	Any process that stops, prevents, or reduces the frequency, rate or extent of epidermal growth factor receptor signaling pathway activity.
negative regulation of epidermal growth factor-activated receptor activity	Any process that stops, prevents, or reduces the frequency, rate or extent of EGF-activated receptor activity.
negative regulation of neuron death	Any process that stops, prevents or reduces the frequency, rate or extent of neuron death.
neuron death	The process of cell death in a neuron.
positive regulation of epidermal growth factor receptor signaling pathway	Any process that activates or increases the frequency, rate or extent of epidermal growth factor receptor signaling pathway activity.
positive regulation of phosphatidylinositol 3-kinase signaling	Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the phosphatidylinositol 3-kinase cascade.
positive regulation of receptor-mediated endocytosis	Any process that activates or increases the frequency, rate or extent of receptor mediated endocytosis, the uptake of external materials by cells, utilizing receptors to ensure specificity of transport.
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 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 ubiquitination	The process in which one or more ubiquitin groups are added to a protein.
regulation of platelet-derived growth factor receptor-alpha signaling pathway	Any process that modulates the frequency, rate or extent of platelet-derived growth factor receptor-alpha signaling pathway.
regulation of Rap protein signal transduction	Any process that modulates the frequency, rate or extent of Rap protein signal transduction.
response to activity	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 activity stimulus.
response to antibiotic	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 antibiotic stimulus. An antibiotic is a chemical substance produced by a microorganism which has the capacity to inhibit the growth of or to kill other microorganisms.
response to ethanol	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 ethanol stimulus.
response to gamma radiation	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 gamma radiation stimulus. Gamma radiation is a form of electromagnetic radiation (EMR) or light emission of a specific frequency produced from sub-atomic particle interaction, such as electron-positron annihilation and radioactive decay. Gamma rays are generally characterized as EMR having the highest frequency and energy, and also the shortest wavelength, within the electromagnetic radiation spectrum.
response to starvation	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 starvation stimulus, deprivation of nourishment.
response to testosterone	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 testosterone stimulus.
signal transduction	The cellular process in which a signal is conveyed to trigger a change in the activity or state of a cell. Signal transduction begins with reception of a signal (e.g. a ligand binding to a receptor or receptor activation by a stimulus such as light), or for signal transduction in the absence of ligand, signal-withdrawal or the activity of a constitutively active receptor. Signal transduction ends with regulation of a downstream cellular process, e.g. regulation of transcription or regulation of a metabolic process. Signal transduction covers signaling from receptors located on the surface of the cell and signaling via molecules located within the cell. For signaling between cells, signal transduction is restricted to events at and within the receiving cell.
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.

7 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q13191	CBLB	E3 ubiquitin-protein ligase CBL-B	Homo sapiens (Human)	EV
Q9ULV8	CBLC	E3 ubiquitin-protein ligase CBL-C	Homo sapiens (Human)	SS
Q3TTA7	Cblb	E3 ubiquitin-protein ligase CBL-B	Mus musculus (Mouse)	SS
Q80XL1	Cblc	E3 ubiquitin-protein ligase CBL-C	Mus musculus (Mouse)	SS
P22682	Cbl	E3 ubiquitin-protein ligase CBL	Mus musculus (Mouse)	SS
Q8K4S7	Cblb	E3 ubiquitin-protein ligase CBL-B	Rattus norvegicus (Rat)	SS
G3V8H4	Cblc	E3 ubiquitin-protein ligase CBL-C	Rattus norvegicus (Rat)	SS

10	20	30	40	50	60
MAGNVKKSSG	AGGGSGSGGS	GSGGLIGLMK	DAFQPHHHHH	HHLSPHPPGT	VDKKMVEKCW
70	80	90	100	110	120
KLMDKVVRLC	QNPKLALKNS	PPYILDLLPD	TYQHLRTILS	RYEGKMETLG	ENEYFRVFME
130	140	150	160	170	180
NLMKKTKQTI	SLFKEGKERM	YEENSQPRRN	LTKLSLIFSH	MLAELKGIFP	SGLFQGDTFR
190	200	210	220	230	240
ITKADAAEFW	RKAFGEKTIV	PWKSFRQALH	EVHPISSGLE	AMALKSTIDL	TCNDYISVFE
250	260	270	280	290	300
FDIFTRLFQP	WSSLLRNWNS	LAVTHPGYMA	FLTYDEVKAR	LQKFIHKPGS	YIFRLSCTRL
310	320	330	340	350	360
GQWAIGYVTA	DGNILQTIPH	NKPLFQALID	GFREGFYLFP	DGRNQNPDLT	GLCEPTPQDH
370	380	390	400	410	420
IKVTQEQYEL	YCEMGSTFQL	CKICAENDKD	VKIEPCGHLM	CTSCLTSWQE	SEGQGCPFCR
430	440	450	460	470	480
CEIKGTEPIV	VDPFDPRGSG	SLLRQGAEGA	PSPNYDDDDD	ERADDTLFMM	KELAGAKVER
490	500	510	520	530	540
PPSPFSMAPQ	ASLPPVPPRL	DLLPQRVCVP	SSASALGTAS	KAASGSLHKD	KPLPVPPTLR
550	560	570	580	590	600
DLPPPPPPDR	PYSVGAESRP	QRRPLPCTPG	DCPSRDKLPP	VPSSRLGDSW	LPRPIPKVPV
610	620	630	640	650	660
SAPSSSDPWT	GRELTNRHSL	PFSLPSQMEP	RPDVPRLGST	FSLDTSMSMN	SSPLVGPECD
670	680	690	700	710	720
HPKIKPSSSA	NAIYSLAARP	LPVPKLPPGE	QCEGEEDTEY	MTPSSRPLRP	LDTSQSSRAC
730	740	750	760	770	780
DCDQQIDSCT	YEAMYNIQSQ	APSITESSTF	GEGNLAAAHA	NTGPEESENE	DDGYDVPKPP
790	800	810	820	830	840
VPAVLARRTL	SDISNASSSF	GWLSLDGDPT	TNVTEGSQVP	ERPPKPFPRR	INSERKAGSC
850	860	870	880	890	900
QQGSGPAASA	ATASPQLSSE	IENLMSQGYS	YQDIQKALVI	AQNNIEMAKN	ILREFVSISS

PAHVAT