AiPD: Autoinhibited Protein Database

Q8IV61

Gene name	RASGRP3 (GRP3, KIAA0846)
Protein name	Ras guanyl-releasing protein 3
Names	Calcium and DAG-regulated guanine nucleotide exchange factor III, Guanine nucleotide exchange factor for Rap1
Species	Homo sapiens (Human)
KEGG Pathway	hsa:25780
EC number
Protein Class

Descriptions

Ras regulation in B cells involves a Ras-guanyl nucleotide exchange factor. RasGRP, a member of the cdc25 family of Ras guanyl nucleotide exchange factors (Ras-GEFs), has a DAG-binding C1 domain, DAG generated upon antigen receptor stimulation contributes to recruiting RasGRP to the membrane, where it interacts with Ras. PKC, after being activated by diacylglycerol, phosphorylates RasGRP3, thereby contributing to the full activation of RasGRP3. Mutation of Thr-133 in the Cdc25 domain of RasGRP3 alone severely impairs its ability to activate Ras in B cell signaling, which represents an autoinhibition mechanism in RasGRP3. The Thr-133 site is conserved in human, mouse, and chicken.
In other RasGRP proteins, the phosphorylation of the Cdc25 domain could aid in removal of the inhibitory linker between Cdc25 and EF domain. Briefly, inactive RasGRP is stabilized by the C1-dimer interface, which sequesters the membrane-interacting surface of the C1 domain, and the active-site blocking RasGEF catalytic domain (Cdc25)-EF domain linker. The C-terminal coiled-coil stabilizes the dimer, thereby preventing inappropriate Ras activation. The autoinhibited form is activated by multiple signaling inputs that enhance nucleotide exchange activity. Diacylglycerol binding disrupts C1 dimerization, while Ca2+ binding to EF1 causes a conformational change that contributes to C1 reorientation, and the release of the inhibitory segment from the Ras-binding surface. Phosphorylation of the Cdc25 domain could aid in removal of the inhibitory linker.

Autoinhibitory domains (AIDs)

384-419 (RasGEF catalytic domain-EF domain linker) SS

Target domain	148-384 (Ras guanine-nucleotide exchange factors catalytic domain)
Relief mechanism	Ligand binding, PTM
Assay

AID

384-419 (RasGEF catalytic domain-EF domain linker)

Target domain

148-384 (Ras guanine-nucleotide exchange factors catalytic domain)

Relief mechanism

Ligand binding (Ca2+ binding to EF domain and diacylglycerol binding to C1 domain), PTM (Phosphorylation of the RasGEF catalytic domain)

Assay

494-544 (C1 domain) SS

Target domain	420-484 (EF domain)
Relief mechanism	Ligand binding, PTM
Assay

AID

494-544 (C1 domain)

Target domain

420-484 (EF domain)

Relief mechanism

Ligand binding (Ca2+ binding to EF domain and diacylglycerol binding to C1 domain), PTM (Phosphorylation of the RasGEF catalytic domain)

Assay

Accessory elements

No accessory elements

References

Czikora A et al. (2016) "Structural Basis for the Failure of the C1 Domain of Ras Guanine Nucleotide Releasing Protein 2 (RasGRP2) to Bind Phorbol Ester with High Affinity", The Journal of biological chemistry, 291, 11133-47

Canault M et al. (2020) "RasGRP2 Structure, Function and Genetic Variants in Platelet Pathophysiology", International journal of molecular sciences, 21,

Aiba Y et al. (2004) "Activation of RasGRP3 by phosphorylation of Thr-133 is required for B cell receptor-mediated Ras activation", Proceedings of the National Academy of Sciences of the United States of America, 101, 16612-7

Ren J et al. (2016) "A negative-feedback loop regulating ERK1/2 activation and mediated by RasGPR2 phosphorylation", Biochemical and biophysical research communications, 474, 193-198

Autoinhibited structure

Activated structure

1 structures for Q8IV61

Entry ID	Method	Resolution	Chain	Position	Source
AF-Q8IV61-F1	Predicted				AlphaFoldDB

558 variants for Q8IV61

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
rs368361129 CA1608416	3	S>T		No	ClinGen ESP ExAC TOPMed gnomAD
rs1558469822 CA346568174	6	L>F		No	ClinGen Ensembl
rs757953919 CA1608418	6	L>P		No	ClinGen ExAC TOPMed gnomAD
CA1608420 rs202227874	8	K>N		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA44880013 rs1030753010	8	K>Q		No	ClinGen Ensembl
rs1426464915 CA346568192	9	A>G		No	ClinGen TOPMed
rs529397346 CA1608422	9	A>T		No	ClinGen 1000Genomes ExAC gnomAD
rs1186512307 CA346568200	11	T>S		No	ClinGen TOPMed
rs749428928 CA1608423	13	D>G		No	ClinGen ExAC gnomAD
rs1250089127 CA346568229	15	L>V		No	ClinGen gnomAD
CA346568241 rs1359663560	17	C>Y		No	ClinGen gnomAD
CA1608425 rs774482287	20	I>T		No	ClinGen ExAC TOPMed gnomAD
CA346568268 rs1424634763	21	E>K		No	ClinGen gnomAD
rs1162089311 CA346568281	22	M>I		No	ClinGen gnomAD
rs1188745468 CA346568283	23	F>I		No	ClinGen TOPMed
rs200383320 CA1608443	24	D>G		No	ClinGen 1000Genomes ExAC gnomAD
rs200383320 CA1608444	24	D>V		No	ClinGen 1000Genomes ExAC gnomAD
rs1257553074 CA346568313	25	D>G		No	ClinGen TOPMed gnomAD
rs1257553074 CA346568314	25	D>V		No	ClinGen TOPMed gnomAD
rs772223353 CA346568321	26	N>I		No	ClinGen ExAC TOPMed gnomAD
CA1608445 rs772223353	26	N>S		No	ClinGen ExAC TOPMed gnomAD
CA1608446 rs775737039	28	E>D		No	ClinGen ExAC gnomAD
CA346568337 rs1258950155	29	L>M		No	ClinGen gnomAD
rs890617442 CA44881536	30	D>G		No	ClinGen Ensembl
rs768686449 CA1608448	32	S>R		No	ClinGen ExAC TOPMed gnomAD
rs776482716 CA1608449	32	S>T		No	ClinGen ExAC gnomAD
rs761656022 CA1608450	34	L>W		No	ClinGen ExAC gnomAD
rs1192293060 CA346568379	35	P>S		No	ClinGen gnomAD
CA1608451 rs532104316	36	R>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1022847861 CA44881571	37	I>R		No	ClinGen TOPMed
CA346568399 rs1478524677	38	V>A		No	ClinGen gnomAD
CA346568402 rs1170864671	39	L>V		No	ClinGen gnomAD
rs765835018 CA1608454	43	R>*		No	ClinGen ExAC gnomAD
COSM3939080 rs751036038 CA1608455	43	R>Q	oesophagus [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs759770045 CA44881625	44	W>*		No	ClinGen ExAC gnomAD
rs778326528 CA1608457	44	W>C		No	ClinGen ExAC gnomAD
rs759770045 CA1608456	44	W>L		No	ClinGen ExAC gnomAD
CA1608458 rs754373181	45	Y>C		No	ClinGen ExAC gnomAD
rs757579464 CA1608459	46	L>V		No	ClinGen ExAC gnomAD
rs1220572415 CA346568460	48	S>F		No	ClinGen gnomAD
CA346568463 rs1344634984	49	T>A		No	ClinGen gnomAD
rs867545035 CA44881704	51	L>F		No	ClinGen Ensembl
CA346568485 rs1281248284	52	A>V		No	ClinGen gnomAD
CA44881706 rs1027412929	53	E>D		No	ClinGen Ensembl
rs1216450777 CA346568492	53	E>G		No	ClinGen gnomAD
rs545928016 CA1608460	55	L>F		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA1608461 rs74600205	56	L>V		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs528323494 CA1608462	57	C>G		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA1608476 rs200007507	58	M>I		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA346568541 rs200007507	58	M>I		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA346568522 rs1376697079	58	M>V		No	ClinGen gnomAD
CA346568551 COSM1407884 rs757730510	60	R>*	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs757730510 CA1608477	60	R>G		No	ClinGen ExAC TOPMed gnomAD
COSM277021 rs369611073 CA1608478	60	R>Q	oesophagus large_intestine endometrium [Cosmic]	No	ClinGen cosmic curated 1000Genomes ESP ExAC TOPMed gnomAD
CA1608479 rs750786013	62	A>G		No	ClinGen ExAC gnomAD
rs1366677906 CA346568585	65	E>D		No	ClinGen gnomAD
rs372849070 CA1608480	66	S>I		No	ClinGen ESP ExAC gnomAD
CA44884804 rs985985680	67	C>G		No	ClinGen TOPMed gnomAD
CA346568596 rs1395457474	67	C>Y		No	ClinGen gnomAD
rs1329719519 CA346568601	68	N>H		No	ClinGen gnomAD
rs377114910 CA1608481	68	N>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs866243572 CA44884807	69	E>K		No	ClinGen Ensembl
CA1608482 rs747302924	71	R>*		No	ClinGen ExAC gnomAD
CA346568624 rs1312568209	71	R>Q		No	ClinGen gnomAD
rs974747435 CA44884816	72	L>V		No	ClinGen Ensembl
CA1608483 COSM263263 rs755026837	73	K>N	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA346568651 rs1246330254	75	C>S		No	ClinGen gnomAD
rs1196295087 CA346568677	78	M>I		No	ClinGen gnomAD
rs1463456194 CA346568674	78	M>T		No	ClinGen gnomAD
rs1316921636 CA346568673	78	M>V		No	ClinGen gnomAD
rs756271456 CA1608504 COSM1407885	80	Y>H	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA1608506 rs749224315	81	W>*		No	ClinGen ExAC TOPMed gnomAD
rs980422189 CA44885365	82	I>V		No	ClinGen Ensembl
CA1608507 rs770658018	84	K>R		No	ClinGen ExAC TOPMed gnomAD
CA1608508 rs778703968	85	F>L		No	ClinGen ExAC TOPMed gnomAD
CA346568741 rs1360484949	86	P>S		No	ClinGen gnomAD
CA1608510 rs771596671	88	E>K		No	ClinGen ExAC gnomAD
CA346568785 rs1454247444	92	D>G		No	ClinGen TOPMed
CA346568797 rs1456061747	94	G>S		No	ClinGen gnomAD
rs1039192555 CA44885379	95	L>*		No	ClinGen TOPMed gnomAD
CA44885378 rs760091052	95	L>M		No	ClinGen ExAC TOPMed gnomAD
CA1608512 rs760091052	95	L>V		No	ClinGen ExAC TOPMed gnomAD
rs1039192555 CA346568802	95	L>W		No	ClinGen TOPMed gnomAD
rs1271183651 CA346568806	96	I>V		No	ClinGen TOPMed
CA346568814 COSM1020541 rs1313672455	97	R>C	endometrium [Cosmic]	No	ClinGen cosmic curated gnomAD
rs201148346 CA1608513	97	R>H		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs201148346 CA346568816	97	R>L		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA346568818 rs1285164743	98	M>V		No	ClinGen TOPMed gnomAD
CA1608514 rs773790361	100	E>K		No	ClinGen ExAC TOPMed gnomAD
rs763575605 CA1608515	101	E>K		No	ClinGen ExAC gnomAD
CA1608517 rs184551261	103	R>Q		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs371205458 CA1608516 COSM1020542	103	R>W	endometrium [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
rs767616744 CA1608519	104	E>D		No	ClinGen ExAC gnomAD
rs759993903 CA1608518	104	E>Q		No	ClinGen ExAC gnomAD
CA1608520 rs11680495	105	V>A		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs756078687 CA1608521	106	A>D		No	ClinGen ExAC gnomAD
CA346568869 rs1174701629	106	A>S		No	ClinGen gnomAD
rs891692430 CA44885454	111	Y>C		No	ClinGen TOPMed gnomAD
rs777846483 CA1608522	114	H>P		No	ClinGen ExAC gnomAD
rs753729020 CA1608523	115	V>I		No	ClinGen ExAC TOPMed gnomAD
CA346568938 rs1374571663	116	S>N		No	ClinGen gnomAD
rs369357266 CA44885481	117	L>F		No	ClinGen gnomAD
rs372240212 CA1608525	118	I>V		No	ClinGen ESP ExAC TOPMed gnomAD
CA44885501 rs913758973 COSM1223231	119	D>N	large_intestine [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
CA346568971 rs1558478164	121	S>Y		No	ClinGen Ensembl
CA44885514 rs1001563892	122	S>G		No	ClinGen TOPMed
CA44886858 rs780509512	128	W>*		No	ClinGen Ensembl
rs781039769 CA1608551	128	W>R		No	ClinGen ExAC gnomAD
CA346569058 rs1430667867	132	V>L		No	ClinGen TOPMed
CA346569076 rs1234001408 COSM263264	134	Q>H	large_intestine [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
CA346569077 rs1234001408 COSM263264	134	Q>H	large_intestine [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
rs1407565966 CA346569080	135	R>K		No	ClinGen TOPMed
rs747648068 CA1608552	136	K>E		No	ClinGen ExAC gnomAD
CA346569089 rs1316335412	136	K>I		No	ClinGen gnomAD
rs774650493 CA1608554	137	K>N		No	ClinGen ExAC gnomAD
rs772279264 CA1608556	139	S>F		No	ClinGen ExAC gnomAD
rs746397814 CA1608555	139	S>P		No	ClinGen ExAC TOPMed gnomAD
rs746397814 CA346569105	139	S>T		No	ClinGen ExAC TOPMed gnomAD
rs1234139209 CA346569114	140	K>N		No	ClinGen TOPMed
CA44886954 rs1001398919	140	K>R		No	ClinGen gnomAD
rs1260562029 CA346569123	141	K>N		No	ClinGen gnomAD
CA346569120 rs1192352566	141	K>R		No	ClinGen gnomAD
rs1476223442 CA346569125	142	G>R		No	ClinGen gnomAD
rs1490085123 CA346569132	143	K>*		No	ClinGen TOPMed
CA346569140 rs1266501844	144	A>S		No	ClinGen TOPMed
rs761072531 CA1608558	144	A>V		No	ClinGen ExAC gnomAD
rs992652466 CA44886963	145	C>Y		No	ClinGen TOPMed
CA1608561 rs761878056	149	D>H		No	ClinGen ExAC gnomAD
rs917075235 CA44886970	150	H>L		No	ClinGen TOPMed
rs917075235 CA346569179	150	H>R		No	ClinGen TOPMed
CA346569177 rs1175382205	150	H>Y		No	ClinGen gnomAD
rs750271899 CA1608563	153	P>A		No	ClinGen ExAC TOPMed gnomAD
CA1608564 rs758389634	153	P>L		No	ClinGen ExAC TOPMed gnomAD
CA346569196 rs750271899	153	P>S		No	ClinGen ExAC TOPMed gnomAD
CA1608565 rs766266040	154	I>V		No	ClinGen ExAC gnomAD
CA44886989 rs199925389	156	L>V		No	ClinGen ESP ExAC TOPMed gnomAD
CA346569220 rs1558480278	157	A>P		No	ClinGen Ensembl
rs1415655905 CA346569226	158	E>K		No	ClinGen gnomAD
rs780984138 CA1608568	161	T>S		No	ClinGen ExAC gnomAD
CA346569257 rs1574413009	162	F>S		No	ClinGen Ensembl
rs747803233 CA1608569	165	H>D		No	ClinGen ExAC TOPMed gnomAD
rs747803233 CA346569273	165	H>N		No	ClinGen ExAC TOPMed gnomAD
rs755625249 CA1608570	165	H>R		No	ClinGen ExAC gnomAD
rs1301658039 CA346569285	166	K>N		No	ClinGen TOPMed
rs777363208 CA1608571	166	K>R		No	ClinGen ExAC gnomAD
CA1608572 rs746323230	168	F>C		No	ClinGen ExAC gnomAD
rs1439105380 CA346569293	168	F>L		No	ClinGen TOPMed
rs1193381754 CA346569304	169	R>S		No	ClinGen gnomAD
rs1350865038 CA346569308	170	R>K		No	ClinGen TOPMed
rs1215100332 CA346569345	173	F>L		No	ClinGen gnomAD
rs1043302019 CA44888776	176	Y>C		No	ClinGen gnomAD
rs1457124865 CA346569368	177	Q>K		No	ClinGen gnomAD
CA1608590 rs777334234	178	S>T		No	ClinGen ExAC gnomAD
rs753370792 CA1608591	182	H>R		No	ClinGen ExAC TOPMed gnomAD
CA346569448 rs1276523993	184	C>Y		No	ClinGen gnomAD
rs1438384311 CA346569492	187	N>K		No	ClinGen gnomAD
CA44888807 rs904208199	194	S>L		No	ClinGen Ensembl
rs768952854 CA1608595	200	G>R		No	ClinGen ExAC gnomAD
CA346569672 rs1167303229	201	I>T		No	ClinGen gnomAD
rs781561676 CA1608596	202	S>T		No	ClinGen ExAC gnomAD
CA346569705 rs1296190573	204	W>C		No	ClinGen TOPMed
CA1608597 rs748550600	204	W>L		No	ClinGen ExAC gnomAD
CA346569727 rs1465402089	206	Q>R		No	ClinGen gnomAD
CA346569772 rs377431465	209	V>F		No	ClinGen ESP ExAC TOPMed gnomAD
CA1608598 rs377431465	209	V>I		No	ClinGen ESP ExAC TOPMed gnomAD
rs370214673 CA44888840	213	P>A		No	ClinGen 1000Genomes ESP ExAC gnomAD
rs900955931 CA44888854	213	P>L		No	ClinGen gnomAD
rs370214673 CA1608599	213	P>S		No	ClinGen 1000Genomes ESP ExAC gnomAD
rs1289024955 CA346569837	214	T>I		No	ClinGen TOPMed
CA1608601 rs770916153	216	Q>L		No	ClinGen ExAC gnomAD
rs374183857 CA1608603	221	V>I		No	ClinGen ESP ExAC gnomAD
rs1216554204 CA346569975	225	F>L		No	ClinGen gnomAD
rs564758640 CA346570012	227	N>I		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA1608606 rs564758640 COSM1631991	227	N>S	liver [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
CA346570031 rs1389524456	229	A>E		No	ClinGen TOPMed
rs1184940059 CA346570101	231	K>N		No	ClinGen gnomAD
rs1325954858 CA346570136	234	Q>H		No	ClinGen TOPMed
CA1608623 rs192425371	234	Q>R		No	ClinGen 1000Genomes ExAC gnomAD
CA346570144 rs1429453840	235	L>F		No	ClinGen gnomAD
rs1429453840 CA346570142	235	L>V		No	ClinGen gnomAD
rs1393796799 CA346570174	237	N>I		No	ClinGen gnomAD
CA346570215 rs1174820463	240	T>N		No	ClinGen gnomAD
CA346570232 rs1434129545	241	L>P		No	ClinGen gnomAD
rs370017312 CA1608626	242	M>L		No	ClinGen ESP ExAC TOPMed gnomAD
rs1362272018 CA346570262	243	A>V		No	ClinGen gnomAD
rs575846499 CA1608627	244	V>A		No	ClinGen 1000Genomes ExAC gnomAD
CA346570263 rs1274257859	244	V>M		No	ClinGen gnomAD
CA1608628 rs753473160	245	V>A		No	ClinGen ExAC gnomAD
rs1234843156 CA346570286	246	G>E		No	ClinGen gnomAD
CA44889376 rs970638430	247	G>R		No	ClinGen Ensembl
CA1608629 rs761396516	248	L>F		No	ClinGen ExAC TOPMed gnomAD
rs764688660 CA1608630	249	S>N		No	ClinGen ExAC TOPMed gnomAD
CA346570335 rs1213787952	250	H>Y		No	ClinGen gnomAD
rs1366985049 CA346570364	252	S>C		No	ClinGen TOPMed gnomAD
rs1486351349 CA346570391	254	S>L		No	ClinGen gnomAD
rs757960166 CA1608632	255	R>C		No	ClinGen ExAC gnomAD
rs1251452351 CA346570403	255	R>H		No	ClinGen TOPMed gnomAD
CA346570429 rs1380257467	257	K>R		No	ClinGen gnomAD
rs1370844290 CA346570439	258	E>K		No	ClinGen TOPMed
rs1194878821 CA346570467	259	T>I		No	ClinGen TOPMed
rs778017498 CA1608637	262	H>R		No	ClinGen ExAC gnomAD
CA1608638 rs201170179	263	L>I		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1396327886 CA346570520	263	L>R		No	ClinGen gnomAD
CA346570581 rs1275697879	268	T>R		No	ClinGen Ensembl
CA1608641 rs745932386	269	K>N		No	ClinGen ExAC gnomAD
rs1417056708 CA346571145	272	N>S		No	ClinGen gnomAD
rs1057230990 CA44891967	274	M>I		No	ClinGen TOPMed
CA346571174 rs1057230990	274	M>I		No	ClinGen TOPMed
CA1608666 rs563560790	275	T>A		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA44891971 rs1038864613	275	T>I		No	ClinGen gnomAD
CA44891995 rs779293482	277	L>F		No	ClinGen TOPMed gnomAD
CA346571208 rs1434159061	277	L>S		No	ClinGen gnomAD
rs930572941 CA44891996	278	V>I		No	ClinGen TOPMed gnomAD
CA346571235 rs1269838430	279	S>F		No	ClinGen gnomAD
CA1608669 rs772789171	281	N>S		No	ClinGen ExAC gnomAD
CA1608671 rs142000180	282	G>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
COSM116527 CA346571699 rs1208098851	283	N>S	ovary [Cosmic]	No	ClinGen cosmic curated gnomAD
rs1456455257 CA346571723	285	C>R		No	ClinGen TOPMed
rs1191968157 CA346571734	286	N>H		No	ClinGen gnomAD
CA1608672 rs200209664	286	N>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1476254460 CA346571762	288	R>C		No	ClinGen TOPMed gnomAD
rs371456335 CA1608673	288	R>H		No	ClinGen ESP ExAC TOPMed gnomAD
COSM721117 CA1608674 rs371456335	288	R>L	lung [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
CA346571758 rs1476254460	288	R>S		No	ClinGen TOPMed gnomAD
rs202202384 CA1608675	289	K>E		No	ClinGen ExAC gnomAD
rs758815762 CA44892011	290	A>D		No	ClinGen ExAC gnomAD
CA1608676 rs762202577	290	A>T		No	ClinGen ExAC gnomAD
rs758815762 CA1608677	290	A>V		No	ClinGen ExAC gnomAD
CA346571791 rs1184350879	291	F>L		No	ClinGen TOPMed
rs751571321 CA1608681	293	D>N		No	ClinGen ExAC TOPMed gnomAD
CA346571829 rs1343692726	294	C>S		No	ClinGen gnomAD
CA1608683 rs780921595	295	D>N		No	ClinGen ExAC TOPMed gnomAD
CA1608685 rs769525309	296	G>A		No	ClinGen ExAC TOPMed gnomAD
CA1608684 rs748086884	296	G>S		No	ClinGen ExAC gnomAD
rs749120154 CA1608687	297	F>L		No	ClinGen ExAC gnomAD
CA1608686 rs777576243	297	F>V		No	ClinGen ExAC gnomAD
rs559300824 CA44892063	299	I>T		No	ClinGen 1000Genomes
CA346571934 rs1204080133	301	I>T		No	ClinGen TOPMed gnomAD
rs1245598180 CA346571928	301	I>V		No	ClinGen gnomAD
rs1448428671 CA346571966	304	V>I		No	ClinGen gnomAD
rs1195366284 CA346572007	306	L>F		No	ClinGen gnomAD
rs1452355941 CA346572001	306	L>S		No	ClinGen gnomAD
CA346572017 rs1395643665	307	K>T		No	ClinGen gnomAD
CA346572030 rs1478377291	308	D>Y		No	ClinGen gnomAD
rs1553355457 CA346572051	309	L>W		No	ClinGen Ensembl
CA1608692 rs777220535	310	I>T		No	ClinGen ExAC gnomAD
CA1608691 rs771617664	310	I>V		No	ClinGen ExAC gnomAD
rs762437399 CA1608693	311	A>S		No	ClinGen ExAC gnomAD
rs765661757 CA346572080	312	V>I		No	ClinGen ExAC gnomAD
rs765661757 CA1608695	312	V>L		No	ClinGen ExAC gnomAD
rs750789666 CA1608696	313	H>Q		No	ClinGen ExAC gnomAD
CA346572118 rs1237682972	315	I>V		No	ClinGen TOPMed gnomAD
rs552600627 CA44892098	318	D>E		No	ClinGen ExAC TOPMed gnomAD
rs1352221731 CA346572183	319	W>C		No	ClinGen gnomAD
rs1303780415 CA346572195	320	T>R		No	ClinGen TOPMed
CA346572219 rs1405978087 COSM3839453	322	E>K	breast [Cosmic]	No	ClinGen cosmic curated TOPMed
CA346572255 rs1466935898	324	K>E		No	ClinGen gnomAD
rs751807930 CA1608700	324	K>N		No	ClinGen ExAC gnomAD
CA1608702 rs754952310	327	I>L		No	ClinGen ExAC TOPMed gnomAD
CA1608701 rs754952310	327	I>V		No	ClinGen ExAC TOPMed gnomAD
rs1437239596 CA346572308	328	V>A		No	ClinGen gnomAD
rs1362078749 CA346572322	330	M>T		No	ClinGen gnomAD
rs756013046 CA1608704	331	H>R		No	ClinGen ExAC gnomAD
rs1471215091 CA346572329	331	H>Y		No	ClinGen gnomAD
CA346572335 rs866819887	332	Q>E		No	ClinGen gnomAD
rs866819887 CA44892122	332	Q>K		No	ClinGen gnomAD
rs1460182800 CA346572345	333	L>P		No	ClinGen TOPMed gnomAD
CA1608706 rs749067768	335	V>I		No	ClinGen ExAC TOPMed gnomAD
CA346572365 rs1458697352	336	T>S		No	ClinGen gnomAD
rs1327450456 CA346572386	339	E>K		No	ClinGen TOPMed gnomAD
rs1327450456 CA346572387	339	E>Q		No	ClinGen TOPMed gnomAD
rs778364897 CA1608708	340	L>I		No	ClinGen ExAC gnomAD
CA44892134 rs967356985	341	V>L		No	ClinGen Ensembl
CA346572425 rs1273511505	345	N>I		No	ClinGen TOPMed gnomAD
CA1608711 rs775176221	346	A>P		No	ClinGen ExAC TOPMed gnomAD
rs770406000 CA1608713	347	S>C		No	ClinGen ExAC gnomAD
rs146365956 CA1608712	347	S>P		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1558488772 CA346572440	348	H>Y		No	ClinGen Ensembl
rs763158947 CA1608715	351	E>D		No	ClinGen ExAC gnomAD
rs974433968 CA44892178	351	E>G		No	ClinGen Ensembl
CA346572473 rs1346004453	352	P>L		No	ClinGen TOPMed
CA346572487 rs1342523958	354	M>I		No	ClinGen gnomAD
CA44892193 rs921773367	354	M>T		No	ClinGen gnomAD
CA346572484 rs1474386298	354	M>V		No	ClinGen TOPMed gnomAD
CA346572514 rs1343569601	358	N>H		No	ClinGen TOPMed
rs774383856 CA1608717	358	N>S		No	ClinGen ExAC TOPMed gnomAD
rs759830804 CA1608718	359	L>P		No	ClinGen ExAC gnomAD
rs1401542785 CA346572520	359	L>V		No	ClinGen TOPMed
CA44892197 rs372381371	361	T>M		No	ClinGen gnomAD
rs1186421034 CA346573143	365	D>E		No	ClinGen gnomAD
CA1608736 rs774746107	365	D>N		No	ClinGen ExAC gnomAD
CA346573181 rs1372993754	368	H>R		No	ClinGen Ensembl
CA1608737 rs759866276	369	T>I		No	ClinGen ExAC gnomAD
CA346573217 rs1289925037	371	D>N		No	ClinGen TOPMed
rs1212385952 CA346573261	373	I>M		No	ClinGen gnomAD
CA346573370 rs1485697457	382	P>T		No	ClinGen gnomAD
rs1203749442 CA346573417	385	S>C		No	ClinGen gnomAD
rs1264233996 CA346573430	386	K>I		No	ClinGen gnomAD
CA1608739 rs775753875	387	S>L		No	ClinGen ExAC gnomAD
rs370036907 CA1608758	388	Q>H		No	ClinGen ESP ExAC TOPMed gnomAD
CA346573600 rs1290422051	388	Q>K		No	ClinGen gnomAD
CA1608757 rs747647775	388	Q>P		No	ClinGen ExAC gnomAD
rs1276050842 CA346573618	390	T>I		No	ClinGen gnomAD
CA346573613 rs1553359795	390	T>P		No	ClinGen Ensembl
rs1553359795 CA346573614	390	T>S		No	ClinGen Ensembl
rs1271590462 CA346573626	392	P>A		No	ClinGen gnomAD
rs13388394 VAR_051901 CA1608759	393	T>A		No	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs746238359 CA1608760	393	T>M		No	ClinGen ExAC TOPMed gnomAD
CA1608762 rs370150483 COSM3782194	394	T>M	pancreas [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
CA346573635 rs1574459129	394	T>P		No	ClinGen Ensembl
rs768682900 CA1608764	395	P>H		No	ClinGen ExAC gnomAD
rs1252072728 CA346573641	395	P>S		No	ClinGen gnomAD
CA1608766 rs761850658	396	N>K		No	ClinGen ExAC gnomAD
CA346573660 rs1202810725	398	P>T		No	ClinGen gnomAD
rs1405773090 CA346573683	401	P>L		No	ClinGen gnomAD
rs1317614176 CA346573680	401	P>S		No	ClinGen TOPMed
rs1169619926 CA346573687	402	L>P		No	ClinGen gnomAD
rs765210280 CA346573696	403	E>D		No	ClinGen ExAC gnomAD
rs1352741684 CA346573690	403	E>Q		No	ClinGen gnomAD
rs1034396389 CA44900359	404	W>*		No	ClinGen TOPMed
rs923565510 CA44900362	405	A>V		No	ClinGen TOPMed
rs1433649873 CA346573712	406	L>*		No	ClinGen gnomAD
CA346573713 rs1433649873	406	L>*		No	ClinGen gnomAD
CA1608769 rs750398272	407	G>E		No	ClinGen ExAC TOPMed gnomAD
CA346573717 rs1310010313	407	G>R		No	ClinGen TOPMed gnomAD
rs1574459389 CA346573737	409	M>T		No	ClinGen Ensembl
CA1608771 rs766297182	410	P>A		No	ClinGen ExAC gnomAD
CA1608773 rs576622336	412	P>S		No	ClinGen 1000Genomes ExAC gnomAD
CA346573794 rs201653344	413	D>E		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA346573801 rs1274644905	414	P>A		No	ClinGen gnomAD
rs267599361 CA44900377	414	P>L		No	ClinGen ExAC
rs267599361 CA1608775	414	P>R		No	ClinGen ExAC
rs200573011 CA1608776	415	T>K		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
COSM304211 rs200573011 CA1608777	415	T>M	large_intestine [Cosmic]	No	ClinGen cosmic curated 1000Genomes ESP ExAC TOPMed gnomAD
rs1238887002 CA346573846	418	N>D		No	ClinGen gnomAD
rs1185776254 CA346573856	418	N>K		No	ClinGen TOPMed gnomAD
CA346573852 rs1472991398	418	N>S		No	ClinGen gnomAD
rs866531213 CA44900395	421	I>T		No	ClinGen Ensembl
CA346573906 rs1451186183	422	R>G		No	ClinGen gnomAD
rs368466918 CA1608779	424	L>*		No	ClinGen ESP ExAC gnomAD
rs368145185 CA44902826	428	V>A		No	ClinGen ESP gnomAD
rs748338356 CA1608804	432	Y>C		No	ClinGen ExAC TOPMed gnomAD
CA346574188 rs1467132284	432	Y>D		No	ClinGen gnomAD
CA1608807 rs773130349	435	D>H		No	ClinGen ExAC TOPMed gnomAD
CA1608806 rs773130349	435	D>N		No	ClinGen ExAC TOPMed gnomAD
rs1410096651 CA346574210	435	D>V		No	ClinGen gnomAD
rs1459146579 CA346574219	436	H>R		No	ClinGen TOPMed gnomAD
rs1488685842 CA346574229	437	D>E		No	ClinGen gnomAD
rs774497562 CA1608809	437	D>H		No	ClinGen ExAC TOPMed gnomAD
rs774497562 CA44902837	437	D>N		No	ClinGen ExAC TOPMed gnomAD
rs1211554483 CA346574232	438	G>E		No	ClinGen gnomAD
CA1608810 rs759335946	438	G>W		No	ClinGen ExAC TOPMed gnomAD
CA44902857 rs764726554	439	Y>H		No	ClinGen Ensembl
CA1608811 rs767228263	441	S>Y		No	ClinGen ExAC gnomAD
rs62149026 CA1608812	443	E>Q		No	ClinGen ESP ExAC TOPMed gnomAD
CA1608813 rs760277344	445	F>S		No	ClinGen ExAC gnomAD
rs1352009569 CA346574452	447	S>G		No	ClinGen gnomAD
rs763847141 CA1608814	448	I>R		No	ClinGen ExAC gnomAD
rs1455860457 CA346574485	449	A>S		No	ClinGen TOPMed
rs1272238519 CA346574511	451	N>S		No	ClinGen gnomAD
rs766871041 CA1608817	456	D>G		No	ClinGen ExAC gnomAD
rs371780555 CA1608816	456	D>N		No	ClinGen ESP ExAC TOPMed gnomAD
CA1608819 rs755315317	460	V>A		No	ClinGen ExAC gnomAD
CA1608818 rs752067507	460	V>F		No	ClinGen ExAC gnomAD
CA1608820 rs781437850	464	D>V		No	ClinGen ExAC gnomAD
rs1371813406 CA346566584	466	D>N		No	ClinGen gnomAD
rs1399690209 CA346566611	470	S>G		No	ClinGen gnomAD
CA346566623 rs1397559121	471	K>I		No	ClinGen gnomAD
CA346566629 rs1334491468	472	D>G		No	ClinGen gnomAD
CA346566628 rs1458786884	472	D>N		No	ClinGen gnomAD
CA1608837 rs752018377	473	E>K		No	ClinGen ExAC gnomAD
rs998036130 CA44852275	474	M>I		No	ClinGen TOPMed gnomAD
rs1261453543 CA346566652	475	M>T		No	ClinGen TOPMed
rs755406186 CA1608838	475	M>V		No	ClinGen ExAC TOPMed gnomAD
CA346566670 rs939849907	477	Y>*		No	ClinGen TOPMed gnomAD
rs768115065 CA1608839	478	F>L		No	ClinGen ExAC gnomAD
CA346566675 rs1482435483	478	F>Y		No	ClinGen gnomAD
CA346566682 rs1364856797	479	L>R		No	ClinGen TOPMed
CA44852322 rs906347656	482	K>E		No	ClinGen TOPMed
CA346566716 rs1446807646	484	Q>H		No	ClinGen gnomAD
rs1301805329 CA346566709	484	Q>K		No	ClinGen TOPMed
CA1608842 rs778073822	485	L>P		No	ClinGen ExAC gnomAD
CA346566730 rs1449518042	487	C>G		No	ClinGen gnomAD
rs1172549288 CA346566738	488	K>E		No	ClinGen TOPMed gnomAD
CA346566737 rs1172549288	488	K>Q		No	ClinGen TOPMed gnomAD
rs757361406 CA1608844	489	M>I		No	ClinGen ExAC gnomAD
rs779167087 CA1608845	491	P>R		No	ClinGen ExAC TOPMed gnomAD
CA1608846 rs190747493	494	I>F		No	ClinGen 1000Genomes ExAC gnomAD
rs190747493 CA1608847	494	I>V		No	ClinGen 1000Genomes ExAC gnomAD
rs1320578213 CA346566795	496	N>S		No	ClinGen TOPMed gnomAD
rs1558517933 CA346566806	497	F>L		No	ClinGen Ensembl
CA346566810 rs1172260708	498	Q>*		No	ClinGen TOPMed
rs376375359 CA1608850	500	M>I		No	ClinGen ESP ExAC TOPMed gnomAD
CA346566848 rs1255353464	503	L>F		No	ClinGen TOPMed
rs776210676 CA1608851	506	T>S		No	ClinGen ExAC gnomAD
rs769473930 COSM230908 CA1608853	509	E>K	skin [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA1608855 rs553822665	510	H>Q		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs553822665 CA1608854	510	H>Q		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA346566895 rs1574485282	510	H>Y		No	ClinGen Ensembl
rs199562103 CA44852384	512	A>V		No	ClinGen TOPMed gnomAD
CA1608857 rs753252206	513	G>R		No	ClinGen ExAC gnomAD
CA44857333 rs772751607	516	W>*		No	ClinGen Ensembl
rs1553365989 CA346566950	516	W>C		No	ClinGen Ensembl
CA346566957 rs1474774593	517	G>V		No	ClinGen gnomAD
CA1608875 rs761275507	518	I>L		No	ClinGen ExAC TOPMed gnomAD
CA44857339 rs998234673	518	I>T		No	ClinGen Ensembl
rs1351593927 CA346566977	520	K>N		No	ClinGen gnomAD
CA1608876 rs764738808	522	G>V		No	ClinGen ExAC gnomAD
CA1608877 rs375017489	523	Y>C		No	ClinGen ESP ExAC gnomAD
rs1294120508 CA346566992	523	Y>H		No	ClinGen gnomAD
CA346566991 rs1294120508	523	Y>N		No	ClinGen gnomAD
CA44857401 rs367667575	524	K>R		No	ClinGen ESP TOPMed gnomAD
rs1187818482 CA346567052	529	G>R		No	ClinGen gnomAD
rs1246171417 CA346567065	531	N>D		No	ClinGen gnomAD
CA346567068 rs1447722683	531	N>S		No	ClinGen gnomAD
rs1170640437 CA346567076	532	C>S		No	ClinGen gnomAD
CA346567090 rs1574506248	534	K>Q		No	ClinGen Ensembl
CA1608896 rs762202668	534	K>R		No	ClinGen ExAC TOPMed gnomAD
CA1608897 rs765650374	535	Q>P		No	ClinGen ExAC gnomAD
CA346567103 rs773260697	536	C>R		No	ClinGen ExAC TOPMed gnomAD
CA1608898 rs773260697	536	C>S		No	ClinGen ExAC TOPMed gnomAD
CA346567127 rs1401980415	539	L>F		No	ClinGen TOPMed
CA346567145 rs1320443853	542	L>P		No	ClinGen gnomAD
rs1017316019 CA44859733	545	R>K		No	ClinGen TOPMed
CA346567173 rs1436639104	546	R>S		No	ClinGen gnomAD
CA1608901 rs766552880	547	F>S		No	ClinGen ExAC gnomAD
rs766552880 CA346567177	547	F>Y		No	ClinGen ExAC gnomAD
CA346567185 rs1343701557	548	A>G		No	ClinGen gnomAD
rs1343701557 CA346567186	548	A>V		No	ClinGen gnomAD
CA1608903 COSM258675 rs375130686	549	R>Q	large_intestine endometrium [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
rs751642105 CA1608902	549	R>W		No	ClinGen ExAC TOPMed gnomAD
rs767373620 CA1608904	550	A>V		No	ClinGen ExAC TOPMed gnomAD
CA346567195 rs1266164773	551	P>T		No	ClinGen gnomAD
rs369940541 CA1608906	552	S>C		No	ClinGen ESP ExAC gnomAD
rs369940541 CA44859762	552	S>F		No	ClinGen ESP ExAC gnomAD
CA346567218 rs1379393420	554	S>R		No	ClinGen gnomAD
CA1608907 rs77880464	558	G>R		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA44859785 rs552684879	560	L>M		No	ClinGen 1000Genomes gnomAD
CA346567276 rs1427585150	563	S>R		No	ClinGen gnomAD
CA1608909 rs192400130	565	S>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA346567287 rs192400130	565	S>W		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA346567322 rs1283511125	569	A>G		No	ClinGen gnomAD
CA346567321 rs1283511125	569	A>V		No	ClinGen gnomAD
CA1608929 rs750115304	570	Q>P		No	ClinGen ExAC gnomAD
CA44860140 rs865988343	571	D>N		No	ClinGen Ensembl
CA1608930 rs141310174	572	E>D		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1023238992 CA44860158	575	E>Q		No	ClinGen TOPMed gnomAD
rs779745078 CA1608931	576	F>S		No	ClinGen ExAC TOPMed gnomAD
CA1608932 rs746562760	577	P>S		No	ClinGen ExAC gnomAD
rs981775178 CA44860185	578	G>R		No	ClinGen TOPMed
rs1456144494 CA346567382	579	V>I		No	ClinGen gnomAD
rs377213456 CA346567397	581	A>D		No	ClinGen ESP ExAC TOPMed gnomAD
rs377213456 CA1608933	581	A>G		No	ClinGen ESP ExAC TOPMed gnomAD
CA346567398 rs377213456	581	A>V		No	ClinGen ESP ExAC TOPMed gnomAD
CA346567404 rs1332249397	582	G>A		No	ClinGen TOPMed
rs1034729503 CA44860194	583	H>R		No	ClinGen TOPMed gnomAD
rs1038743866 CA44860224	585	D>A		No	ClinGen Ensembl
rs778207490 CA1608934	587	D>E		No	ClinGen ExAC TOPMed gnomAD
rs749596181 CA1608935	590	A>T		No	ClinGen ExAC TOPMed gnomAD
rs771210387 CA1608936	591	I>M		No	ClinGen ExAC gnomAD
CA346567477 rs1558529353	594	V>I		No	ClinGen Ensembl
CA1608940 rs75531739	596	G>R		No	ClinGen 1000Genomes ExAC gnomAD
CA1608939 rs75531739 COSM1020548	596	G>S	endometrium [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC gnomAD
CA1608941 rs369191574	598	S>P		No	ClinGen ESP ExAC TOPMed gnomAD
rs1372082644 CA346567504	599	R>C		No	ClinGen gnomAD
rs760725569 CA1608942	599	R>H		No	ClinGen ExAC TOPMed gnomAD
rs760725569 CA346567507	599	R>P		No	ClinGen ExAC TOPMed gnomAD
rs1372082644 CA346567506	599	R>S		No	ClinGen gnomAD
CA1608943 rs764088220	600	K>N		No	ClinGen ExAC gnomAD
CA346567537 rs1338498740	604	R>K		No	ClinGen gnomAD
CA346567557 rs1478230710	607	R>K		No	ClinGen TOPMed
CA346567563 rs1574508220	608	A>P		No	ClinGen Ensembl
CA346567567 rs1246839954	608	A>V		No	ClinGen gnomAD
CA346567573 rs1190877252	609	T>I		No	ClinGen TOPMed
CA346567568 rs1574508252	609	T>P		No	ClinGen Ensembl
rs1574508294 CA346567574	610	T>A		No	ClinGen Ensembl
rs1574508294 CA346567576	610	T>P		No	ClinGen Ensembl
rs753725548 CA1608945	613	A>P		No	ClinGen ExAC TOPMed gnomAD
CA1608944 rs753725548	613	A>T		No	ClinGen ExAC TOPMed gnomAD
rs1265345700 CA346567601	614	T>A		No	ClinGen TOPMed
rs1272745783 CA346567624	617	E>G		No	ClinGen gnomAD
CA346567632 rs1196613275	618	P>L		No	ClinGen gnomAD
CA346567629 rs750058298	618	P>S		No	ClinGen ExAC gnomAD
CA1608947 rs750058298	618	P>T		No	ClinGen ExAC gnomAD
rs1374614921 CA346567633	619	V>L		No	ClinGen gnomAD
rs1485502441 CA346567646	620	W>*		No	ClinGen TOPMed
CA44860324 rs1048803468	620	W>R		No	ClinGen gnomAD
CA1608950 rs751106969	624	G>S		No	ClinGen ExAC gnomAD
CA44860340 rs886289478	624	G>V		No	ClinGen Ensembl
CA44860364 rs749778639	625	W>L		No	ClinGen ExAC gnomAD
CA1608954 rs749778639	625	W>S		No	ClinGen ExAC gnomAD
CA346567688 rs1574508590	627	D>G		No	ClinGen Ensembl
rs1221337261 CA346567685	627	D>H		No	ClinGen TOPMed
rs1221337261 CA346567684	627	D>N		No	ClinGen TOPMed
rs779215448 CA1608956	628	S>L		No	ClinGen ExAC TOPMed gnomAD
CA44860385 rs907139899	629	G>E		No	ClinGen TOPMed gnomAD
rs1574508649 CA346567704	630	S>A		No	ClinGen Ensembl
rs775755947 CA1608959	630	S>Y		No	ClinGen ExAC
rs1432812945 CA346567734	634	P>L		No	ClinGen gnomAD
CA346567730 rs1364451456	634	P>S		No	ClinGen gnomAD
CA44860437 rs867905331	636	M>I		No	ClinGen Ensembl
CA346567752 rs1348507031	637	K>E		No	ClinGen gnomAD
rs761689219 CA1608963	640	F>L		No	ClinGen ExAC gnomAD
rs776584170 CA1608962	640	F>S		No	ClinGen ExAC gnomAD
CA1608964 rs765308856	641	H>Y		No	ClinGen ExAC gnomAD
rs762903539 CA1608966	642	D>A		No	ClinGen ExAC gnomAD
CA1608967 rs766058863	644	A>V		No	ClinGen ExAC gnomAD
rs371403036 CA1608969	646	K>E		No	ClinGen ESP ExAC TOPMed gnomAD
rs1033676571 CA44860460	648	K>I		No	ClinGen Ensembl
rs1187244297 CA346567838	649	G>A		No	ClinGen gnomAD
rs1187244297 CA346567839	649	G>V		No	ClinGen gnomAD
rs376151198 CA1608970	651	A>V		No	ClinGen ESP ExAC TOPMed gnomAD
rs1553367245 CA346567855	652	K>*		No	ClinGen Ensembl
CA346567858 rs1222463905	652	K>I		No	ClinGen Ensembl
CA346567867 rs1428626694	653	W>*		No	ClinGen gnomAD
rs1428626694 CA346567868	653	W>C		No	ClinGen gnomAD
CA1608971 rs752289882	656	E>K		No	ClinGen ExAC gnomAD
rs752289882 CA44860467	656	E>Q		No	ClinGen ExAC gnomAD
CA1608972 rs757739271	657	K>N		No	ClinGen ExAC TOPMed gnomAD
rs779454015 CA1608973	658	P>A		No	ClinGen ExAC gnomAD
rs1176802302 CA346567910	659	R>S		No	ClinGen gnomAD
CA1608974 rs746228453	660	V>A		No	ClinGen ExAC gnomAD
CA346567912 rs1387649551	660	V>L		No	ClinGen gnomAD
CA346567921 rs1322499215	661	H>L		No	ClinGen TOPMed gnomAD
CA346567920 rs1322499215	661	H>R		No	ClinGen TOPMed gnomAD
rs758767268 CA1608975	664	V>M		No	ClinGen ExAC gnomAD
CA1608976 rs780193334	666	V>A		No	ClinGen ExAC gnomAD
rs1485532851 CA346567964	668	D>V		No	ClinGen gnomAD
rs1329639869 CA346567960	668	D>Y		No	ClinGen gnomAD
CA346567969 rs768744751	669	R>P		No	ClinGen ExAC TOPMed gnomAD
CA1608978 rs768744751	669	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs376854458 COSM1631992 CA1608977	669	R>W	liver [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
CA346567971 rs1328933012	670	G>C		No	ClinGen gnomAD
rs1474901537 CA346567974	670	G>D		No	ClinGen TOPMed
CA1608979 rs776544925	671	T>M		No	ClinGen ExAC TOPMed gnomAD
rs1208793297 CA346567993	673	F>C		No	ClinGen gnomAD
rs769845170 CA1608981	673	F>I		No	ClinGen ExAC gnomAD
rs1264657124 CA346567996	673	F>L		No	ClinGen gnomAD
CA346567994 rs1208793297	673	F>S		No	ClinGen gnomAD
rs769845170 CA346567991	673	F>V		No	ClinGen ExAC gnomAD
rs1434481347 CA346568005	675	L>I		No	ClinGen TOPMed gnomAD
rs773283474 CA346568011	676	D>H		No	ClinGen ExAC gnomAD
rs773283474 CA1608982	676	D>N		No	ClinGen ExAC gnomAD
rs762776188 CA1608983	677	Q>*		No	ClinGen ExAC gnomAD
rs766297017 CA1608984	678	D>E		No	ClinGen ExAC
rs1161260791 CA346568027	678	D>N		No	ClinGen gnomAD
rs967294674 CA44860522	679	E>D		No	ClinGen Ensembl
CA346568042 rs559847817	680	G>A		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA1608985 rs559847817	680	G>E		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs759076984 CA1608986	681	E>D		No	ClinGen ExAC gnomAD
rs1279384866 CA346568052	682	E>Q		No	ClinGen TOPMed
rs1292950605 CA346568064	683	T>I		No	ClinGen gnomAD
CA44860530 rs767246316	684	R>K		No	ClinGen ExAC gnomAD
CA1608987 rs767246316	684	R>T		No	ClinGen ExAC gnomAD
rs200904355 CA1608989	685	Q>H		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA1608988 rs752133952	685	Q>K		No	ClinGen ExAC gnomAD
CA346568117 rs1188905604	689	D>G		No	ClinGen gnomAD
CA346568124 rs1420561504	690	G>D		No	ClinGen TOPMed gnomAD

No associated diseases with Q8IV61

4 regional properties for Q8IV61

Type	Name	Position	InterPro Accession
binding_site	IQ motif, EF-hand binding site	785 - 807	IPR000048
domain	Myosin head, motor domain	79 - 784	IPR001609
domain	Myosin tail	848 - 1928	IPR002928
domain	Myosin, N-terminal, SH3-like	31 - 81	IPR004009

Functions

		Description
EC Number
Subcellular Localization
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

4 GO annotations of cellular component

Name	Definition
guanyl-nucleotide exchange factor complex	A protein complex that stimulates the exchange of guanyl nucleotides associated with a GTPase.
integral component of plasma membrane	The component of the plasma membrane consisting of the gene products and protein complexes having at least some part of their peptide sequence embedded in the hydrophobic region of the membrane.
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.

6 GO annotations of molecular function

Name	Definition
calcium ion binding	Binding to a calcium ion (Ca2+).
diacylglycerol binding	Binding to a diacylglycerol, a diester of glycerol and two fatty acids.
GTPase activator activity	Binds to and increases the activity of a GTPase, an enzyme that catalyzes the hydrolysis of GTP.
guanyl-nucleotide exchange factor activity	Stimulates the exchange of GDP to GTP on a signaling GTPase, changing its conformation to its active form. Guanine nucleotide exchange factors (GEFs) act by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP), which is more abundant in the cell under normal cellular physiological conditions.
kinase binding	Binding to a kinase, any enzyme that catalyzes the transfer of a phosphate group.
small GTPase binding	Binding to a small monomeric GTPase.

4 GO annotations of biological process

Name	Definition
MAPK cascade	An intracellular protein kinase cascade containing at least a MAPK, a MAPKK and a MAP3K. The cascade can also contain an additional tiers: the upstream MAP4K. The kinases in each tier phosphorylate and activate the kinase in the downstream tier to transmit a signal within a cell.
Ras protein signal transduction	The series of molecular signals within the cell that are mediated by a member of the Ras superfamily of proteins switching to a GTP-bound active state.
regulation of GTPase activity	Any process that modulates the rate of GTP hydrolysis by a GTPase.
small GTPase mediated signal transduction	The series of molecular signals in which a small monomeric GTPase relays a signal.

30 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
A6N9I4	RASGRP2	RAS guanyl-releasing protein 2	Bos taurus (Bovine)	SS
Q1LZ97	RASGRP4	RAS guanyl-releasing protein 4	Bos taurus (Bovine)	SS
A0A3S5ZPR1	RASGRP3	RAS guanyl releasing protein 3	Gallus gallus (Chicken)	SS
P26675	Sos	Protein son of sevenless	Drosophila melanogaster (Fruit fly)	SS
Q07890	SOS2	Son of sevenless homolog 2	Homo sapiens (Human)	SS
Q07889	SOS1	Son of sevenless homolog 1	Homo sapiens (Human)	EV
Q13905	RAPGEF1	Rap guanine nucleotide exchange factor 1	Homo sapiens (Human)	PR
O95398	RAPGEF3	Rap guanine nucleotide exchange factor 3	Homo sapiens (Human)	EV
Q8WZA2	RAPGEF4	Rap guanine nucleotide exchange factor 4	Homo sapiens (Human)	SS
Q8N431	RASGEF1C	Ras-GEF domain-containing family member 1C	Homo sapiens (Human)	PR
Q8N9B8	RASGEF1A	Ras-GEF domain-containing family member 1A	Homo sapiens (Human)	PR
Q8IZJ4	RGL4	Ral-GDS-related protein	Homo sapiens (Human)	PR
Q12967	RALGDS	Ral guanine nucleotide dissociation stimulator	Homo sapiens (Human)	PR
O95267	RASGRP1	RAS guanyl-releasing protein 1	Homo sapiens (Human)	EV
Q8TDF6	RASGRP4	RAS guanyl-releasing protein 4	Homo sapiens (Human)	SS
Q7LDG7	RASGRP2	RAS guanyl-releasing protein 2	Homo sapiens (Human)	EV SS
Q86X27	RALGPS2	Ras-specific guanine nucleotide-releasing factor RalGPS2	Homo sapiens (Human)	PR
Q5JS13	RALGPS1	Ras-specific guanine nucleotide-releasing factor RalGPS1	Homo sapiens (Human)	PR
Q62245	Sos1	Son of sevenless homolog 1	Mus musculus (Mouse)	SS
A2AR50	Ralgps1	Ras-specific guanine nucleotide-releasing factor RalGPS1	Mus musculus (Mouse)	PR
Q8BTM9	Rasgrp4	RAS guanyl-releasing protein 4	Mus musculus (Mouse)	SS
Q9ERD6	Ralgps2	Ras-specific guanine nucleotide-releasing factor RalGPS2	Mus musculus (Mouse)	PR
Q02384	Sos2	Son of sevenless homolog 2	Mus musculus (Mouse)	SS
Q9QUG9	Rasgrp2	RAS guanyl-releasing protein 2	Mus musculus (Mouse)	SS
Q9Z1S3	Rasgrp1	RAS guanyl-releasing protein 1	Mus musculus (Mouse)	SS
P0C643	Rasgrp2	RAS guanyl-releasing protein 2	Rattus norvegicus (Rat)	SS
Q8R5I4	Rasgrp4	RAS guanyl-releasing protein 4	Rattus norvegicus (Rat)	SS
Q9R1K8	Rasgrp1	RAS guanyl-releasing protein 1	Rattus norvegicus (Rat)	SS
Q9N5D3	sos-1	Son of sevenless homolog	Caenorhabditis elegans	EV
A4IJ06	rasgrp1	RAS guanyl-releasing protein 1	Xenopus tropicalis (Western clawed frog) (Silurana tropicalis)	SS

10	20	30	40	50	60
MGSSGLGKAA	TLDELLCTCI	EMFDDNGELD	NSYLPRIVLL	MHRWYLSSTE	LAEKLLCMYR
70	80	90	100	110	120
NATGESCNEF	RLKICYFMRY	WILKFPAEFN	LDLGLIRMTE	EFREVASQLG	YEKHVSLIDI
130	140	150	160	170	180
SSIPSYDWMR	RVTQRKKVSK	KGKACLLFDH	LEPIELAEHL	TFLEHKSFRR	ISFTDYQSYV
190	200	210	220	230	240
IHGCLENNPT	LERSIALFNG	ISKWVQLMVL	SKPTPQQRAE	VITKFINVAK	KLLQLKNFNT
250	260	270	280	290	300
LMAVVGGLSH	SSISRLKETH	SHLSSEVTKN	WNEMTELVSS	NGNYCNYRKA	FADCDGFKIP
310	320	330	340	350	360
ILGVHLKDLI	AVHVIFPDWT	EENKVNIVKM	HQLSVTLSEL	VSLQNASHHL	EPNMDLINLL
370	380	390	400	410	420
TLSLDLYHTE	DDIYKLSLVL	EPRNSKSQPT	SPTTPNKPVV	PLEWALGVMP	KPDPTVINKH
430	440	450	460	470	480
IRKLVESVFR	NYDHDHDGYI	SQEDFESIAA	NFPFLDSFCV	LDKDQDGLIS	KDEMMAYFLR
490	500	510	520	530	540
AKSQLHCKMG	PGFIHNFQEM	TYLKPTFCEH	CAGFLWGIIK	QGYKCKDCGA	NCHKQCKDLL
550	560	570	580	590	600
VLACRRFARA	PSLSSGHGSL	PGSPSLPPAQ	DEVFEFPGVT	AGHRDLDSRA	ITLVTGSSRK
610	620	630	640	650	660
ISVRLQRATT	SQATQTEPVW	SEAGWGDSGS	HTFPKMKSKF	HDKAAKDKGF	AKWENEKPRV
670	680
HAGVDVVDRG	TEFELDQDEG	EETRQDGEDG