AiPD: Autoinhibited Protein Database

O75676

Gene name	RPS6KA4 (MSK2)
Protein name	Ribosomal protein S6 kinase alpha-4
Names	S6K-alpha-4, 90 kDa ribosomal protein S6 kinase 4, Nuclear mitogen- and stress-activated protein kinase 2, Ribosomal protein kinase B, RSKB
Species	Homo sapiens (Human)
KEGG Pathway	hsa:8986
EC number	2.7.11.1: Protein-serine/threonine kinases
Protein Class

Descriptions

MSK2 is a member of p90 ribosomal S6 kinases (RSKs) containing two distinct kinase catalytic domains. Extracellular signal-regulated kinase (ERK) releases phosphorylated RSKs and activates RSK. Truncation of the autoinhibitory alpha helix results in constitutively active RSK, and it is suggested that autoinhibitory alpha helix may be the mode of regulation for each of the RSKs. The alteration of autoinhibitory alpha helix activates the C-terminal kinase domain (CTD), and increases N-terminal kinase domain (NTD) activity toward exogenous substrate.

Autoinhibitory domains (AIDs)

689-703 (Putative autoinhibitory alpha helix) SS

Target domain	422-679 (C-terminal kinase domain, CTD)
Relief mechanism	PTM
Assay

AID

689-703 (Putative autoinhibitory alpha helix)

Target domain

422-679 (C-terminal kinase domain, CTD)

Relief mechanism

PTM (Phosphorylation of Thr577 and Ser369 by ERK, autophosphorylation of Ser386)

Assay

Accessory elements

178-202 (Activation loop from InterPro)

Target domain	32-364 (N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2)
Relief mechanism
Assay

References

Vermeulen L et al. (2003) "Transcriptional activation of the NF-kappaB p65 subunit by mitogen- and stress-activated protein kinase-1 (MSK1)", The EMBO journal, 22, 1313-24

Poteet-Smith CE et al. (1999) "Generation of constitutively active p90 ribosomal S6 kinase in vivo. Implications for the mitogen-activated protein kinase-activated protein kinase family", The Journal of biological chemistry, 274, 22135-8

Zhao Y et al. (1995) "RSK3 encodes a novel pp90rsk isoform with a unique N-terminal sequence: growth factor-stimulated kinase function and nuclear translocation", Molecular and cellular biology, 15, 4353-63

Martinez EC et al. (2015) "RSK3: A regulator of pathological cardiac remodeling", IUBMB life, 67, 331-7

Anjum R et al. (2008) "The RSK family of kinases: emerging roles in cellular signalling", Nature reviews. Molecular cell biology, 9, 747-58

Malakhova M et al. (2008) "Structural basis for activation of the autoinhibitory C-terminal kinase domain of p90 RSK2", Nature structural & molecular biology, 15, 112-3

Li D et al. (2012) "Structural basis for the autoinhibition of the C-terminal kinase domain of human RSK1", Acta crystallographica. Section D, Biological crystallography, 68, 680-5

Li D et al. (2013) "The prometastatic ribosomal S6 kinase 2-cAMP response element-binding protein (RSK2-CREB) signaling pathway up-regulates the actin-binding protein fascin-1 to promote tumor metastasis", The Journal of biological chemistry, 288, 32528-32538

Autoinhibited structure

Activated structure

1 structures for O75676

Entry ID	Method	Resolution	Chain	Position	Source
AF-O75676-F1	Predicted				AlphaFoldDB

525 variants for O75676

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
CA381152623 rs1387092141	3	D>N		No	ClinGen gnomAD
rs1398692927 CA381152660	4	E>K		No	ClinGen gnomAD
CA6075651 rs777596426	4	E>V		No	ClinGen ExAC TOPMed gnomAD
CA381152686 rs1383087661	5	D>N		No	ClinGen TOPMed
CA6075652 rs746602059	6	D>E		No	ClinGen ExAC TOPMed gnomAD
rs1160458687 CA381152739	6	D>N		No	ClinGen TOPMed
CA223864939 rs941211750	7	D>G		No	ClinGen TOPMed
rs1254130389 CA381152840	9	S>G		No	ClinGen TOPMed
CA223864946 rs867790126	9	S>I		No	ClinGen Ensembl
CA6075654 rs776261307	12	V>L		No	ClinGen ExAC TOPMed gnomAD
CA6075655 rs745365364	14	L>M		No	ClinGen ExAC gnomAD
rs745365364 CA381153009	14	L>V		No	ClinGen ExAC gnomAD
CA381153030 rs1349190074	15	R>Q		No	ClinGen gnomAD
rs769760950 CA6075656	16	I>L		No	ClinGen ExAC gnomAD
rs1037252498 CA223864958	17	T>I		No	ClinGen TOPMed
rs1488427053 CA381153370	20	N>S		No	ClinGen TOPMed
rs369313779 CA223865078	22	T>I		No	ClinGen ESP TOPMed gnomAD
rs1208112059 CA381153412	23	G>R		No	ClinGen TOPMed
CA6075674 rs571660732	24	H>Q		No	ClinGen ExAC TOPMed gnomAD
rs571660732 CA223865080	24	H>Q		No	ClinGen ExAC TOPMed gnomAD
CA6075675 rs749166781	25	E>K		No	ClinGen ExAC gnomAD
CA381153612 rs1279322734	28	V>A		No	ClinGen TOPMed
CA381153624 rs768572474	29	S>N		No	ClinGen ExAC gnomAD
rs768572474 CA6075676	29	S>T		No	ClinGen ExAC gnomAD
rs1299964500 CA381153688	31	E>*		No	ClinGen gnomAD
CA381154000 rs1400337592	40	G>R		No	ClinGen TOPMed
CA381154001 rs1400337592	40	G>S		No	ClinGen TOPMed
CA6075679 rs767831211	41	T>M		No	ClinGen ExAC TOPMed gnomAD
rs749978034 CA6075690	43	A>D		No	ClinGen ExAC
rs935368943 CA223865688	50	V>A		No	ClinGen TOPMed
CA381154839 rs1291878532	53	A>V		No	ClinGen gnomAD
CA223865694 rs896590892	56	H>Q		No	ClinGen TOPMed
rs1220240625 CA381154979	57	D>H		No	ClinGen gnomAD
CA381155077 rs1188068976	59	G>V		No	ClinGen TOPMed gnomAD
CA381155081 rs1591309036	60	K>E		No	ClinGen Ensembl
CA381155136 rs1259841353	61	L>P		No	ClinGen gnomAD
CA381155188 rs1387218415	63	A>T		No	ClinGen gnomAD
CA381155376 rs1454040874	67	L>Q		No	ClinGen gnomAD
rs866130178 CA223865700	68	R>S		No	ClinGen TOPMed gnomAD
CA381155601 rs1591309070	73	V>G		No	ClinGen Ensembl
rs1455628289 CA381155668	75	R>H		No	ClinGen gnomAD
CA381155755 rs1382241546	78	T>M		No	ClinGen gnomAD
rs521950 CA223865713	79	Q>H		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA223865707 rs521950	79	Q>H		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1384414238 CA381155797	80	E>*		No	ClinGen gnomAD
CA6075694 rs768623912	80	E>D		No	ClinGen ExAC TOPMed
CA381155816 rs768623912	80	E>D		No	ClinGen ExAC TOPMed
CA223865734 rs1045275022	82	T>M		No	ClinGen TOPMed gnomAD
rs1045275022 CA381155888	82	T>R		No	ClinGen TOPMed gnomAD
CA381155924 rs1317458504	83	R>C		No	ClinGen gnomAD
rs905329669 CA223865736	90	E>*		No	ClinGen TOPMed gnomAD
rs1591309153 CA381156157	92	V>G		No	ClinGen Ensembl
rs1464599604 CA381156205	95	A>T		No	ClinGen gnomAD
CA223865756 rs951423161	99	V>A		No	ClinGen Ensembl
rs1442820168 CA381156296	99	V>I		No	ClinGen gnomAD
rs1409285677 CA381156378	102	H>Y		No	ClinGen gnomAD
CA381156452 rs1421404980	103	Y>*		No	ClinGen TOPMed gnomAD
rs1157369829 CA381156535	106	Q>*		No	ClinGen gnomAD
rs1411766081 CA381156563	107	T>M		No	ClinGen gnomAD
CA381156662 rs1336935756	109	A>G		No	ClinGen gnomAD
CA6075696 rs575584890	109	A>T		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA381156781 rs1346923383	115	L>V		No	ClinGen TOPMed
rs760918515 CA6075699	116	D>H		No	ClinGen ExAC gnomAD
CA223865781 rs760918515	116	D>N		No	ClinGen ExAC gnomAD
rs1202551847 CA381157003	119	S>N		No	ClinGen gnomAD
rs562882417 CA6075736	119	S>R		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1490657245 CA381157039	120	G>C		No	ClinGen gnomAD
rs746849149 CA6075737	122	E>G		No	ClinGen ExAC
rs568380775 CA223865975	123	M>R		No	ClinGen Ensembl
CA381157119 rs1591309486	123	M>V		No	ClinGen Ensembl
rs1591309500 CA381157261	129	Q>P		No	ClinGen Ensembl
rs1476822864 CA381157273	130	R>C		No	ClinGen gnomAD
CA381157306 rs1190309564	131	Q>P		No	ClinGen gnomAD
CA6075738 rs757067643	132	Y>C		No	ClinGen ExAC gnomAD
CA381157486 rs1166193347	138	V>A		No	ClinGen gnomAD
CA381157483 rs1166193347	138	V>G		No	ClinGen gnomAD
rs781570977 CA6075739	139	R>H		No	ClinGen ExAC gnomAD
rs746032255 CA6075741	140	V>L		No	ClinGen ExAC gnomAD
rs746032255 CA6075740	140	V>L		No	ClinGen ExAC gnomAD
CA6075742 rs775501166	141	Y>C		No	ClinGen ExAC gnomAD
CA6075743 rs138221123	143	G>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs949665366 CA223865988	143	G>V		No	ClinGen Ensembl
rs1364367548 CA381157612	146	V>A		No	ClinGen gnomAD
rs1270950927 CA381157599	146	V>M		No	ClinGen gnomAD
rs1262453471 CA381157857	156	G>D		No	ClinGen gnomAD
rs774847511 CA6075762	157	I>V		No	ClinGen ExAC gnomAD
CA223866312 rs926742511	158	I>V		No	ClinGen Ensembl
rs1338155891 CA381157891	159	Y>D		No	ClinGen TOPMed
CA381157911 rs748593601	160	R>*		No	ClinGen ExAC TOPMed gnomAD
CA6075763 rs748593601	160	R>G		No	ClinGen ExAC TOPMed gnomAD
CA223866325 rs750658903	161	D>H		No	ClinGen Ensembl
rs149154456 CA381157942	162	L>M		No	ClinGen ESP ExAC TOPMed gnomAD
CA381157949 rs1454598017	162	L>Q		No	ClinGen gnomAD
rs761066886 CA6075766	172	E>D		No	ClinGen ExAC gnomAD
CA6075767 rs769380916	175	I>L		No	ClinGen ExAC gnomAD
CA6075771 rs751103067	183	S>G		No	ClinGen ExAC gnomAD
rs761908390 CA6075772	184	K>T		No	ClinGen ExAC gnomAD
CA6075773 rs547821788	185	E>D		No	ClinGen 1000Genomes ExAC gnomAD
CA381159761 rs1471457488	186	F>L		No	ClinGen gnomAD
rs750237150 CA6075774	187	L>P		No	ClinGen ExAC gnomAD
rs561332088 COSM3728278 COSM3728277 CA6075775	188	T>M	haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
CA381159808 rs1471119722	188	T>S		No	ClinGen gnomAD
rs1392451655 CA381159876	190	E>K		No	ClinGen gnomAD
CA223866612 rs143154193	193	R>Q		No	ClinGen ESP TOPMed
rs750338757 CA6075792	193	R>W		No	ClinGen ExAC TOPMed gnomAD
CA6075795 rs551883273	197	F>Y		No	ClinGen 1000Genomes ExAC gnomAD
rs1429343428 CA381160295	202	E>K		No	ClinGen gnomAD
rs779071799 CA6075798	209	I>F		No	ClinGen ExAC gnomAD
rs141880979 CA6075799	210	R>C		No	ClinGen ESP ExAC TOPMed gnomAD
rs565625025 CA6075801	210	R>H		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA6075800 rs565625025	210	R>L		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA6075804 rs781669147	213	T>M		No	ClinGen ExAC TOPMed gnomAD
CA6075824 rs746258369	218	A>S		No	ClinGen ExAC gnomAD
CA381160943 rs1381249006	219	V>M		No	ClinGen gnomAD
CA6075825 rs376465072	221	W>*		No	ClinGen ESP ExAC TOPMed gnomAD
rs1591310792 CA381161059	222	W>G		No	ClinGen Ensembl
CA381161154 rs1317249461	224	L>P		No	ClinGen gnomAD
CA381161140 rs1311706676	224	L>V		No	ClinGen gnomAD
CA223866771 rs61736651	232	L>M		No	ClinGen Ensembl
CA6075827 rs537223935	233	T>M		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs905501710 CA381161346	235	A>P		No	ClinGen TOPMed gnomAD
rs905501710 CA223866785	235	A>T		No	ClinGen TOPMed gnomAD
rs746466314 VAR_040632 COSM642 CA6075830	236	S>L	a breast infiltrating ductal carcinoma sample; somatic mutation breast [UniProt, Cosmic]	No	ClinGen cosmic curated UniProt ExAC TOPMed dbSNP gnomAD
rs1172046742 CA381161557	239	T>I		No	ClinGen TOPMed
rs1410108225 CA381161630	242	G>D		No	ClinGen TOPMed
CA6075832 rs776498965	242	G>S		No	ClinGen ExAC gnomAD
rs764942671 CA6075834	243	E>K		No	ClinGen ExAC gnomAD
rs1179545716 CA381161724	245	N>S		No	ClinGen TOPMed
rs545430280 CA6075835	246	T>M		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA6075837 rs764191979	249	E>D		No	ClinGen ExAC TOPMed gnomAD
rs769176176 CA223866828	250	V>M		No	ClinGen Ensembl
rs1373979853 CA381162002	252	R>*		No	ClinGen gnomAD
CA6075839 rs757236334	252	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA381162194 rs376604355	253	R>G		No	ClinGen ESP TOPMed gnomAD
rs755246792 CA6075864	253	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA223866968 rs376604355	253	R>W		No	ClinGen ESP TOPMed gnomAD
rs1490524789 CA381162214	254	I>V		No	ClinGen TOPMed
CA223866979 rs1030087990	256	K>T		No	ClinGen Ensembl
CA6075867 rs756803659	259	P>H		No	ClinGen ExAC gnomAD
CA6075866 rs751104668	259	P>T		No	ClinGen ExAC gnomAD
rs780738455 CA381162451	260	P>S		No	ClinGen ExAC TOPMed gnomAD
CA6075868 rs780738455	260	P>T		No	ClinGen ExAC TOPMed gnomAD
CA381162484 rs561017906	261	F>I		No	ClinGen 1000Genomes TOPMed gnomAD
rs561017906 CA223867009	261	F>V		No	ClinGen 1000Genomes TOPMed gnomAD
rs1405684525 CA381162545	262	P>L		No	ClinGen TOPMed gnomAD
rs1405684525 CA381162553	262	P>R		No	ClinGen TOPMed gnomAD
CA381162534 rs1369902429	262	P>S		No	ClinGen gnomAD
rs772788703 CA6075870	263	P>A		No	ClinGen ExAC TOPMed gnomAD
CA6075869 rs772788703	263	P>T		No	ClinGen ExAC TOPMed gnomAD
CA6075871 rs779918376	264	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs1348353894 CA381162595	264	R>W		No	ClinGen TOPMed gnomAD
CA381162634 rs138093547	265	I>M		No	ClinGen ESP ExAC TOPMed gnomAD
CA6075873 COSM689715 rs768271371 COSM689716	266	G>R	lung [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs1591311236 CA381162687	267	P>T		No	ClinGen Ensembl
rs1480837394 CA381162748	268	V>G		No	ClinGen TOPMed
COSM1676146 rs762003590 COSM76290 CA6075875	268	V>M	ovary large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA6075876 rs142374327	269	A>V		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1230379380 CA381162805	270	Q>E		No	ClinGen gnomAD
CA223867061 rs760259954	274	Q>E		No	ClinGen gnomAD
rs1449489033 CA381162950	274	Q>R		No	ClinGen gnomAD
rs767012701 CA6075879	275	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA6075878 rs139519834	275	R>W		No	ClinGen ESP ExAC TOPMed gnomAD
rs987918706 CA223867083	276	L>P		No	ClinGen TOPMed
CA6075881 rs759948849	277	L>V		No	ClinGen ExAC gnomAD
CA381163077 rs1359934341	278	C>R		No	ClinGen gnomAD
rs753092734 CA6075883	281	P>T		No	ClinGen ExAC gnomAD
rs367990117 CA6075887	287	A>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs367990117 CA6075888	287	A>T		No	ClinGen ESP ExAC TOPMed gnomAD
rs61736650 CA6075889 RCV000970230	287	A>V		No	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA6075892 rs747947296	291	G>E		No	ClinGen ExAC gnomAD
CA381163499 rs1341577756	292	A>V		No	ClinGen gnomAD
rs772469366 CA6075893	295	V>I		No	ClinGen ExAC gnomAD
rs200299338 CA6075895	296	R>Q		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA6075894 rs773514684	296	R>W		No	ClinGen ExAC gnomAD
rs1480887243 CA381163657	298	H>Q		No	ClinGen TOPMed
rs1423129476 CA381163689	299	P>L		No	ClinGen TOPMed
rs747168125 CA6075913	303	G>V		No	ClinGen ExAC TOPMed gnomAD
rs776640922 CA6075915	305	D>H		No	ClinGen ExAC gnomAD
rs776640922 CA6075916	305	D>N		No	ClinGen ExAC gnomAD
CA6075917 rs770225401	305	D>V		No	ClinGen ExAC gnomAD
rs1276336560 CA381065526	306	W>L		No	ClinGen gnomAD
rs771260141 CA6075919	307	V>E		No	ClinGen ExAC gnomAD
CA6075920 rs764386623	309	L>V		No	ClinGen ExAC gnomAD
rs1383189072 CA381065578	312	R>G		No	ClinGen gnomAD
rs774686500 CA6075921	313	K>Q		No	ClinGen ExAC TOPMed gnomAD
rs201253556 CA6075923	315	P>L		No	ClinGen 1000Genomes ExAC
rs760389975 CA6075922	315	P>S		No	ClinGen ExAC gnomAD
CA381065642 rs1378452659	318	F>I		No	ClinGen gnomAD
rs754458110 CA6075925	319	R>W		No	ClinGen ExAC TOPMed gnomAD
rs765113912 CA6075926	320	P>H		No	ClinGen ExAC TOPMed gnomAD
CA381065681 rs1402118908	321	Q>P		No	ClinGen gnomAD
CA381065701 rs1447050686	323	R>C		No	ClinGen TOPMed gnomAD
CA223829693 rs752611628	323	R>H		No	ClinGen ExAC TOPMed gnomAD
rs752611628 CA6075927	323	R>L		No	ClinGen ExAC TOPMed gnomAD
CA6075928 rs148763785	326	L>V		No	ClinGen ESP ExAC TOPMed gnomAD
rs777766293 CA6075929	329	G>S		No	ClinGen ExAC TOPMed gnomAD
rs780739331 CA223829695	331	F>S		No	ClinGen Ensembl
CA6075930 rs751393577	332	A>V		No	ClinGen ExAC TOPMed gnomAD
CA6075933 rs144792776	336	T>I		No	ClinGen ESP ExAC gnomAD
rs1591314389 CA381065842	336	T>P		No	ClinGen Ensembl
rs780440960 CA6075935	337	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs746182941 CA223829697	337	R>W		No	ClinGen TOPMed gnomAD
CA6075936 rs749853745	338	L>V		No	ClinGen ExAC TOPMed gnomAD
rs1370463382 CA381065856	339	E>K		No	ClinGen TOPMed
rs951024884 CA223829706	344	P>L		No	ClinGen gnomAD
CA381065915 rs1196829024	345	P>T		No	ClinGen gnomAD
CA223829709 rs868566063	347	S>N		No	ClinGen Ensembl
rs1450606547 CA381065938	347	S>R		No	ClinGen gnomAD
CA381065949 rs774741441	347	S>R		No	ClinGen ExAC TOPMed gnomAD
CA381065952 rs1429436804	348	P>H		No	ClinGen gnomAD
rs374065485 CA6075939	348	P>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA6075941 rs200447389	349	P>L		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs200447389 CA6075940	349	P>Q		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs200447389 CA223829715	349	P>R		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA6075943 rs141809902	350	P>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA6075942 rs758970427	350	P>S		No	ClinGen ExAC gnomAD
rs752239607 CA381065986	352	D>E		No	ClinGen ExAC TOPMed gnomAD
rs1591314505 CA381065983	352	D>G		No	ClinGen Ensembl
COSM3666507 CA381066006 COSM3666506 rs145356210	354	R>L	liver [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
CA6075946 rs145356210	354	R>Q		No	ClinGen ESP ExAC TOPMed gnomAD
rs751448590 CA6075947	355	I>M		No	ClinGen ExAC gnomAD
rs767405530 CA6075966	358	G>R		No	ClinGen ExAC gnomAD
rs1182908241 CA381066737	362	V>L		No	ClinGen gnomAD
rs1258902660 CA381066760	364	P>S		No	ClinGen TOPMed gnomAD
CA6075967 rs757849416	365	S>A		No	ClinGen ExAC TOPMed gnomAD
CA381066779 rs1187689165	365	S>F		No	ClinGen gnomAD
CA6075968 rs756402058	366	I>V		No	ClinGen ExAC gnomAD
CA381066875 rs1457498232	371	N>S		No	ClinGen gnomAD
CA6075970 rs753939915	373	A>P		No	ClinGen ExAC TOPMed gnomAD
CA381066898 rs753939915	373	A>T		No	ClinGen ExAC TOPMed gnomAD
CA6075972 rs779393153	376	T>I		No	ClinGen ExAC TOPMed gnomAD
rs1292506720 CA381066957	377	D>G		No	ClinGen gnomAD
CA381066951 rs1394062340	377	D>Y		No	ClinGen gnomAD
rs1351312231 CA381066965	378	G>R		No	ClinGen gnomAD
rs112357475 CA223830403	379	L>P		No	ClinGen Ensembl
CA6075975 rs778265336	380	E>V		No	ClinGen ExAC
CA223830405 rs199836004	381	A>V		No	ClinGen 1000Genomes
rs769619036 CA6075977	382	P>A		No	ClinGen ExAC gnomAD
rs1348207276 CA381067042	384	A>T		No	ClinGen TOPMed
CA381067070 rs1258214116	386	D>G		No	ClinGen gnomAD
CA6075979 rs368450242	387	R>Q		No	ClinGen ESP ExAC TOPMed gnomAD
CA6075978 rs151034403	387	R>W		No	ClinGen ESP ExAC TOPMed gnomAD
rs768224928 CA6075980	390	R>G		No	ClinGen ExAC gnomAD
rs1183849913 CA381067112	390	R>Q		No	ClinGen TOPMed gnomAD
CA381067206 rs1176235771	395	R>S		No	ClinGen gnomAD
rs1360811119 CA381067224	397	A>T		No	ClinGen gnomAD
CA381067234 rs1464523089	397	A>V		No	ClinGen gnomAD
rs1312009585 CA381067284	399	M>I		No	ClinGen gnomAD
CA381067472 rs1221790001	402	S>L		No	ClinGen gnomAD
rs1183864197 CA381067539	405	F>V		No	ClinGen TOPMed
rs568222796 CA6076007	406	Q>R		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA381067634 rs1591317924	407	Q>H		No	ClinGen Ensembl
rs1358883814 CA381067651	408	Y>S		No	ClinGen gnomAD
rs1451318965 CA381067673	409	E>K		No	ClinGen gnomAD
CA6076009 rs772065473	413	R>W		No	ClinGen ExAC TOPMed gnomAD
rs905604419 CA381067769	415	P>A		No	ClinGen Ensembl
rs905604419 CA223830519	415	P>S		No	ClinGen Ensembl
CA381067889 rs1167125963	421	S>N		No	ClinGen gnomAD
CA381067938 rs1320316259	423	S>F		No	ClinGen TOPMed
CA381067941 rs1392576844	424	V>M		No	ClinGen gnomAD
rs1440181729 CA381067984	426	R>C		No	ClinGen gnomAD
CA6076010 rs772979035	427	R>C		No	ClinGen ExAC gnomAD
CA6076011 rs199674030	427	R>H		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1330641044 CA381068048	428	C>F		No	ClinGen gnomAD
rs142633104 CA381068071	429	R>L		No	ClinGen gnomAD
CA223830521 rs142633104	429	R>P		No	ClinGen gnomAD
rs1380280944 CA381068104	431	R>C		No	ClinGen gnomAD
CA381068172 rs1591318030	432	Q>H		No	ClinGen Ensembl
rs1397460841 CA381068164	432	Q>R		No	ClinGen TOPMed
rs1379442123 CA381068194	433	S>N		No	ClinGen TOPMed
rs144214742 CA223830524	435	Q>H		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs144214742 CA381068246	435	Q>H		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1230400460 CA381068240	435	Q>R		No	ClinGen gnomAD
rs1281800303 CA381068250	436	E>K		No	ClinGen gnomAD
rs1331977876 CA381068298	438	A>E		No	ClinGen TOPMed
CA6076014 rs759823850	438	A>S		No	ClinGen ExAC gnomAD
CA381068394 rs1366537542	442	L>F		No	ClinGen TOPMed
CA381068443 rs1239878372	444	R>C		No	ClinGen gnomAD
CA381068440 rs1239878372	444	R>G		No	ClinGen gnomAD
CA381068641 rs1172263382	445	R>S		No	ClinGen gnomAD
CA381068729 rs1395024381	448	A>V		No	ClinGen gnomAD
CA6076046 rs777217932	450	T>M		No	ClinGen ExAC TOPMed gnomAD
CA381068793 rs1446769146	451	Q>E		No	ClinGen gnomAD
CA381068817 rs1170953272	452	R>C		No	ClinGen gnomAD
rs1398172112 CA381068818	452	R>H		No	ClinGen gnomAD
CA223830593 rs868709887	454	V>A		No	ClinGen Ensembl
rs746494252 CA6076047	456	A>G		No	ClinGen ExAC gnomAD
CA381068900 rs1307528142	457	L>V		No	ClinGen gnomAD
rs770905584 CA6076048	458	R>C		No	ClinGen ExAC gnomAD
CA6076049 rs371615792	458	R>H		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA6076050 rs745695509	462	S>*		No	ClinGen ExAC TOPMed
rs1347144121 CA381069000	466	V>M		No	ClinGen gnomAD
rs1228851069 CA381069007	467	V>M		No	ClinGen gnomAD
CA381069022 rs1265697275	468	N>Y		No	ClinGen gnomAD
CA381069062 rs1252902389	470	H>Q		No	ClinGen gnomAD
CA223830600 rs865818619	474	H>N		No	ClinGen Ensembl
rs769409471 CA381069145	474	H>Q		No	ClinGen ExAC TOPMed gnomAD
rs769409471 CA381069146	474	H>Q		No	ClinGen ExAC TOPMed gnomAD
CA381069175 rs1195406507	476	Q>E		No	ClinGen gnomAD
CA223830899 rs559409352	479	T>M		No	ClinGen 1000Genomes TOPMed gnomAD
rs1416733757 CA381070746	481	L>P		No	ClinGen gnomAD
CA381070793 rs1361985675	484	E>D		No	ClinGen gnomAD
rs749917386 CA6076085	487	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs767081339 CA6076084	487	R>W		No	ClinGen ExAC gnomAD
CA223830908 rs893218751	489	G>R		No	ClinGen gnomAD
rs1295058694 CA381070896	492	L>P		No	ClinGen TOPMed
rs1033677759 CA223830910	494	H>Y		No	ClinGen TOPMed gnomAD
rs756054451 CA6076086	496	R>C		No	ClinGen ExAC TOPMed gnomAD
rs779990907 CA6076087	496	R>L		No	ClinGen ExAC gnomAD
rs749066246 CA6076088	498	K>T		No	ClinGen ExAC gnomAD
rs1234553487 CA381071011	499	R>P		No	ClinGen TOPMed gnomAD
rs1234553487 CA381071008	499	R>Q		No	ClinGen TOPMed gnomAD
rs1157020356 CA381071005	499	R>W		No	ClinGen TOPMed
CA381071130 rs1480788742	504	S>L		No	ClinGen gnomAD
rs1034712821 CA223830924	509	I>V		No	ClinGen Ensembl
rs1174133485 CA381071220	511	R>C		No	ClinGen gnomAD
CA6076094 rs372901217	511	R>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA6076098 rs759826654	515	S>L		No	ClinGen ExAC TOPMed gnomAD
CA381071274 COSM1355706 COSM1355707 rs1372636808	517	V>M	large_intestine [Cosmic]	No	ClinGen cosmic curated gnomAD
CA381071282 rs1387440651	518	S>T		No	ClinGen gnomAD
CA223830940 rs369855912	520	M>I		No	ClinGen ESP TOPMed gnomAD
CA6076099 rs190425139	520	M>L		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs375458215 CA223830938	520	M>T		No	ClinGen ESP gnomAD
CA381071301 rs1275863869	521	H>Y		No	ClinGen gnomAD
CA6076101 rs775819303	522	E>K		No	ClinGen ExAC gnomAD
CA6076100 rs775819303	522	E>Q		No	ClinGen ExAC gnomAD
CA223830944 rs370422690	524	A>V		No	ClinGen gnomAD
rs767134558 CA6076102	526	V>L		No	ClinGen ExAC gnomAD
CA381071334 rs767134558	526	V>M		No	ClinGen ExAC gnomAD
CA6076104 rs760190325	531	L>I		No	ClinGen ExAC gnomAD
rs1312916143 CA381071382	532	K>*		No	ClinGen gnomAD
CA223830985 rs914558358	540	D>E		No	ClinGen Ensembl
rs752564591 CA6076130	540	D>N		No	ClinGen ExAC gnomAD
CA223830987 rs946014920	541	D>G		No	ClinGen TOPMed gnomAD
rs1339408476 CA381071523	541	D>N		No	ClinGen TOPMed gnomAD
CA381071529 rs946014920	541	D>V		No	ClinGen TOPMed gnomAD
rs1339408476 CA381071525	541	D>Y		No	ClinGen TOPMed gnomAD
rs777863280 CA6076132	543	P>S		No	ClinGen ExAC gnomAD
rs1422279060 CA381071559	544	G>E		No	ClinGen gnomAD
CA381071556 rs1284865222	544	G>R		No	ClinGen gnomAD
rs1448724977 CA381071573	545	A>V		No	ClinGen gnomAD
rs781399940 CA6076135	547	V>A		No	ClinGen ExAC gnomAD
CA223830996 rs867799091	553	G>V		No	ClinGen Ensembl
CA381071683 rs1410769083	555	A>T		No	ClinGen gnomAD
rs1318280282 CA381071698	556	R>L		No	ClinGen gnomAD
CA381071692 rs1465545014	556	R>W		No	ClinGen TOPMed
CA381071739 rs774562817	559	P>L		No	ClinGen ExAC gnomAD
CA6076141 rs774562817	559	P>Q		No	ClinGen ExAC gnomAD
rs565756385 CA6076140	559	P>S		No	ClinGen 1000Genomes ExAC gnomAD
CA381071757 rs1353251077	560	Q>H		No	ClinGen gnomAD
CA381071781 rs1398636953	562	P>S		No	ClinGen TOPMed
CA223831006 rs907280871	564	V>L		No	ClinGen TOPMed gnomAD
CA6076144 rs776257181	565	P>S		No	ClinGen ExAC TOPMed gnomAD
rs765300511 CA6076146	566	M>T		No	ClinGen ExAC gnomAD
CA381071876 rs1212766689	568	T>K		No	ClinGen gnomAD
rs1485494116 CA381071883	569	P>T		No	ClinGen gnomAD
rs775503713 CA6076147	571	F>Y		No	ClinGen ExAC TOPMed gnomAD
rs1244409522 CA381072016	577	A>V		No	ClinGen TOPMed
COSM930106 COSM930107 CA381072034 rs1396215443	579	E>K	endometrium [Cosmic]	No	ClinGen cosmic curated gnomAD
CA381072086 rs1373217672	582	A>S		No	ClinGen gnomAD
CA6076151 rs757547013	584	Q>R		No	ClinGen ExAC TOPMed gnomAD
rs750531289 CA6076153	588	E>Q		No	ClinGen ExAC TOPMed gnomAD
CA381072210 rs1242846017	588	E>V		No	ClinGen TOPMed
rs1277967478 CA381072285	592	L>V		No	ClinGen gnomAD
rs1196552562 CA381072315	593	W>R		No	ClinGen gnomAD
CA6076156 rs749850019	593	W>S		No	ClinGen ExAC gnomAD
CA381072358 rs1436083596	594	S>I		No	ClinGen gnomAD
CA381072478 rs1254160868	599	L>V		No	ClinGen gnomAD
rs767781874 CA6076171	602	M>I		No	ClinGen ExAC gnomAD
CA381072741 rs1441850972	604	S>L		No	ClinGen TOPMed
rs1441850972 CA381072739	604	S>W		No	ClinGen TOPMed
rs1324782839 CA381072752	605	G>E		No	ClinGen TOPMed
CA381072792 rs1217714007	608	P>H		No	ClinGen TOPMed
CA6076175 rs753880345	611	G>R		No	ClinGen ExAC gnomAD
CA6076176 rs755555210	611	G>V		No	ClinGen ExAC gnomAD
CA6076178 rs753141796	612	A>S		No	ClinGen ExAC TOPMed gnomAD
CA223831102 rs1003600611	616	G>V		No	ClinGen TOPMed
rs201085797 CA6076179	617	G>R		No	ClinGen ExAC TOPMed gnomAD
rs201085797 CA381072953	617	G>W		No	ClinGen ExAC TOPMed gnomAD
CA381073049 rs1488188178	621	A>T		No	ClinGen gnomAD
CA381073103 rs1176040217	623	E>D		No	ClinGen gnomAD
rs1169689830 CA381073133	625	M>T		No	ClinGen TOPMed
CA381073148 rs1475895833	626	C>Y		No	ClinGen gnomAD
CA381073157 rs1162255066	627	K>E		No	ClinGen gnomAD
CA381073194 rs779751342	629	R>H		No	ClinGen ExAC TOPMed gnomAD
CA6076183 rs779751342	629	R>L		No	ClinGen ExAC TOPMed gnomAD
rs200894902 CA381073202	630	E>K		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs200894902 CA6076185	630	E>Q		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs774087398 CA6076186	632	R>C		No	ClinGen ExAC TOPMed gnomAD
rs1462155407 COSM1636986 CA381073233 COSM1636987	632	R>H	bone [Cosmic]	No	ClinGen cosmic curated TOPMed
rs774087398 CA381073229	632	R>S		No	ClinGen ExAC TOPMed gnomAD
CA6076188 rs771817507	634	S>F		No	ClinGen ExAC gnomAD
rs1317621508 CA381073311	636	D>E		No	ClinGen gnomAD
CA6076190 rs146485043	636	D>Y		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1241759385 CA381073327	637	G>A		No	ClinGen gnomAD
COSM1355709 COSM1355708 rs1565074849 CA381073317	637	G>R	large_intestine [Cosmic]	No	ClinGen cosmic curated Ensembl
CA381073345 rs1309583390	638	E>A		No	ClinGen TOPMed
CA6076192 rs753939688	639	A>S		No	ClinGen ExAC gnomAD
CA381073355 rs753939688	639	A>T		No	ClinGen ExAC gnomAD
CA6076196 rs758931204	645	E>A		No	ClinGen ExAC gnomAD
CA6076195 rs753090599	645	E>K		No	ClinGen ExAC gnomAD
rs1419182914 CA381073495	647	A>V		No	ClinGen gnomAD
rs142345188 CA223831104	648	K>R		No	ClinGen Ensembl
rs1029921176 CA223831105	649	E>K		No	ClinGen Ensembl
rs778349519 CA6076197	650	L>V		No	ClinGen ExAC gnomAD
CA381073523 rs1418849349	651	V>I		No	ClinGen gnomAD
rs751943246 CA6076198	652	R>G		No	ClinGen ExAC gnomAD
COSM1355713 COSM1355712 CA6076199 rs755881487	652	R>Q	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs907434307 CA223831117	657	V>A		No	ClinGen TOPMed
rs1042013912 CA381073608	657	V>L		No	ClinGen TOPMed gnomAD
rs1042013912 CA381073609	657	V>L		No	ClinGen TOPMed gnomAD
rs1042013912 CA223831116	657	V>M		No	ClinGen TOPMed gnomAD
CA381073628 rs753491076	658	D>E		No	ClinGen ExAC gnomAD
CA223831118 rs372267009	660	A>D		No	ClinGen TOPMed
CA381073661 rs372267009	660	A>V		No	ClinGen TOPMed
CA381073698 rs1190984898	662	R>Q		No	ClinGen TOPMed
CA381073737 rs1430570360	665	L>V		No	ClinGen gnomAD
CA381073757 rs1266358650	666	E>Q		No	ClinGen TOPMed
CA381073782 rs1422959153	667	G>R		No	ClinGen gnomAD
rs777650305 CA6076223	669	R>Q		No	ClinGen ExAC gnomAD
CA381073825 rs1328444508	669	R>W		No	ClinGen gnomAD
rs566414593 CA6076224	671	S>R		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs776476997 CA6076226	673	W>G		No	ClinGen ExAC
rs770027305 CA6076228	674	L>Q		No	ClinGen ExAC TOPMed gnomAD
CA381073973 rs1275923269	676	D>H		No	ClinGen gnomAD
CA381074042 rs1449835853	679	A>V		No	ClinGen gnomAD
rs1242437574 CA381074045	680	R>C		No	ClinGen gnomAD
rs1486743665 CA381074055	680	R>P		No	ClinGen gnomAD
rs1475568224 CA381074101	683	P>R		No	ClinGen gnomAD
rs763078981 CA6076230	683	P>T		No	ClinGen ExAC TOPMed gnomAD
COSM394615 CA6076231 COSM394614 rs764701644	684	P>L	lung [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs764701644 CA6076232	684	P>R		No	ClinGen ExAC TOPMed gnomAD
rs1412221175 CA381074111	684	P>S		No	ClinGen gnomAD
CA381074137 rs1398560402	686	R>Q		No	ClinGen gnomAD
rs762396567 CA6076233	686	R>W		No	ClinGen ExAC gnomAD
CA381074167 rs1339519954	688	P>S		No	ClinGen gnomAD
CA381074198 rs1353671388	689	D>E		No	ClinGen gnomAD
CA6076238 rs752176858	689	D>N		No	ClinGen ExAC gnomAD
rs757839757 CA6076239	690	V>M		No	ClinGen ExAC TOPMed gnomAD
rs966333030 CA223831122	693	S>C		No	ClinGen TOPMed gnomAD
rs747011048 CA6076241	694	S>F		No	ClinGen ExAC gnomAD
rs757185670 CA6076242	696	P>L		No	ClinGen ExAC gnomAD
rs1017388898 CA223831124	697	A>S		No	ClinGen gnomAD
CA381074259 rs1017388898	697	A>T		No	ClinGen gnomAD
rs1455350613 CA381074286	699	R>H		No	ClinGen TOPMed
rs1472525320 CA381074298	701	G>R		No	ClinGen gnomAD
rs1472525320 CA381074297	701	G>S		No	ClinGen gnomAD
CA6076245 rs769932538	702	L>V		No	ClinGen ExAC gnomAD
CA381074317 rs1418251990	704	A>T		No	ClinGen gnomAD
CA381074338 rs1335815556	707	M>K		No	ClinGen gnomAD
rs374804549 CA6076248	707	M>L		No	ClinGen ESP ExAC TOPMed gnomAD
rs1344632464 CA381074451	710	N>S		No	ClinGen gnomAD
rs1260024144 CA381074464	711	R>Q		No	ClinGen gnomAD
rs548831584 CA6076269	711	R>W		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA223831266 rs901715491	714	R>Q		No	ClinGen TOPMed gnomAD
CA223831264 rs568464055	714	R>W		No	ClinGen 1000Genomes TOPMed
CA381074539 rs1197280301	717	F>L		No	ClinGen gnomAD
rs902255820 CA223831270	722	V>M		No	ClinGen Ensembl
CA6076274 rs762637985	725	A>T		No	ClinGen ExAC gnomAD
rs1463606947 CA381074655	727	L>P		No	ClinGen TOPMed gnomAD
rs1463606947 CA381074654	727	L>R		No	ClinGen TOPMed gnomAD
CA381074687 rs1395218082	730	R>Q		No	ClinGen gnomAD
CA6076276 rs751093165	731	R>G		No	ClinGen ExAC
rs1388266879 CA381074695	731	R>Q		No	ClinGen gnomAD
rs761347218 CA381074753	736	R>L		No	ClinGen ExAC TOPMed gnomAD
rs761347218 CA6076277	736	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA381074749 rs1321401996	736	R>W		No	ClinGen gnomAD
rs767367328 CA381074765	737	S>R		No	ClinGen ExAC TOPMed gnomAD
rs761843231 CA223831275	738	A>P		No	ClinGen ExAC TOPMed gnomAD
CA6076279 rs761843231	738	A>T		No	ClinGen ExAC TOPMed gnomAD
rs780033520 CA381074784	740	A>S		No	ClinGen ExAC TOPMed gnomAD
CA6076281 rs780033520	740	A>T		No	ClinGen ExAC TOPMed gnomAD
CA381074792 rs755269861	741	S>F		No	ClinGen ExAC gnomAD
rs755269861 CA6076283	741	S>Y		No	ClinGen ExAC gnomAD
CA6076284 rs779234584	742	R>C		No	ClinGen ExAC TOPMed gnomAD
CA223831280 rs111697527	742	R>L		No	ClinGen gnomAD
CA381074800 rs1221879191	743	R>Q		No	ClinGen TOPMed
rs1264895487 CA381074802	744	G>S		No	ClinGen gnomAD
rs772135024 CA381074814	746	P>A		No	ClinGen ExAC TOPMed gnomAD
CA6076286 rs772135024	746	P>T		No	ClinGen ExAC TOPMed gnomAD
rs777705512 CA6076287	747	A>P		No	ClinGen ExAC TOPMed gnomAD
CA6076288 rs777705512	747	A>S		No	ClinGen ExAC TOPMed gnomAD
rs1459338472 CA381074830	747	A>V		No	ClinGen gnomAD
CA381074835 rs1565075884	748	P>S		No	ClinGen Ensembl
rs771314909 CA6076289	749	A>V		No	ClinGen ExAC gnomAD
CA6076290 rs749499893	750	N>T		No	ClinGen ExAC gnomAD
CA381074873 rs1382584499	751	P>L		No	ClinGen gnomAD
rs768330809 CA6076292	752	G>S		No	ClinGen ExAC TOPMed gnomAD
rs889008728 CA223831293	753	R>Q		No	ClinGen TOPMed gnomAD
CA6076293 rs773928869	754	A>S		No	ClinGen ExAC TOPMed gnomAD
rs773928869 CA223831295	754	A>T		No	ClinGen ExAC TOPMed gnomAD
rs761356018 CA6076294	754	A>V		No	ClinGen ExAC gnomAD
CA6076297 rs200411554	756	V>I		No	ClinGen ExAC gnomAD
rs1192515568 CA381074968	757	A>S		No	ClinGen TOPMed gnomAD
rs1192515568 CA381074964	757	A>T		No	ClinGen TOPMed gnomAD
VAR_040633 rs17857342 CA6076302	758	S>A		No	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs17857342 CA6076303	758	S>P		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA6076304 rs758548221	759	K>T		No	ClinGen ExAC gnomAD
rs757804588 CA381075912	761	A>D		No	ClinGen ExAC gnomAD
rs747042462 CA6076307	761	A>P		No	ClinGen ExAC TOPMed
rs757804588 CA6076308	761	A>V		No	ClinGen ExAC gnomAD
CA6076309 rs781635747	762	P>L		No	ClinGen ExAC
CA223831323 rs950765689	762	P>S		No	ClinGen TOPMed gnomAD
CA381075927 rs770200186	763	R>C		No	ClinGen ExAC TOPMed gnomAD
CA381075928 rs1313744795	763	R>H		No	ClinGen gnomAD
CA381075932 rs1313744795	763	R>L		No	ClinGen gnomAD
CA381075930 rs1313744795	763	R>P		No	ClinGen gnomAD
rs770200186 CA6076311	763	R>S		No	ClinGen ExAC TOPMed gnomAD
rs747874901 CA381075935	764	R>*		No	ClinGen ExAC TOPMed
rs1268525057 CA381075938	764	R>P		No	ClinGen TOPMed
rs1268525057 CA381075937	764	R>Q		No	ClinGen TOPMed
rs1222604582 CA381075950	765	A>V		No	ClinGen TOPMed
rs1591323222 CA381075953	766	N>H		No	ClinGen Ensembl
rs772796720 CA6076315	766	N>S		No	ClinGen ExAC gnomAD
CA6076316 rs760060325	767	G>S		No	ClinGen ExAC TOPMed gnomAD
rs766421645 CA6076317	768	P>S		No	ClinGen ExAC gnomAD
rs1310621541 CA381075988	769	L>P		No	ClinGen TOPMed gnomAD
rs759536028 CA6076319	770	P>H		No	ClinGen ExAC gnomAD
rs776650038 CA6076318	770	P>S		No	ClinGen ExAC TOPMed gnomAD
rs1199762712 CA381076006	771	P>R		No	ClinGen gnomAD
CA381076020 rs1256240522	772	S>F		No	ClinGen TOPMed gnomAD
CA223831339 rs1011966004	772	S>P		No	ClinGen TOPMed gnomAD
rs1256240522 CA381076018	772	S>Y		No	ClinGen TOPMed gnomAD
CA381076022 rs1456668308	773	S>Q		No	ClinGen gnomAD
rs1483940507 CA381076025	773	S>S		No	ClinGen gnomAD

No associated diseases with O75676

9 regional properties for O75676

Type	Name	Position	InterPro Accession
domain	Protein kinase domain	33 - 301	IPR000719-1
domain	Protein kinase domain	411 - 674	IPR000719-2
domain	AGC-kinase, C-terminal	302 - 371	IPR000961
active_site	Serine/threonine-protein kinase, active site	157 - 169	IPR008271-1
active_site	Serine/threonine-protein kinase, active site	526 - 538	IPR008271-2
binding_site	Protein kinase, ATP binding site	39 - 65	IPR017441-1
binding_site	Protein kinase, ATP binding site	417 - 440	IPR017441-2
domain	Protein kinase, C-terminal	322 - 361	IPR017892
domain	MSK2, N-terminal catalytic domain	32 - 364	IPR037714

Functions

		Description
EC Number	2.7.11.1	Protein-serine/threonine kinases
Subcellular Localization	Nucleus
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

4 GO annotations of cellular component

Name	Definition
cytoplasm	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
nucleoplasm	That part of the nuclear content other than the chromosomes or the nucleolus.
nucleus	A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.

6 GO annotations of molecular function

Name	Definition
ATP binding	Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
magnesium ion binding	Binding to a magnesium (Mg) ion.
protein serine kinase activity	Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate.
protein serine/threonine kinase activity	Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate.
protein serine/threonine/tyrosine kinase activity	Catalysis of the reactions: ATP + a protein serine = ADP + protein serine phosphate; ATP + a protein threonine = ADP + protein threonine phosphate; and ATP + a protein tyrosine = ADP + protein tyrosine phosphate.
ribosomal protein S6 kinase activity	Catalysis of the reaction: ribosomal protein S6 + ATP = ribosomal protein S6 phosphate + ATP.

15 GO annotations of biological process

Name	Definition
histone H3-S10 phosphorylation	OBSOLETE. The modification of histone H3 by the addition of an phosphate group to a serine residue at position 10 of the histone.
histone H3-S28 phosphorylation	OBSOLETE. The modification of histone H3 by the addition of an phosphate group to a serine residue at position 28 of the histone.
histone phosphorylation	OBSOLETE. The modification of histones by addition of phosphate groups.
inflammatory response	The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages.
interleukin-1-mediated signaling pathway	The series of molecular signals initiated by interleukin-1 binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
intracellular signal transduction	The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell.
negative regulation of cytokine production	Any process that stops, prevents, or reduces the rate of production of a cytokine.
peptidyl-serine phosphorylation	The phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine.
positive regulation of CREB transcription factor activity	Any process that activates or increases the frequency, rate or extent of activity of the transcription factor CREB.
positive regulation of histone acetylation	Any process that activates or increases the frequency, rate or extent of the addition of an acetyl group to a histone protein.
positive regulation of histone phosphorylation	OBSOLETE. Any process that activates or increases the frequency, rate or extent of the addition of one or more phosphate groups to a histone protein.
positive regulation of NF-kappaB transcription factor activity	Any process that activates or increases the frequency, rate or extent of activity of the transcription factor NF-kappaB.
positive regulation of transcription by RNA polymerase II	Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter.
protein phosphorylation	The process of introducing a phosphate group on to a protein.
regulation of transcription, DNA-templated	Any process that modulates the frequency, rate or extent of cellular DNA-templated transcription.

19 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
P18652	RPS6KA	Ribosomal protein S6 kinase 2 alpha	Gallus gallus (Chicken)	SS
Q5F3L1	RPS6KA5	Ribosomal protein S6 kinase alpha-5	Gallus gallus (Chicken)	SS
Q96S38	RPS6KC1	Ribosomal protein S6 kinase delta-1	Homo sapiens (Human)	PR
Q15349	RPS6KA2	Ribosomal protein S6 kinase alpha-2	Homo sapiens (Human)	SS
Q15418	RPS6KA1	Ribosomal protein S6 kinase alpha-1	Homo sapiens (Human)	EV
Q9UK32	RPS6KA6	Ribosomal protein S6 kinase alpha-6	Homo sapiens (Human)	SS
P51812	RPS6KA3	Ribosomal protein S6 kinase alpha-3	Homo sapiens (Human)	EV
O75582	RPS6KA5	Ribosomal protein S6 kinase alpha-5	Homo sapiens (Human)	SS
Q9UBS0	RPS6KB2	Ribosomal protein S6 kinase beta-2	Homo sapiens (Human)	PR
P23443	RPS6KB1	Ribosomal protein S6 kinase beta-1	Homo sapiens (Human)	EV SS
Q9WUT3	Rps6ka2	Ribosomal protein S6 kinase alpha-2	Mus musculus (Mouse)	SS
P18654	Rps6ka3	Ribosomal protein S6 kinase alpha-3	Mus musculus (Mouse)	SS
Q8C050	Rps6ka5	Ribosomal protein S6 kinase alpha-5	Mus musculus (Mouse)	PR
Q8BLK9	Rps6kc1	Ribosomal protein S6 kinase delta-1	Mus musculus (Mouse)	PR
P18653	Rps6ka1	Ribosomal protein S6 kinase alpha-1	Mus musculus (Mouse)	SS
Q9Z2B9	Rps6ka4	Ribosomal protein S6 kinase alpha-4	Mus musculus (Mouse)	SS
Q63531	Rps6ka1	Ribosomal protein S6 kinase alpha-1	Rattus norvegicus (Rat)	SS
Q21734	rskn-1	Putative ribosomal protein S6 kinase alpha-1	Caenorhabditis elegans	SS
Q18846	rskn-2	Putative ribosomal protein S6 kinase alpha-2	Caenorhabditis elegans	PR

10	20	30	40	50	60
MGDEDDDESC	AVELRITEAN	LTGHEEKVSV	ENFELLKVLG	TGAYGKVFLV	RKAGGHDAGK
70	80	90	100	110	120
LYAMKVLRKA	ALVQRAKTQE	HTRTERSVLE	LVRQAPFLVT	LHYAFQTDAK	LHLILDYVSG
130	140	150	160	170	180
GEMFTHLYQR	QYFKEAEVRV	YGGEIVLALE	HLHKLGIIYR	DLKLENVLLD	SEGHIVLTDF
190	200	210	220	230	240
GLSKEFLTEE	KERTFSFCGT	IEYMAPEIIR	SKTGHGKAVD	WWSLGILLFE	LLTGASPFTL
250	260	270	280	290	300
EGERNTQAEV	SRRILKCSPP	FPPRIGPVAQ	DLLQRLLCKD	PKKRLGAGPQ	GAQEVRNHPF
310	320	330	340	350	360
FQGLDWVALA	ARKIPAPFRP	QIRSELDVGN	FAEEFTRLEP	VYSPPGSPPP	GDPRIFQGYS
370	380	390	400	410	420
FVAPSILFDH	NNAVMTDGLE	APGAGDRPGR	AAVARSAMMQ	DSPFFQQYEL	DLREPALGQG
430	440	450	460	470	480
SFSVCRRCRQ	RQSGQEFAVK	ILSRRLEANT	QREVAALRLC	QSHPNVVNLH	EVHHDQLHTY
490	500	510	520	530	540
LVLELLRGGE	LLEHIRKKRH	FSESEASQIL	RSLVSAVSFM	HEEAGVVHRD	LKPENILYAD
550	560	570	580	590	600
DTPGAPVKII	DFGFARLRPQ	SPGVPMQTPC	FTLQYAAPEL	LAQQGYDESC	DLWSLGVILY
610	620	630	640	650	660
MMLSGQVPFQ	GASGQGGQSQ	AAEIMCKIRE	GRFSLDGEAW	QGVSEEAKEL	VRGLLTVDPA
670	680	690	700	710	720
KRLKLEGLRG	SSWLQDGSAR	SSPPLRTPDV	LESSGPAVRS	GLNATFMAFN	RGKREGFFLK
730	740	750	760	770
SVENAPLAKR	RKQKLRSATA	SRRGSPAPAN	PGRAPVASKG	APRRANGPLP	PS