AiPD: Autoinhibited Protein Database

Q15349

Gene name	RPS6KA2 (MAPKAPK1C, RSK3)
Protein name	Ribosomal protein S6 kinase alpha-2
Names	S6K-alpha-2, 90 kDa ribosomal protein S6 kinase 2, p90-RSK 2, p90RSK2, MAP kinase-activated protein kinase 1c, MAPK-activated protein kinase 1c, MAPKAP kinase 1c, MAPKAPK-1c, Ribosomal S6 kinase 3, RSK-3, pp90RSK3
Species	Homo sapiens (Human)
KEGG Pathway	hsa:6196
EC number	2.7.11.1: Protein-serine/threonine kinases
Protein Class

Descriptions

RSK3 shares significant homology with other RSK isoforms throughout both kinase catalytic domains; however, RSK3 is structurally distinct from the other RSKs in which it has a different 33-amino-acid N-terminal domain that contains a nuclear localization sequence. RSK3 translocates to the nucleus of HeLa cells arrested in G0/G1 transition and phosphorylates nuclear proteins such as c-Fos and histones.
All four RSKs contain two catalytic domains, N-terminal kinase domain (NTKD) and C-terminal kinase domain (CTKD). In inactive RSK, the CTKD binds the autoinhibitory domain α-helix. When activated, ERK prebound to the ERK binding domain (D-domain) phosphorylates RSK residues, including the CTKD activation loop (T570). The CTKD then autophosphorylates S377, permitting PDK1 binding and phosphorylation of the NTKD activation loop (S218). The NTKD then phosphorylates RSK substrates.

Autoinhibitory domains (AIDs)

686-703 (αL-helix) SS

Target domain	411-703 (C-terminal catalytic domain)
Relief mechanism	PTM
Assay

AID

686-703 (αL-helix)

Target domain

411-703 (C-terminal catalytic domain)

Relief mechanism

PTM (Phosphorylation of CTKD activation loop by ERK)

Assay

Accessory elements

201-224 (Activation loop from InterPro)

Target domain	59-318 (Protein kinase domain)
Relief mechanism
Assay

553-576 (Activation loop from InterPro)

Target domain	411-703 (C-terminal catalytic domain)
Relief mechanism
Assay

References

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

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

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

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

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. (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 Q15349

Entry ID	Method	Resolution	Chain	Position	Source
AF-Q15349-F1	Predicted				AlphaFoldDB

525 variants for Q15349

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
RCV001291500 rs1254821821 CA366397821	566	G>R	Autism spectrum disorder [ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP
CA366486760 rs1368149067	2	D>E		No	ClinGen gnomAD
CA151911807 rs201386032	5	M>L		No	ClinGen 1000Genomes TOPMed gnomAD
CA366486745 rs201386032	5	M>V		No	ClinGen 1000Genomes TOPMed gnomAD
CA4094668 rs760945888	8	F>L		No	ClinGen ExAC TOPMed gnomAD
CA4094666 rs773366632	10	V>M		No	ClinGen ExAC gnomAD
CA366486702 rs1173233562	11	R>C		No	ClinGen gnomAD
CA4094664 rs200753346	11	R>H		No	ClinGen ESP ExAC TOPMed gnomAD
CA4094665 rs200753346	11	R>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA366486701 rs200753346	11	R>P		No	ClinGen ESP ExAC TOPMed gnomAD
rs769095050 CA4094662	12	R>G		No	ClinGen ExAC gnomAD
rs749795260 CA4094661	13	F>L		No	ClinGen ExAC gnomAD
CA4094660 rs776053456	13	F>L		No	ClinGen ExAC gnomAD
rs1184806707 CA366486687	14	F>L		No	ClinGen gnomAD
CA366486678 rs1483581606	15	S>A		No	ClinGen gnomAD
CA366486680 rs1483581606	15	S>T		No	ClinGen gnomAD
CA366486656 rs1167490461	18	L>P		No	ClinGen gnomAD
CA366486650 rs1257263966	19	R>L		No	ClinGen gnomAD
rs1342318405 CA366486655	19	R>S		No	ClinGen TOPMed gnomAD
CA366486649 rs1233285857	20	R>G		No	ClinGen gnomAD
CA4094656 rs756812092	21	K>E		No	ClinGen ExAC gnomAD
rs1350880636 CA366486626	23	R>H		No	ClinGen TOPMed gnomAD
CA366486617 rs1583342275	25	K>Q		No	ClinGen Ensembl
CA151911664 rs758337138	27	S>C		No	ClinGen ExAC TOPMed gnomAD
CA4094653 rs758337138	27	S>Y		No	ClinGen ExAC TOPMed gnomAD
rs931703550 CA151911656	28	S>R		No	ClinGen gnomAD
CA151911640 rs867412985	29	L>P		No	ClinGen Ensembl
CA151911597 rs925959760	30	S>N		No	ClinGen TOPMed gnomAD
rs921777725 CA151911606	30	S>R		No	ClinGen TOPMed
CA366486578 rs1362629068	31	R>Q		No	ClinGen gnomAD
CA366486579 rs1162438574	31	R>W		No	ClinGen gnomAD
rs750679847 CA366486569	33	E>K		No	ClinGen ExAC gnomAD
rs750679847 CA4094649	33	E>Q		No	ClinGen ExAC gnomAD
COSM1442202 CA4094619 COSM1442201 rs771315271	37	V>I	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs1453166931 CA366405426	38	V>M		No	ClinGen TOPMed gnomAD
CA366405399 rs1194968628	41	I>M		No	ClinGen gnomAD
CA4094617 rs772855774	41	I>T		No	ClinGen ExAC TOPMed gnomAD
rs771516996 CA4094616	42	D>A		No	ClinGen ExAC gnomAD
CA4094615 rs747612401	43	I>V		No	ClinGen ExAC TOPMed gnomAD
rs377088777 CA4094614	44	S>G		No	ClinGen ESP ExAC TOPMed gnomAD
CA366405375 rs1442099325	45	H>R		No	ClinGen gnomAD
rs1583256569 COSM1698276 COSM1698275 CA366405376 COSM1698274	45	H>Y	skin [Cosmic]	No	ClinGen cosmic curated Ensembl
CA4094613 rs768623721	48	K>T		No	ClinGen ExAC gnomAD
rs1233952853 CA366405346	49	E>A		No	ClinGen TOPMed
CA4094612 rs571609144	50	G>C		No	ClinGen 1000Genomes ExAC gnomAD
rs1296770935 CA366405339	50	G>D		No	ClinGen TOPMed
CA366405335 rs1394285604	51	F>L		No	ClinGen gnomAD
CA4094611 rs779723845	52	E>G		No	ClinGen ExAC gnomAD
CA4094610 rs755866815	53	K>M		No	ClinGen ExAC gnomAD
CA366405314 rs751757241	54	A>P		No	ClinGen ExAC gnomAD
CA4094609 rs751757241	54	A>T		No	ClinGen ExAC gnomAD
CA366405283 rs924459795	58	Q>H		No	ClinGen gnomAD
CA366405280 rs1170092698	59	F>L		No	ClinGen gnomAD
rs778001747 CA4094608	69	S>C		No	ClinGen ExAC gnomAD
CA366405166 rs1449672354	74	F>Y		No	ClinGen gnomAD
CA4094573 COSM1442200 rs769808652 COSM1442199	76	V>M	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA4094572 rs745788218	77	R>K		No	ClinGen ExAC gnomAD
rs1414042106 CA366405127	80	K>R		No	ClinGen gnomAD
rs770792530 CA4094570	81	G>E		No	ClinGen ExAC TOPMed gnomAD
CA366405112 rs1411978945	83	D>N		No	ClinGen TOPMed gnomAD
CA151926086 rs142745071	84	A>G		No	ClinGen ESP TOPMed
CA4094567 rs367768019	84	A>T		No	ClinGen ESP ExAC TOPMed gnomAD
rs142745071 CA151926070	84	A>V		No	ClinGen ESP TOPMed
CA366405098 rs1247512587	85	G>E		No	ClinGen TOPMed gnomAD
rs749436925 CA4094566	86	Q>K		No	ClinGen ExAC
rs756715388 CA4094564	89	A>T		No	ClinGen ExAC
CA366405069 rs1466645670	90	M>L		No	ClinGen gnomAD
rs200392254 CA4094563	94	K>E		No	ClinGen 1000Genomes ExAC gnomAD
rs556333976 CA151926030	96	A>V		No	ClinGen Ensembl
rs767869031 CA4094562	97	T>I		No	ClinGen ExAC gnomAD
rs1310193297 CA366405009	99	K>E		No	ClinGen gnomAD
rs367869691 CA4094541	101	R>Q		No	ClinGen ESP ExAC TOPMed gnomAD
CA4094542 rs371650855	101	R>W		No	ClinGen ESP ExAC TOPMed gnomAD
rs778104770 CA4094539	103	R>*		No	ClinGen ExAC TOPMed gnomAD
rs749147718 CA366404971	103	R>P		No	ClinGen ExAC TOPMed gnomAD
rs749147718 CA4094538	103	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA151910207 rs1023354158	104	V>L		No	ClinGen Ensembl
rs1198191747 CA366404961	105	R>I		No	ClinGen gnomAD
CA4094535 rs758929555	106	S>L		No	ClinGen ExAC gnomAD
rs1273517205 CA366404909	112	I>N		No	ClinGen gnomAD
rs373999139 CA4094534	112	I>V		No	ClinGen ESP ExAC gnomAD
rs760661054 CA4094532	116	V>M		No	ClinGen ExAC TOPMed gnomAD
rs1251413024 CA366404879	117	N>Y		No	ClinGen gnomAD
rs1310377211 CA366404871	118	H>L		No	ClinGen TOPMed gnomAD
CA4094530 rs771754359	118	H>Q		No	ClinGen ExAC gnomAD
CA4094531 COSM1698273 COSM1698271 rs773211344 COSM1698272	118	H>Y	skin [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs763254036 CA4094529	119	P>S		No	ClinGen ExAC gnomAD
CA366404852 rs1319562841	121	I>F		No	ClinGen gnomAD
rs940379608 CA151910126	124	L>F		No	ClinGen Ensembl
rs371324950 CA4094526	125	H>Q		No	ClinGen ESP ExAC TOPMed gnomAD
CA4094527 rs769935461	125	H>R		No	ClinGen ExAC gnomAD
CA4094525 rs781215230	126	Y>C		No	ClinGen ExAC TOPMed gnomAD
CA366404814 rs376705101	127	A>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA4094524 rs376705101	127	A>T		No	ClinGen ESP ExAC TOPMed gnomAD
CA151908335 rs942970630	128	F>L		No	ClinGen TOPMed gnomAD
rs760698571 CA4094486	130	T>M		No	ClinGen ExAC TOPMed gnomAD
rs760698571 CA366404779	130	T>R		No	ClinGen ExAC TOPMed gnomAD
rs772497351 CA4094484	131	E>K		No	ClinGen ExAC TOPMed gnomAD
CA366404749 rs1292756034	135	Y>C		No	ClinGen gnomAD
CA151908288 rs746976259	135	Y>H		No	ClinGen TOPMed
CA151908302 rs746976259	135	Y>N		No	ClinGen TOPMed
rs1487766948 CA366404730	138	L>P		No	ClinGen gnomAD
CA151908274 rs777617149	142	R>Q		No	ClinGen Ensembl
rs769087421 CA4094481	142	R>W		No	ClinGen ExAC gnomAD
CA366404701 rs915792923	143	G>E		No	ClinGen Ensembl
rs915792923 CA151908268	143	G>V		No	ClinGen Ensembl
CA366404697 rs1242233008	144	G>E		No	ClinGen TOPMed
CA4094479 rs779800296	144	G>R		No	ClinGen ExAC TOPMed gnomAD
CA366404690 rs1330994029	145	D>A		No	ClinGen gnomAD
CA366404693 rs1583220204	145	D>N		No	ClinGen Ensembl
CA366404675 rs1321993873	147	F>C		No	ClinGen gnomAD
rs745406617 CA4094477	148	T>N		No	ClinGen ExAC TOPMed gnomAD
rs755803143 CA4094478	148	T>P		No	ClinGen ExAC gnomAD
rs757197437 CA366404667	149	R>P		No	ClinGen ExAC TOPMed gnomAD
CA4094475 rs757197437	149	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs780746369 CA4094476	149	R>W		No	ClinGen ExAC TOPMed gnomAD
CA4094474 rs751455528	151	S>T		No	ClinGen ExAC gnomAD
CA4094473 rs777547963	152	K>R		No	ClinGen ExAC gnomAD
CA4094442 rs750603576	154	V>I		No	ClinGen ExAC gnomAD
CA4094440 rs761917338	157	T>M		No	ClinGen ExAC TOPMed gnomAD
rs763546969 CA4094437	162	K>R		No	ClinGen ExAC TOPMed gnomAD
rs763546969 CA366404566	162	K>T		No	ClinGen ExAC TOPMed gnomAD
rs770224078 CA4094435	173	D>H		No	ClinGen ExAC TOPMed gnomAD
rs770224078 CA366404496	173	D>Y		No	ClinGen ExAC TOPMed gnomAD
rs759113587 CA4094434	174	H>R		No	ClinGen ExAC gnomAD
rs1450100331 CA366404464	177	S>R		No	ClinGen TOPMed
CA4094433 rs776306101	177	S>T		No	ClinGen ExAC
CA4094432 rs770370189	180	I>V		No	ClinGen ExAC TOPMed gnomAD
rs1363899841 CA366404444	181	I>V		No	ClinGen TOPMed
CA366404387 rs1471480401	189	N>D		No	ClinGen gnomAD
rs768362969 CA4094407	191	L>F		No	ClinGen ExAC gnomAD
rs768362969 CA366404360	191	L>V		No	ClinGen ExAC gnomAD
rs1296850926 CA366404348	193	D>G		No	ClinGen gnomAD
rs749143875 CA4094405	193	D>N		No	ClinGen ExAC gnomAD
rs919966866 CA151900911	197	H>R		No	ClinGen Ensembl
CA151900905 rs974278371	198	I>V		No	ClinGen TOPMed
CA366404262 rs369851246	203	F>L		No	ClinGen ESP ExAC TOPMed gnomAD
rs764071051 CA4094383	204	G>S		No	ClinGen ExAC gnomAD
CA4094382 rs747258086	206	S>C		No	ClinGen ExAC gnomAD
rs1250595277 CA366404217	210	I>T		No	ClinGen gnomAD
rs200188704 CA151898823	212	H>Q		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1460310382 CA366404196	213	D>A		No	ClinGen TOPMed
CA366404199 rs1251863380	213	D>N		No	ClinGen TOPMed gnomAD
CA366404181 rs1284967726	215	R>K		No	ClinGen gnomAD
rs1284967726 CA366404180	215	R>T		No	ClinGen gnomAD
rs1223838046 CA366404171	216	A>V		No	ClinGen TOPMed gnomAD
rs780478422 CA4094374	217	Y>S		No	ClinGen ExAC gnomAD
rs756419383 CA4094373	218	S>P		No	ClinGen ExAC gnomAD
CA366404157 rs1439447338	219	F>L		No	ClinGen TOPMed gnomAD
rs761446246 CA4094370	221	G>R		No	ClinGen ExAC gnomAD
COSM450889 CA4094369 rs751151339 COSM450890	222	T>M	large_intestine breast [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA366404130 rs1456317510	223	I>N		No	ClinGen gnomAD
rs775243470 CA4094366	223	I>V		No	ClinGen ExAC gnomAD
rs762918941 CA151898774	224	E>K		No	ClinGen Ensembl
COSM1663981 CA366404104 COSM1663980 COSM1663982 rs1337171535	226	M>I	kidney [Cosmic]	No	ClinGen cosmic curated TOPMed
rs776613761 CA151898771	227	A>T		No	ClinGen TOPMed
rs748313908 CA4094361	229	E>K		No	ClinGen ExAC gnomAD
rs367668575 CA4094360	231	V>A		No	ClinGen ESP ExAC TOPMed gnomAD
CA366404071 rs1204141327	232	N>Y		No	ClinGen gnomAD
rs749821922 CA4094358	233	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA4094359 rs768559227	233	R>W		No	ClinGen ExAC gnomAD
CA4094357 rs777363632	234	R>*		No	ClinGen ExAC TOPMed
rs756578915 CA4094356	234	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA151898736 rs757805752	237	T>K		No	ClinGen ExAC TOPMed gnomAD
CA4094355 COSM125946 rs757805752	237	T>M	upper_aerodigestive_tract [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA4094353 rs374086277	238	Q>K		No	ClinGen ESP ExAC gnomAD
CA4094352 rs751117148	238	Q>R		No	ClinGen ExAC gnomAD
rs1337929737 CA366404033	239	S>C		No	ClinGen gnomAD
rs762332596 CA4094350	241	D>N		No	ClinGen ExAC TOPMed gnomAD
rs1455025827 CA366404001	243	W>S		No	ClinGen gnomAD
CA366403994 rs1583209074	244	S>A		No	ClinGen Ensembl
CA4094347 rs759533908 COSM1663977 COSM1663979 COSM1663978	246	G>S	kidney [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA4094346 rs776635505	247	V>M		No	ClinGen ExAC gnomAD
rs942701076 CA151898662	248	L>F		No	ClinGen TOPMed
rs201871471 CA4094343	249	M>V		No	ClinGen 1000Genomes ExAC gnomAD
CA4094318 rs747383955	252	M>K		No	ClinGen ExAC gnomAD
CA366403781 rs1398737433	253	L>F		No	ClinGen TOPMed
rs758053401 CA4094316	254	T>M		No	ClinGen ExAC TOPMed gnomAD
CA366403765 rs1583200202	256	S>P		No	ClinGen Ensembl
CA151891742 rs201008426	258	P>L		No	ClinGen TOPMed gnomAD
rs753855528 CA4094312	261	G>R		No	ClinGen ExAC gnomAD
CA366403683 COSM1075918 rs1353018457 COSM1075919	268	M>V	endometrium [Cosmic]	No	ClinGen cosmic curated gnomAD
rs1032203484 CA151891714	271	I>N		No	ClinGen Ensembl
rs767280677 CA4094308	272	L>F		No	ClinGen ExAC gnomAD
rs746706428 CA151891013	274	A>T		No	ClinGen Ensembl
CA366403415 rs1340850194	276	L>M		No	ClinGen TOPMed
rs778666535 CA4094297	279	P>L		No	ClinGen ExAC TOPMed gnomAD
rs768390505 CA4094296	280	Q>H		No	ClinGen ExAC TOPMed gnomAD
rs1206011934 CA366403371	282	L>P		No	ClinGen gnomAD
rs151128520 CA4094295	284	G>A		No	ClinGen ESP ExAC TOPMed gnomAD
CA366403360 rs1306030262	284	G>R		No	ClinGen TOPMed gnomAD
CA366403348 rs1222882427	286	A>T		No	ClinGen TOPMed gnomAD
CA151890988 rs868447311	291	R>*		No	ClinGen gnomAD
rs200011293 CA151890980	291	R>P		No	ClinGen 1000Genomes ExAC gnomAD
rs200011293 CA4094293	291	R>Q		No	ClinGen 1000Genomes ExAC gnomAD
rs750322063 CA4094292	293	L>V		No	ClinGen ExAC gnomAD
rs1406573345 CA366403283	296	R>Q		No	ClinGen gnomAD
rs1470862955 CA366403284	296	R>W		No	ClinGen gnomAD
CA366403276 rs1158053787	297	N>S		No	ClinGen gnomAD
rs1399182458 CA366403263	299	C>Y		No	ClinGen gnomAD
CA4094290 rs757007952	301	R>L		No	ClinGen ExAC gnomAD
CA366403248 rs757007952	301	R>Q		No	ClinGen ExAC gnomAD
rs1410370964 CA366403249	301	R>W		No	ClinGen gnomAD
rs1264721800 CA366402181	304	A>T		No	ClinGen gnomAD
CA151925050 rs895377824	304	A>V		No	ClinGen Ensembl
rs756422709 CA4094226	305	G>D		No	ClinGen ExAC gnomAD
CA4094227 rs778556848	305	G>S		No	ClinGen ExAC gnomAD
rs746006416 CA4094225	306	I>T		No	ClinGen ExAC TOPMed gnomAD
rs753493013 CA4094224	307	D>E		No	ClinGen ExAC
rs751663530 CA4094222	307	D>E		No	ClinGen ExAC gnomAD
CA4094223 rs147505453	307	D>G		No	ClinGen ESP ExAC TOPMed gnomAD
rs758821702 CA4094219	308	G>*		No	ClinGen ExAC TOPMed gnomAD
rs758821702 CA4094220	308	G>R		No	ClinGen ExAC TOPMed gnomAD
rs1408796769 CA366402154	309	V>A		No	ClinGen gnomAD
rs1468616542 CA366402158	309	V>M		No	ClinGen gnomAD
rs377350122 CA4094216	311	E>D		No	ClinGen ESP ExAC TOPMed gnomAD
VAR_040627 rs267600891 COSM21036 CA151924953	311	E>K	a metastatic melanoma sample; somatic mutation skin [UniProt, Cosmic]	No	ClinGen cosmic curated UniProt Ensembl dbSNP
CA4094217 rs753174588	311	E>V		No	ClinGen ExAC gnomAD
COSM1578701 CA151924927 rs886598955 COSM1578702	314	R>C	meninges [Cosmic]	No	ClinGen cosmic curated gnomAD
CA4094215 rs759240466	314	R>H		No	ClinGen ExAC TOPMed gnomAD
rs759240466 CA366402121	314	R>L		No	ClinGen ExAC TOPMed gnomAD
CA4094214 rs753441237	315	H>Q		No	ClinGen ExAC TOPMed gnomAD
rs760218344 CA4094212	320	T>A		No	ClinGen ExAC gnomAD
rs772054144 CA4094210	321	I>T		No	ClinGen ExAC gnomAD
CA4094211 rs530808493	321	I>V		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1361490886 CA366402062	323	W>*		No	ClinGen TOPMed
CA4094185 rs78598590	325	T>M		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs78598590 CA4094186	325	T>R		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA4094187 rs771350281	325	T>S		No	ClinGen ExAC gnomAD
rs1478302296 CA366401679	327	Y>*		No	ClinGen TOPMed gnomAD
rs1478302296 CA366401680	327	Y>*		No	ClinGen TOPMed gnomAD
rs779326307 CA4094181	327	Y>H		No	ClinGen ExAC gnomAD
COSM277123 rs181011882 CA4094179 COSM277122	328	R>Q	large_intestine [Cosmic]	No	ClinGen cosmic curated 1000Genomes ESP ExAC TOPMed gnomAD
COSM296328 CA4094180 COSM296329 rs755486763	328	R>W	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs780391199 CA4094178	331	I>T		No	ClinGen ExAC TOPMed gnomAD
CA4094176 rs750016078	337	P>L		No	ClinGen ExAC gnomAD
CA4094174 rs756678287	341	R>K		No	ClinGen ExAC
rs368566488 CA366401532	341	R>S		No	ClinGen 1000Genomes ExAC gnomAD
CA151915173 rs1013530441	342	P>H		No	ClinGen Ensembl
rs1313066017 CA366401521	343	E>Q		No	ClinGen TOPMed
rs1583162533 CA366401503	344	D>A		No	ClinGen Ensembl
rs896528675 CA151915166	345	T>I		No	ClinGen gnomAD
CA4094171 rs762983002	345	T>P		No	ClinGen ExAC gnomAD
rs1282213477 CA366401437	350	P>S		No	ClinGen gnomAD
rs1282213477 CA366401440	350	P>T		No	ClinGen gnomAD
CA366401429 rs1330601345	351	E>K		No	ClinGen TOPMed gnomAD
rs765067636 CA4094169	354	A>V		No	ClinGen ExAC TOPMed gnomAD
CA4094167 COSM1442185 rs367918929 COSM1442186	355	R>Q	large_intestine [Cosmic]	No	ClinGen cosmic curated 1000Genomes ESP ExAC TOPMed gnomAD
COSM595028 COSM595029 CA366401388 rs1394229232	355	R>W	lung [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
rs748224061 CA4094166	356	T>K		No	ClinGen ExAC TOPMed gnomAD
rs748224061 CA4094165	356	T>M		No	ClinGen ExAC TOPMed gnomAD
rs777679632 CA151915129	358	T>I		No	ClinGen TOPMed gnomAD
CA366401362 rs777679632	358	T>R		No	ClinGen TOPMed gnomAD
CA366400449 rs1241691757	359	D>G		No	ClinGen gnomAD
rs775933664 CA4094144	362	G>R		No	ClinGen ExAC gnomAD
rs781619977 CA4094142	363	V>F		No	ClinGen ExAC TOPMed gnomAD
rs1310758457 CA366400411	363	V>G		No	ClinGen gnomAD
COSM741177 rs781619977 CA4094141 COSM741178	363	V>I	lung [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs746616311 CA4094139	365	P>L		No	ClinGen ExAC TOPMed gnomAD
CA4094140 rs770497302	365	P>S		No	ClinGen ExAC gnomAD
rs1334511707 CA366400393	366	S>R		No	ClinGen gnomAD
CA4094136 rs752225232	369	A>G		No	ClinGen ExAC gnomAD
rs936064171 CA151908320	369	A>P		No	ClinGen TOPMed gnomAD
CA366400359 rs936064171	369	A>T		No	ClinGen TOPMed gnomAD
CA366400348 rs1159263593	370	H>L		No	ClinGen gnomAD
COSM3777305 COSM3777303 rs779040713 COSM3777304 CA4094135	370	H>Y	urinary_tract [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs1383917602 CA366400340	371	H>P		No	ClinGen gnomAD
CA4094134 rs61733655	371	H>Y		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA366400303 rs1180152382	374	R>S		No	ClinGen TOPMed
rs1335867515 CA366400260	378	F>S		No	ClinGen TOPMed
CA366400263 rs1214670472	378	F>V		No	ClinGen gnomAD
CA366400204 rs1175903046	384	I>F		No	ClinGen TOPMed
rs1003055278 CA151908281	387	P>R		No	ClinGen TOPMed
CA366400167 rs1287558271	387	P>S		No	ClinGen gnomAD
CA366400130 rs1303831764	390	Q>H		No	ClinGen TOPMed
CA366400117 rs1312794334	392	L>M		No	ClinGen TOPMed gnomAD
rs1562502433 CA366400113	392	L>P		No	ClinGen Ensembl
rs189613279 CA4094128	394	K>N		No	ClinGen 1000Genomes ExAC gnomAD
rs1311747202 CA366400086	395	V>I		No	ClinGen TOPMed
rs760026527 CA4094125	397	V>G		No	ClinGen ExAC gnomAD
rs747699856 CA151908266	398	H>Q		No	ClinGen Ensembl
rs569060210 CA4094124	399	P>T		No	ClinGen 1000Genomes ExAC gnomAD
CA4094123 rs771278598	400	I>V		No	ClinGen ExAC gnomAD
CA366400027 rs1167550999	401	V>M		No	ClinGen TOPMed gnomAD
CA366400012 rs1424863340	402	Q>P		No	ClinGen gnomAD
CA151905789 rs1041322336	403	Q>R		No	ClinGen TOPMed gnomAD
CA366399587 rs1237904328	406	G>E		No	ClinGen gnomAD
rs749209578 CA4094098	406	G>R		No	ClinGen ExAC TOPMed gnomAD
rs750081205 CA151905767	407	N>S		No	ClinGen Ensembl
rs1296934475 CA366399576	408	N>D		No	ClinGen gnomAD
CA151905760 rs889981680	409	I>S		No	ClinGen Ensembl
rs1583147828 CA366399559	410	H>R		No	ClinGen Ensembl
CA366399554 rs1182451077	411	F>L		No	ClinGen TOPMed
CA366399542 rs1401523347	412	T>I		No	ClinGen gnomAD
CA366399547 rs1449593352	412	T>P		No	ClinGen gnomAD
CA4094095 rs201444480	413	D>H		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
COSM1442183 COSM1442184 CA4094096 rs201444480	413	D>N	large_intestine [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
CA4094092 rs752872463	416	E>K		No	ClinGen ExAC TOPMed gnomAD
CA366399484 rs1249146964	420	D>E		No	ClinGen gnomAD
rs1265712668 CA366399488	420	D>G		No	ClinGen gnomAD
rs1176733248 CA366399481	421	I>F		No	ClinGen gnomAD
rs1238574693 CA366399476	422	G>R		No	ClinGen gnomAD
rs755127089 CA366399461	424	G>D		No	ClinGen ExAC TOPMed gnomAD
CA4094090 rs755127089	424	G>V		No	ClinGen ExAC TOPMed gnomAD
CA4094089 rs753840735	426	Y>N		No	ClinGen ExAC gnomAD
CA366399442 rs1369091057	427	S>L		No	ClinGen TOPMed
CA4094088 rs766970028	428	V>A		No	ClinGen ExAC gnomAD
rs140501908 CA151905734	431	R>*		No	ClinGen ESP
rs761079978 CA4094087	431	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA4094086 rs773714891	434	H>R		No	ClinGen ExAC
rs186164269 CA4094085	436	A>G		No	ClinGen 1000Genomes ExAC gnomAD
CA366399377 COSM1075906 COSM1075905 rs1308840936	437	T>I	endometrium [Cosmic]	No	ClinGen cosmic curated TOPMed
CA4094083 rs774102654	438	D>H		No	ClinGen ExAC TOPMed gnomAD
CA366399376 COSM207704 COSM207705 rs774102654	438	D>N	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs1450913451 CA366399363	440	E>K		No	ClinGen gnomAD
CA4094081 rs547406661	443	V>M		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA4094058 rs746866176	446	I>T		No	ClinGen ExAC gnomAD
CA366399208 rs1208581644	448	K>R		No	ClinGen gnomAD
CA4094057 rs777428566	449	S>R		No	ClinGen ExAC gnomAD
CA4094055 rs369131300	450	K>N		No	ClinGen ESP ExAC gnomAD
rs768924917 CA4094056	450	K>R		No	ClinGen ExAC gnomAD
CA366399188 rs1339486677	451	R>K		No	ClinGen gnomAD
rs1275887588 CA366399184	452	D>N		No	ClinGen gnomAD
rs1401409203 CA366399176	453	P>T		No	ClinGen gnomAD
rs780204450 CA4094054	454	S>*		No	ClinGen ExAC gnomAD
COSM1075903 rs780204450 CA366399166 COSM1075902	454	S>L	endometrium [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs1454861783 CA366399158	455	E>D		No	ClinGen TOPMed
CA366399118 rs1168268653	461	L>P		No	ClinGen TOPMed
CA366399115 rs1403549805	462	R>Q		No	ClinGen gnomAD
rs913725245 CA151891758	462	R>W		No	ClinGen Ensembl
CA151891755 rs866000385	464	G>D		No	ClinGen Ensembl
rs1411672142 CA366399104	464	G>S		No	ClinGen TOPMed
CA366399097 rs1163695053	465	Q>*		No	ClinGen gnomAD
rs1329648698 CA366399088	466	H>P		No	ClinGen TOPMed
rs781776035 CA4094051	467	P>L		No	ClinGen ExAC gnomAD
CA366399081 rs1461271089	467	P>S		No	ClinGen gnomAD
rs1434269109 CA366399077	468	N>D		No	ClinGen TOPMed
CA4094049 rs75225867	469	I>V		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs371987754 CA151891753	472	L>F		No	ClinGen ESP TOPMed
rs370360100 CA4094028	475	V>I		No	ClinGen ESP ExAC TOPMed gnomAD
CA4094027 rs759186088	477	D>E		No	ClinGen ExAC gnomAD
rs1428454447 CA366398894	477	D>G		No	ClinGen Ensembl
CA366398864 rs1358852770	480	K>Q		No	ClinGen gnomAD
rs1332463868 CA366398861	480	K>T		No	ClinGen gnomAD
rs866748533 CA151890933	481	F>C		No	ClinGen Ensembl
CA4094025 rs765815045	481	F>V		No	ClinGen ExAC gnomAD
rs1158064861 CA366398838	482	V>G		No	ClinGen gnomAD
rs760682842 CA4094024	485	V>I		No	ClinGen ExAC TOPMed gnomAD
rs376246711 CA4094023	489	M>T		No	ClinGen ESP ExAC
CA4094022 rs779109340	490	R>C		No	ClinGen ExAC gnomAD
rs200672567 CA4094021	490	R>H		No	ClinGen ESP ExAC TOPMed gnomAD
CA4094019 rs540391944	491	G>A		No	ClinGen 1000Genomes ExAC gnomAD
CA4094018 rs540391944	491	G>V		No	ClinGen 1000Genomes ExAC gnomAD
CA366398750 rs1583123580	492	G>R		No	ClinGen Ensembl
CA366398738 rs1448597310	493	E>*		No	ClinGen TOPMed
rs776876681 CA4094017	493	E>D		No	ClinGen ExAC gnomAD
CA366398726 rs1297401090	494	L>F		No	ClinGen TOPMed
rs1351508293 CA366398708	496	D>A		No	ClinGen gnomAD
rs747084939 CA4094015	496	D>N		No	ClinGen ExAC gnomAD
CA4094014 rs778197293	497	R>C		No	ClinGen ExAC TOPMed gnomAD
COSM3410783 COSM3410782 COSM3410781 rs758931117 CA4094013	497	R>H	central_nervous_system [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs758931117 CA151890908	497	R>P		No	ClinGen ExAC TOPMed gnomAD
rs754636268 COSM595032 CA4094010 COSM595033	500	R>Q	lung [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs779184447 CA4094011	500	R>W		No	ClinGen ExAC TOPMed gnomAD
CA4094009 rs753437594	501	Q>E		No	ClinGen ExAC gnomAD
CA4094008 rs370742632	503	Y>C		No	ClinGen ESP ExAC TOPMed gnomAD
CA366398617 rs1211356934	505	S>A		No	ClinGen TOPMed
CA4094007 rs145694057	505	S>L		No	ClinGen ESP ExAC
rs1479894219 CA366398609	506	E>K		No	ClinGen TOPMed
CA4094005 rs554281318	507	R>H		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1183944423 CA366398589	508	E>K		No	ClinGen gnomAD
rs1193743329 CA366398551	512	V>F		No	ClinGen TOPMed gnomAD
rs1193743329 CA366398553	512	V>I		No	ClinGen TOPMed gnomAD
CA4094001 rs759869997	515	T>A		No	ClinGen ExAC gnomAD
CA4094000 rs777034389	515	T>I		No	ClinGen ExAC gnomAD
CA366398534 rs759869997	515	T>P		No	ClinGen ExAC gnomAD
CA366398523 rs1583123318	517	T>P		No	ClinGen Ensembl
rs771162151 CA4093999	520	M>I		No	ClinGen ExAC gnomAD
rs147934464 CA4093998	521	D>N		No	ClinGen ESP ExAC TOPMed gnomAD
CA366398485 rs1583123280	522	Y>S		No	ClinGen Ensembl
CA366398455 rs1583123235	525	S>P		No	ClinGen Ensembl
rs1583123215 CA366398442	526	Q>R		No	ClinGen Ensembl
CA4093994 rs779268655	527	G>R		No	ClinGen ExAC TOPMed gnomAD
CA366398435 rs779268655	527	G>R		No	ClinGen ExAC TOPMed gnomAD
CA366398065 rs1264808638	528	V>A		No	ClinGen TOPMed
rs1295819344 CA366398069	528	V>I		No	ClinGen gnomAD
CA366398055 rs1437727592	530	H>Y		No	ClinGen TOPMed gnomAD
CA4093978 rs762336366	532	D>Y		No	ClinGen ExAC gnomAD
CA366398027 rs1326649327	534	K>M		No	ClinGen gnomAD
rs1414977760 CA366398019	535	P>L		No	ClinGen TOPMed
CA366398022 rs1432075896	535	P>S		No	ClinGen gnomAD
CA366397963 rs1468824854	543	E>G		No	ClinGen gnomAD
COSM1698270 CA4093973 rs571872261 COSM1698269 COSM1698268	544	S>L	skin [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
rs780461931 CA4093974	544	S>P		No	ClinGen ExAC TOPMed gnomAD
rs780461931 CA151888441	544	S>T		No	ClinGen ExAC TOPMed gnomAD
rs571872261 CA366397958	544	S>W		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA151888421 rs938788617	550	I>T		No	ClinGen Ensembl
rs1310523412 CA366397915	551	R>*		No	ClinGen TOPMed gnomAD
CA4093969 rs776642914	551	R>Q		No	ClinGen ExAC
CA4093968 rs777915458	552	V>G		No	ClinGen ExAC gnomAD
rs868543322 CA151888416	552	V>I		No	ClinGen Ensembl
rs1292801193 CA366397907	553	C>R		No	ClinGen TOPMed
COSM247120 CA4093965 rs369744218 COSM247119	556	G>S	prostate [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
CA4093964 rs760832013	558	A>V		No	ClinGen ExAC gnomAD
CA151888413 rs879101141	559	K>T		No	ClinGen Ensembl
CA4093962 rs767600252	560	Q>R		No	ClinGen ExAC gnomAD
rs538021247 CA4093961	563	A>G		No	ClinGen 1000Genomes ExAC gnomAD
rs548653229 CA4093956	569	M>V		No	ClinGen 1000Genomes ExAC gnomAD
CA4093955 rs770145794	571	P>R		No	ClinGen ExAC gnomAD
CA4093954 rs746190111	574	T>M		No	ClinGen ExAC TOPMed gnomAD
CA151888345 rs199856597	577	F>Y		No	ClinGen 1000Genomes
rs777355798 CA4093950	578	V>M		No	ClinGen ExAC TOPMed gnomAD
CA366397734 rs1242873180	579	A>V		No	ClinGen gnomAD
CA366397729 rs1554270758	580	P>L		No	ClinGen Ensembl
CA366397691 rs1316899182	584	K>N		No	ClinGen gnomAD
CA151887191 rs992765141	584	K>Q		No	ClinGen Ensembl
CA4093922 rs758524783 COSM1075896 COSM1075897	585	R>C	endometrium [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA4093921 rs146174629	585	R>H		No	ClinGen ESP ExAC TOPMed gnomAD
CA4093920 COSM343093 COSM343094 rs765840354	588	Y>C	lung [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA366397656 rs1157701321	590	A>T		No	ClinGen TOPMed
COSM1075894 rs141868317 COSM1075893 CA4093919	590	A>V	endometrium [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
CA366397651 rs1323005236	591	A>T		No	ClinGen TOPMed
CA4093917 rs766805003	591	A>V		No	ClinGen ExAC TOPMed gnomAD
rs1335040113 CA366397630	594	I>L		No	ClinGen TOPMed
CA366397565 rs1377077535	603	T>A		No	ClinGen gnomAD
rs1198195311 CA366397461 COSM139690	617	D>N	skin [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
rs866956037 CA151886957	621	E>K		No	ClinGen Ensembl
rs200077411 COSM1075887 COSM1075888 CA4093897	624	A>V	endometrium [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
rs773924400 CA4093894	625	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs761302415 CA4093895	625	R>W		No	ClinGen ExAC gnomAD
CA4093892 rs571504052	627	G>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1340065928 CA366397391	628	S>N		No	ClinGen gnomAD
CA151886956 rs994788762	628	S>R		No	ClinGen Ensembl
rs775445065 CA4093891	629	G>E		No	ClinGen ExAC TOPMed gnomAD
CA366397381 rs78905238	630	K>*		No	ClinGen gnomAD
CA151886955 rs78905238	630	K>E		No	ClinGen gnomAD
CA4093889 rs745730689	631	Y>C		No	ClinGen ExAC gnomAD
rs1583105515 CA366397374	631	Y>D		No	ClinGen Ensembl
rs780898160 CA4093888	632	A>T		No	ClinGen ExAC TOPMed gnomAD
rs1374181056 CA366397364	632	A>V		No	ClinGen gnomAD
CA366397361 rs1410648771	633	L>F		No	ClinGen gnomAD
rs1410648771 CA366397363	633	L>I		No	ClinGen gnomAD
rs1325191035 CA366397351	635	G>R		No	ClinGen gnomAD
CA366397342 rs1470328931	636	G>E		No	ClinGen gnomAD
rs1184889974 CA366397334	637	N>I		No	ClinGen gnomAD
rs748273135 CA4093886	639	D>N		No	ClinGen ExAC TOPMed gnomAD
CA4093885 COSM1075878 rs779085045 COSM1075879	640	S>L	endometrium [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs377303184 CA151886954	641	I>M		No	ClinGen ESP TOPMed
rs201987457 CA4093882	643	D>N		No	ClinGen 1000Genomes ExAC gnomAD
CA4093880 rs750818492	644	A>T		No	ClinGen ExAC gnomAD
rs781643229 CA4093859	647	D>E		No	ClinGen ExAC gnomAD
CA4093858 rs373005161	648	V>I		No	ClinGen ESP ExAC TOPMed gnomAD
CA4093856 rs368787835	649	V>L		No	ClinGen ESP ExAC TOPMed gnomAD
rs368787835 CA4093855	649	V>M		No	ClinGen ESP ExAC TOPMed gnomAD
CA4093853 COSM1075873 rs764678473 COSM1075872	655	V>M	endometrium [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA366397198 rs1420942137	656	D>Y		No	ClinGen gnomAD
rs972192952 CA151886416	658	H>D		No	ClinGen Ensembl
rs1477628615 CA366397169	660	R>C		No	ClinGen gnomAD
CA366397168 rs1250960043	660	R>H		No	ClinGen TOPMed gnomAD
CA151886415 rs751920891	661	L>Q		No	ClinGen Ensembl
COSM329604 COSM329603 rs760448739 CA4093849	662	T>M	haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs768763548 CA4093847	663	A>V		No	ClinGen ExAC TOPMed gnomAD
rs775732936 CA4093845	664	M>L		No	ClinGen ExAC TOPMed gnomAD
CA366397128 rs1239869493	667	L>I		No	ClinGen gnomAD
CA366397118 rs1366077760	668	K>R		No	ClinGen gnomAD
CA366397109 rs1297824161	669	H>L		No	ClinGen TOPMed
rs1297824161 CA366397111	669	H>P		No	ClinGen TOPMed
CA4093843 rs745909830	670	P>L		No	ClinGen ExAC gnomAD
rs993542212 CA151886414	672	V>M		No	ClinGen TOPMed gnomAD
CA366397077 rs1289563536	674	N>S		No	ClinGen TOPMed
CA366397057 rs1355794135	677	Y>D		No	ClinGen gnomAD
rs1583099093 CA366397055	677	Y>S		No	ClinGen Ensembl
CA366397038 rs1170506834	680	P>A		No	ClinGen gnomAD
CA366397024 rs1393185896	682	Q>E		No	ClinGen gnomAD
CA151886411 rs899256213	684	S>R		No	ClinGen TOPMed
COSM1442167 CA366397003 COSM1442168 rs1195326963	685	R>*	large_intestine [Cosmic]	No	ClinGen cosmic curated gnomAD
CA4093840 COSM3393975 rs747341069 COSM3393974 COSM3393973	685	R>Q	pancreas [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs1028632989 CA151886410	688	V>M		No	ClinGen gnomAD
rs758070445 CA4093838	689	H>Q		No	ClinGen ExAC TOPMed gnomAD
rs1000269721 CA151886409	689	H>Y		No	ClinGen Ensembl
CA4093837 rs377599195	690	L>M		No	ClinGen ESP ExAC TOPMed gnomAD
rs937555187 CA151911512	693	G>S		No	ClinGen TOPMed gnomAD
CA366402759 rs1164389789	694	A>T		No	ClinGen gnomAD
rs1420173811 CA366402749	695	M>T		No	ClinGen gnomAD
CA366402740 rs1188708514	696	A>G		No	ClinGen gnomAD
rs1188708514 CA366402739	696	A>V		No	ClinGen gnomAD
CA366402727 rs1488288240	698	T>I		No	ClinGen gnomAD
rs1450316339 CA366402718	700	F>I		No	ClinGen TOPMed
rs1026910105 CA151911504	700	F>L		No	ClinGen Ensembl
CA366402694 rs147673764	703	N>K		No	ClinGen ESP ExAC TOPMed gnomAD
CA4093810 rs571045780	704	R>G		No	ClinGen 1000Genomes ExAC gnomAD
rs1216450782 CA366402691	704	R>K		No	ClinGen gnomAD
CA366402685 rs1445796089	705	T>A		No	ClinGen TOPMed gnomAD
CA366402675 rs1583097449	706	P>L		No	ClinGen Ensembl
CA366402664 rs1332181842	708	A>D		No	ClinGen gnomAD
CA4093809 rs751385395	708	A>T		No	ClinGen ExAC TOPMed gnomAD
rs555832127 CA151911470	709	P>L		No	ClinGen 1000Genomes
rs555832127 CA151911477	709	P>Q		No	ClinGen 1000Genomes
CA366402659 rs1261947668	709	P>S		No	ClinGen TOPMed
rs776598020 CA151911440	710	R>P		No	ClinGen ExAC gnomAD
rs776598020 CA4093806	710	R>Q		No	ClinGen ExAC gnomAD
rs1461298020 COSM207694 COSM3662282 CA366402656 COSM207693	710	R>W	liver large_intestine [Cosmic]	No	ClinGen cosmic curated TOPMed
CA4093805 rs771004489	711	L>P		No	ClinGen ExAC
rs1316138179 CA366402648	712	E>*		No	ClinGen gnomAD
rs890556346 CA366402635	714	V>L		No	ClinGen gnomAD
rs890556346 CA151911432	714	V>L		No	ClinGen gnomAD
rs890556346 CA366402636	714	V>M		No	ClinGen gnomAD
CA4093802 rs772558151	718	N>S		No	ClinGen ExAC gnomAD
rs779178485 CA4093800	719	L>P		No	ClinGen ExAC gnomAD
CA366402600 rs1195989175	720	A>V		No	ClinGen gnomAD
rs768306540 CA366402588	722	R>C		No	ClinGen ExAC TOPMed gnomAD
CA366402585 rs1267156660	722	R>H		No	ClinGen gnomAD
CA4093799 rs768306540	722	R>S		No	ClinGen ExAC TOPMed gnomAD
CA151911385 rs990145079	723	R>G		No	ClinGen TOPMed
CA4093797 rs779459363	724	G>D		No	ClinGen ExAC TOPMed gnomAD
CA151911349 rs760886545	725	M>I		No	ClinGen Ensembl
rs755688028 CA4093796	725	M>K		No	ClinGen ExAC gnomAD
CA366402551 rs1338218673	728	L>I		No	ClinGen gnomAD
COSM3697663 rs781336018 COSM3697662 CA4093794 COSM3697664	729	T>M	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs1302492538 CA366402538	730	S>A		No	ClinGen gnomAD
CA366402536 rs1438424358	730	S>C		No	ClinGen gnomAD
COSM20427 rs376029388 CA4093791 VAR_040628	732	R>Q	large_intestine a colorectal adenocarcinoma sample; somatic mutation [Cosmic, UniProt]	No	ClinGen cosmic curated UniProt ESP ExAC TOPMed dbSNP gnomAD
rs1326828401 CA366402527	732	R>W		No	ClinGen TOPMed gnomAD
CA366402524 rs909631	733	L>M		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA366402523 rs909631	733	L>V		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD

No associated diseases with Q15349

9 regional properties for Q15349

Type	Name	Position	InterPro Accession
domain	Protein kinase domain	59 - 318	IPR000719-1
domain	Protein kinase domain	415 - 672	IPR000719-2
domain	AGC-kinase, C-terminal	319 - 388	IPR000961
active_site	Serine/threonine-protein kinase, active site	180 - 192	IPR008271-1
active_site	Serine/threonine-protein kinase, active site	528 - 540	IPR008271-2
binding_site	Protein kinase, ATP binding site	65 - 91	IPR017441-1
binding_site	Protein kinase, ATP binding site	421 - 444	IPR017441-2
domain	Protein kinase, C-terminal	342 - 378	IPR017892
domain	RSK3, C-terminal catalytic domain	411 - 703	IPR042766

Functions

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

6 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.
meiotic spindle	A spindle that forms as part of meiosis. Several proteins, such as budding yeast Spo21p, fission yeast Spo2 and Spo13, and C. elegans mei-1, localize specifically to the meiotic spindle and are absent from the mitotic spindle.
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.
synapse	The junction between an axon of one neuron and a dendrite of another neuron, a muscle fiber or a glial cell. As the axon approaches the synapse it enlarges into a specialized structure, the presynaptic terminal bouton, which contains mitochondria and synaptic vesicles. At the tip of the terminal bouton is the presynaptic membrane; facing it, and separated from it by a minute cleft (the synaptic cleft) is a specialized area of membrane on the receiving cell, known as the postsynaptic membrane. In response to the arrival of nerve impulses, the presynaptic terminal bouton secretes molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane.

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.

16 GO annotations of biological process

Name	Definition
brain renin-angiotensin system	The process in which an angiotensin-mediated signaling system present in the brain regulates the force with which blood passes through the circulatory system.
cardiac muscle cell apoptotic process	A form of programmed cell death induced by external or internal signals that trigger the activity of proteolytic caspases, whose actions dismantle a cardiac muscle cell and result in its death. Cardiac muscle cells are striated muscle cells that are responsible for heart contraction.
cellular response to carbohydrate 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 carbohydrate stimulus.
chemical synaptic transmission	The vesicular release of classical neurotransmitter molecules from a presynapse, across a chemical synapse, the subsequent activation of neurotransmitter receptors at the postsynapse of a target cell (neuron, muscle, or secretory cell) and the effects of this activation on the postsynaptic membrane potential and ionic composition of the postsynaptic cytosol. This process encompasses both spontaneous and evoked release of neurotransmitter and all parts of synaptic vesicle exocytosis. Evoked transmission starts with the arrival of an action potential at the presynapse.
heart contraction	The multicellular organismal process in which the heart decreases in volume in a characteristic way to propel blood through the body.
heart development	The process whose specific outcome is the progression of the heart over time, from its formation to the mature structure. The heart is a hollow, muscular organ, which, by contracting rhythmically, keeps up the circulation of the blood.
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 cell cycle	Any process that stops, prevents or reduces the rate or extent of progression through the cell cycle.
negative regulation of cell population proliferation	Any process that stops, prevents or reduces the rate or extent of cell proliferation.
negative regulation of meiotic nuclear division	Any process that stops, prevents, or reduces the frequency, rate or extent of meiosis.
oocyte maturation	A developmental process, independent of morphogenetic (shape) change, that is required for an oocyte to attain its fully functional state. Oocyte maturation commences after reinitiation of meiosis commonly starting with germinal vesicle breakdown, and continues up to the second meiotic arrest prior to fertilization.
peptidyl-serine phosphorylation	The phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine.
positive regulation of apoptotic process	Any process that activates or increases the frequency, rate or extent of cell death by apoptotic process.
positive regulation of gene expression	Any process that increases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
regulation of protein processing	Any process that modulates the frequency, rate or extent of protein processing, a protein maturation process achieved by the cleavage of a peptide bond or bonds within a protein.
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.

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
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
O75676	RPS6KA4	Ribosomal protein S6 kinase alpha-4	Homo sapiens (Human)	SS
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
Q9Z2B9	Rps6ka4	Ribosomal protein S6 kinase alpha-4	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
Q9WUT3	Rps6ka2	Ribosomal protein S6 kinase alpha-2	Mus musculus (Mouse)	SS
Q63531	Rps6ka1	Ribosomal protein S6 kinase alpha-1	Rattus norvegicus (Rat)	SS
Q18846	rskn-2	Putative ribosomal protein S6 kinase alpha-2	Caenorhabditis elegans	PR
Q21734	rskn-1	Putative ribosomal protein S6 kinase alpha-1	Caenorhabditis elegans	SS

10	20	30	40	50	60
MDLSMKKFAV	RRFFSVYLRR	KSRSKSSSLS	RLEEEGVVKE	IDISHHVKEG	FEKADPSQFE
70	80	90	100	110	120
LLKVLGQGSY	GKVFLVRKVK	GSDAGQLYAM	KVLKKATLKV	RDRVRSKMER	DILAEVNHPF
130	140	150	160	170	180
IVKLHYAFQT	EGKLYLILDF	LRGGDLFTRL	SKEVMFTEED	VKFYLAELAL	ALDHLHSLGI
190	200	210	220	230	240
IYRDLKPENI	LLDEEGHIKI	TDFGLSKEAI	DHDKRAYSFC	GTIEYMAPEV	VNRRGHTQSA
250	260	270	280	290	300
DWWSFGVLMF	EMLTGSLPFQ	GKDRKETMAL	ILKAKLGMPQ	FLSGEAQSLL	RALFKRNPCN
310	320	330	340	350	360
RLGAGIDGVE	EIKRHPFFVT	IDWNTLYRKE	IKPPFKPAVG	RPEDTFHFDP	EFTARTPTDS
370	380	390	400	410	420
PGVPPSANAH	HLFRGFSFVA	SSLIQEPSQQ	DLHKVPVHPI	VQQLHGNNIH	FTDGYEIKED
430	440	450	460	470	480
IGVGSYSVCK	RCVHKATDTE	YAVKIIDKSK	RDPSEEIEIL	LRYGQHPNII	TLKDVYDDGK
490	500	510	520	530	540
FVYLVMELMR	GGELLDRILR	QRYFSEREAS	DVLCTITKTM	DYLHSQGVVH	RDLKPSNILY
550	560	570	580	590	600
RDESGSPESI	RVCDFGFAKQ	LRAGNGLLMT	PCYTANFVAP	EVLKRQGYDA	ACDIWSLGIL
610	620	630	640	650	660
LYTMLAGFTP	FANGPDDTPE	EILARIGSGK	YALSGGNWDS	ISDAAKDVVS	KMLHVDPHQR
670	680	690	700	710	720
LTAMQVLKHP	WVVNREYLSP	NQLSRQDVHL	VKGAMAATYF	ALNRTPQAPR	LEPVLSSNLA
730
QRRGMKRLTS	TRL