AiPD: Autoinhibited Protein Database

Q16659

Gene name	MAPK6 (ERK3, PRKM6)
Protein name	Mitogen-activated protein kinase 6
Names	MAP kinase 6 , MAPK 6 , EC 2.7.11.24 , Extracellular signal-regulated kinase 3 , ERK-3 , MAP kinase isoform p97 , p97-MAPK
Species	Homo sapiens (Human)
KEGG Pathway	hsa:5597
EC number	2.7.11.-: Protein-serine/threonine kinases
Protein Class

Descriptions

MAPK1 encodes Mitogen-activated protein kinase 1, and is involved in diverse cellular responses by phosphorylating cytoplasmic and nuclear proteins. Unlike other MAP kinases, MAPK1 activates via dual phosphorylation of Thr-186 and Tyr-193 within the activation lip, and mutations at Q105 alone were sufficient for autoactivation. Additionally, in the inactive form, L76, Q10 and I87 form a structural unit that restrains intramolecular autophosphorylation by preventing interactions between activation lip residues and the catalytic base (D149) needed for phosphoryl transfer. Mutations at L76, I87 and additionally S153 increased basal specific activity via autophosphorylation of Thr-186 and Tyr-193.

Autoinhibitory domains (AIDs)

67-154 (Autoinhibitory region) SS

Target domain	20-316 (Protein kinase domain)
Relief mechanism	PTM
Assay

AID

67-154 (Autoinhibitory region)

Target domain

20-316 (Protein kinase domain)

Relief mechanism

PTM (Autophosphorylation at Thr-186 and Tyr-193)

Assay

Accessory elements

170-196 (Activation loop from InterPro)

Target domain	20-316 (Protein kinase domain)
Relief mechanism
Assay

References

Emrick MA et al. (2006) "The gatekeeper residue controls autoactivation of ERK2 via a pathway of intramolecular connectivity", Proceedings of the National Academy of Sciences of the United States of America, 103, 18101-6

Emrick MA et al. (2001) "Constitutive activation of extracellular signal-regulated kinase 2 by synergistic point mutations", The Journal of biological chemistry, 276, 46469-79

Autoinhibited structure

Activated structure

5 structures for Q16659

Entry ID	Method	Resolution	Chain	Position	Source
6YKY	X-ray	252 A	A/B/C/D	9-327	PDB
6YLC	X-ray	243 A	A/B/C/D	9-327	PDB
6YLL	X-ray	289 A	A/B	9-327	PDB
7AQB	X-ray	225 A	A/B	9-327	PDB
AF-Q16659-F1	Predicted				AlphaFoldDB

732 variants for Q16659

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
rs1362297704	3	E>G		No	TOPMed gnomAD
COSM1373468	3	E>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1290997772	3	E>Q		No	gnomAD
rs760301718	4	K>E		No	ExAC gnomAD
rs1325106933	4	K>T		No	gnomAD
rs1223537318	5	F>I		No	gnomAD
rs1439629302	5	F>Y		No	TOPMed
rs1566909364	9	M>I		No	Ensembl
rs1807220325	11	I>V		No	TOPMed
rs1445061101	12	H>D		No	gnomAD
rs1248586183	12	H>P		No	TOPMed gnomAD
rs1248586183	12	H>R		No	TOPMed gnomAD
rs1195390961	13	G>A		No	Ensembl
rs2031596173	17	G>S		No	Ensembl
rs1214809211	18	S>F		No	gnomAD
COSM962781	18	S>Y	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1348871504	21	M>T		No	TOPMed gnomAD
rs761678467	21	M>V		No	ExAC gnomAD
rs1261241478	22	D>Y		No	gnomAD
rs765071980	27	G>D		No	ExAC gnomAD
rs750413811	28	C>F		No	ExAC TOPMed gnomAD
rs750413811	28	C>Y		No	ExAC TOPMed gnomAD
rs1488753095	30	G>S		No	gnomAD
rs1413256139	30	G>V		No	gnomAD
rs1346166702	31	N>S		No	TOPMed gnomAD
rs762948597	33	L>F		No	ExAC
rs1595997177	34	V>A		No	Ensembl
COSM190757	34	V>F	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1595997177	34	V>G		No	Ensembl
rs1347670085	34	V>I		No	TOPMed gnomAD
rs2031598013	37	A>P		No	gnomAD
rs2031598096	37	A>V		No	TOPMed
rs1399743987	38	V>A		No	gnomAD
rs1845193334	40	N>D		No	TOPMed gnomAD
rs1845193334	40	N>H		No	TOPMed gnomAD
rs1195894281	40	N>S		No	TOPMed gnomAD
rs889829521	41	D>E		No	TOPMed gnomAD
rs1396212482	42	C>R		No	TOPMed gnomAD
rs2031598629	42	C>S		No	gnomAD
rs2031598724	43	D>Y		No	gnomAD
rs1405074584	44	K>Q		No	TOPMed gnomAD
rs1427239863	45	R>G		No	gnomAD
rs2141086896	47	A>D		No	Ensembl
COSM1373469	47	A>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
TCGA novel	48	I>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1480162460	48	I>V		No	TOPMed gnomAD
COSM434024	49	K>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs2031599631	51	I>T		No	TOPMed
rs1433835276	51	I>V		No	TOPMed gnomAD
rs1365478169	52	V>A		No	gnomAD
rs2031599779	52	V>I		No	TOPMed
TCGA novel	54	T>A	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1225407473	54	T>S		No	TOPMed gnomAD
rs536294389	54	T>S		No	1000Genomes ExAC TOPMed gnomAD
rs1316152850	56	P>A		No	gnomAD
rs2031600484	56	P>L		No	Ensembl
rs756361678	58	S>N		No	ExAC gnomAD
rs756361678	58	S>T		No	ExAC gnomAD
TCGA novel	59	V>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1427869474	61	H>R		No	gnomAD
rs1200298736 COSM48544	64	R>C	lung Variant assessed as Somatic; MODERATE impact. large_intestine [Cosmic, NCI-TCGA]	No	NCI-TCGA Cosmic cosmic curated NCI-TCGA gnomAD
rs1362070965	66	I>N		No	TOPMed gnomAD
rs1566909466	67	K>R		No	Ensembl
rs757641589	70	R>G		No	ExAC gnomAD
TCGA novel	70	R>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1181215244	70	R>T		No	TOPMed
rs779209290	71	R>K		No	ExAC gnomAD
rs140290030	72	L>V		No	ESP ExAC TOPMed gnomAD
rs1259843918	73	D>G		No	TOPMed
rs2031601993	74	H>L		No	gnomAD
rs2031602095 COSM3988003	75	D>G	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic Ensembl
rs371245995	77	I>V		No	ESP ExAC TOPMed gnomAD
rs746532599	79	K>T		No	ExAC gnomAD
rs1485546571	80	V>A		No	TOPMed gnomAD
rs1038749513	81	F>L		No	TOPMed
rs2031602764	81	F>L		No	TOPMed
rs767991240	81	F>S		No	ExAC gnomAD
rs1225918128	82	E>K		No	TOPMed gnomAD
rs1328852820	84	L>I		No	gnomAD
rs2031603181	85	G>S		No	gnomAD
rs1349165927	86	P>S		No	TOPMed
rs776366789	87	S>T		No	ExAC gnomAD
rs761329295	88	G>E		No	ExAC gnomAD
rs2031603609	90	Q>K		No	Ensembl
rs1316872383	92	T>A		No	TOPMed gnomAD
rs773115522	92	T>I		No	ExAC gnomAD
rs774091539	94	D>A		No	ExAC gnomAD
rs760824918	94	D>E		No	ExAC TOPMed gnomAD
rs774091539	94	D>G		No	ExAC gnomAD
rs766419636	94	D>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA gnomAD
rs766419636	94	D>Y		No	ExAC gnomAD
rs1595997380	95	V>M		No	Ensembl
rs1320054630	96	G>A		No	TOPMed
rs897147276	96	G>C		No	TOPMed
rs1234011548	97	S>F		No	TOPMed gnomAD
rs554991448	99	T>M		No	1000Genomes ExAC TOPMed gnomAD
rs554991448	99	T>R		No	1000Genomes ExAC TOPMed gnomAD
rs2031604894	99	T>S		No	TOPMed gnomAD
rs757440608	102	N>T		No	ExAC gnomAD
rs758693564	105	Y>F		No	ExAC gnomAD
rs367726654	105	Y>H		No	ESP ExAC TOPMed gnomAD
rs780623512	106	I>V		No	ExAC TOPMed gnomAD
rs760966150	107	V>F		No	Ensembl
rs1399530794	111	M>I		No	TOPMed gnomAD
rs763386764	111	M>L		No	TOPMed gnomAD
rs763386764	111	M>V		No	TOPMed gnomAD
rs2031606321	114	D>E		No	Ensembl
rs2031606530	117	N>Y		No	gnomAD
rs2031606631	120	E>K		No	TOPMed
rs2031606720	121	Q>H		No	TOPMed
rs1338544237	122	G>S		No	gnomAD
rs1693495031	123	P>S		No	gnomAD
TCGA novel rs1243728321	124	L>F	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	gnomAD NCI-TCGA
rs2141087530	126	E>Q		No	Ensembl
TCGA novel	127	E>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs780533110	129	A>T		No	ExAC TOPMed gnomAD
rs1354474545	129	A>V		No	gnomAD
rs1216474317	130	R>S		No	gnomAD
rs144986992	133	M>T		No	ESP ExAC TOPMed gnomAD
rs1445686875	134	Y>C		No	TOPMed gnomAD
rs2031607802	135	Q>H		No	gnomAD
rs1258782191	136	L>M		No	gnomAD
rs2031608180	138	R>Q		No	TOPMed
rs2031608105	138	R>W		No	Ensembl
rs749102467	140	L>F		No	ExAC gnomAD
rs774370270	143	I>V		No	ExAC gnomAD
rs1232233983	145	S>F		No	TOPMed gnomAD
rs1362268703	147	N>K		No	TOPMed gnomAD
rs2031609103	148	V>L		No	TOPMed
rs202143631	149	L>V		No	Ensembl
TCGA novel	152	D>Y	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1338642987	153	L>I		No	gnomAD
COSM3502127	155	P>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs200525670	158	L>I		No	ExAC TOPMed gnomAD
rs200525670	158	L>V		No	ExAC TOPMed gnomAD
rs1331949688	159	F>C		No	gnomAD
COSM3936782 rs1003338661	159	F>L	oesophagus [Cosmic]	No	cosmic curated TOPMed
rs1682902720	160	I>V		No	TOPMed
rs1033451433	162	T>A		No	TOPMed
TCGA novel rs2031610253	162	T>M	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA gnomAD
rs1033451433	162	T>S		No	TOPMed
rs2031610489	164	D>E		No	TOPMed
rs762089050	165	L>W		No	ExAC gnomAD
rs2031610765	166	V>L		No	Ensembl
rs2031610917	171	D>N		No	Ensembl
rs765450216	176	R>Q		No	ExAC gnomAD
TCGA novel	176	R>W	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs750584368	178	M>I		No	ExAC TOPMed gnomAD
COSM266898	178	M>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs55946048	178	M>V		No	Ensembl
rs1595997599	181	H>Y		No	Ensembl
rs2031611681	183	S>A		No	TOPMed
rs758783352	184	H>Y		No	ExAC TOPMed gnomAD
rs2031725355	186	G>R		No	Ensembl
rs867422980	187	H>Y		No	Ensembl
rs1201035408	188	L>F		No	TOPMed gnomAD
rs1201035408	188	L>V		No	TOPMed gnomAD
TCGA novel	189	S>C	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs751853146	189	S>T		No	ExAC TOPMed gnomAD
rs1161213582	194	T>A		No	gnomAD
rs767917772	194	T>S		No	ExAC TOPMed gnomAD
rs2141095206	196	W>R		No	Ensembl
COSM962783	198	R>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1260019013	199	S>A		No	TOPMed
rs368204873	201	R>C		No	ESP ExAC gnomAD
rs372390092	201	R>H		No	ESP ExAC TOPMed gnomAD
rs149172685	202	L>F		No	ESP ExAC TOPMed gnomAD
rs2031726893	203	L>V		No	gnomAD
rs1305114560	205	S>C		No	TOPMed gnomAD
TCGA novel	206	P>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1596000555	207	N>K		No	Ensembl
rs2031727117	208	N>D		No	TOPMed
rs778827251	208	N>S		No	ExAC
rs1450590391	212	A>V		No	TOPMed gnomAD
rs1051140368	214	D>G		No	Ensembl
rs1382300618	215	M>V		No	TOPMed gnomAD
rs745653526	217	A>D		No	ExAC gnomAD
TCGA novel	217	A>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs375629911	218	A>G		No	ESP ExAC TOPMed gnomAD
rs1241418488	221	I>M		No	TOPMed gnomAD
rs143281288	221	I>V		No	ESP ExAC TOPMed gnomAD
rs1009011804	222	F>S		No	Ensembl
rs755468164	225	M>I		No	ExAC TOPMed gnomAD
COSM1196228 rs368830524	225	M>L	lung [Cosmic]	No	cosmic curated ESP ExAC TOPMed gnomAD
rs1036940376	227	T>I		No	TOPMed gnomAD
rs1036940376	227	T>S		No	TOPMed gnomAD
rs1265626471	228	G>A		No	TOPMed gnomAD
COSM962784	229	K>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1443555806	229	K>Q		No	TOPMed gnomAD
rs200584462	230	T>A		No	1000Genomes ExAC TOPMed gnomAD
rs1207529953	230	T>I		No	gnomAD
TCGA novel	231	L>R	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs372421487	233	A>P		No	ESP TOPMed
rs772606063	234	G>A		No	ExAC gnomAD
rs772606063	234	G>D		No	ExAC gnomAD
rs1318026281	237	E>K		No	gnomAD
rs2032077949	239	E>Q		No	TOPMed
rs2032078084	239	E>V		No	TOPMed
rs1044057471	241	M>I		No	Ensembl
rs2032078462	242	Q>*		No	TOPMed
rs1204475819	242	Q>R		No	TOPMed
rs903708167	243	L>V		No	TOPMed gnomAD
rs1210622437	247	S>F		No	gnomAD
COSM962785	247	S>Y	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1049603	248	I>S		No	Ensembl
rs764695453	248	I>V		No	ExAC TOPMed gnomAD
rs1408874553	250	V>I		No	gnomAD
rs1596010312	251	V>I		No	TOPMed
rs1596010312 COSM1708184	251	V>L	skin [Cosmic]	No	cosmic curated TOPMed
rs761251549	252	H>R		No	ExAC gnomAD
rs878987980	254	E>K		No	Ensembl
rs2032080343	254	E>V		No	Ensembl
COSM1373473 rs1049605	256	R>C	Variant assessed as Somatic; MODERATE impact. large_intestine [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated ExAC NCI-TCGA TOPMed gnomAD
rs750081816	256	R>H		No	ExAC TOPMed gnomAD
rs2032080967	258	E>D		No	gnomAD
rs1193003371	258	E>K		No	TOPMed gnomAD
rs1193003371	258	E>Q		No	TOPMed gnomAD
rs1895132548	259	L>V		No	TOPMed
rs145613421	260	L>F		No	ESP ExAC TOPMed gnomAD
rs145613421	260	L>V		No	ESP ExAC TOPMed gnomAD
rs766216226	261	S>G		No	ExAC TOPMed gnomAD
rs199765167	261	S>R		No	ESP ExAC TOPMed gnomAD
rs2032081410	261	S>T		No	gnomAD
rs754697688	262	V>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA TOPMed gnomAD
COSM1478187	262	V>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs757316726	265	V>L		No	ExAC TOPMed gnomAD
rs779023544	267	I>F		No	ExAC gnomAD
rs779023544	267	I>V		No	ExAC gnomAD
rs746125698	268	R>G		No	ExAC gnomAD
rs1021505158	271	M>L		No	TOPMed
rs1021505158	271	M>V		No	TOPMed
rs1245737384	272	T>A		No	gnomAD
rs2032083333	274	P>S		No	TOPMed
rs1486229979	275	H>Q		No	TOPMed gnomAD
rs372747726	278	L>F		No	ESP ExAC gnomAD
rs545834817	279	T>I		No	1000Genomes ExAC TOPMed gnomAD
rs545834817	279	T>S		No	1000Genomes ExAC TOPMed gnomAD
rs1277784402	280	Q>R		No	TOPMed gnomAD
rs2032084182	282	L>F		No	TOPMed
rs1337458953	283	P>L		No	gnomAD
rs1310244633	286	S>N		No	gnomAD
rs374976142	287	R>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	ESP ExAC NCI-TCGA TOPMed gnomAD
rs374976142	287	R>G		No	ESP ExAC TOPMed gnomAD
rs769091408	287	R>Q		No	ExAC TOPMed gnomAD
rs2141119706	288	E>V		No	Ensembl
rs2032188193	289	A>G		No	Ensembl
rs2032188193	289	A>V		No	Ensembl
rs35697691 COSM48546 VAR_042256	290	L>V	lung large_intestine skin [Cosmic]	No	cosmic curated UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
TCGA novel	299	F>C	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1238912551	300	S>C		No	gnomAD
rs1162220794 COSM962787	301	P>L	Variant assessed as Somatic; MODERATE impact. endometrium [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated NCI-TCGA gnomAD
rs1411001522	302	M>T		No	gnomAD
rs554429888	302	M>V		No	TOPMed gnomAD
rs758581383	303	D>N		No	ExAC gnomAD
rs1383832953 COSM4441644	304	R>Q	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic NCI-TCGA TOPMed gnomAD
rs1171356031	304	R>W		No	gnomAD
TCGA novel	308	E>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs141979362	309	E>A		No	ESP ExAC TOPMed gnomAD
rs1340782751	309	E>D		No	gnomAD
rs2032190646	310	A>S		No	TOPMed
TCGA novel	310	A>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1283774283	311	L>P		No	gnomAD
rs755211001	312	S>F		No	ExAC gnomAD
rs1220525297	312	S>P		No	gnomAD
TCGA novel rs1194496791	314	P>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA TOPMed gnomAD
rs1194496791	314	P>R		No	TOPMed gnomAD
rs2032191177	314	P>T		No	Ensembl
rs200049070	315	Y>*		No	1000Genomes ExAC TOPMed gnomAD
rs1596013809	316	M>T		No	Ensembl
rs1454864264	316	M>V		No	TOPMed gnomAD
rs914522706	317	S>G		No	TOPMed
rs914522706	317	S>R		No	TOPMed
rs769991884	318	I>M		No	ExAC gnomAD
rs1444804091	318	I>V		No	TOPMed
rs2032192023	320	S>C		No	TOPMed
TCGA novel	320	S>Y	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs770472180	323	M>I		No	ExAC TOPMed gnomAD
rs186820701	323	M>V		No	1000Genomes ExAC TOPMed gnomAD
rs2032192325	325	E>K		No	Ensembl
rs759245310	327	I>V		No	ExAC gnomAD
rs771752371	329	S>I		No	ExAC TOPMed gnomAD
rs774940749	330	H>Y		No	ExAC gnomAD
TCGA novel	331	P>S	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
COSM701041	333	H>D	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs544725848	338	V>I		No	1000Genomes ExAC TOPMed gnomAD
rs763755408	339	D>G	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA gnomAD
rs761820104	340	D>G		No	ExAC gnomAD
rs1225886999	340	D>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA gnomAD
rs2032194359	342	L>F		No	Ensembl
rs1346210918	342	L>V		No	TOPMed gnomAD
rs766623251	342	L>W		No	ExAC gnomAD
rs751681991	345	D>G		No	ExAC TOPMed gnomAD
rs751681991	345	D>V		No	ExAC TOPMed gnomAD
COSM701040	346	E>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs754942332	347	T>I		No	ExAC TOPMed gnomAD
rs1489059021	347	T>P		No	gnomAD
rs754942332	347	T>S		No	ExAC TOPMed gnomAD
rs1596013953	348	H>Q		No	Ensembl
rs2032195145	349	S>G		No	gnomAD
rs1261836881	350	H>Q		No	gnomAD
rs2032195268	350	H>Y		No	Ensembl
rs752810357	351	I>T		No	ExAC gnomAD
rs201785438	351	I>V		No	1000Genomes ExAC TOPMed gnomAD
rs1477600166	352	Y>C		No	gnomAD
rs1340286099	354	W>*		No	TOPMed gnomAD
rs2032196186	354	W>C		No	TOPMed
rs1369155923	357	Y>D		No	gnomAD
rs180742711	358	H>Q		No	1000Genomes ExAC TOPMed gnomAD
rs762771625	358	H>Y		No	ExAC gnomAD
rs775423389	359	D>Y	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA gnomAD
rs764304859	361	Q>*		No	ExAC TOPMed gnomAD
rs764304859	361	Q>E		No	ExAC TOPMed gnomAD
rs199741074	361	Q>H		No	1000Genomes ExAC TOPMed gnomAD
rs762189147	362	F>C		No	ExAC gnomAD
rs762189147	362	F>Y		No	ExAC gnomAD
rs765547248	363	S>T		No	ExAC gnomAD
TCGA novel	364	E>D	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs2032307358	365	H>R		No	TOPMed
rs758817453	366	D>E		No	ExAC
rs750986501	366	D>H		No	ExAC gnomAD
rs750986501	366	D>N		No	ExAC gnomAD
rs2032307723	367	W>S		No	gnomAD
rs200832424	368	P>L		No	TOPMed gnomAD
rs200832424	368	P>R		No	TOPMed gnomAD
rs751035223	369	V>E		No	ExAC gnomAD
rs150250447	369	V>I		No	1000Genomes ESP ExAC TOPMed gnomAD
rs150250447	369	V>L		No	1000Genomes ESP ExAC TOPMed gnomAD
rs781010995	370	H>D		No	ExAC TOPMed gnomAD
rs781010995	370	H>N		No	ExAC TOPMed gnomAD
rs2032308427	370	H>R		No	TOPMed
rs747760300	371	N>D		No	ExAC gnomAD
rs75263468	371	N>K		No	1000Genomes ExAC TOPMed gnomAD
rs950225095	373	F>L		No	TOPMed gnomAD
rs777412286	374	D>E		No	ExAC gnomAD
rs1044574424	374	D>V		No	TOPMed gnomAD
rs1303119327	374	D>Y		No	TOPMed gnomAD
rs1566915885	375	I>T		No	Ensembl
rs2032309450	376	D>E		No	TOPMed
rs749309066	376	D>H		No	ExAC gnomAD
rs770773215	377	E>G		No	ExAC gnomAD
rs1293290049	378	V>A		No	gnomAD
rs1384956576	379	Q>H		No	TOPMed gnomAD
rs774278533	379	Q>K		No	ExAC gnomAD
rs1475929459	380	L>V		No	TOPMed gnomAD
TCGA novel	381	D>E	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs2141135877	381	D>G		No	Ensembl
COSM3502128	382	P>S	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs760758118	384	A>T		No	ExAC gnomAD
rs367920269	387	D>H		No	ESP ExAC TOPMed gnomAD
rs367920269 COSM3502129	387	D>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic ESP ExAC NCI-TCGA TOPMed gnomAD
COSM1478188	387	D>Y	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs2141135905	388	V>D		No	Ensembl
rs1208932197	388	V>L		No	gnomAD
rs375131138	389	T>I		No	ESP ExAC TOPMed gnomAD
rs2032310846	391	E>D		No	TOPMed
rs1566915933	391	E>K		No	Ensembl
rs1566915933	391	E>Q		No	Ensembl
rs2141135948	392	E>D		No	Ensembl
rs368383251	393	E>V		No	ESP ExAC TOPMed gnomAD
rs763310448	394	V>I		No	ExAC gnomAD
TCGA novel	395	Q>E	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs2032311162	395	Q>R		No	gnomAD
rs779470068	396	V>I		No	ExAC gnomAD
COSM261914 rs1215512430	399	R>Q	Variant assessed as Somatic; MODERATE impact. large_intestine endometrium breast [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated NCI-TCGA TOPMed
rs2032311570	401	Y>C		No	TOPMed gnomAD
rs1432483696	402	L>V		No	TOPMed gnomAD
rs2032311844	403	D>E		No	TOPMed
rs1293063988	405	D>G		No	TOPMed gnomAD
rs1299609609	405	D>Y		No	TOPMed gnomAD
rs559503234	406	R>G		No	1000Genomes ExAC TOPMed gnomAD
rs755817710	406	R>Q		No	ExAC TOPMed gnomAD
rs559503234	406	R>W		No	1000Genomes ExAC TOPMed gnomAD
rs2032312342 COSM1686219	407	E>*	skin [Cosmic]	No	cosmic curated Ensembl
TCGA novel rs2032312419	407	E>G	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Ensembl
rs55939916	410	L>P		No	Ensembl
rs2032312696	412	D>N		No	TOPMed
rs2032312778	413	P>S		No	Ensembl
rs1219650566	414	A>D		No	TOPMed gnomAD
rs1369633387	414	A>T		No	gnomAD
TCGA novel	415	F>L	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs1326333441	416	D>A		No	TOPMed
TCGA novel	416	D>H	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs372617340	417	T>I		No	ESP ExAC TOPMed
rs778739025	418	N>H		No	ExAC gnomAD
rs1288368055	418	N>K		No	gnomAD
rs138879227	418	N>S		No	1000Genomes ESP ExAC TOPMed gnomAD
rs1488687526	420	S>C		No	gnomAD
rs998009786	421	T>A		No	TOPMed gnomAD
rs2032313913	422	E>Q		No	TOPMed
rs374575355	423	P>A		No	ESP ExAC TOPMed gnomAD
rs1394884509	424	C>F		No	gnomAD
rs1452908889	424	C>W		No	gnomAD
rs1394884509	424	C>Y		No	gnomAD
rs1421263117	425	W>L		No	TOPMed
rs1160135863	426	Q>R		No	gnomAD
rs1596017529	427	Y>F		No	Ensembl
rs1596017529	427	Y>S		No	Ensembl
rs2032314833	428	S>L		No	Ensembl
rs149495146	428	S>P		No	1000Genomes ESP ExAC TOPMed gnomAD
rs2050485322	429	D>H		No	Ensembl
rs1156300038	429	D>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA TOPMed gnomAD
rs2032315252	431	H>D		No	TOPMed
rs1596017552	432	E>K		No	Ensembl
TCGA novel	434	K>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1467091337	434	K>T		No	TOPMed gnomAD
rs748664934	435	Y>C		No	Ensembl
rs763244655	437	D>H		No	ExAC gnomAD
rs760100760	438	L>R		No	ExAC
rs766722888	438	L>V		No	ExAC gnomAD
rs755623270	439	E>D		No	ExAC TOPMed gnomAD
rs1223371225	439	E>Q		No	TOPMed gnomAD
rs752254034	439	E>V		No	ExAC
rs200909174	440	C>F		No	ExAC gnomAD
rs2032316562	440	C>G		No	TOPMed
rs140354959	441	S>G		No	ESP TOPMed gnomAD
rs1222972692	442	H>R		No	TOPMed gnomAD
rs142704242	443	T>S		No	ESP ExAC TOPMed gnomAD
rs2032317218	447	K>T		No	Ensembl
TCGA novel	448	T>A	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs190252061	448	T>K		No	1000Genomes ExAC TOPMed gnomAD
rs190252061	448	T>M		No	1000Genomes ExAC TOPMed gnomAD
rs190252061	448	T>R		No	1000Genomes ExAC TOPMed gnomAD
rs779899775	449	R>S		No	ExAC
rs749492052	453	Y>C		No	ExAC gnomAD
rs1249736793	454	L>S		No	gnomAD
rs774845359	456	N>K		No	ExAC gnomAD
rs1467053457	458	V>L		No	gnomAD
rs768147270	459	W>L		No	ExAC TOPMed gnomAD
rs1440069166	460	R>G		No	TOPMed gnomAD
rs534617445	460	R>K		No	1000Genomes ExAC TOPMed gnomAD
rs2032320676	461	E>D		No	Ensembl
rs763621068	461	E>G		No	ExAC TOPMed gnomAD
rs760125835	461	E>Q		No	ExAC TOPMed gnomAD
rs2141136611	462	S>C		No	Ensembl
rs753474808	462	S>I		No	ExAC gnomAD
rs753474808	462	S>N		No	ExAC gnomAD
rs753474808	462	S>T		No	ExAC gnomAD
rs1273182871	463	E>D		No	gnomAD
rs1480971892	463	E>G		No	TOPMed
rs1234703044	464	V>D		No	TOPMed
rs1423017092	464	V>L		No	gnomAD
rs2032321788	466	H>R		No	TOPMed
rs756914214	466	H>Y		No	ExAC gnomAD
rs765007291	467	Y>C		No	ExAC gnomAD
rs750222974	468	Y>C		No	ExAC TOPMed gnomAD
rs2032322315	468	Y>H		No	Ensembl
rs750222974	468	Y>S		No	ExAC TOPMed gnomAD
rs1281490811	472	L>I		No	TOPMed gnomAD
rs2032322673	472	L>P		No	Ensembl
rs779988135	473	I>V		No	ExAC gnomAD
rs1346319120	476	L>F		No	TOPMed
COSM3887133	477	S>F	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1186604432	477	S>P		No	gnomAD
rs1555400802	478	N>I		No	TOPMed
rs1301132670	478	N>S		No	TOPMed gnomAD
rs1224859877	480	K>E		No	Ensembl
rs147343540	483	S>N		No	ESP ExAC TOPMed gnomAD
rs749533258	484	K>*		No	ExAC
rs771182469	486	K>I		No	ExAC gnomAD
rs1441005292	487	S>P		No	TOPMed gnomAD
rs375012210	488	D>A		No	ESP TOPMed gnomAD
rs375012210	488	D>G		No	ESP TOPMed gnomAD
COSM71563	489	K>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs746252225	490	K>E		No	ExAC TOPMed gnomAD
rs1394273765	491	G>S	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA TOPMed gnomAD
rs2032325389	491	G>V		No	TOPMed gnomAD
TCGA novel	492	K>R	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1361109316	495	C>R		No	gnomAD
rs1415535953	495	C>Y		No	gnomAD
rs2032326039	497	R>K		No	Ensembl
rs1292761098	505	I>L		No	gnomAD
rs200496473	506	A>V		No	ExAC TOPMed gnomAD
COSM137005 rs1311972596	508	E>K	skin [Cosmic]	No	cosmic curated gnomAD
rs2032327076	510	A>T		No	gnomAD
rs768101670	510	A>V		No	ExAC TOPMed gnomAD
rs776198020	511	S>P		No	ExAC gnomAD
rs1485788043	513	Q>H		No	gnomAD
rs1213324777	514	L>R		No	Ensembl
rs761159355	515	A>S		No	ExAC gnomAD
rs761159355 COSM701039	515	A>T	lung [Cosmic]	No	cosmic curated ExAC gnomAD
rs2032328513	516	G>E		No	Ensembl
rs1254814283	516	G>R		No	gnomAD
COSM962788	516	G>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs371262771 COSM1517470	518	E>Q	lung [Cosmic]	No	cosmic curated ESP ExAC TOPMed gnomAD
rs142670170	520	E>D		No	1000Genomes ESP ExAC TOPMed gnomAD
rs374841305	520	E>K		No	ESP ExAC TOPMed gnomAD
TCGA novel rs766130172	521	K>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC gnomAD NCI-TCGA
rs2032329427	522	N>S		No	TOPMed
rs751499153	524	G>R		No	ExAC TOPMed gnomAD
rs754927155	524	G>V		No	ExAC gnomAD
rs777783622	526	D>H		No	ExAC TOPMed gnomAD
rs777783622	526	D>N		No	ExAC TOPMed gnomAD
rs777783622	526	D>Y		No	ExAC TOPMed gnomAD
rs1401899119	527	F>I		No	gnomAD
COSM3420416	527	F>S	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1319606557	528	D>V		No	gnomAD
rs1326357446	529	S>C		No	TOPMed gnomAD
COSM3887134	529	S>F	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
TCGA novel	529	S>P	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1401148589	531	I>F		No	TOPMed gnomAD
rs1289291339	533	G>A		No	TOPMed gnomAD
rs779300139	534	T>I		No	ExAC gnomAD
rs1348996844	534	T>S		No	gnomAD
COSM1323949	535	I>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs772608176	535	I>S		No	ExAC gnomAD
rs368094632	535	I>V		No	1000Genomes ESP ExAC TOPMed gnomAD
rs751900303	536	Q>K		No	Ensembl
rs1261024218	536	Q>P		No	gnomAD
rs2032332416	537	L>I		No	TOPMed
rs1445223382	537	L>P		No	gnomAD
rs2032332416	537	L>V		No	TOPMed
rs1156987091	538	S>N		No	TOPMed
COSM6142728 COSM1517469 rs1156987091	538	S>T	lung Variant assessed as Somatic; MODERATE impact. [Cosmic, NCI-TCGA]	No	cosmic curated NCI-TCGA Cosmic TOPMed
rs866931478	539	S>C		No	Ensembl
rs1200827226	539	S>P		No	gnomAD
COSM1373476	539	S>Y	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
TCGA novel	540	Q>H	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs747529399	541	H>D		No	ExAC gnomAD
rs747529399	541	H>Y		No	ExAC gnomAD
rs1393470147	543	P>S		No	gnomAD
rs1418710403	544	T>I		No	TOPMed gnomAD
rs1418710403	544	T>S		No	TOPMed gnomAD
rs2032333819	545	D>G		No	Ensembl
rs769208660	545	D>N		No	ExAC gnomAD
rs776941865	546	V>D		No	ExAC TOPMed gnomAD
rs776941865	546	V>G		No	ExAC TOPMed gnomAD
rs2032334343	548	D>G		No	gnomAD
rs1187534070	548	D>N		No	TOPMed
rs769249333	552	D>E		No	ExAC TOPMed gnomAD
rs2032334899	553	L>F		No	TOPMed
rs2032334827	553	L>W		No	gnomAD
rs772891162	555	S>R		No	ExAC TOPMed gnomAD
rs139563932	556	S>A		No	1000Genomes ESP ExAC TOPMed gnomAD
rs139563932	556	S>T		No	1000Genomes ESP ExAC TOPMed gnomAD
rs766218454	558	S>C		No	ExAC TOPMed gnomAD
rs766218454	558	S>F		No	ExAC TOPMed gnomAD
rs2032335589	559	Q>H		No	Ensembl
rs2032335506	559	Q>P		No	Ensembl
rs1211590081	561	E>D		No	TOPMed gnomAD
rs2032335831	561	E>Q		No	TOPMed gnomAD
rs1017123008	562	L>W		No	TOPMed
rs2032336033	563	K>Q		No	TOPMed
rs759188992	563	K>R		No	ExAC gnomAD
rs1191514706	564	S>N		No	TOPMed gnomAD
rs767505442	564	S>R		No	ExAC
rs2032336530	565	L>F		No	TOPMed
rs752528392	565	L>S		No	ExAC gnomAD
rs1421124344	566	I>L		No	gnomAD
rs1421124344	566	I>V		No	gnomAD
rs1451691176	569	S>L		No	gnomAD
rs757448967	571	S>R		No	ExAC gnomAD
rs779108097	571	S>R		No	ExAC TOPMed gnomAD
rs1461302188	572	Q>K		No	gnomAD
rs750726475	573	E>K		No	ExAC gnomAD
rs143744875	575	Q>K		No	ESP ExAC TOPMed gnomAD
rs376638037	575	Q>R		No	ESP ExAC gnomAD
rs747410314	576	E>K		No	ExAC TOPMed gnomAD
rs747410314	576	E>Q		No	ExAC TOPMed gnomAD
rs368759134	578	G>E		No	ESP ExAC gnomAD
rs1273808558	581	N>H		No	gnomAD
rs781736100	582	L>M		No	ExAC gnomAD
rs781736100	582	L>V		No	ExAC gnomAD
rs748571787	583	A>G		No	ExAC
rs1259760349	584	Q>P		No	gnomAD
rs1566916472	585	L>S		No	gnomAD
rs772694895	586	E>K		No	ExAC TOPMed
rs772694895	586	E>Q		No	ExAC TOPMed
rs1250040312	587	A>V		No	gnomAD
TCGA novel	589	Y>C	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1417471855	589	Y>H		No	TOPMed gnomAD
rs1167259516	590	Q>*		No	TOPMed
rs1190137502	590	Q>R		No	gnomAD
rs537289987	592	S>C		No	TOPMed gnomAD
rs537289987	592	S>F	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA TOPMed gnomAD
rs773819403	593	W>R		No	ExAC TOPMed gnomAD
rs759397866	594	D>A		No	ExAC gnomAD
rs1462797665	594	D>E		No	TOPMed gnomAD
rs1764481098	594	D>H		No	TOPMed
rs2032339798	596	Q>H		No	TOPMed
rs1393873249	599	S>T		No	gnomAD
rs575423229	600	G>A		No	1000Genomes ExAC TOPMed gnomAD
rs575423229	600	G>D		No	1000Genomes ExAC TOPMed gnomAD
rs2032340408	602	E>D		No	TOPMed
rs2032340338	602	E>Q		No	Ensembl
rs2032340557	603	D>E		No	TOPMed
rs1430614252	603	D>N		No	TOPMed
TCGA novel	603	D>Y	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs765474727	605	F>C		No	ExAC gnomAD
rs1354199372	605	F>V		No	TOPMed gnomAD
rs750530035 TCGA novel	606	F>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC gnomAD NCI-TCGA
rs758492531	607	I>V		No	ExAC TOPMed gnomAD
TCGA novel	608	N>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
COSM4818551	609	Q>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
COSM4916432 rs766643187	609	Q>R	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic ExAC NCI-TCGA TOPMed gnomAD
rs144209444	610	F>S		No	ExAC TOPMed gnomAD
rs1213205140	611	C>S		No	gnomAD
rs2032341884	611	C>W		No	TOPMed
rs1213205140	611	C>Y		No	gnomAD
rs1254330272	614	R>S		No	TOPMed gnomAD
rs146538100	616	D>H		No	ESP ExAC TOPMed gnomAD
rs781388541	617	E>D		No	ExAC gnomAD
rs1186490254	617	E>G		No	gnomAD
rs1355183977	619	V>G		No	TOPMed gnomAD
rs2032342554	620	E>Q		No	TOPMed
rs778184504	622	E>*		No	ExAC TOPMed gnomAD
rs778184504	622	E>Q		No	ExAC TOPMed gnomAD
rs748812099	623	N>D		No	ExAC gnomAD
rs201436164	624	T>S		No	1000Genomes ExAC TOPMed gnomAD
rs187167606	624	T>S		No	1000Genomes
rs371736330	625	Y>*		No	ESP ExAC
rs2141137990	625	Y>S		No	Ensembl
rs771954953	626	T>S		No	ExAC gnomAD
rs2032343735	626	T>S		No	Ensembl
rs2032343958	627	S>G		No	Ensembl
rs1277060970	628	Y>*		No	TOPMed gnomAD
rs2141138030	628	Y>N		No	Ensembl
rs1390136007	630	D>E		No	TOPMed
rs1566916592	630	D>N		No	Ensembl
rs760763262	631	K>R		No	ExAC gnomAD
rs2032344531	632	F>L		No	TOPMed
rs1596018534	634	S>C		No	Ensembl
rs1596018534	634	S>G		No	Ensembl
rs776658192	635	R>K		No	ExAC TOPMed gnomAD
rs776658192	635	R>M		No	ExAC TOPMed gnomAD
rs143385036	635	R>S		No	1000Genomes ESP ExAC TOPMed gnomAD
rs2032345196	637	E>*		No	Ensembl
rs1244390748	637	E>D		No	gnomAD
rs2032345518	638	D>G		No	TOPMed
rs1486489557	638	D>N		No	gnomAD
rs1210632088	639	T>S		No	gnomAD
rs541397063	640	E>A		No	1000Genomes ExAC gnomAD
rs1260126798	640	E>D		No	gnomAD
COSM962789	643	E>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs753062718	643	E>G		No	ExAC TOPMed gnomAD
rs756415242	644	T>S		No	ExAC gnomAD
rs2032346727	645	E>Q		No	Ensembl
rs1160670156	646	P>A		No	TOPMed gnomAD
rs1160670156	646	P>T		No	TOPMed gnomAD
rs1429974555	647	V>E		No	TOPMed gnomAD
rs1429974555	647	V>G		No	TOPMed gnomAD
rs2032347381	648	E>G		No	TOPMed
rs1250624385	649	D>Y		No	TOPMed
rs1372975234	650	G>R		No	gnomAD
rs756832443	651	K>N		No	ExAC gnomAD
rs757108172	651	K>Q		No	TOPMed
TCGA novel	652	L>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1370511392	652	L>P		No	TOPMed gnomAD
rs778268878	653	G>R		No	ExAC TOPMed gnomAD
rs2141138305	653	G>V		No	Ensembl
rs778268878	653	G>W		No	ExAC TOPMed gnomAD
rs574779395	654	E>G		No	1000Genomes ExAC TOPMed gnomAD
rs1815368548	654	E>K		No	TOPMed
rs2032348449	655	R>G		No	gnomAD
rs148363441	655	R>K		No	ESP ExAC TOPMed gnomAD
rs1301093848	656	G>A		No	TOPMed gnomAD
rs1301093848	656	G>E		No	TOPMed gnomAD
rs1215738297	656	G>R		No	gnomAD
rs1301093848	656	G>V		No	TOPMed gnomAD
rs889695827	657	H>L		No	TOPMed gnomAD
COSM1257317 rs1566916684	657	H>N	oesophagus [Cosmic]	No	cosmic curated Ensembl
rs889695827	657	H>R		No	TOPMed gnomAD
rs1470159211	658	E>K		No	gnomAD
rs1252697587	659	E>G		No	gnomAD
rs746820376	659	E>K		No	ExAC TOPMed gnomAD
rs1368993332	660	G>A		No	TOPMed gnomAD
rs1368993332	660	G>V		No	TOPMed gnomAD
rs768529082	661	F>L		No	ExAC gnomAD
rs1408103658	662	L>P		No	TOPMed gnomAD
rs1178534312	662	L>V		No	TOPMed gnomAD
rs761816188	663	N>Y		No	ExAC TOPMed gnomAD
rs1650134787	664	N>D		No	gnomAD
rs1650134787	664	N>H		No	gnomAD
rs2032350274	665	S>N		No	TOPMed gnomAD
rs941225101	665	S>R		No	TOPMed gnomAD
rs771100536	666	G>R		No	ExAC TOPMed gnomAD
rs2032350563	667	E>V		No	Ensembl
rs200110762	668	F>I		No	ExAC TOPMed gnomAD
rs2032350799	669	L>I		No	Ensembl
rs2032350875	670	F>L		No	Ensembl
rs1368435941	670	F>S		No	gnomAD
rs2032351185	673	Q>R		No	Ensembl
rs2032351262	674	L>P		No	Ensembl
COSM962790 rs752870440	675	E>K	Variant assessed as Somatic; MODERATE impact. endometrium [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated ExAC NCI-TCGA TOPMed gnomAD
rs1486506446	677	I>T		No	TOPMed
rs2032351549	677	I>V		No	gnomAD
rs1277928348	679	I>M		No	TOPMed
rs140553940	681	Q>H		No	1000Genomes ESP ExAC TOPMed gnomAD
rs2141138634	681	Q>R		No	Ensembl
rs1566916764	682	F>C		No	Ensembl
rs530931440	683	H>N		No	1000Genomes ExAC TOPMed gnomAD
rs530931440	683	H>Y		No	1000Genomes ExAC TOPMed gnomAD
rs2032352680	684	S>N		No	TOPMed
rs2032352602	684	S>R		No	Ensembl
rs2032352744	684	S>R		No	Ensembl
rs778555440	685	P>L		No	ExAC gnomAD
rs757873826	686	V>I		No	ExAC gnomAD
rs377715204	687	G>E		No	ESP ExAC TOPMed gnomAD
rs1297220936	687	G>R		No	TOPMed gnomAD
rs1297220936	687	G>W		No	TOPMed gnomAD
rs552216494	690	L>F		No	1000Genomes ExAC TOPMed gnomAD
rs1164084902	691	K>N		No	gnomAD
rs781121113	691	K>R		No	ExAC gnomAD
rs769620879	693	I>M		No	ExAC TOPMed gnomAD
rs147078476	693	I>V		No	1000Genomes ESP ExAC TOPMed gnomAD
rs773142942	694	Q>E		No	ExAC gnomAD
rs528265673	695	A>T		No	1000Genomes ExAC gnomAD
rs764503300	698	T>P		No	ExAC gnomAD
rs754202123	699	P>L		No	ExAC TOPMed gnomAD
rs2032354183	699	P>T		No	TOPMed
rs765679331	700	S>F		No	ExAC gnomAD
rs2032354549	700	S>P		No	TOPMed
rs1001192086	701	A>T		No	Ensembl
rs568337067	702	M>L		No	1000Genomes ExAC TOPMed gnomAD
rs568337067	702	M>V		No	1000Genomes ExAC TOPMed gnomAD
rs1259047451	703	K>R		No	gnomAD
rs779683989	704	S>A		No	ExAC gnomAD
rs2032355258	704	S>Y		No	TOPMed
rs2032355456	705	S>F		No	TOPMed
rs780925007 COSM3706622	706	P>S	liver [Cosmic]	No	cosmic curated ExAC TOPMed gnomAD
rs138740566	710	H>N		No	ESP TOPMed gnomAD
rs2032355855	710	H>Q		No	TOPMed
rs1327084787	711	Q>E		No	TOPMed
rs558995287	711	Q>H		No	1000Genomes TOPMed gnomAD
rs1418443387	712	T>R		No	gnomAD
rs1166893636	714	S>N		No	TOPMed gnomAD
rs967444012	715	S>N		No	TOPMed gnomAD
rs777603708	715	S>R		No	ExAC gnomAD
rs967444012	715	S>T		No	TOPMed gnomAD
rs1415443297	717	L>V		No	gnomAD
rs2032358132	719	H>R		No	Ensembl
COSM3816321 rs1339215784	720	L>V	breast [Cosmic]	No	cosmic curated gnomAD
COSM4922923	722	N>=	Variant assessed as Somatic; LOW impact. [NCI-TCGA]	No	NCI-TCGA Cosmic

No associated diseases with Q16659

4 regional properties for Q16659

Type	Name	Position	InterPro Accession
domain	Protein kinase domain	286 - 539	IPR000719
domain	Serine-threonine/tyrosine-protein kinase, catalytic domain	286 - 535	IPR001245
domain	ACT domain	174 - 249	IPR002912
active_site	Serine/threonine-protein kinase, active site	403 - 415	IPR008271

Functions

		Description
EC Number	2.7.11.-	Protein-serine/threonine kinases
Subcellular Localization	Cytoplasm Nucleus	Translocates to the cytoplasm following interaction with MAPKAPK5
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.
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.
protein-containing complex	A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together.
septin cytoskeleton	The part of the cytoskeleton (the internal framework of a cell) composed of septins and associated proteins. Includes septin cytoskeleton-associated complexes.

6 GO annotations of molecular function

Name	Definition
ATP binding	Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
MAP kinase activity	Catalysis of the reaction
protein heterodimerization activity	Binding to a nonidentical protein to form a heterodimer.
protein kinase binding	Binding to a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate.
protein serine kinase activity	Catalysis of the reactions
protein serine/threonine kinase activity	Catalysis of the reactions

5 GO annotations of biological process

Name	Definition
cell cycle	The progression of biochemical and morphological phases and events that occur in a cell during successive cell replication or nuclear replication events. Canonically, the cell cycle comprises the replication and segregation of genetic material followed by the division of the cell, but in endocycles or syncytial cells nuclear replication or nuclear division may not be followed by cell division.
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.
positive regulation of dendritic spine development	Any process that increases the rate, frequency, or extent of dendritic spine development, the process whose specific outcome is the progression of the dendritic spine over time, from its formation to the mature structure.
protein phosphorylation	The process of introducing a phosphate group on to 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.

92 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
P16892	FUS3	Mitogen-activated protein kinase FUS3	Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)	SS
P14681	KSS1	Mitogen-activated protein kinase KSS1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)	SS
A5PKJ4	MAPK7	Mitogen-activated protein kinase 7	Bos taurus (Bovine)	SS
Q3T0N5	MAPK13	Mitogen-activated protein kinase 13	Bos taurus (Bovine)	SS
P46196	MAPK1	Mitogen-activated protein kinase 1	Bos taurus (Bovine)	SS
Q5F3W3	MAPK6	Mitogen-activated protein kinase 6	Gallus gallus (Chicken)	SS
Q95NE7	MAPK14	Mitogen-activated protein kinase 14	Pan troglodytes (Chimpanzee)	SS
Q9N272	MAPK13	Mitogen-activated protein kinase 13	Pan troglodytes (Chimpanzee)	SS
Q9W354	Erk7	Extracellular signal-regulated kinase 7	Drosophila melanogaster (Fruit fly)	SS
O61443	p38b	Mitogen-activated protein kinase p38b	Drosophila melanogaster (Fruit fly)	SS
O62618	p38a	Mitogen-activated protein kinase p38a	Drosophila melanogaster (Fruit fly)	SS
P83100	p38c	Putative mitogen-activated protein kinase 14C	Drosophila melanogaster (Fruit fly)	SS
P40417	rl	Mitogen-activated protein kinase ERK-A	Drosophila melanogaster (Fruit fly)	SS
P31152	MAPK4	Mitogen-activated protein kinase 4	Homo sapiens (Human)	SS
P20794	MAK	Serine/threonine-protein kinase MAK	Homo sapiens (Human)	PR
Q9UQ07	MOK	MAPK/MAK/MRK overlapping kinase	Homo sapiens (Human)	PR
Q8TD08	MAPK15	Mitogen-activated protein kinase 15	Homo sapiens (Human)	SS
P45984	MAPK9	Mitogen-activated protein kinase 9	Homo sapiens (Human)	SS
P45983	MAPK8	Mitogen-activated protein kinase 8	Homo sapiens (Human)	EV
P53779	MAPK10	Mitogen-activated protein kinase 10	Homo sapiens (Human)	EV
Q9UBE8	NLK	Serine/threonine-protein kinase NLK	Homo sapiens (Human)	SS
P27361	MAPK3	Mitogen-activated protein kinase 3	Homo sapiens (Human)	SS
P28482	MAPK1	Mitogen-activated protein kinase 1	Homo sapiens (Human)	EV
Q13164	MAPK7	Mitogen-activated protein kinase 7	Homo sapiens (Human)	SS
P53778	MAPK12	Mitogen-activated protein kinase 12	Homo sapiens (Human)	SS
O15264	MAPK13	Mitogen-activated protein kinase 13	Homo sapiens (Human)	SS
Q15759	MAPK11	Mitogen-activated protein kinase 11	Homo sapiens (Human)	SS
Q16539	MAPK14	Mitogen-activated protein kinase 14	Homo sapiens (Human)	SS
Q9Z1B7	Mapk13	Mitogen-activated protein kinase 13	Mus musculus (Mouse)	SS
P47811	Mapk14	Mitogen-activated protein kinase 14	Mus musculus (Mouse)	SS
Q63844	Mapk3	Mitogen-activated protein kinase 3	Mus musculus (Mouse)	SS
P63085	Mapk1	Mitogen-activated protein kinase 1	Mus musculus (Mouse)	SS
Q9WVS8	Mapk7	Mitogen-activated protein kinase 7	Mus musculus (Mouse)	SS
Q9WUI1	Mapk11	Mitogen-activated protein kinase 11	Mus musculus (Mouse)	SS
O08911	Mapk12	Mitogen-activated protein kinase 12	Mus musculus (Mouse)	SS
Q80Y86	Mapk15	Mitogen-activated protein kinase 15	Mus musculus (Mouse)	SS
Q61532	Mapk6	Mitogen-activated protein kinase 6	Mus musculus (Mouse)	SS
Q6P5G0	Mapk4	Mitogen-activated protein kinase 4	Mus musculus (Mouse)	SS
P70618	Mapk14	Mitogen-activated protein kinase 14	Rattus norvegicus (Rat)	SS
Q9WTY9	Mapk13	Mitogen-activated protein kinase 13	Rattus norvegicus (Rat)	SS
P63086	Mapk1	Mitogen-activated protein kinase 1	Rattus norvegicus (Rat)	SS
Q9Z2A6	Mapk15	Mitogen-activated protein kinase 15	Rattus norvegicus (Rat)	SS
P21708	Mapk3	Mitogen-activated protein kinase 3	Rattus norvegicus (Rat)	SS
Q63538	Mapk12	Mitogen-activated protein kinase 12	Rattus norvegicus (Rat)	SS
Q63454	Mapk4	Mitogen-activated protein kinase 4	Rattus norvegicus (Rat)	SS
P0C865	Mapk7	Mitogen-activated protein kinase 7	Rattus norvegicus (Rat)	SS
P27704	Mapk6	Mitogen-activated protein kinase 6	Rattus norvegicus (Rat)	SS
Q5ZCI1	MPK10	Mitogen-activated protein kinase 10	Oryza sativa subsp. japonica (Rice)	SS
Q5VP69	MPK16	Mitogen-activated protein kinase 16	Oryza sativa subsp. japonica (Rice)	SS
Q5SN53	MPK8	Mitogen-activated protein kinase 8	Oryza sativa subsp. japonica (Rice)	SS
Q0E459	MPK13	Mitogen-activated protein kinase 13	Oryza sativa subsp. japonica (Rice)	SS
Q6Z437	MPK3	Mitogen-activated protein kinase 3	Oryza sativa subsp. japonica (Rice)	SS
Q75KK8	MPK14	Mitogen-activated protein kinase 14	Oryza sativa subsp. japonica (Rice)	SS
Q67C40	MPK7	Mitogen-activated protein kinase 7	Oryza sativa subsp. japonica (Rice)	SS
Q6L5F7	MPK17	Mitogen-activated protein kinase 17	Oryza sativa subsp. japonica (Rice)	SS
Q5VN19	MPK11	Mitogen-activated protein kinase 11	Oryza sativa subsp. japonica (Rice)	SS
Q5Z859	MPK4	Mitogen-activated protein kinase 4	Oryza sativa subsp. japonica (Rice)	SS
Q5Z9J0	MPK12	Mitogen-activated protein kinase 12	Oryza sativa subsp. japonica (Rice)	SS
Q53N72	MPK15	Mitogen-activated protein kinase 15	Oryza sativa subsp. japonica (Rice)	SS
Q336X9	MPK6	Mitogen-activated protein kinase 6	Oryza sativa subsp. japonica (Rice)	SS
Q5J4W4	MPK2	Mitogen-activated protein kinase 2	Oryza sativa subsp. japonica (Rice)	SS
Q84UI5	MPK1	Mitogen-activated protein kinase 1	Oryza sativa subsp. japonica (Rice)	SS
Q10N20	MPK5	Mitogen-activated protein kinase 5	Oryza sativa subsp. japonica (Rice)	SS
Q17446	pmk-1	Mitogen-activated protein kinase pmk-1	Caenorhabditis elegans	SS
Q11179	mapk-15	Mitogen-activated protein kinase 15	Caenorhabditis elegans	SS
Q8MXI4	pmk-2	Mitogen-activated protein kinase pmk-2	Caenorhabditis elegans	SS
O44514	pmk-3	Mitogen-activated protein kinase pmk-3	Caenorhabditis elegans	PR
G5EBT1	sma-5	Mitogen-activated protein kinase sma-5	Caenorhabditis elegans	SS
P39745	mpk-1	Mitogen-activated protein kinase mpk-1	Caenorhabditis elegans	SS
Q39021	MPK1	Mitogen-activated protein kinase 1	Arabidopsis thaliana (Mouse-ear cress)	SS
Q9LM33	MPK8	Mitogen-activated protein kinase 8	Arabidopsis thaliana (Mouse-ear cress)	SS
Q9C5C0	MPK18	Mitogen-activated protein kinase 18	Arabidopsis thaliana (Mouse-ear cress)	SS
Q39022	MPK2	Mitogen-activated protein kinase 2	Arabidopsis thaliana (Mouse-ear cress)	SS
Q9C9U4	MPK15	Mitogen-activated protein kinase 15	Arabidopsis thaliana (Mouse-ear cress)	SS
Q84M93	MPK17	Mitogen-activated protein kinase 17	Arabidopsis thaliana (Mouse-ear cress)	SS
Q39027	MPK7	Mitogen-activated protein kinase 7	Arabidopsis thaliana (Mouse-ear cress)	SS
Q9SJG9	MPK20	Mitogen-activated protein kinase 20	Arabidopsis thaliana (Mouse-ear cress)	SS
Q9LUC3	MPK19	Mitogen-activated protein kinase 19	Arabidopsis thaliana (Mouse-ear cress)	SS
Q9LV37	MPK9	Mitogen-activated protein kinase 9	Arabidopsis thaliana (Mouse-ear cress)	SS
O23236	MPK14	Mitogen-activated protein kinase 14	Arabidopsis thaliana (Mouse-ear cress)	SS
Q8W4J2	MPK16	Mitogen-activated protein kinase 16	Arabidopsis thaliana (Mouse-ear cress)	SS
Q39023	MPK3	Mitogen-activated protein kinase 3	Arabidopsis thaliana (Mouse-ear cress)	SS
Q39024	MPK4	Mitogen-activated protein kinase 4	Arabidopsis thaliana (Mouse-ear cress)	SS
Q39025	MPK5	Mitogen-activated protein kinase 5	Arabidopsis thaliana (Mouse-ear cress)	SS
Q39026	MPK6	Mitogen-activated protein kinase 6	Arabidopsis thaliana (Mouse-ear cress)	SS
Q9M1Z5	MPK10	Mitogen-activated protein kinase 10	Arabidopsis thaliana (Mouse-ear cress)	SS
Q8GYQ5	MPK12	Mitogen-activated protein kinase 12	Arabidopsis thaliana (Mouse-ear cress)	SS
Q9LMM5	MPK11	Mitogen-activated protein kinase 11	Arabidopsis thaliana (Mouse-ear cress)	SS
Q9LQQ9	MPK13	Mitogen-activated protein kinase 13	Arabidopsis thaliana (Mouse-ear cress)	SS
O42376	mapk12	Mitogen-activated protein kinase 12	Danio rerio (Zebrafish) (Brachydanio rerio)	SS
Q9DGE1	mapk14b	Mitogen-activated protein kinase 14B	Danio rerio (Zebrafish) (Brachydanio rerio)	SS
Q9DGE2	mapk14a	Mitogen-activated protein kinase 14A	Danio rerio (Zebrafish) (Brachydanio rerio)	SS

10	20	30	40	50	60
MAEKFESLMN	IHGFDLGSRY	MDLKPLGCGG	NGLVFSAVDN	DCDKRVAIKK	IVLTDPQSVK
70	80	90	100	110	120
HALREIKIIR	RLDHDNIVKV	FEILGPSGSQ	LTDDVGSLTE	LNSVYIVQEY	METDLANVLE
130	140	150	160	170	180
QGPLLEEHAR	LFMYQLLRGL	KYIHSANVLH	RDLKPANLFI	NTEDLVLKIG	DFGLARIMDP
190	200	210	220	230	240
HYSHKGHLSE	GLVTKWYRSP	RLLLSPNNYT	KAIDMWAAGC	IFAEMLTGKT	LFAGAHELEQ
250	260	270	280	290	300
MQLILESIPV	VHEEDRQELL	SVIPVYIRND	MTEPHKPLTQ	LLPGISREAL	DFLEQILTFS
310	320	330	340	350	360
PMDRLTAEEA	LSHPYMSIYS	FPMDEPISSH	PFHIEDEVDD	ILLMDETHSH	IYNWERYHDC
370	380	390	400	410	420
QFSEHDWPVH	NNFDIDEVQL	DPRALSDVTD	EEEVQVDPRK	YLDGDREKYL	EDPAFDTNYS
430	440	450	460	470	480
TEPCWQYSDH	HENKYCDLEC	SHTCNYKTRS	SSYLDNLVWR	ESEVNHYYEP	KLIIDLSNWK
490	500	510	520	530	540
EQSKEKSDKK	GKSKCERNGL	VKAQIALEEA	SQQLAGKERE	KNQGFDFDSF	IAGTIQLSSQ
550	560	570	580	590	600
HEPTDVVDKL	NDLNSSVSQL	ELKSLISKSV	SQEKQEKGMA	NLAQLEALYQ	SSWDSQFVSG
610	620	630	640	650	660
GEDCFFINQF	CEVRKDEQVE	KENTYTSYLD	KFFSRKEDTE	MLETEPVEDG	KLGERGHEEG
670	680	690	700	710	720
FLNNSGEFLF	NKQLESIGIP	QFHSPVGSPL	KSIQATLTPS	AMKSSPQIPH	QTYSSILKHL

N