AiPD: Autoinhibited Protein Database

Q8NB16

Gene name	MLKL
Protein name	Mixed lineage kinase domain-like protein
Names	hMLKL
Species	Homo sapiens (Human)
KEGG Pathway	hsa:197259
EC number
Protein Class

Descriptions

MLKL (mixed-lineage kinase domain-like protein) is a key effector in necroptosis, consisting of two domains connected by brace helices. The N-terminal executioner domain forms a four-helix bundle crucial for its function. MLKL’s autoinhibited state is maintained by the brace helix α6, which interacts with the four-helix bundle. This interaction prevents MLKL from oligomerizing and integrating into the plasma membrane, which is necessary for necroptosis. Upon phosphorylation by RIPK3, the autoinhibitory brace helix α6 detaches, leading to MLKL oligomerization and membrane integration, resulting in cell death. Covalent inhibitors targeting MLKL can stabilize its autoinhibited state by reinforcing the interaction between brace helix α6 and the four-helix bundle, thus preventing necroptosis.

Autoinhibitory domains (AIDs)

Target domain	2-154 (N-terminal executioner domain)
Relief mechanism	PTM
Assay	Structural analysis, Peptide inhibitor test

AID

133-146 (Autoinhibitory brace helix α6)

Target domain

2-154 (N-terminal executioner domain)

Relief mechanism

PTM (Phosphorylation of Thr357 and Ser358 by RIP3 kinase)

Assay

Structural analysis, Peptide inhibitor test

Accessory elements

No accessory elements

References

Rübbelke M et al. (2020) "Locking mixed-lineage kinase domain-like protein in its auto-inhibited state prevents necroptosis", Proceedings of the National Academy of Sciences of the United States of America, 117, 33272-33281

Autoinhibited structure

Activated structure

23 structures for Q8NB16

Entry ID	Method	Resolution	Chain	Position	Source
2MSV	NMR	-	A	1-154	PDB
4M67	X-ray	190 A	A	179-471	PDB
4MWI	X-ray	170 A	A	183-471	PDB
5KNJ	X-ray	288 A	A/B	191-471	PDB
5KO1	X-ray	216 A	A	191-471	PDB
6BWK	X-ray	279 A	A	190-471	PDB
6D74	NMR	-	A	1-156	PDB
6LK5	X-ray	250 A	A	1-471	PDB
6LK6	X-ray	241 A	A	179-471	PDB
6O5Z	X-ray	229 A	A/B	190-471	PDB
6UX8	X-ray	250 A	A	5-154	PDB
6ZLE	NMR	-	A	2-154	PDB
6ZPR	NMR	-	A	2-154	PDB
6ZVO	X-ray	137 A	A/B/C	2-150	PDB
6ZZ1	X-ray	164 A	A/B	2-150	PDB
7JW7	X-ray	263 A	A	190-471	PDB
7JXU	X-ray	244 A	A/B	190-471	PDB
7MON	X-ray	223 A	A	190-471	PDB
7NM2	NMR	-	A	2-154	PDB
7NM4	NMR	-	A	2-154	PDB
7NM5	NMR	-	A	2-154	PDB
8SLZ	X-ray	230 A	A	190-471	PDB
AF-Q8NB16-F1	Predicted				AlphaFoldDB

505 variants for Q8NB16

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
CA8170195 rs35589326 VAR_041352 RCV001250661	132	S>P	Chronic multifocal osteomyelitis [ClinVar]	Yes	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
RCV001250662 CA8170185 rs34515646 VAR_041353	146	R>Q	Chronic multifocal osteomyelitis [ClinVar]	Yes	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
RCV001533784 rs375490660 CA8169962	316	G>D	Maturity onset diabetes mellitus in young [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
RCV000949995 rs33972728	1	M>V		No	ClinVar dbSNP
rs776122195 CA396768026	2	E>D		No	ClinGen ExAC TOPMed gnomAD
CA396768030 rs1468514688	2	E>K		No	ClinGen gnomAD
TCGA novel	3	N>T	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA283743731 rs1005758761	4	L>F		No	ClinGen Ensembl
rs1458315561 CA396768012	4	L>W		No	ClinGen gnomAD
rs1361327800 CA396768002	6	H>Y		No	ClinGen TOPMed
CA8170276 rs149379960	7	I>V		No	ClinGen ESP ExAC gnomAD
CA8170275 rs745946446	8	I>V		No	ClinGen ExAC gnomAD
rs776790744 CA396767975	10	L>F		No	ClinGen ExAC gnomAD
rs749561556 CA8170273	10	L>R		No	ClinGen ExAC TOPMed gnomAD
CA8170274 rs776790744	10	L>V		No	ClinGen ExAC gnomAD
CA396767970 rs1223623544	11	G>C		No	ClinGen gnomAD
rs1438402885 CA396767967	11	G>D		No	ClinGen gnomAD
rs1194182863 CA396767943	15	H>Y		No	ClinGen TOPMed
CA8170272 rs139095706	17	R>Q		No	ClinGen ESP ExAC TOPMed gnomAD
CA396767914 rs1381414565	19	E>G		No	ClinGen gnomAD
CA8170271 rs146865744	19	E>K		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA8170270 rs754864424	21	M>I		No	ClinGen ExAC gnomAD
CA8170269 rs749037454	22	K>E		No	ClinGen ExAC TOPMed gnomAD
CA8170267 rs755990531	24	C>G		No	ClinGen ExAC TOPMed gnomAD
CA396767878 rs755990531	24	C>S		No	ClinGen ExAC TOPMed gnomAD
rs1398800197 CA396767867	25	K>R		No	ClinGen gnomAD
CA8170264 rs756729633	29	R>G		No	ClinGen ExAC gnomAD
rs751275783 CA8170263	29	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA8170262 rs374998172	30	R>H		No	ClinGen ESP ExAC TOPMed gnomAD
CA8170261 rs374998172	30	R>L		No	ClinGen ESP ExAC TOPMed gnomAD
rs891179950 CA283743666	30	R>S		No	ClinGen TOPMed
CA8170260 rs775648581	31	L>R		No	ClinGen ExAC TOPMed gnomAD
CA396767827 rs544777846	32	G>D		No	ClinGen 1000Genomes ExAC gnomAD
CA8170258 rs760068264	32	G>S		No	ClinGen ExAC
rs544777846 CA8170257	32	G>V		No	ClinGen 1000Genomes ExAC gnomAD
rs1381344181 CA396767820	33	H>Q		No	ClinGen gnomAD
CA8170256 rs771172547	33	H>R		No	ClinGen ExAC gnomAD
rs1286882746 CA396767823	33	H>Y		No	ClinGen gnomAD
CA283743648 rs199701374	34	R>C		No	ClinGen TOPMed gnomAD
CA8170255 rs747075913	34	R>H	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
CA283743651 rs199701374	34	R>S		No	ClinGen TOPMed gnomAD
rs201556027 CA8170253	35	V>F		No	ClinGen ExAC TOPMed gnomAD
rs201556027 CA8170254	35	V>I		No	ClinGen ExAC TOPMed gnomAD
rs749125563 CA8170252	36	L>I		No	ClinGen ExAC gnomAD
rs749125563 CA396767810	36	L>V		No	ClinGen ExAC gnomAD
CA8170250 rs756077475	37	G>C	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
CA8170251 rs756077475	37	G>R		No	ClinGen ExAC gnomAD
CA396767806 rs756077475	37	G>S		No	ClinGen ExAC gnomAD
rs1423954864 CA396767797	39	I>F		No	ClinGen TOPMed gnomAD
rs372742021 CA8170249	40	K>N		No	ClinGen ESP ExAC TOPMed gnomAD
rs1383353288 CA396767786	40	K>R		No	ClinGen TOPMed gnomAD
CA396767778 rs1257052664	41	P>R		No	ClinGen gnomAD
rs916129802 CA283743630	41	P>S		No	ClinGen TOPMed gnomAD
rs781086252 CA8170248	42	L>V		No	ClinGen ExAC gnomAD
CA396767756 rs1485076407	44	M>I		No	ClinGen gnomAD
rs756817494 CA8170247	45	L>F	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
CA396767746 rs751026065	46	Q>L		No	ClinGen ExAC gnomAD
rs751026065 CA8170246	46	Q>R		No	ClinGen ExAC gnomAD
CA396767737 rs1359307283	47	D>E		No	ClinGen TOPMed gnomAD
CA396767741 rs1181742148	47	D>Y		No	ClinGen gnomAD
CA8170245 rs763812068	48	Q>*		No	ClinGen ExAC TOPMed gnomAD
CA283743600 rs760614994	48	Q>P		No	ClinGen gnomAD
rs757930351 CA8170244	49	G>R		No	ClinGen ExAC gnomAD
CA8170242 rs765653663	50	K>E		No	ClinGen ExAC gnomAD
CA8170241 rs759945567	51	R>G		No	ClinGen ExAC gnomAD
rs1298551900 CA396767716	51	R>K		No	ClinGen gnomAD
COSM1379766 rs34251827 CA283743574	52	S>N	large_intestine [Cosmic]	No	ClinGen cosmic curated 1000Genomes ESP ExAC TOPMed gnomAD
rs760844660 CA8170239	52	S>R		No	ClinGen ExAC gnomAD
CA8170240 rs34251827 VAR_041350	52	S>T		No	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs773111996 CA8170237	53	V>M		No	ClinGen ExAC gnomAD
rs1485371575 CA396767697	54	P>L		No	ClinGen TOPMed gnomAD
rs991245627 CA283743566	54	P>S		No	ClinGen TOPMed
rs1276819379 CA396767694	55	S>F		No	ClinGen TOPMed gnomAD
rs772365648 CA8170236	55	S>P		No	ClinGen ExAC gnomAD
rs1169953158 CA396767685	56	E>D		No	ClinGen gnomAD
CA8170235 rs761901618	56	E>K		No	ClinGen ExAC gnomAD
CA283743547 rs977560670	58	L>F		No	ClinGen Ensembl
rs76874498 CA283743544	60	T>P		No	ClinGen Ensembl
CA8170233 rs769628250	61	A>T		No	ClinGen ExAC TOPMed gnomAD
rs1490304310 CA396767650	62	M>T	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
CA8170231 TCGA novel rs558899390	63	N>K	Variant assessed as Somatic; impact. [NCI-TCGA]	No	ClinGen 1000Genomes ExAC gnomAD NCI-TCGA
CA283743531 rs753060513	64	R>C		No	ClinGen TOPMed gnomAD
rs1488498666 CA396767636	64	R>H	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
CA283743532 rs753060513	64	R>S		No	ClinGen TOPMed gnomAD
CA8170229 rs201194709	65	F>L		No	ClinGen ExAC TOPMed gnomAD
CA8170228 rs777097320	68	A>T		No	ClinGen ExAC TOPMed gnomAD
rs758096672 CA8170227	69	L>P		No	ClinGen ExAC gnomAD
rs1341252206 CA396767602	70	E>*		No	ClinGen TOPMed
rs1278510971 CA396767601	70	E>A		No	ClinGen gnomAD
rs1222613938 CA396767596	71	E>K		No	ClinGen TOPMed gnomAD
CA8170226 rs752330049	72	A>T		No	ClinGen ExAC gnomAD
CA396767583 rs1281397634	73	N>H		No	ClinGen TOPMed
CA8170225 rs778682910	73	N>S		No	ClinGen ExAC gnomAD
CA396767571 rs1395752000	74	G>E	Variant assessed as Somatic; 0.0001386 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
rs1460586936 CA396767565	75	E>V		No	ClinGen gnomAD
CA283743517 rs967179340	77	E>*		No	ClinGen TOPMed
CA8170222 CA396767542 rs767010693	78	K>N		No	ClinGen ExAC TOPMed gnomAD
rs761041264 CA8170221	81	N>S		No	ClinGen ExAC TOPMed gnomAD
CA8170220 rs112620118	82	R>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs761933582 CA8170218	83	S>A		No	ClinGen ExAC TOPMed gnomAD
CA8170217 rs751964122	83	S>C		No	ClinGen ExAC TOPMed gnomAD
CA396767504 rs1196681452	84	N>S		No	ClinGen TOPMed
CA283743501 rs569140125	87	R>W		No	ClinGen 1000Genomes
CA396767478 rs1567620129	88	F>I		No	ClinGen Ensembl
TCGA novel	89	L>I	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs201376894 CA396767449	92	S>I		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs201376894 CA8170215 COSM3691173	92	S>N	large_intestine [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
rs759329204 CA8170214	94	D>N		No	ClinGen ExAC TOPMed gnomAD
CA8170213 rs192549642	96	I>M		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA396767417 rs1202678835	97	L>F		No	ClinGen TOPMed gnomAD
CA8170211 rs746877297	98	F>L		No	ClinGen ExAC gnomAD
RCV000970794 rs33987771 VAR_041351 CA8170208	100	D>E		No	ClinGen ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs140587704 CA8170209	100	D>G		No	ClinGen ESP ExAC TOPMed gnomAD
rs777730857 CA396767395	100	D>N		No	ClinGen ExAC TOPMed gnomAD
rs777730857 CA8170210	100	D>Y		No	ClinGen ExAC TOPMed gnomAD
rs778715646 CA8170207	101	V>L		No	ClinGen ExAC gnomAD
CA396767380 rs1567620032	102	N>K		No	ClinGen Ensembl
CA396767365 rs1220095071	104	K>N		No	ClinGen TOPMed
rs907256455 CA283743483	105	L>V		No	ClinGen TOPMed
rs1332249750 CA396767356	106	S>N	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
CA283743482 rs762339211	108	V>A		No	ClinGen Ensembl
CA8170205 rs754281531	109	W>C		No	ClinGen ExAC gnomAD
CA396767318 rs1404245879	111	E>G		No	ClinGen gnomAD
rs1174643441 CA396767309	112	L>R		No	ClinGen TOPMed gnomAD
rs1363671025 CA396767299	114	L>P		No	ClinGen gnomAD
rs1180293947 CA396767288	116	L>F		No	ClinGen gnomAD
CA8170203 rs756471541	117	Q>H		No	ClinGen ExAC TOPMed gnomAD
TCGA novel	118	V>I	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA396767264 rs1459677090	119	E>D		No	ClinGen gnomAD
rs1182504213 CA396767267	119	E>G		No	ClinGen gnomAD
CA396767266 rs1182504213	119	E>V		No	ClinGen gnomAD
rs1244667955 CA396767263	120	Q>K		No	ClinGen gnomAD
rs1183489785 CA396767259	120	Q>R		No	ClinGen gnomAD
TCGA novel	121	R>C	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs764970932 CA8170200	121	R>H	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
rs764970932 CA8170201	121	R>L		No	ClinGen ExAC gnomAD
CA8170199 rs370897232	122	M>L		No	ClinGen ESP ExAC TOPMed gnomAD
rs894519336 CA283743472	122	M>T		No	ClinGen TOPMed
CA8170198 rs370897232	122	M>V		No	ClinGen ESP ExAC TOPMed gnomAD
rs1258818407 CA396767237	124	V>F		No	ClinGen gnomAD
CA8170197 rs763113053	126	P>A		No	ClinGen ExAC TOPMed gnomAD
CA396767224 rs1488508681	126	P>R		No	ClinGen TOPMed
CA396767226 rs763113053	126	P>S		No	ClinGen ExAC TOPMed gnomAD
rs760642888 CA283743465	127	I>V		No	ClinGen Ensembl
CA8170196 rs776440641	130	G>R		No	ClinGen ExAC gnomAD
CA396767195 rs1235789519	131	A>T		No	ClinGen gnomAD
CA283743458 rs1055108157	131	A>V	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
CA8170194 rs376500500	133	W>*		No	ClinGen ESP ExAC TOPMed gnomAD
CA396767182 rs1248015811	133	W>*		No	ClinGen TOPMed
rs1443150936 CA396767175	134	A>S		No	ClinGen gnomAD
rs924754449 CA283743444	134	A>V		No	ClinGen Ensembl
CA8170193 rs773078940	135	Q>E		No	ClinGen ExAC gnomAD
rs1567619769 CA396767168	135	Q>L		No	ClinGen Ensembl
rs1384741329 CA396767157	137	D>N		No	ClinGen gnomAD
CA8170192 rs143888906	139	Q>*		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs143888906 CA283743437	139	Q>K		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs747627247 CA8170191	140	D>E		No	ClinGen ExAC TOPMed gnomAD
CA396767130 rs1330913532	140	D>V		No	ClinGen gnomAD
CA8170190 rs773954047	141	A>T		No	ClinGen ExAC gnomAD
COSM973657 rs748989197 CA8170188	143	E>K	Variant assessed as Somatic; 0.0 impact. endometrium [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated ExAC NCI-TCGA gnomAD
CA8170187 rs779830958	144	D>N		No	ClinGen ExAC gnomAD
CA396767098 rs1437247932	145	R>T		No	ClinGen TOPMed
rs756494877 CA8170186	146	R>*		No	ClinGen ExAC TOPMed gnomAD
rs975173255 CA283743422	147	A>D		No	ClinGen Ensembl
CA8170183 rs757722690	150	M>I		No	ClinGen ExAC gnomAD
CA396767066 rs200016075	150	M>K		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs200016075 CA8170184	150	M>R		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA396767061 rs1291032554	151	L>Q		No	ClinGen gnomAD
CA396767049 rs1597513497	153	R>K		No	ClinGen Ensembl
CA396767027 rs1197074163	154	D>G		No	ClinGen gnomAD
rs144118564 CA283742014	156	E>G		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs144118564 CA8170155	156	E>V		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs376888407 CA8170154	157	K>N		No	ClinGen ESP ExAC TOPMed gnomAD
CA396767001 rs1437332595	158	I>L		No	ClinGen gnomAD
rs1379653862 CA396766996	158	I>M		No	ClinGen TOPMed
CA396766982 rs1213734132	160	A>D		No	ClinGen TOPMed
rs762558431 CA8170152	162	L>V		No	ClinGen ExAC gnomAD
CA8170151 rs775005556	163	R>K		No	ClinGen ExAC TOPMed gnomAD
rs994770593 CA283741983	164	R>*	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA TOPMed gnomAD
CA283741978 rs769352532	164	R>L		No	ClinGen ExAC TOPMed gnomAD
CA8170150 rs769352532	164	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs759186839 CA8170149	166	E>Q		No	ClinGen ExAC TOPMed gnomAD
CA283741967 rs771330406 CA8170147	168	N>K		No	ClinGen ExAC TOPMed gnomAD
rs367623802 CA283741970	168	N>S		No	ClinGen ESP ExAC gnomAD
rs367623802 CA8170148	168	N>T		No	ClinGen ESP ExAC gnomAD
CA8170144 rs772498653 CA396766934	169	M>I		No	ClinGen ExAC gnomAD
VAR_041354 CA8170146 rs55929310	169	M>L		No	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA8170145 rs778315589	169	M>T		No	ClinGen ExAC gnomAD
CA396766938 rs55929310	169	M>V		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA396766929 rs1246738015	170	K>I		No	ClinGen TOPMed
CA396766911 rs1451860840	172	I>M		No	ClinGen TOPMed
rs748201635 CA8170143	172	I>T		No	ClinGen ExAC gnomAD
rs1168747970 CA396766897	174	E>V		No	ClinGen TOPMed
rs779013495 CA8170142	178	Q>*		No	ClinGen ExAC gnomAD
rs144533467 CA283741948	178	Q>R		No	ClinGen ESP TOPMed gnomAD
CA8170141 rs754985251	179	Y>H		No	ClinGen ExAC gnomAD
CA396766842 rs1483132599	181	P>A		No	ClinGen TOPMed
rs761947740 CA396766836	182	P>A		No	ClinGen ExAC TOPMed gnomAD
CA8170112 rs761947740	182	P>S		No	ClinGen ExAC TOPMed gnomAD
rs1567615572 CA396766812	185	M>T		No	ClinGen Ensembl
rs1365061830 CA396766805	186	Q>*		No	ClinGen gnomAD
rs1365061830 CA396766806	186	Q>E		No	ClinGen gnomAD
rs762075271 CA8170108	186	Q>L		No	ClinGen ExAC gnomAD
rs762075271 CA8170110	186	Q>P		No	ClinGen ExAC gnomAD
rs762075271 CA8170109	186	Q>R		No	ClinGen ExAC gnomAD
CA8170107 rs774989464	187	E>A		No	ClinGen ExAC gnomAD
CA396766800 rs1425751077	187	E>K		No	ClinGen TOPMed gnomAD
rs1186283623 CA396766786	189	P>A		No	ClinGen gnomAD
CA8170106 COSM1709391 rs768978509	189	P>L	skin [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA8170103 rs770169241	191	E>G		No	ClinGen ExAC TOPMed gnomAD
rs775665192 CA8170104	191	E>K		No	ClinGen ExAC TOPMed gnomAD
rs746131233 CA8170102	192	Q>E		No	ClinGen ExAC TOPMed gnomAD
rs1383496417 CA396766761	193	I>V		No	ClinGen TOPMed
CA8170100 rs758270591	194	K>R		No	ClinGen ExAC TOPMed gnomAD
CA396766747 rs1567615459	195	E>Q		No	ClinGen Ensembl
rs747886552 CA396766740	196	I>L		No	ClinGen ExAC TOPMed gnomAD
rs1342146650 CA396766735	196	I>M		No	ClinGen gnomAD
TCGA novel	196	I>S	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs747886552 CA8170099	196	I>V		No	ClinGen ExAC TOPMed gnomAD
rs778911112 CA8170098	197	K>R		No	ClinGen ExAC gnomAD
rs1291856142 CA396766709	200	Q>*		No	ClinGen TOPMed gnomAD
rs1291856142 CA396766710	200	Q>E		No	ClinGen TOPMed gnomAD
rs139601728 CA283741482	200	Q>H		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA396766704 rs371470408	201	L>F		No	ClinGen ESP ExAC TOPMed gnomAD
CA283741478 rs371470408	201	L>I		No	ClinGen ESP ExAC TOPMed gnomAD
CA8170095 rs371470408	201	L>V		No	ClinGen ESP ExAC TOPMed gnomAD
TCGA novel	202	S>L	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs750137483 CA8170093	205	P>A		No	ClinGen ExAC gnomAD
rs767152998 CA8170092	205	P>L		No	ClinGen ExAC TOPMed gnomAD
CA396766672 rs1450795293	206	W>*		No	ClinGen TOPMed
CA396766670 rs1450795293	206	W>C		No	ClinGen TOPMed
CA8170089 rs764685187	207	I>S		No	ClinGen ExAC gnomAD
CA8170088 rs763327142	208	L>P		No	ClinGen ExAC TOPMed gnomAD
CA8170087 rs776108720	210	R>T		No	ClinGen ExAC gnomAD
CA8170086 rs770041469	216	T>A		No	ClinGen ExAC gnomAD
CA396766608 rs1258433793	216	T>I		No	ClinGen gnomAD
CA396766610 rs770041469	216	T>P		No	ClinGen ExAC gnomAD
rs1329263314 CA396766603	217	L>F		No	ClinGen gnomAD
CA396766604 rs1329263314	217	L>V		No	ClinGen gnomAD
CA396766594 rs1388526444	218	Y>*		No	ClinGen gnomAD
CA8170085 rs745930027	218	Y>C		No	ClinGen ExAC gnomAD
rs777056620 CA8170084	219	K>I		No	ClinGen ExAC gnomAD
rs905560818 CA283741403	220	G>R		No	ClinGen gnomAD
rs1444806091 CA396766577	221	E>A		No	ClinGen gnomAD
rs1402776840 CA396766572	222	Y>N		No	ClinGen gnomAD
rs1597505947 CA396766569	222	Y>S		No	ClinGen Ensembl
rs770987862 CA8170083	224	R>K		No	ClinGen ExAC
CA8170081 rs778520480	227	V>A		No	ClinGen ExAC gnomAD
rs1465902874 CA396766536	227	V>L		No	ClinGen gnomAD
CA396766531 rs1424116431	228	A>S		No	ClinGen TOPMed
CA8170078 rs577105895	231	V>I		No	ClinGen 1000Genomes TOPMed
CA8170079 rs577105895	231	V>L	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen 1000Genomes NCI-TCGA TOPMed
CA8170076 rs749275387	232	F>L		No	ClinGen ExAC gnomAD
CA8170075 rs779957254	233	K>E		No	ClinGen ExAC gnomAD
rs893059949 CA283741357	234	K>E		No	ClinGen Ensembl
rs755691598 CA8170074	234	K>I		No	ClinGen ExAC TOPMed gnomAD
rs1202737257 CA396766485	235	L>H		No	ClinGen gnomAD
CA396766484 rs1202737257	235	L>P		No	ClinGen gnomAD
rs147269187 CA8170072	236	Q>R		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs756812874 CA396766471	237	A>G		No	ClinGen ExAC gnomAD
rs756812874 CA8170071	237	A>V		No	ClinGen ExAC gnomAD
CA8170068 rs763353269	238	G>A		No	ClinGen ExAC TOPMed
CA8170069 rs764404469	238	G>C		No	ClinGen ExAC
CA396766468 rs763353269	238	G>D		No	ClinGen ExAC TOPMed
CA396766463 rs1270838673	239	S>N		No	ClinGen TOPMed
rs1316315605 CA396766460	239	S>R		No	ClinGen gnomAD
rs765831445 CA8170066	240	I>V		No	ClinGen ExAC gnomAD
rs759693357 CA8170065	241	A>V	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
rs746520537 CA8170036	242	I>T		No	ClinGen ExAC TOPMed gnomAD
CA8170035 rs777291314	243	V>A		No	ClinGen ExAC TOPMed gnomAD
rs758066791 CA8170034	244	R>K		No	ClinGen ExAC gnomAD
CA283737776 rs967924476	244	R>S		No	ClinGen TOPMed gnomAD
CA283737773 rs867785638	245	Q>*		No	ClinGen Ensembl
rs1286797922 CA396765579	245	Q>P		No	ClinGen gnomAD
CA396765569 rs1209386455	246	T>I		No	ClinGen gnomAD
rs748545390 CA8170033	249	K>M		No	ClinGen ExAC TOPMed gnomAD
rs1182526299 CA396765547	249	K>N		No	ClinGen TOPMed
rs972047824 CA283737772	251	I>M	Variant assessed as Somatic; impact. [NCI-TCGA]	No	ClinGen NCI-TCGA TOPMed
CA396765515 rs1350201409	254	M>K		No	ClinGen TOPMed
CA8170031 rs755361676	254	M>V		No	ClinGen ExAC gnomAD
rs1340332574 CA396765500	256	K>E		No	ClinGen gnomAD
CA8170029 rs568554020	257	F>L		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA396765485 rs554636664	258	E>*		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
COSM973651 rs554636664 CA8170028	258	E>K	Variant assessed as Somatic; 0.0 impact. large_intestine endometrium [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC NCI-TCGA TOPMed gnomAD
rs1006877776 CA283737726	260	P>A		No	ClinGen TOPMed
CA8170027 rs538254592	262	I>F		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA8170025 rs761986332	263	L>R		No	ClinGen ExAC
rs148145220 CA8170024	264	R>C		No	ClinGen ESP ExAC TOPMed gnomAD
COSM973650 rs765063923 CA8170023	264	R>H	kidney endometrium Variant assessed as Somatic; 4.622e-05 impact. [Cosmic, NCI-TCGA]	No	ClinGen cosmic curated ExAC NCI-TCGA TOPMed gnomAD
CA396765440 rs1464871865	265	I>M		No	ClinGen TOPMed gnomAD
rs759358906 CA8170022	266	F>L		No	ClinGen ExAC gnomAD
rs776495259 CA8170021	267	G>R		No	ClinGen ExAC gnomAD
CA396765426 rs1478089022	268	I>V		No	ClinGen gnomAD
rs746513546 CA396765416	269	C>F		No	ClinGen ExAC gnomAD
rs1360582368 CA396765418	269	C>G		No	ClinGen TOPMed
rs746513546 CA8170019	269	C>S		No	ClinGen ExAC gnomAD
rs746513546 CA396765417	269	C>Y		No	ClinGen ExAC gnomAD
CA396765413 rs772728950	270	I>L		No	ClinGen ExAC TOPMed gnomAD
rs1292246704 CA396765411	270	I>N		No	ClinGen TOPMed gnomAD
rs1292246704 CA396765410	270	I>T		No	ClinGen TOPMed gnomAD
CA8170018 rs772728950	270	I>V		No	ClinGen ExAC TOPMed gnomAD
rs771880061 CA8170017	271	D>Y		No	ClinGen ExAC gnomAD
rs1484288485 CA723824256	272	E>*		No	ClinGen TOPMed
rs1317576306 CA396765385	274	V>L		No	ClinGen gnomAD
CA283735412 rs951313891	275	T>N		No	ClinGen TOPMed
CA8169993 rs377446580 COSM1379765	276	P>L	Variant assessed as Somatic; 0.0 impact. large_intestine [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated 1000Genomes ESP ExAC NCI-TCGA TOPMed gnomAD
TCGA novel	276	P>S	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1481137634 CA396765247	280	S>F		No	ClinGen gnomAD
rs768951882 CA8169990	283	M>K		No	ClinGen ExAC TOPMed gnomAD
rs1237242622 CA396765230	283	M>L		No	ClinGen gnomAD
rs768951882 CA396765229	283	M>T		No	ClinGen ExAC TOPMed gnomAD
CA396765231 rs1237242622	283	M>V		No	ClinGen gnomAD
CA8169989 rs781652925	285	Y>*		No	ClinGen ExAC gnomAD
CA396765212 rs1187587021	285	Y>C		No	ClinGen TOPMed
rs1215178196 CA396765199	287	E>A		No	ClinGen TOPMed gnomAD
rs757391457 CA8169988	287	E>K		No	ClinGen ExAC gnomAD
CA8169987 rs751568674	288	L>V		No	ClinGen ExAC gnomAD
TCGA novel	289	G>E	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA8169984 rs150170082 CA396765189	289	G>R		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA283735352 rs150170082 COSM472105	289	G>W	prostate [Cosmic]	No	ClinGen cosmic curated 1000Genomes ESP ExAC TOPMed gnomAD
rs374190030 CA8169981	290	T>I		No	ClinGen ESP ExAC TOPMed gnomAD
COSM20537 CA396765177 rs1313508921 VAR_041355	291	L>P	stomach a gastric adenocarcinoma sample; somatic mutation [Cosmic, UniProt]	No	ClinGen cosmic curated UniProt TOPMed dbSNP
CA8169978 rs761422302	293	E>K		No	ClinGen ExAC TOPMed gnomAD
CA396765161 rs80226077	294	L>V		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA396765151 rs1419131968	295	L>F		No	ClinGen gnomAD
rs1008783024 CA283735263	296	D>E		No	ClinGen TOPMed
rs374835950 CA8169975	296	D>G		No	ClinGen ESP ExAC TOPMed gnomAD
CA396765143 rs369487505	297	R>G		No	ClinGen ESP ExAC gnomAD
rs770254333 CA8169973	297	R>S		No	ClinGen ExAC TOPMed gnomAD
CA8169974 rs369487505	297	R>W		No	ClinGen ESP ExAC gnomAD
CA396765135 rs1284644578	298	E>G		No	ClinGen TOPMed
CA396765117 rs1473980936	300	D>E		No	ClinGen gnomAD
rs146464193 CA8169972	300	D>H		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
TCGA novel	300	D>Y	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1195384962 CA396765111	301	L>P		No	ClinGen TOPMed
rs771365412 CA8169970	302	T>S		No	ClinGen ExAC gnomAD
rs145371410 CA8169969	306	R>C		No	ClinGen ESP ExAC TOPMed gnomAD
CA8169967 rs201073938 COSM1215166	306	R>H	large_intestine [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
CA8169968 rs201073938	306	R>P		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA283735202 rs1038884324	307	M>T		No	ClinGen gnomAD
rs140270252 CA8169966	307	M>V		No	ClinGen ESP ExAC TOPMed gnomAD
rs1174385114 CA396765067	309	L>R		No	ClinGen TOPMed
CA8169965 rs778988353	309	L>V		No	ClinGen ExAC TOPMed gnomAD
CA396765062 rs1229755885	310	V>F		No	ClinGen TOPMed gnomAD
rs1417877222 CA396765049	312	G>A		No	ClinGen TOPMed
CA396765047 rs1300282072	313	A>T		No	ClinGen TOPMed
TCGA novel	314	A>V	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs755943569 CA8169964	315	R>*		No	ClinGen ExAC TOPMed gnomAD
rs755943569 CA396765035	315	R>G		No	ClinGen ExAC TOPMed gnomAD
CA8169963 rs531258289	315	R>Q		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA8169961 rs375490660	316	G>V		No	ClinGen ESP ExAC TOPMed gnomAD
rs151198441 CA283735118	319	R>G		No	ClinGen ESP ExAC TOPMed gnomAD
rs756756618 CA8169958	319	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs151198441 CA283735116	319	R>W		No	ClinGen ESP ExAC TOPMed gnomAD
rs142142079 CA396764997	320	L>P		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs142142079 CA8169923	320	L>R		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1305330818 CA396764992	321	H>R		No	ClinGen TOPMed
CA396764994 rs1456761465	321	H>Y		No	ClinGen TOPMed
CA396764977 rs1465955164	323	S>L		No	ClinGen gnomAD
rs758216519 CA396764966	325	A>P		No	ClinGen ExAC TOPMed gnomAD
rs758216519 CA8169922	325	A>T		No	ClinGen ExAC TOPMed gnomAD
rs371361992 CA8169921	325	A>V		No	ClinGen ESP ExAC gnomAD
COSM1189320 rs778326056 CA8169920	326	P>A	lung [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA8169919 rs566645790	327	E>*		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA396764955 rs1176417737	327	E>A		No	ClinGen gnomAD
CA8169915 CA8169916 rs367604583	329	H>Q		No	ClinGen ESP ExAC TOPMed gnomAD
CA8169913 COSM973649 rs145083759	330	G>R	Variant assessed as Somatic; 0.0 impact. endometrium [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated ESP ExAC NCI-TCGA TOPMed gnomAD
CA396764911 rs1257699830	334	S>G		No	ClinGen gnomAD
rs535912872 CA8169912	334	S>I		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1567602908 CA396764905	334	S>R		No	ClinGen Ensembl
CA396764881 rs1308742298	338	L>V		No	ClinGen gnomAD
CA8169910 rs763123716	339	V>A		No	ClinGen ExAC
rs1567602872 CA396764865	341	Q>E		No	ClinGen Ensembl
CA8169909 rs775863416	342	G>D		No	ClinGen ExAC TOPMed gnomAD
rs770081045 CA8169908	344	Q>K		No	ClinGen ExAC TOPMed gnomAD
CA8169907 rs746841264	345	V>M		No	ClinGen ExAC TOPMed gnomAD
CA283786381 rs373659058	347	L>F		No	ClinGen ESP TOPMed gnomAD
rs1597479662 CA396766423	349	G>E		No	ClinGen Ensembl
rs1396312276 CA396766395	353	R>K		No	ClinGen gnomAD
CA8169870 rs776783727	354	K>R		No	ClinGen ExAC gnomAD
TCGA novel	356	Q>H	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA8169869 rs766555410	357	T>S		No	ClinGen ExAC gnomAD
rs868343997 CA283786357	358	S>F		No	ClinGen Ensembl
rs1330299374 CA396766358	359	M>V		No	ClinGen TOPMed gnomAD
rs1169611627 CA396766346	360	S>N		No	ClinGen TOPMed gnomAD
TCGA novel	362	G>E	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA8169867 rs746526189	362	G>E		No	ClinGen ExAC gnomAD
CA8169865 rs34389205	364	T>K		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
VAR_041356 rs34389205 CA8169864 COSM3691171	364	T>M	large_intestine [Cosmic]	No	ClinGen cosmic curated UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA396766293 rs1214630696	368	T>I		No	ClinGen gnomAD
rs745320078 CA8169862	368	T>S		No	ClinGen ExAC gnomAD
rs140693425 CA8169860	369	D>E		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA8169861 rs780725407	369	D>G		No	ClinGen ExAC gnomAD
rs758149009 CA283786327	369	D>N		No	ClinGen TOPMed
rs747405061 CA8169859	370	R>G		No	ClinGen ExAC gnomAD
rs758810586 CA8169856	372	K>R		No	ClinGen ExAC TOPMed gnomAD
rs535530016 CA8169854	374	T>I		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA8169851 rs760927683	376	Y>F		No	ClinGen ExAC TOPMed gnomAD
rs753897196 CA8169852	376	Y>H		No	ClinGen ExAC gnomAD
CA8169850 rs760927683	376	Y>S		No	ClinGen ExAC TOPMed gnomAD
CA396766246 rs1401477823	377	L>I		No	ClinGen gnomAD
rs1475983140 CA396766238	378	S>A		No	ClinGen gnomAD
CA8169849 rs750054698	378	S>L	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
rs757057991 CA283786278	379	P>H		No	ClinGen ExAC TOPMed gnomAD
CA283786277 rs757057991	379	P>L		No	ClinGen ExAC TOPMed gnomAD
CA8169848 rs757057991	379	P>R		No	ClinGen ExAC TOPMed gnomAD
CA396766216 rs1397073092	382	L>M		No	ClinGen gnomAD
rs762735921 CA8169847	382	L>R		No	ClinGen ExAC gnomAD
CA396766172 rs1439367287	388	Q>*		No	ClinGen TOPMed gnomAD
CA8169846 rs147237331	389	Y>C		No	ClinGen ESP ExAC TOPMed gnomAD
CA396766158 rs1207153775	390	D>H		No	ClinGen TOPMed gnomAD
rs1207153775 CA396766157	390	D>Y		No	ClinGen TOPMed gnomAD
CA8169845 rs769718663	391	V>I		No	ClinGen ExAC TOPMed gnomAD
rs143920466 CA8169843	392	K>N		No	ClinGen ESP ExAC TOPMed gnomAD
CA396766138 rs1378620503	393	S>P		No	ClinGen TOPMed
CA396766133 rs1349463559	394	E>K		No	ClinGen gnomAD
rs770311254 CA8169842	395	I>M		No	ClinGen ExAC gnomAD
CA8169841 rs139283905	396	Y>H		No	ClinGen ESP ExAC TOPMed gnomAD
rs1161596437 CA396766094	397	S>R		No	ClinGen gnomAD
CA396766109 rs1204588793	397	S>T		No	ClinGen TOPMed gnomAD
VAR_041357	398	F>I	a gastric adenocarcinoma sample; somatic mutation [UniProt]	No	UniProt
CA8169819 rs768880382	399	G>A		No	ClinGen ExAC
TCGA novel	399	G>V	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA283785935 rs774435575	400	I>V		No	ClinGen Ensembl
CA8169816 COSM1679272 rs756192894	401	V>I	Variant assessed as Somatic; 0.0 impact. haematopoietic_and_lymphoid_tissue [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated ExAC NCI-TCGA gnomAD
CA8169815 rs750447838	402	L>F		No	ClinGen ExAC gnomAD
rs1476464511 CA396766057	402	L>R		No	ClinGen gnomAD
rs878885887 CA283785888	404	E>D		No	ClinGen gnomAD
rs751697660 CA8169812	407	T>A		No	ClinGen ExAC gnomAD
rs751697660 CA396766020	407	T>P		No	ClinGen ExAC gnomAD
CA8169810 rs759236585	408	G>V		No	ClinGen ExAC gnomAD
CA8169809 rs753876998	409	D>A		No	ClinGen ExAC gnomAD
rs1271028872 CA396765998	409	D>E		No	ClinGen gnomAD
CA8169808 rs766350576	410	I>V		No	ClinGen ExAC gnomAD
rs372730333 CA8169806	411	P>L		No	ClinGen ExAC TOPMed gnomAD
CA396765989 rs1413494823	411	P>S		No	ClinGen TOPMed gnomAD
CA8169804 rs371428321	412	F>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA8169803 COSM1679271 rs773862525	413	Q>L	haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA396765972 rs773862525	413	Q>R		No	ClinGen ExAC TOPMed gnomAD
rs372403777 CA8169766	418	E>K		No	ClinGen ESP ExAC TOPMed gnomAD
rs372403777 CA8169767	418	E>Q		No	ClinGen ESP ExAC TOPMed gnomAD
rs148386905 CA8169764	421	R>C		No	ClinGen ESP ExAC TOPMed gnomAD
CA283785492 rs55987292 VAR_041358	421	R>H	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen UniProt NCI-TCGA TOPMed dbSNP gnomAD
rs55987292 CA396765837	421	R>L		No	ClinGen TOPMed gnomAD
CA8169763 rs148386905	421	R>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA396765822 rs775105387	424	V>L		No	ClinGen ExAC TOPMed gnomAD
CA8169762 rs775105387	424	V>M		No	ClinGen ExAC TOPMed gnomAD
rs1175020291 CA396765816	425	A>S		No	ClinGen gnomAD
CA396765809 rs1356782950	426	V>A		No	ClinGen TOPMed
CA8169761 rs201982707	426	V>M		No	ClinGen ExAC gnomAD
CA8169759 rs555966640	428	R>Q		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs769303810 CA8169760	428	R>W		No	ClinGen ExAC TOPMed gnomAD
CA8169758 rs771283794	429	Q>H		No	ClinGen ExAC TOPMed gnomAD
rs1597478255 CA396765792	429	Q>R		No	ClinGen Ensembl
CA396765788 rs1597478249	430	Q>E		No	ClinGen Ensembl
rs760829214 CA8169757	430	Q>R		No	ClinGen ExAC gnomAD
rs200979480 CA283785455	431	E>*		No	ClinGen Ensembl
rs370069495 CA283785449	431	E>D		No	ClinGen ESP ExAC TOPMed gnomAD
CA8169754 rs748439336	432	P>L		No	ClinGen ExAC gnomAD
rs772159528 CA8169755	432	P>T		No	ClinGen ExAC gnomAD
CA8169753 rs769718074	433	L>V		No	ClinGen ExAC TOPMed gnomAD
rs190638372 CA8169751	435	E>A		No	ClinGen 1000Genomes ExAC gnomAD
TCGA novel	436	D>A	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA396765749 rs185833033	436	D>E		No	ClinGen 1000Genomes TOPMed
rs1211951596 CA396765742	437	C>*		No	ClinGen TOPMed
rs1009945747 CA396765743	437	C>F		No	ClinGen TOPMed gnomAD
rs1009945747 CA283785394	437	C>S		No	ClinGen TOPMed gnomAD
CA396765739 rs1567598593	438	P>A		No	ClinGen Ensembl
CA8169750 rs781303255	440	E>G		No	ClinGen ExAC TOPMed gnomAD
CA8169747 COSM1640553 rs200915860	442	R>Q	stomach [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
rs751486602 CA8169748	442	R>W	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
rs1454254344 CA396765708	443	E>V		No	ClinGen TOPMed
CA8169746 rs757908581	444	I>N		No	ClinGen ExAC gnomAD
CA8169745 rs145153968	445	I>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs764801287 CA8169744	445	I>S		No	ClinGen ExAC gnomAD
rs764801287 CA283785364	445	I>T		No	ClinGen ExAC gnomAD
CA283785359 rs866534564	446	D>H		No	ClinGen Ensembl
CA283785358 rs779745242	446	D>V	Variant assessed as Somatic; impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
rs142380694 CA8169743	447	E>*		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs754151136 CA8169742	447	E>D		No	ClinGen ExAC gnomAD
rs761124985 CA8169740	449	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA8169741 rs372228840	449	R>W		No	ClinGen ESP ExAC TOPMed gnomAD
CA396765670 rs1190078953	450	A>P		No	ClinGen gnomAD
rs1190078953 CA396765671	450	A>T		No	ClinGen gnomAD
rs773746539 CA8169739	451	H>Y		No	ClinGen ExAC TOPMed gnomAD
rs761918387 CA8169737	452	D>E		No	ClinGen ExAC gnomAD
CA283785321 rs940763334	453	P>S		No	ClinGen Ensembl
rs1567598450 CA396765642	454	S>F	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen Ensembl NCI-TCGA
rs1177801061 CA396765638	455	V>A		No	ClinGen TOPMed gnomAD
CA283785319 rs537319501	455	V>L		No	ClinGen Ensembl
CA8169733 rs145199275	456	R>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA8169735 rs145199275	456	R>P		No	ClinGen ESP ExAC TOPMed gnomAD
CA8169734 rs145199275	456	R>Q		No	ClinGen ESP ExAC TOPMed gnomAD
CA396765635 rs1486995519	456	R>W	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA TOPMed gnomAD
CA8169731 rs746981374	458	S>C		No	ClinGen ExAC gnomAD
rs777757518 CA8169730	459	V>M		No	ClinGen ExAC TOPMed
rs1295685416 CA396765603	460	D>E		No	ClinGen gnomAD
CA8169729 rs146795832	461	E>*		No	ClinGen 1000Genomes ExAC gnomAD
rs1232644152 CA8169710	462	I>T		No	ClinGen TOPMed
CA283783538 rs902204767	463	L>S		No	ClinGen Ensembl
COSM3742040 rs747685717 CA8169708	467	S>F	liver [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs778433840 CA8169707	468	T>S		No	ClinGen ExAC gnomAD
CA283783509 rs769646595	471	K>E		No	ClinGen Ensembl
rs754461843 CA8169706	471	K>R		No	ClinGen ExAC
CA8169704 rs779690580	472	K>Q		No	ClinGen ExAC gnomAD

No associated diseases with Q8NB16

2 regional properties for Q8NB16

Type	Name	Position	InterPro Accession
domain	ABC1 atypical kinase-like domain	297 - 536	IPR004147
domain	ADCK3-like domain	292 - 542	IPR034646

Functions

		Description
EC Number
Subcellular Localization	Cytoplasm Cell membrane Nucleus	Localizes to the cytoplasm and translocates to the plasma membrane on necroptosis induction (PubMed:24316671) Localizes to the nucleus in response to orthomyxoviruses infection (By similarity)
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

5 GO annotations of cellular component

Name	Definition
cell junction	A cellular component that forms a specialized region of connection between two or more cells, or between a cell and the extracellular matrix, or between two membrane-bound components of a cell, such as flagella.
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.
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.
plasma membrane	The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.

4 GO annotations of molecular function

Name	Definition
ATP binding	Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
identical protein binding	Binding to an identical protein or proteins.
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-containing complex binding	Binding to a macromolecular complex.

7 GO annotations of biological process

Name	Definition
cell surface receptor signaling pathway	The series of molecular signals initiated by activation of a receptor on the surface of a cell. The pathway begins with binding of an extracellular ligand to a cell surface receptor, or for receptors that signal in the absence of a ligand, by ligand-withdrawal or the activity of a constitutively active receptor. The pathway ends with regulation of a downstream cellular process, e.g. transcription.
defense response to virus	Reactions triggered in response to the presence of a virus that act to protect the cell or organism.
execution phase of necroptosis	A stage of the necroptotic process that starts after a necroptotic signal has been relayed to the execution machinery. Key steps of the execution phase are swelling of organelles, minor ultrastructural modifications of the nucleus (specifically, dilatation of the nuclear membrane and condensation of chromatin into small, irregular, circumscribed patches) and increased cell volume (oncosis), culminating in the disruption of the plasma membrane and subsequent loss of intracellular contents. The execution phase ends when the cell has died.
necroptotic process	A programmed necrotic cell death process which begins when a cell receives a signal (e.g. a ligand binding to a death receptor or to a Toll-like receptor), and proceeds through a series of biochemical events (signaling pathways), characterized by activation of receptor-interacting serine/threonine-protein kinase 1 and/or 3 (RIPK1/3, also called RIP1/3) and by critical dependence on mixed lineage kinase domain-like (MLKL), and which typically lead to common morphological features of necrotic cell death. The process ends when the cell has died. The process is divided into a signaling phase, and an execution phase, which is triggered by the former.
necroptotic signaling pathway	The series of molecular signals which triggers the necroptotic death of a cell. The pathway starts with reception of a signal, is characterized by activation of receptor-interacting serine/threonine-protein kinase 1 and/or 3 (RIPK1/3, also called RIP1/3), and ends when the execution phase of necroptosis is triggered.
protein homotrimerization	The formation of a protein homotrimer, a macromolecular structure consisting of three noncovalently associated identical subunits.
protein phosphorylation	The process of introducing a phosphate group on to a protein.

43 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
A2VDU3	MAP3K7	Mitogen-activated protein kinase kinase kinase 7	Bos taurus (Bovine)	SS
Q4TVR5	DSTYK	Dual serine/threonine and tyrosine protein kinase	Bos taurus (Bovine)	PR
Q3SZJ2	RIPK2	Receptor-interacting serine/threonine-protein kinase 2	Bos taurus (Bovine)	PR
Q6XUX0	DSTYK	Dual serine/threonine and tyrosine protein kinase	Gallus gallus (Chicken)	PR
P83104	Takl1	Putative mitogen-activated protein kinase kinase kinase 7-like	Drosophila melanogaster (Fruit fly)	PR
Q95UN8	slpr	Mitogen-activated protein kinase kinase kinase	Drosophila melanogaster (Fruit fly)	EV
P11346	Raf	Raf homolog serine/threonine-protein kinase Raf	Drosophila melanogaster (Fruit fly)	PR
P00540	MOS	Proto-oncogene serine/threonine-protein kinase mos	Homo sapiens (Human)	PR
Q5TCX8	MAP3K21	Mitogen-activated protein kinase kinase kinase 21	Homo sapiens (Human)	PR
Q6XUX3	DSTYK	Dual serine/threonine and tyrosine protein kinase	Homo sapiens (Human)	PR
O43318	MAP3K7	Mitogen-activated protein kinase kinase kinase 7	Homo sapiens (Human)	SS
Q9NYL2	MAP3K20	Mitogen-activated protein kinase kinase kinase 20	Homo sapiens (Human)	PR
Q38SD2	LRRK1	Leucine-rich repeat serine/threonine-protein kinase 1	Homo sapiens (Human)	EV
O43353	RIPK2	Receptor-interacting serine/threonine-protein kinase 2	Homo sapiens (Human)	PR
Q02779	MAP3K10	Mitogen-activated protein kinase kinase kinase 10	Homo sapiens (Human)	SS
P80192	MAP3K9	Mitogen-activated protein kinase kinase kinase 9	Homo sapiens (Human)	SS
Q16584	MAP3K11	Mitogen-activated protein kinase kinase kinase 11	Homo sapiens (Human)	EV
Q13418	ILK	Integrin-linked protein kinase	Homo sapiens (Human)	PR
P04049	RAF1	RAF proto-oncogene serine/threonine-protein kinase	Homo sapiens (Human)	EV
P10398	ARAF	Serine/threonine-protein kinase A-Raf	Homo sapiens (Human)	PR
P15056	BRAF	Serine/threonine-protein kinase B-raf	Homo sapiens (Human)	EV
Q80XI6	Map3k11	Mitogen-activated protein kinase kinase kinase 11	Mus musculus (Mouse)	PR
Q8VDG6	Map3k21	Mitogen-activated protein kinase kinase kinase 21	Mus musculus (Mouse)	PR
P58801	Ripk2	Receptor-interacting serine/threonine-protein kinase 2	Mus musculus (Mouse)	PR
Q62073	Map3k7	Mitogen-activated protein kinase kinase kinase 7	Mus musculus (Mouse)	EV
Q3U1V8	Map3k9	Mitogen-activated protein kinase kinase kinase 9	Mus musculus (Mouse)	SS
Q9ESL4	Map3k20	Mitogen-activated protein kinase kinase kinase 20	Mus musculus (Mouse)	PR
P00536	Mos	Proto-oncogene serine/threonine-protein kinase mos	Mus musculus (Mouse)	PR
Q66L42	Map3k10	Mitogen-activated protein kinase kinase kinase 10	Mus musculus (Mouse)	SS
Q9D2Y4	Mlkl	Mixed lineage kinase domain-like protein	Mus musculus (Mouse)	SS
P0C8E4	Map3k7	Mitogen-activated protein kinase kinase kinase 7	Rattus norvegicus (Rat)	SS
Q66HA1	Map3k11	Mitogen-activated protein kinase kinase kinase 11	Rattus norvegicus (Rat)	PR
D3ZG83	Map3k10	Mitogen-activated protein kinase kinase kinase 10	Rattus norvegicus (Rat)	SS
P00539	Mos	Proto-oncogene serine/threonine-protein kinase mos	Rattus norvegicus (Rat)	PR
Q9TZM3	lrk-1	Leucine-rich repeat serine/threonine-protein kinase 1	Caenorhabditis elegans	SS
Q07292	lin-45	Raf homolog serine/threonine-protein kinase	Caenorhabditis elegans	PR
Q9FPR3	EDR1	Serine/threonine-protein kinase EDR1	Arabidopsis thaliana (Mouse-ear cress)	PR
Q2MHE4	HT1	Serine/threonine/tyrosine-protein kinase HT1	Arabidopsis thaliana (Mouse-ear cress)	PR
O22558	STY8	Serine/threonine-protein kinase STY8	Arabidopsis thaliana (Mouse-ear cress)	PR
Q8RWL6	STY17	Serine/threonine-protein kinase STY17	Arabidopsis thaliana (Mouse-ear cress)	PR
F4JTP5	STY46	Serine/threonine-protein kinase STY46	Arabidopsis thaliana (Mouse-ear cress)	PR
Q05609	CTR1	Serine/threonine-protein kinase CTR1	Arabidopsis thaliana (Mouse-ear cress)	PR
Q67E00	dstyk	Dual serine/threonine and tyrosine protein kinase	Xenopus tropicalis (Western clawed frog) (Silurana tropicalis)	PR

10	20	30	40	50	60
MENLKHIITL	GQVIHKRCEE	MKYCKKQCRR	LGHRVLGLIK	PLEMLQDQGK	RSVPSEKLTT
70	80	90	100	110	120
AMNRFKAALE	EANGEIEKFS	NRSNICRFLT	ASQDKILFKD	VNRKLSDVWK	ELSLLLQVEQ
130	140	150	160	170	180
RMPVSPISQG	ASWAQEDQQD	ADEDRRAFQM	LRRDNEKIEA	SLRRLEINMK	EIKETLRQYL
190	200	210	220	230	240
PPKCMQEIPQ	EQIKEIKKEQ	LSGSPWILLR	ENEVSTLYKG	EYHRAPVAIK	VFKKLQAGSI
250	260	270	280	290	300
AIVRQTFNKE	IKTMKKFESP	NILRIFGICI	DETVTPPQFS	IVMEYCELGT	LRELLDREKD
310	320	330	340	350	360
LTLGKRMVLV	LGAARGLYRL	HHSEAPELHG	KIRSSNFLVT	QGYQVKLAGF	ELRKTQTSMS
370	380	390	400	410	420
LGTTREKTDR	VKSTAYLSPQ	ELEDVFYQYD	VKSEIYSFGI	VLWEIATGDI	PFQGCNSEKI
430	440	450	460	470
RKLVAVKRQQ	EPLGEDCPSE	LREIIDECRA	HDPSVRPSVD	EILKKLSTFS	K