AiPD: Autoinhibited Protein Database

Q8NFU0

Gene name	BEST4 (VMD2L2)
Protein name	Bestrophin-4
Names	Vitelliform macular dystrophy 2-like protein 2
Species	Homo sapiens (Human)
KEGG Pathway	hsa:266675
EC number
Protein Class

Descriptions

Best3, a member of the bestrophin Cl- channel family, is a candidate of cGMP-sensitive, Ca2+-activated Cl- channel in vascular smooth muscle cells. Best3 has an autoinhibitory domain (356-362) and deletion of the domain robustly activates Best3 channel. <br>Best3 also has a C-terminal membrane association domain (368-383) and basic residue domain (384-397). The basic residue domain (384–397) is also partially involved in the membrane association. Dissociation of Best3 from membrane activates Best3.

Autoinhibitory domains (AIDs)

371-378 (Autoinhibitory domain) SS

Target domain	1-446 (Bestrophin)
Relief mechanism	Ligand binding
Assay

AID

371-378 (Autoinhibitory domain)

Target domain

1-446 (Bestrophin)

Relief mechanism

Ligand binding (Ca2+ binding to Best3)

Assay

Accessory elements

No accessory elements

References

Han X et al. (2013) "C-terminal membrane association of Bestrophin 3 and its activation as a chloride channel", The Journal of membrane biology, 246, 177-82

Autoinhibited structure

Activated structure

1 structures for Q8NFU0

Entry ID	Method	Resolution	Chain	Position	Source
AF-Q8NFU0-F1	Predicted				AlphaFoldDB

484 variants for Q8NFU0

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
rs201159196	3	V>L		No	1000Genomes
rs1211861078	4	S>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA gnomAD
rs1651299225	5	Y>H		No	gnomAD
rs1314873599	7	L>I		No	gnomAD
rs1224148316	8	K>N		No	gnomAD
rs777358726	8	K>T		No	ExAC gnomAD
rs1651298847	9	V>A		No	Ensembl
rs16832247	10	A>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA gnomAD
TCGA novel	12	A>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs375683037	13	R>C		No	ESP ExAC gnomAD
rs549654949	13	R>H		No	TOPMed gnomAD
rs1303619493	14	F>C		No	gnomAD
TCGA novel	15	G>A	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs140513742	15	G>R	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ESP ExAC TOPMed gnomAD NCI-TCGA
rs1651295840	18	S>C		No	gnomAD
rs1651295939	18	S>P		No	Ensembl
rs202035513	20	L>V		No	1000Genomes ExAC gnomAD
rs1255821741	21	L>F		No	TOPMed
rs1573600332	22	L>F		No	Ensembl
COSM1343000 rs750519483	23	R>C	Variant assessed as Somatic; MODERATE impact. large_intestine breast [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated ExAC NCI-TCGA TOPMed gnomAD
COSM3977693 rs765495466	23	R>H	lung [Cosmic]	No	cosmic curated ExAC TOPMed gnomAD
COSM3782475 rs1484659087	24	W>*	Variant assessed as Somatic; HIGH impact. prostate [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated NCI-TCGA gnomAD
rs762145388	24	W>C		No	ExAC gnomAD
rs754211951	25	R>K		No	ExAC TOPMed gnomAD
rs1331026019	25	R>S		No	gnomAD
rs868432487	26	G>E		No	Ensembl
rs764597609	30	K>R		No	ExAC TOPMed gnomAD
rs377504585	34	K>E		No	ESP ExAC TOPMed gnomAD
TCGA novel	34	K>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs377504585	34	K>Q		No	ESP ExAC TOPMed gnomAD
TCGA novel	35	E>G	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs2148849056	36	F>L		No	Ensembl
rs1651292343	38	L>F		No	TOPMed
rs370982160	40	G>A		No	ESP ExAC TOPMed gnomAD
rs370982160	40	G>E		No	ESP ExAC TOPMed gnomAD
rs772792729	40	G>R		No	ExAC gnomAD
rs768496607	41	A>D		No	ExAC gnomAD
rs768496607	41	A>V		No	ExAC gnomAD
rs1328703401	42	L>F		No	gnomAD
rs746960370	42	L>S		No	ExAC TOPMed gnomAD
rs779787042	43	Y>C		No	ExAC gnomAD
rs959321258	44	A>S		No	TOPMed gnomAD
rs959321258	44	A>T		No	TOPMed gnomAD
TCGA novel	44	A>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1651290186	45	V>A		No	Ensembl
rs1440060506	45	V>L		No	TOPMed gnomAD
COSM1296487	46	L>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1651289526	47	S>G		No	TOPMed
rs1166211611	48	I>T		No	gnomAD
rs1426221741	49	T>A		No	gnomAD
rs1426221741	49	T>S		No	gnomAD
rs1651289257	49	T>S		No	TOPMed
rs540517521	50	Y>H		No	1000Genomes ExAC gnomAD
rs148576399	51	R>P		No	ESP ExAC TOPMed gnomAD
rs148576399	51	R>Q		No	ESP ExAC TOPMed gnomAD
rs75504010	51	R>W	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	1000Genomes ESP ExAC NCI-TCGA TOPMed gnomAD
rs1269355261	53	L>P		No	gnomAD
rs1651285555	54	L>V		No	Ensembl
rs1477542017	55	T>S		No	TOPMed gnomAD
rs374914946	56	Q>L		No	ESP ExAC TOPMed gnomAD
rs754111733	57	E>K		No	ExAC gnomAD
TCGA novel	61	V>A	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs147375981	61	V>L		No	1000Genomes ESP ExAC TOPMed gnomAD
rs147375981	61	V>M		No	1000Genomes ESP ExAC TOPMed gnomAD
rs16832245 VAR_048411	62	Y>C		No	UniProt Ensembl dbSNP
rs1301445953	63	A>D		No	TOPMed gnomAD
COSM535286 COSM6063438 rs138830699	64	Q>*	lung Variant assessed as Somatic; HIGH impact. [Cosmic, NCI-TCGA]	No	cosmic curated NCI-TCGA Cosmic 1000Genomes ESP ExAC NCI-TCGA TOPMed gnomAD
rs1651283892	65	V>M		No	TOPMed
rs1228567414	66	A>D		No	TOPMed gnomAD
rs138395354	67	R>Q		No	1000Genomes ESP ExAC TOPMed gnomAD
rs752957577 COSM681205	67	R>W	lung Variant assessed as Somatic; MODERATE impact. [Cosmic, NCI-TCGA]	No	NCI-TCGA Cosmic cosmic curated ExAC NCI-TCGA TOPMed gnomAD
rs755410207	69	C>R		No	ExAC TOPMed gnomAD
rs1387386856	71	R>C		No	gnomAD
rs933903611 COSM1342998	71	R>H	Variant assessed as Somatic; MODERATE impact. large_intestine [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated NCI-TCGA TOPMed gnomAD
rs933903611	71	R>L		No	TOPMed gnomAD
TCGA novel	73	A>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1308058250 COSM4828547	74	D>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic NCI-TCGA gnomAD
COSM3490148	75	L>F	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1274422282	76	I>T		No	TOPMed
rs1651251971	84	F>Y		No	gnomAD
rs1651251887	85	Y>H		No	Ensembl
rs2148848370	88	L>V		No	Ensembl
rs781388761	90	V>M		No	ExAC gnomAD
rs935366567	92	R>C		No	TOPMed gnomAD
rs935366567	92	R>G		No	TOPMed gnomAD
COSM910063 rs1368631475	92	R>H	Variant assessed as Somatic; MODERATE impact. endometrium [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated TOPMed gnomAD
rs1368631475	92	R>L		No	TOPMed gnomAD
rs1651250653	94	W>*		No	Ensembl
rs1203754375	94	W>L		No	gnomAD
rs1421116690	94	W>R		No	TOPMed gnomAD
rs1328979301	95	S>A		No	gnomAD
rs1283035360	99	S>T		No	gnomAD
rs1651249899	100	I>L		No	TOPMed gnomAD
rs1573599251	100	I>T		No	Ensembl
rs1448135854	101	P>L		No	TOPMed gnomAD
rs1341823885	102	L>Q		No	gnomAD
rs1315866566	104	D>E		No	TOPMed gnomAD
rs1043965383	104	D>N		No	TOPMed gnomAD
COSM1342997	106	L>P	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1447340904	106	L>R		No	TOPMed gnomAD
rs143675241	108	C>S		No	1000Genomes ESP ExAC TOPMed gnomAD
rs751925750	109	V>L		No	ExAC gnomAD
rs1651248502	110	I>V		No	TOPMed
rs1417096111	113	S>N		No	gnomAD
rs1573599186	114	V>G		No	Ensembl
rs1473207314	114	V>M		No	TOPMed gnomAD
rs770329575	117	V>M		No	TOPMed gnomAD
rs1573599156	118	D>A		No	Ensembl
rs373896908	118	D>E		No	ESP TOPMed gnomAD
rs1172321034	118	D>G		No	gnomAD
rs966216849	119	Q>*		No	TOPMed
rs766811788	120	R>L		No	ExAC gnomAD
rs1248988468	120	R>W		No	gnomAD
rs1289798454	121	G>D		No	TOPMed gnomAD
rs1289798454	121	G>V		No	TOPMed gnomAD
rs1176327720	122	R>G		No	TOPMed gnomAD
rs1557613876	124	L>P		No	Ensembl
rs1357918762	126	R>H		No	gnomAD
rs1357918762	126	R>L		No	gnomAD
rs758926133	127	T>I		No	ExAC gnomAD
rs758926133	127	T>N		No	ExAC gnomAD
rs1268022094	127	T>P		No	gnomAD
rs1268022094	127	T>S		No	gnomAD
rs1322233557	128	L>F		No	gnomAD
rs1174138569	129	I>T		No	Ensembl
rs1393640445	129	I>V		No	gnomAD
rs1651243635	130	R>C		No	TOPMed
rs1651243529	130	R>L		No	TOPMed
rs983497502	131	Y>*		No	TOPMed gnomAD
rs1651243311	131	Y>C		No	Ensembl
TCGA novel	132	A>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs2148848209	133	N>D		No	Ensembl
rs1416106994	133	N>K		No	gnomAD
rs1557613835	134	L>R		No	Ensembl
rs1005476462	135	A>T		No	TOPMed gnomAD
rs775267719	137	V>L		No	ExAC TOPMed gnomAD
rs775267719	137	V>M		No	ExAC TOPMed gnomAD
rs1391027791	138	L>P		No	gnomAD
rs1467467509	139	V>A		No	TOPMed gnomAD
rs1246624229	141	R>C		No	gnomAD
rs879474294	141	R>P		No	TOPMed gnomAD
rs1246624229	141	R>S		No	gnomAD
rs767215949	142	S>L		No	ExAC TOPMed gnomAD
rs1452802413	142	S>T		No	gnomAD
rs1273421289	143	V>I		No	TOPMed
rs759340108	146	R>C		No	ExAC gnomAD
rs774303743	149	K>*		No	ExAC gnomAD
rs1438469123	150	R>H	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA gnomAD
rs888403850	151	F>Y		No	TOPMed gnomAD
rs1352707997	152	P>L		No	gnomAD
rs41306591	153	T>A		No	1000Genomes ESP ExAC TOPMed gnomAD
rs1371396154	153	T>N		No	gnomAD
rs575564694	154	M>V		No	1000Genomes ExAC TOPMed gnomAD
rs769966232	155	E>D		No	ExAC TOPMed gnomAD
TCGA novel	156	H>Q	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1651238128	156	H>Y		No	TOPMed
rs1424955189	157	V>M		No	TOPMed gnomAD
rs1477615045	158	V>G		No	Ensembl
rs906259275	159	D>E		No	TOPMed gnomAD
rs2148847900	161	G>D		No	Ensembl
rs1557613585	163	M>R		No	Ensembl
rs1651214490	163	M>V		No	TOPMed gnomAD
rs1450610599	164	S>T		No	gnomAD
rs757722278	165	Q>P		No	ExAC gnomAD
rs780600364	166	E>*		No	ExAC gnomAD
rs1573598568	166	E>D		No	Ensembl
rs780600364	166	E>K		No	ExAC gnomAD
rs145787289	167	E>D		No	ESP ExAC TOPMed gnomAD
rs1573598563	167	E>K		No	Ensembl
rs1429714383	168	R>K		No	gnomAD
rs1651213707	168	R>W		No	TOPMed gnomAD
rs1651213483	170	K>M		No	TOPMed
rs1016270608	170	K>N		No	gnomAD
rs1651213483	170	K>R		No	TOPMed
rs1557613552	171	F>C		No	Ensembl
rs766264466	171	F>L		No	ExAC gnomAD
rs1162006117	172	E>K		No	gnomAD
COSM138196	173	S>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1651212188	173	S>R		No	TOPMed
rs1414049714	174	L>P		No	gnomAD
rs762768363	175	K>Q		No	ExAC TOPMed gnomAD
rs1651210352	177	D>E		No	TOPMed
rs1651210159	179	N>K		No	Ensembl
rs1484753171	179	N>S		No	TOPMed gnomAD
TCGA novel	180	K>M	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs750198222	181	Y>C		No	ExAC gnomAD
rs1651210061	181	Y>H		No	Ensembl
rs201152880	182	W>C		No	Ensembl
TCGA novel	183	V>A	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs765171294	183	V>I		No	ExAC gnomAD
rs952595402	185	C>Y		No	Ensembl
rs1271271628	186	V>I		No	TOPMed gnomAD
rs1198712073	187	W>S		No	TOPMed gnomAD
rs900741062	188	F>L		No	TOPMed
rs900741062	188	F>V		No	TOPMed
rs1651208859	191	L>P		No	TOPMed
rs199576518	192	A>V		No	1000Genomes ExAC TOPMed gnomAD
rs760870126	194	Q>*		No	ExAC gnomAD
rs1651208358	194	Q>R		No	TOPMed
rs1368042877	195	A>V		No	TOPMed gnomAD
rs772289177	196	R>G		No	ExAC TOPMed gnomAD
rs772289177	196	R>W		No	ExAC TOPMed gnomAD
rs774605499	198	D>G		No	ExAC
rs1391459895	198	D>N		No	gnomAD
rs771431937	199	G>R		No	ExAC gnomAD
rs749800944	200	R>*		No	ExAC gnomAD
rs1651207225	200	R>Q		No	TOPMed
rs754596132	202	R>H		No	ExAC gnomAD
rs754596132	202	R>P		No	ExAC gnomAD
rs1166332308	203	D>H		No	gnomAD
COSM1296486	204	D>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs906381528	205	I>F		No	TOPMed gnomAD
rs906381528	205	I>V		No	TOPMed gnomAD
rs779794071	206	A>P		No	ExAC TOPMed gnomAD
rs779794071	206	A>S		No	ExAC TOPMed gnomAD
COSM6032401	206	A>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1557613457	206	A>V		No	Ensembl
rs756426747	208	C>R		No	Ensembl
rs1301641591	213	E>A		No	Ensembl
rs1651194035	213	E>D		No	TOPMed
rs1651194222	213	E>K		No	TOPMed gnomAD
rs1276229296	214	L>V		No	TOPMed gnomAD
rs1352680329	215	N>I		No	gnomAD
rs2148847522	215	N>K		No	Ensembl
rs1651193758	216	K>E		No	Ensembl
VAR_048412 rs16832242	217	Y>S		No	UniProt Ensembl dbSNP
rs929028276	218	R>*		No	TOPMed gnomAD
rs929028276	218	R>G		No	TOPMed gnomAD
rs1482147229	219	A>V		No	gnomAD
rs1206185650	222	S>R		No	gnomAD
rs1344617751	223	M>K		No	gnomAD
rs1344617751	223	M>T		No	gnomAD
rs1254582311	224	L>V		No	TOPMed gnomAD
rs898890458	229	W>*		No	TOPMed gnomAD
rs1349381876	229	W>G		No	gnomAD
rs1399631981	230	I>T		No	gnomAD
rs1287173783	232	I>N		No	Ensembl
rs1287173783	232	I>T		No	Ensembl
TCGA novel	233	P>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1651190728	234	L>H		No	Ensembl
rs375067026	235	V>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ESP NCI-TCGA TOPMed gnomAD
rs375067026	235	V>L		No	ESP TOPMed gnomAD
rs2148847457	236	Y>F		No	Ensembl
rs1187156864	241	T>A		No	gnomAD
rs1651178921	242	I>L		No	TOPMed
rs1651178829	242	I>T		No	TOPMed
rs1443246645	243	A>T		No	gnomAD
COSM5753104 rs774495129	244	V>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic ExAC NCI-TCGA TOPMed gnomAD
rs1444828123	249	A>S		No	TOPMed
rs1277111101	250	L>F		No	TOPMed gnomAD
rs1651178147	251	S>Y		No	Ensembl
rs763161362	255	R>C		No	ExAC TOPMed gnomAD
rs773733162 COSM1342996	255	R>H	Variant assessed as Somatic; MODERATE impact. large_intestine [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated ExAC NCI-TCGA TOPMed gnomAD
rs770383413	258	V>M		No	ExAC gnomAD
rs1341915887	259	E>K		No	gnomAD
rs1437874390	261	E>G		No	gnomAD
rs1389280224	262	A>T		No	gnomAD
rs1319470329	262	A>V		No	TOPMed
rs1402492451	264	A>P		No	gnomAD
rs1388623111	264	A>V		No	gnomAD
rs1651176198	265	A>T		No	Ensembl
rs1573597559	266	K>N		No	Ensembl
rs1573597564	266	K>Q		No	Ensembl
rs1651175793	267	P>S		No	Ensembl
rs1473217347	273	P>L		No	gnomAD
rs79969344	274	G>V		No	Ensembl
rs1387320554	277	P>S		No	gnomAD
rs745525188	279	P>A		No	ExAC gnomAD
COSM69816	280	A>P	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1271870219	281	L>Q		No	TOPMed
rs1451920727	282	G>R		No	TOPMed gnomAD
COSM3865664	283	D>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs370479919	284	P>A		No	ESP ExAC TOPMed gnomAD
rs182412775	284	P>L		No	1000Genomes ExAC TOPMed gnomAD
rs370479919	284	P>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ESP ExAC NCI-TCGA TOPMed gnomAD
TCGA novel	285	D>E	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1288464745	286	M>I		No	gnomAD
rs1458908205	286	M>R		No	gnomAD
rs1651174407	286	M>V		No	gnomAD
rs756018869	288	V>M		No	ExAC TOPMed gnomAD
rs1167503951	289	P>H		No	TOPMed gnomAD
rs752684505	291	T>I		No	ExAC TOPMed gnomAD
rs1227368775 COSM910062	296	F>L	Variant assessed as Somatic; MODERATE impact. endometrium [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated TOPMed gnomAD
rs1028650926	297	F>L		No	TOPMed
rs781319855	299	Y>C		No	ExAC
rs1651173062	299	Y>H		No	TOPMed
rs1271748861	303	L>P		No	gnomAD
rs1420709223	311	N>S		No	TOPMed gnomAD
rs1359226841	312	P>L		No	TOPMed gnomAD
rs1651166786	312	P>S		No	TOPMed
rs1651166517	313	F>S		No	Ensembl
rs769636382	317	D>G		No	ExAC gnomAD
rs1355348768	317	D>N		No	gnomAD
rs1651166070	322	T>K		No	TOPMed gnomAD
rs748074273	323	N>D		No	ExAC gnomAD
rs1425064773	324	Q>H		No	gnomAD
rs1173715001	325	L>H		No	gnomAD
rs377207881	326	I>R		No	ESP TOPMed gnomAD
COSM3985099 rs377207881	326	I>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic ESP TOPMed gnomAD
rs1248924819	326	I>V		No	gnomAD
rs1180845593	327	D>Y		No	gnomAD
rs780927449	328	R>C		No	ExAC gnomAD
rs1282131552 COSM1667522	328	R>H	Variant assessed as Somatic; MODERATE impact. haematopoietic_and_lymphoid_tissue [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated NCI-TCGA TOPMed gnomAD
rs372498770	329	N>S		No	ESP ExAC gnomAD
rs372498770	329	N>T		No	ESP ExAC gnomAD
VAR_048413 rs16832241	331	Q>E		No	UniProt Ensembl dbSNP
rs201994250	331	Q>L		No	gnomAD
rs201994250	331	Q>P		No	gnomAD
rs1041631425	332	V>M		No	TOPMed
rs745942679	333	S>A		No	ExAC gnomAD
rs1651159979	338	D>G		No	gnomAD
rs1346410974	341	Y>C		No	gnomAD
rs1573597037	343	N>T		No	Ensembl
rs757574175	344	L>F		No	ExAC TOPMed gnomAD
rs754115252	344	L>P		No	ExAC
TCGA novel	344	L>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs988031054	345	P>L		No	TOPMed gnomAD
rs1422816473	345	P>T		No	gnomAD
rs1256577053	346	P>A		No	TOPMed
COSM4008436	346	P>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1256577053	346	P>S		No	TOPMed
rs2148846826	347	A>D		No	Ensembl
COSM4747117	347	A>L	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1651158632	347	A>S		No	TOPMed
rs1651158374	348	E>G		No	Ensembl
rs1209321839	348	E>K		No	gnomAD
rs1573596984	350	D>A		No	TOPMed
rs1573596984	350	D>G		No	TOPMed
rs1262510638	351	Q>R		No	gnomAD
rs1651157682	352	Y>C		No	gnomAD
rs1557612683	353	W>*		No	TOPMed gnomAD
rs765870318	353	W>G		No	ExAC
rs762383507	354	D>E		No	ExAC TOPMed gnomAD
rs942555009	354	D>G		No	TOPMed gnomAD
COSM3490146 rs1248600356	355	E>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic NCI-TCGA gnomAD
rs772723521	356	D>A		No	ExAC gnomAD
rs1364718786	357	Q>R		No	gnomAD
rs141308464	358	P>L		No	ESP ExAC TOPMed gnomAD
rs776266325	359	Q>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	ExAC NCI-TCGA gnomAD
rs768552808	360	P>L		No	ExAC TOPMed gnomAD
rs533175337	361	P>A		No	1000Genomes ExAC TOPMed gnomAD
COSM1667521 rs772145581	361	P>L	central_nervous_system [Cosmic]	No	cosmic curated ExAC TOPMed gnomAD
rs533175337	361	P>S		No	1000Genomes ExAC TOPMed gnomAD
rs1651155887	362	Y>H		No	Ensembl
rs1651155707	363	T>P		No	Ensembl
rs1193649599	364	V>M		No	gnomAD
rs1651155345	365	A>P		No	TOPMed
rs1220210615	365	A>V		No	gnomAD
rs564255785	366	T>M		No	1000Genomes ExAC TOPMed gnomAD
rs1029183229	367	A>T		No	TOPMed gnomAD
rs777990349 COSM4008435	368	A>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic ExAC NCI-TCGA gnomAD
rs753008617	369	E>*		No	ExAC
rs997168788	369	E>V		No	Ensembl
rs767954927	370	S>P		No	ExAC gnomAD
rs1309779488	372	R>L		No	TOPMed gnomAD
rs1309779488	372	R>Q		No	TOPMed gnomAD
rs749901864	374	S>L		No	ExAC gnomAD
rs376989433	375	F>L		No	1000Genomes ESP ExAC TOPMed gnomAD
rs966114563	377	G>D		No	TOPMed gnomAD
rs1651153483	377	G>R		No	TOPMed
rs966114563	377	G>V		No	TOPMed gnomAD
rs1573596814	379	T>S		No	Ensembl
rs1304463538	381	N>T		No	gnomAD
rs1573596793	383	R>H		No	Ensembl
rs1369563730	383	R>S		No	gnomAD
rs545879066	384	M>K		No	1000Genomes TOPMed gnomAD
rs935246096	385	S>I		No	TOPMed gnomAD
rs935246096	385	S>N		No	TOPMed gnomAD
rs1651144924	386	D>E		No	TOPMed gnomAD
rs868510488	387	D>N		No	TOPMed gnomAD
rs1651144585	388	P>A		No	Ensembl
rs1651144389	390	Q>*		No	TOPMed
rs1384297238	391	S>I		No	gnomAD
rs1159242605	391	S>R		No	TOPMed gnomAD
rs979216533	392	L>M		No	TOPMed gnomAD
rs1573596504	392	L>P		No	Ensembl
rs1422573849	393	Q>R		No	gnomAD
rs1573596490	394	V>G		No	Ensembl
rs1651143524	394	V>L		No	TOPMed
rs1573596480	395	E>G		No	Ensembl
rs921674906	395	E>K		No	TOPMed gnomAD
rs1445667752	396	A>T		No	TOPMed gnomAD
rs976245989	397	S>F		No	TOPMed gnomAD
rs1347617718	399	G>*		No	TOPMed gnomAD
rs1315175940	399	G>A		No	TOPMed gnomAD
rs1315175940	399	G>E		No	TOPMed gnomAD
rs1651141900	400	S>F		No	TOPMed
VAR_048414 rs16832239	402	R>L		No	UniProt TOPMed dbSNP gnomAD
rs16832239	402	R>P		No	TOPMed gnomAD
rs16832239	402	R>Q		No	TOPMed gnomAD
rs1178545992	403	P>A		No	Ensembl
rs1290656722	404	A>P		No	TOPMed gnomAD
rs1290656722	404	A>S		No	TOPMed gnomAD
rs1246415082	405	P>T		No	TOPMed gnomAD
rs1295171017	406	A>P		No	gnomAD
rs1295171017	406	A>T		No	gnomAD
rs1434215737	406	A>V		No	gnomAD
rs983152213	407	A>T		No	Ensembl
rs1651140155	409	T>N		No	Ensembl
rs1239793374	409	T>S		No	TOPMed gnomAD
rs1182068056	411	L>M		No	TOPMed
rs1051850223	414	R>H		No	TOPMed gnomAD
rs1051850223	414	R>P		No	TOPMed gnomAD
rs577052104	416	L>R		No	1000Genomes
rs1573596332	418	V>A		No	TOPMed
rs1573596332	418	V>G		No	TOPMed
rs1651139168	418	V>I		No	Ensembl
rs1388820152	419	G>R		No	gnomAD
rs933431142	420	A>T		No	TOPMed gnomAD
rs1001686246	423	P>A		No	TOPMed gnomAD
rs906037415	423	P>L		No	TOPMed gnomAD
rs906037415	423	P>R		No	TOPMed gnomAD
rs1001686246	423	P>T		No	TOPMed gnomAD
rs1651137495	426	S>G		No	TOPMed
rs1651137404	426	S>R		No	Ensembl
rs1452217821	427	L>H		No	TOPMed gnomAD
rs1651137040	428	R>Q		No	TOPMed
rs1475333235	428	R>W		No	gnomAD
rs1222558067	429	N>I		No	TOPMed
rs756719540	430	F>L		No	ExAC TOPMed gnomAD
rs763749926	431	G>A		No	ExAC gnomAD
rs753296919	431	G>C		No	ExAC TOPMed gnomAD
rs763749926	431	G>D		No	ExAC gnomAD
rs753296919	431	G>S		No	ExAC TOPMed gnomAD
rs1361179331	432	R>H		No	gnomAD
rs1361179331	432	R>L		No	gnomAD
rs2148846330	432	R>S		No	Ensembl
rs1213842577	433	V>A		No	gnomAD
rs59895800	433	V>L		No	1000Genomes ExAC TOPMed gnomAD
rs59895800	433	V>M		No	1000Genomes ExAC TOPMed gnomAD
rs1210165590	434	R>Q		No	Ensembl
rs752507291	435	G>C		No	ExAC gnomAD
rs767472317	435	G>D		No	ExAC TOPMed gnomAD
rs767472317	435	G>V		No	ExAC TOPMed gnomAD
rs1343672016	436	T>I		No	TOPMed gnomAD
rs1343672016	436	T>N		No	TOPMed gnomAD
COSM4747116 rs755252994	438	R>A	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic NCI-TCGA
rs1302652055	438	R>S		No	gnomAD
rs748003416	440	P>A		No	1000Genomes ExAC TOPMed gnomAD
rs958898342	440	P>R		No	TOPMed
rs748003416	440	P>T		No	1000Genomes ExAC TOPMed gnomAD
rs1178265451	441	H>R		No	TOPMed gnomAD
rs35241419	442	L>M		No	TOPMed
rs1573596158	445	F>V		No	Ensembl
rs936027239	446	R>L		No	gnomAD
rs936027239	446	R>Q		No	gnomAD
rs1651131145	446	R>W		No	Ensembl
rs1651130583	447	A>E		No	TOPMed
rs1477345071	447	A>T		No	gnomAD
rs1651130583	447	A>V		No	TOPMed
rs1469421750	448	E>G		No	TOPMed gnomAD
rs1469421750	448	E>V		No	TOPMed gnomAD
rs2148846277	449	E>G		No	Ensembl
rs1379555210	451	G>R		No	TOPMed
rs1573596116	452	D>A		No	Ensembl
rs1199528548	452	D>E		No	TOPMed gnomAD
rs981199645	453	P>H		No	TOPMed gnomAD
rs981199645	453	P>L		No	TOPMed gnomAD
rs1011168159	454	E>*		No	TOPMed
rs1011168159	454	E>K		No	TOPMed
rs1203530909	456	A>S		No	TOPMed gnomAD
rs1203530909	456	A>T		No	TOPMed gnomAD
TCGA novel	456	A>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs892811411	457	A>S		No	TOPMed
rs1438221829	458	R>H		No	gnomAD
rs1438221829	458	R>P		No	gnomAD
rs2148846245	458	R>S		No	Ensembl
rs866382385	459	I>V		No	Ensembl
TCGA novel	460	E>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs1651128769	460	E>K		No	TOPMed gnomAD
rs1258362449	462	E>K		No	Ensembl
rs1573596059	464	A>T		No	Ensembl
rs1274892461	464	A>V		No	gnomAD
rs1651128023	465	E>*		No	TOPMed
rs931801372	465	E>D		No	Ensembl
rs1651127504	467	G>E		No	gnomAD
rs1322745978	467	G>R		No	gnomAD
rs1651127318	468	D>N		No	Ensembl
rs1651127086	469	E>D		No	gnomAD
rs1439308509	469	E>K		No	TOPMed gnomAD
rs2148846215	470	A>D		No	Ensembl
rs975983044	470	A>S		No	gnomAD
rs975983044	470	A>T		No	gnomAD
rs1485542675	471	L>P		No	gnomAD

No associated diseases with Q8NFU0

3 regional properties for Q8NFU0

Type	Name	Position	InterPro Accession
domain	Protein kinase domain	221 - 488	IPR000719
active_site	Serine/threonine-protein kinase, active site	345 - 357	IPR008271
binding_site	Protein kinase, ATP binding site	227 - 250	IPR017441

Functions

		Description
EC Number
Subcellular Localization	Cell membrane; Multi-pass membrane protein
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

2 GO annotations of cellular component

Name	Definition
chloride channel complex	An ion channel complex through which chloride ions pass.
plasma membrane	The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.

2 GO annotations of molecular function

Name	Definition
chloride channel activity	Enables the facilitated diffusion of a chloride (by an energy-independent process) involving passage through a transmembrane aqueous pore or channel without evidence for a carrier-mediated mechanism.
intracellular calcium activated chloride channel activity	Enables the transmembrane transfer of chloride by a channel that opens in response to stimulus by a calcium ion or ions. Transport by a channel involves catalysis of facilitated diffusion of a solute (by an energy-independent process) involving passage through a transmembrane aqueous pore or channel, without evidence for a carrier-mediated mechanism.

No GO annotations of biological process

Name	Definition
No GO annotations for biological process

12 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q8NFU1	BEST2	Bestrophin-2a	Homo sapiens (Human)	SS
Q8N1M1	BEST3	Bestrophin-3	Homo sapiens (Human)	SS
O76090	BEST1	Bestrophin-1	Homo sapiens (Human)	SS
Q6H1V1	Best3	Bestrophin-3	Mus musculus (Mouse)	EV
Q8BGM5	Best2	Bestrophin-2	Mus musculus (Mouse)	SS
O88870	Best1	Bestrophin-1	Mus musculus (Mouse)	SS
O18303	best-25	Bestrophin homolog 25	Caenorhabditis elegans	PR
O45435	best-13	Bestrophin homolog 13	Caenorhabditis elegans	PR
P34319	best-5	Bestrophin homolog 5	Caenorhabditis elegans	PR
P34672	best-24	Bestrophin homolog 24	Caenorhabditis elegans	PR
Q19978	best-14	Bestrophin homolog 14	Caenorhabditis elegans	PR
Q23369	best-22	Bestrophin homolog 22	Caenorhabditis elegans	PR

10	20	30	40	50	60
MTVSYTLKVA	EARFGGFSGL	LLRWRGSIYK	LLYKEFLLFG	ALYAVLSITY	RLLLTQEQRY
70	80	90	100	110	120
VYAQVARYCN	RSADLIPLSF	VLGFYVTLVV	NRWWSQYTSI	PLPDQLMCVI	SASVHGVDQR
130	140	150	160	170	180
GRLLRRTLIR	YANLASVLVL	RSVSTRVLKR	FPTMEHVVDA	GFMSQEERKK	FESLKSDFNK
190	200	210	220	230	240
YWVPCVWFTN	LAAQARRDGR	IRDDIALCLL	LEELNKYRAK	CSMLFHYDWI	SIPLVYTQVV
250	260	270	280	290	300
TIAVYSFFAL	SLVGRQFVEP	EAGAAKPQKL	LKPGQEPAPA	LGDPDMYVPL	TTLLQFFFYA
310	320	330	340	350	360
GWLKVAEQII	NPFGEDDDDF	ETNQLIDRNL	QVSLLSVDEM	YQNLPPAEKD	QYWDEDQPQP
370	380	390	400	410	420
PYTVATAAES	LRPSFLGSTF	NLRMSDDPEQ	SLQVEASPGS	GRPAPAAQTP	LLGRFLGVGA
430	440	450	460	470
PSPAISLRNF	GRVRGTPRPP	HLLRFRAEEG	GDPEAAARIE	EESAESGDEA	LEP