AiPD: Autoinhibited Protein Database

P14653

Gene name	HOXB1 (HOX2I)
Protein name	Homeobox protein Hox-B1
Names	Homeobox protein Hox-2I
Species	Homo sapiens (Human)
KEGG Pathway	hsa:3211
EC number
Protein Class

Descriptions

lab is a member of the Homeotic complex (HOX) family of homeoproteins that are required for specifying cell fates and morphological differences along the anterior-posterior axes of most animals. The lab hexapeptide(also called YPWM motif or pentapeptide) inhibits lab function and activates inappropriate target genes in vivo by inhibiting DNA binding. LAB-EXD interactions functions to remove the inhibitory effect of the hexapeptide and to enhance DNA binding to relevant target sequences by cooperative interactions.

Autoinhibitory domains (AIDs)

173-198 (Hexapeptide) SS

Target domain	207-264 (Homeodomain)
Relief mechanism	Partner binding
Assay

AID

173-198 (Hexapeptide)

Target domain

207-264 (Homeodomain)

Relief mechanism

Partner binding (EXD binding to the hexapeptide of LAB)

Assay

Accessory elements

No accessory elements

References

Chan SK et al. (1996) "An extradenticle-induced conformational change in a HOX protein overcomes an inhibitory function of the conserved hexapeptide motif", The EMBO journal, 15, 2476-87

Autoinhibited structure

Activated structure

2 structures for P14653

Entry ID	Method	Resolution	Chain	Position	Source
1B72	X-ray	235 A	A	170-264	PDB
AF-P14653-F1	Predicted				AlphaFoldDB

364 variants for P14653

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
RCV000585800 rs1247386618 CA400086893	22	Y>*	Facial paresis, hereditary congenital, 3 Facial paresis, hereditary congenital, 3 (hcfp3) [ClinVar, Ensembl]	Yes	ClinGen ClinVar dbSNP gnomAD
RCV000872417 rs150583509 RCV002487917	95	P>T	Facial paresis, hereditary congenital, 3 [ClinVar]	Yes	ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
COSM3937442 rs387907239 VAR_068723 CA129954 RCV000029225	207	R>C	oesophagus Facial paresis, hereditary congenital, 3 Facial paresis, hereditary congenital, 3 (hcfp3) HCFP3; decreased transactivation activity at low DNA concentrations; increased transactivation activity at high DNA concentrations compared to wild-type [Cosmic, ClinVar, Ensembl, UniProt]	Yes	ClinGen cosmic curated ClinVar UniProt ExAC TOPMed dbSNP gnomAD
RCV000585798 rs1555632121 CA400081746	207	R>H	Facial paresis, hereditary congenital, 3 Facial paresis, hereditary congenital, 3 (hcfp3) [ClinVar, Ensembl]	Yes	ClinGen ClinVar Ensembl dbSNP
rs1567932264 RCV000785946	255	R>Q	Facial paresis, hereditary congenital, 3 [ClinVar]	Yes	ClinVar Ensembl dbSNP
rs7226137 VAR_058129 RCV001703117 RCV001692450 RCV001529661	265	E>G	Facial paresis, hereditary congenital, 3 [ClinVar]	Yes	ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs1230978425	2	D>A		No	TOPMed gnomAD
rs1332752056	2	D>Y		No	TOPMed gnomAD
rs763448749	3	Y>C		No	ExAC gnomAD
rs1267410884	6	M>I		No	gnomAD
rs765827877	6	M>V		No	ExAC gnomAD
rs1598733582	7	N>S		No	gnomAD
rs1598733582	7	N>T		No	gnomAD
rs1226418367	7	N>Y		No	TOPMed gnomAD
rs867398927	8	S>F		No	TOPMed gnomAD
rs867398927	8	S>Y		No	TOPMed gnomAD
rs1279822486	10	L>F		No	TOPMed gnomAD
rs760042109	10	L>V		No	ExAC gnomAD
rs1421068863	13	P>S		No	TOPMed gnomAD
rs570793908	14	L>F		No	1000Genomes ExAC TOPMed gnomAD
rs201732118	14	L>H		No	TOPMed gnomAD
rs201732118	14	L>P		No	TOPMed gnomAD
rs570793908	14	L>V		No	1000Genomes ExAC TOPMed gnomAD
rs2068434736	15	C>R		No	Ensembl
rs1327264822	15	C>Y		No	gnomAD
rs768410617	17	R>P		No	ExAC TOPMed gnomAD
rs768410617	17	R>Q		No	ExAC TOPMed gnomAD
rs550774588	17	R>W		No	1000Genomes ExAC TOPMed gnomAD
rs779842484	18	G>*		No	ExAC TOPMed gnomAD
rs2068434544	18	G>E		No	TOPMed
rs779842484	18	G>R		No	ExAC TOPMed gnomAD
rs769774049	19	P>H		No	ExAC TOPMed gnomAD
rs769774049	19	P>L		No	ExAC TOPMed gnomAD
rs2144694324	19	P>S		No	Ensembl
rs537215928	20	S>R		No	1000Genomes ExAC TOPMed gnomAD
rs2068434360	21	A>P		No	gnomAD
rs1251229273	21	A>V		No	TOPMed gnomAD
rs12950537	22	Y>H		No	ExAC gnomAD
rs200375517	24	A>S		No	1000Genomes ExAC TOPMed gnomAD
rs200375517	24	A>T		No	1000Genomes ExAC TOPMed gnomAD
RCV000870526 rs534792734	25	H>missing		No	ClinVar dbSNP
rs1218292839	25	H>Q		No	gnomAD
rs2068433973 COSM3518714	25	H>Y	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic Ensembl
rs200151818	26	S>R		No	gnomAD
VAR_003817	27	A>AHSA	allele HOXB1*B [UniProt]	No	UniProt
rs1305173448	27	A>P	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA gnomAD
rs1441060785	28	P>S	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA gnomAD
rs758818644	29	T>A		No	ExAC gnomAD
rs753115367	29	T>I		No	ExAC TOPMed gnomAD
rs753115367	29	T>N		No	ExAC TOPMed gnomAD
rs753115367 COSM3362190	29	T>S	kidney [Cosmic]	No	cosmic curated ExAC TOPMed gnomAD
rs1347318697	30	S>A		No	gnomAD
rs1393574843	31	F>*		No	gnomAD
rs765599353	31	F>L		No	ExAC gnomAD
rs2144694181	31	F>L		No	Ensembl
rs755545003	32	P>R		No	ExAC gnomAD
rs1247441581	33	P>L		No	gnomAD
rs1341114446	34	S>R		No	TOPMed
rs1567932867	35	S>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA gnomAD
rs1242617119	36	A>T		No	TOPMed gnomAD
rs1401294051	38	A>P		No	TOPMed gnomAD
rs1401294051	38	A>T		No	TOPMed gnomAD
rs766995509	38	A>V		No	ExAC TOPMed gnomAD
TCGA novel	39	V>A	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1282077352	40	D>G		No	gnomAD
COSM1521291 rs944421558 COSM6146820	43	A>S	lung Variant assessed as Somatic; MODERATE impact. [Cosmic, NCI-TCGA]	No	cosmic curated NCI-TCGA Cosmic NCI-TCGA gnomAD
rs944421558	43	A>T		No	gnomAD
rs2068432966	43	A>V		No	TOPMed
rs1314713919	44	S>G		No	TOPMed gnomAD
rs768986218	44	S>I		No	Ensembl
rs768986218	44	S>N		No	Ensembl
COSM561205	45	E>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
COSM4067367	46	G>D	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs201520016	47	R>C		No	ExAC TOPMed gnomAD
rs560538130	47	R>H		No	1000Genomes ExAC TOPMed gnomAD
rs2068432637	49	G>A		No	TOPMed gnomAD
rs376245728	49	G>S		No	ESP ExAC TOPMed gnomAD
rs1315037460	50	G>A		No	TOPMed gnomAD
rs1315037460	50	G>E		No	TOPMed gnomAD
rs745794647	50	G>R		No	ExAC TOPMed gnomAD
rs745794647	50	G>W		No	ExAC TOPMed gnomAD
rs771127422	51	G>A		No	ExAC gnomAD
COSM4528219	51	G>R	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1489587559	53	S>F		No	TOPMed gnomAD
rs1181184045	55	P>S		No	gnomAD
rs1474113817	56	A>G		No	TOPMed gnomAD
rs1474113817	56	A>V		No	TOPMed gnomAD
CA10605593 RCV000352097 rs886043501	57	F>Y		No	ClinGen ClinVar Ensembl dbSNP
rs1211168663	60	N>D		No	gnomAD
rs1206092299	62	G>D		No	gnomAD
rs779359864	62	G>S		No	ExAC gnomAD
rs2068432254	63	Y>D		No	Ensembl
rs1307534184	64	P>L		No	gnomAD
COSM5681252 rs755351120	65	A>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic ExAC NCI-TCGA TOPMed gnomAD
rs1353989107	68	P>L		No	gnomAD
COSM3889818 rs1370259338	70	S>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic NCI-TCGA TOPMed gnomAD
rs1370259338	70	S>W		No	TOPMed gnomAD
VAR_055959 rs35254561	71	T>N		No	UniProt Ensembl dbSNP
rs1366984237	72	L>P		No	TOPMed
rs1355134865	72	L>V		No	TOPMed gnomAD
rs2068431778	73	G>E		No	Ensembl
rs1668267410	73	G>R		No	Ensembl
rs1164029438	74	V>L		No	TOPMed gnomAD
COSM3518712 rs1474149158	75	P>S	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic NCI-TCGA gnomAD
rs1419781550	76	F>L		No	TOPMed gnomAD
rs763670713	77	P>A		No	ExAC TOPMed gnomAD
rs763670713	77	P>S		No	ExAC TOPMed gnomAD
COSM74939	78	S>C	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1343618539	78	S>N		No	gnomAD
rs41306355	79	S>P		No	Ensembl
rs199503961	80	A>S		No	ExAC TOPMed gnomAD
rs199503961	80	A>T		No	ExAC TOPMed gnomAD
COSM4067366 rs765050616	80	A>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic ExAC NCI-TCGA gnomAD
rs776614578	81	P>S		No	ExAC TOPMed gnomAD
rs776614578	81	P>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA TOPMed gnomAD
rs2144693959	82	S>L		No	Ensembl
rs1213632034	83	G>R		No	gnomAD
COSM6081053	83	G>W	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1275593018	84	Y>C		No	gnomAD
COSM705968 rs1023657929	85	A>T	lung Variant assessed as Somatic; MODERATE impact. [Cosmic, NCI-TCGA]	No	NCI-TCGA Cosmic cosmic curated NCI-TCGA gnomAD
rs544516524	85	A>V		No	1000Genomes ExAC TOPMed gnomAD
rs530967477	86	P>S		No	1000Genomes ExAC TOPMed gnomAD
rs1338385831	87	A>T		No	TOPMed
TCGA novel	88	A>S	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs779047774	88	A>T		No	ExAC TOPMed gnomAD
rs2144693906	91	P>L		No	Ensembl
rs1186512882	91	P>S		No	gnomAD
TCGA novel	92	S>A	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs1287270276	93	Y>C		No	TOPMed gnomAD
rs373253731	94	G>E		No	ESP ExAC TOPMed gnomAD
COSM3518711 rs780483178	94	G>R	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic ExAC NCI-TCGA gnomAD
rs150583509	95	P>S		No	1000Genomes ESP ExAC TOPMed gnomAD
rs1285352392	97	Q>R		No	TOPMed
rs777239971	98	Y>*		No	ExAC TOPMed gnomAD
COSM6081054	100	P>H	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs757885753	101	L>V		No	ExAC gnomAD
rs1191279883	102	G>D		No	gnomAD
rs1191279883	102	G>V		No	gnomAD
rs754648348	103	Q>E		No	Ensembl
RCV001637730 VAR_055960 rs12939811	103	Q>H		No	ClinVar UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs764851719	103	Q>R		No	ExAC gnomAD
COSM261317	105	E>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs148460064	105	E>D		No	ESP ExAC gnomAD
COSM4820393	105	E>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1567932695	105	E>Q		No	Ensembl
rs1484691128	106	G>E		No	TOPMed gnomAD
COSM705969	107	D>E	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1026719724	107	D>G		No	TOPMed
rs773334553	108	G>R		No	ExAC gnomAD
rs772165312	109	G>A		No	ExAC gnomAD
rs2068430139	110	Y>C		No	TOPMed
rs2068430107	111	F>L		No	TOPMed
rs761868927	112	H>Q		No	ExAC gnomAD
COSM3795731	113	P>A	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs2068430049	114	S>*		No	TOPMed gnomAD
rs2068430049	114	S>W		No	TOPMed gnomAD
rs572890821	115	S>I		No	1000Genomes ExAC gnomAD
rs2068429964	116	Y>D		No	gnomAD
rs749602209	117	G>A		No	ExAC gnomAD
rs2068429941	117	G>R		No	Ensembl
rs780429744	118	A>D		No	ExAC TOPMed gnomAD
rs1008667115	118	A>P		No	Ensembl
rs780429744	118	A>V		No	ExAC TOPMed gnomAD
rs1454116018	120	L>Q		No	TOPMed gnomAD
rs1376755257	121	G>R		No	gnomAD
rs746343075	122	G>A		No	ExAC gnomAD
rs890668095	123	L>S		No	TOPMed gnomAD
rs2068429623	124	S>F		No	TOPMed
COSM4067365	124	S>P	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs752158237	125	D>G		No	ExAC TOPMed gnomAD
rs1028968103	125	D>H		No	TOPMed gnomAD
rs1028968103	125	D>N		No	TOPMed gnomAD
rs752158237	125	D>V		No	ExAC TOPMed gnomAD
rs1028968103	125	D>Y		No	TOPMed gnomAD
rs778559393	126	G>D		No	ExAC TOPMed gnomAD
rs1486381791	128	G>E		No	TOPMed gnomAD
rs766256495	128	G>R	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA TOPMed gnomAD
rs2068429378	129	A>E		No	Ensembl
TCGA novel	130	G>C	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs200933753	130	G>D		No	1000Genomes ExAC TOPMed gnomAD
rs372920233	130	G>S		No	ESP ExAC TOPMed gnomAD
rs1304170421	132	A>T		No	gnomAD
rs2068429233	132	A>V		No	Ensembl
rs545841960	133	G>C		No	1000Genomes ExAC TOPMed gnomAD
rs545841960	133	G>R		No	1000Genomes ExAC TOPMed gnomAD
rs545841960	133	G>S		No	1000Genomes ExAC TOPMed gnomAD
rs2068429112	133	G>V		No	Ensembl
rs774301837	134	P>L		No	ExAC TOPMed gnomAD
rs774301837	134	P>R		No	ExAC TOPMed gnomAD
TCGA novel	135	G>W	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs763137794	136	P>L		No	ExAC TOPMed gnomAD
TCGA novel	136	P>T	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs1326906734	138	P>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA gnomAD
rs770139021	139	P>L		No	ExAC TOPMed gnomAD
rs530881737	140	Q>R		No	gnomAD
rs902338362	141	H>Q		No	TOPMed
rs2068428744	142	P>H		No	TOPMed gnomAD
COSM1383996	143	P>L	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs777134943	143	P>S		No	ExAC TOPMed gnomAD
rs771343186	144	Y>H		No	ExAC gnomAD
rs368471890	146	N>K		No	ESP ExAC TOPMed gnomAD
rs748921455	147	E>K		No	ExAC TOPMed gnomAD
TCGA novel	148	Q>H	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs2144693668	149	T>I		No	Ensembl
rs1486744106	150	A>E		No	TOPMed gnomAD
rs750258334	150	A>P		No	ExAC TOPMed gnomAD
rs750258334	150	A>S		No	ExAC TOPMed gnomAD
rs750258334	150	A>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA TOPMed gnomAD
rs757174933	151	S>R		No	ExAC gnomAD
rs2068428300	153	A>T		No	TOPMed
COSM1383995 rs751611344	154	P>L	Variant assessed as Somatic; MODERATE impact. large_intestine [NCI-TCGA, Cosmic]	No	cosmic curated ExAC NCI-TCGA TOPMed gnomAD
rs751611344	154	P>R		No	ExAC TOPMed gnomAD
rs2068428268	154	P>S		No	TOPMed
TCGA novel	155	A>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
COSM1630241 rs1219369123	156	Y>F	liver [Cosmic]	No	cosmic curated TOPMed
rs930945042	157	A>D		No	TOPMed gnomAD
rs1354583758	157	A>S		No	TOPMed gnomAD
rs930945042	157	A>V		No	TOPMed gnomAD
TCGA novel	159	L>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
TCGA novel	161	S>Y	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs144625073 RCV000983909	162	E>K		No	ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs144625073	162	E>Q		No	1000Genomes ESP ExAC TOPMed gnomAD
rs368946771	163	D>V		No	ESP ExAC TOPMed gnomAD
rs771417327	164	K>E		No	ExAC gnomAD
rs370348373	165	E>A		No	ESP ExAC TOPMed gnomAD
rs370348373	165	E>G		No	ESP ExAC TOPMed gnomAD
COSM3518709	165	E>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1170181865	166	T>I		No	TOPMed gnomAD
TCGA novel	167	P>H	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1466541070	167	P>S		No	gnomAD
rs200228944	169	P>A		No	TOPMed gnomAD
rs200228944 COSM3518708	169	P>S	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic NCI-TCGA TOPMed gnomAD
COSM6146822	171	E>Q	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1396834936	172	P>S		No	TOPMed gnomAD
rs779796162	174	T>I		No	ExAC TOPMed gnomAD
rs779796162	174	T>N		No	ExAC TOPMed gnomAD
COSM4067364	175	P>H	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs138341371	176	T>K		No	ESP ExAC TOPMed gnomAD
rs138341371	176	T>M	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ESP ExAC NCI-TCGA TOPMed gnomAD
rs916641552	178	R>L		No	gnomAD
rs916641552	178	R>P		No	gnomAD
rs916641552 COSM3421662	178	R>Q	Variant assessed as Somatic; MODERATE impact. large_intestine [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated NCI-TCGA gnomAD
rs948188618	178	R>W		No	TOPMed gnomAD
rs2068427333	179	T>N		No	Ensembl
rs1367574149	181	D>A		No	TOPMed
rs780872597	181	D>N		No	ExAC TOPMed gnomAD
rs2068427218 COSM3518707	182	W>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic Ensembl
COSM2148898	184	K>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs2068427117	186	K>N		No	Ensembl
rs2068427142	186	K>R		No	TOPMed
TCGA novel	188	N>S	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs2068427035	190	P>S		No	TOPMed gnomAD
rs2144693525	192	T>I		No	Ensembl
rs369935545	193	A>G		No	1000Genomes ExAC gnomAD
rs369935545	193	A>V		No	1000Genomes ExAC gnomAD
rs771900693	195	V>A		No	ExAC
rs2068423632	196	S>T		No	Ensembl
rs1279175267	197	E>D		No	gnomAD
rs1324089681	198	P>R		No	TOPMed gnomAD
rs912799933	199	G>D		No	TOPMed
rs2068423520	199	G>R		No	TOPMed
rs2068423460 TCGA novel	200	L>Q	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Ensembl
rs755001724	202	S>L		No	ExAC TOPMed gnomAD
rs755001724	202	S>W		No	ExAC TOPMed gnomAD
rs376040365	203	P>A		No	ESP ExAC TOPMed gnomAD
rs376040365 COSM980618	203	P>S	Variant assessed as Somatic; MODERATE impact. endometrium [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated ESP ExAC NCI-TCGA TOPMed gnomAD
rs756390027	205	G>D		No	ExAC gnomAD
rs767973578	206	L>P		No	ExAC gnomAD
rs1182037537	208	T>N		No	gnomAD
rs2068422997	209	N>S		No	Ensembl
rs1203055487	213	R>G		No	gnomAD
rs2068422900	214	Q>R		No	TOPMed
COSM3518706 rs776236487	221	E>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic ExAC NCI-TCGA TOPMed gnomAD
rs370489961	225	N>S		No	ESP TOPMed gnomAD
rs1396751931	227	Y>*		No	TOPMed gnomAD
rs200261536	229	S>G		No	gnomAD
rs2068422586	229	S>R		No	Ensembl
rs772889095	230	R>Q		No	ExAC TOPMed gnomAD
rs879025404	230	R>W	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	Ensembl NCI-TCGA
rs1444453992	231	A>S		No	gnomAD
rs2068422487	231	A>V		No	TOPMed
rs759845470	232	R>L		No	ExAC TOPMed gnomAD
rs759845470 COSM3795729	232	R>Q	Variant assessed as Somatic; MODERATE impact. urinary_tract [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated ExAC NCI-TCGA TOPMed gnomAD
rs1400987484	232	R>W		No	TOPMed gnomAD
COSM6081056	233	R>S	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1459696170	234	V>A		No	gnomAD
rs768646936 COSM1679893	235	E>D	haematopoietic_and_lymphoid_tissue [Cosmic]	No	cosmic curated ExAC gnomAD
rs774220542	235	E>V		No	ExAC gnomAD
rs2068422237	236	I>V		No	TOPMed
rs1046749207	238	A>T		No	TOPMed gnomAD
COSM6146823	238	A>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs746058907	239	T>P		No	ExAC gnomAD
TCGA novel	241	E>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs2068422052	241	E>Q		No	TOPMed
rs781620828	243	N>S	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA TOPMed gnomAD
COSM4394546	244	E>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs2068421976	249	I>V		No	gnomAD
COSM3518703	250	W>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1191811337	250	W>C		No	TOPMed gnomAD
rs751975967	253	N>T		No	ExAC gnomAD
rs764467860	254	R>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	ExAC NCI-TCGA gnomAD
rs2068421809	254	R>Q		No	Ensembl
COSM6146824	256	M>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs758961981	260	K>N		No	ExAC gnomAD
rs1252047691	260	K>Q		No	gnomAD
rs1461274057	261	R>C		No	TOPMed gnomAD
COSM472949 rs753190451	261	R>H	kidney Variant assessed as Somatic; MODERATE impact. [Cosmic, NCI-TCGA]	No	NCI-TCGA Cosmic cosmic curated ExAC NCI-TCGA TOPMed gnomAD
rs1422685937 COSM3518702	262	E>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic NCI-TCGA TOPMed gnomAD
rs375207701 COSM3958482	263	R>*	lung [Cosmic]	No	cosmic curated 1000Genomes ExAC gnomAD
rs772840168	263	R>Q		No	ExAC TOPMed gnomAD
rs7226137	265	E>A		No	1000Genomes ESP ExAC TOPMed gnomAD
COSM3518701	265	E>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs7226137	265	E>V		No	1000Genomes ESP ExAC TOPMed gnomAD
rs1396433565	266	G>R		No	gnomAD
rs373075655	267	R>Q		No	ESP ExAC TOPMed gnomAD
rs200541812	267	R>W		No	Ensembl
rs1598732645	268	V>A		No	Ensembl
rs768428755	269	P>H		No	ExAC gnomAD
rs1393885598	270	P>L		No	TOPMed gnomAD
rs1393885598	270	P>Q		No	TOPMed gnomAD
rs1393885598	270	P>R		No	TOPMed gnomAD
rs749227419	270	P>S		No	ExAC TOPMed gnomAD
rs749227419	270	P>T		No	ExAC TOPMed gnomAD
rs1467570373	271	A>T		No	gnomAD
rs745957228	272	P>L		No	ExAC gnomAD
rs769915103	272	P>S		No	ExAC TOPMed gnomAD
rs2068420672	273	P>Q		No	TOPMed
rs2068420701	273	P>S		No	Ensembl
rs1222424600	274	G>D		No	Ensembl
rs1219019432	276	P>S		No	gnomAD
rs1354511832	277	K>R		No	TOPMed gnomAD
rs1376632156	278	E>G		No	Ensembl
COSM1710411	278	E>K	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs757584432	279	A>E		No	ExAC
rs2068420454	280	A>D		No	gnomAD
rs1567932201	281	G>R		No	Ensembl
rs1567932198	282	D>E		No	Ensembl
rs1203520570	282	D>G		No	TOPMed gnomAD
rs2068420398	282	D>N		No	TOPMed
rs747329214 COSM4067362	283	A>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic ExAC NCI-TCGA gnomAD
rs778173379	284	S>A		No	ExAC TOPMed gnomAD
COSM3795728	284	S>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs778173379	284	S>P		No	ExAC TOPMed gnomAD
rs2068420240	286	Q>P		No	TOPMed gnomAD
rs758725882	287	S>L		No	ExAC TOPMed gnomAD
COSM1383993	288	T>A	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
TCGA novel	289	C>F	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1598732577	290	T>P		No	Ensembl
rs145376006	291	S>F		No	1000Genomes ESP ExAC TOPMed gnomAD
rs1567932171 RCV000711985	291	S>N		No	ClinVar Ensembl dbSNP
rs147689555	291	S>T		No	ESP ExAC TOPMed gnomAD
rs145376006	291	S>Y		No	1000Genomes ESP ExAC TOPMed gnomAD
rs761476529	292	P>L		No	ExAC TOPMed gnomAD
rs1171274369	292	P>S		No	TOPMed gnomAD
rs1598732555	294	A>P		No	gnomAD
rs1598732555	294	A>S		No	gnomAD
rs1428323607	295	S>L		No	TOPMed gnomAD
rs2068419717	296	P>L		No	TOPMed
rs912529803	297	S>N		No	Ensembl
rs2068419680	297	S>R		No	TOPMed
rs2068419639	299	V>A		No	Ensembl
rs200443029	300	T>N		No	ExAC TOPMed gnomAD
rs1598732534	300	T>P		No	TOPMed
rs1598732534	300	T>S		No	TOPMed

1 associated diseases with P14653

[MIM: 614744]: Facial paresis, hereditary congenital, 3 (HCFP3)

A form of facial paresis, a disease characterized by isolated dysfunction of the facial nerve (CN VII). HCFP3 patients are affected by bilateral facial palsy, facial muscle weakness of muscles innervated by CN VII, hearing loss, and strabismus. . Note=The disease is caused by variants affecting the gene represented in this entry.

Without disease ID

A form of facial paresis, a disease characterized by isolated dysfunction of the facial nerve (CN VII). HCFP3 patients are affected by bilateral facial palsy, facial muscle weakness of muscles innervated by CN VII, hearing loss, and strabismus. . Note=The disease is caused by variants affecting the gene represented in this entry.

4 regional properties for P14653

Type	Name	Position	InterPro Accession
domain	Homeodomain	201 - 265	IPR001356
conserved_site	Homeobox, conserved site	236 - 259	IPR017970
domain	Homeodomain, metazoa	225 - 236	IPR020479-1
domain	Homeodomain, metazoa	240 - 259	IPR020479-2

Functions

		Description
EC Number
Subcellular Localization	Nucleus
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

3 GO annotations of cellular component

Name	Definition
chromatin	The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome.
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.

7 GO annotations of molecular function

Name	Definition
DNA binding	Any molecular function by which a gene product interacts selectively and non-covalently with DNA (deoxyribonucleic acid).
DNA-binding transcription activator activity, RNA polymerase II-specific	A DNA-binding transcription factor activity that activates or increases transcription of specific gene sets transcribed by RNA polymerase II.
DNA-binding transcription factor activity, RNA polymerase II-specific	A DNA-binding transcription factor activity that modulates the transcription of specific gene sets transcribed by RNA polymerase II.
protein domain specific binding	Binding to a specific domain of a protein.
RNA polymerase II cis-regulatory region sequence-specific DNA binding	Binding to a specific upstream regulatory DNA sequence (transcription factor recognition sequence or binding site) located in cis relative to the transcription start site (i.e., on the same strand of DNA) of a gene transcribed by RNA polymerase II.
RNA polymerase II transcription regulatory region sequence-specific DNA binding	Binding to a specific sequence of DNA that is part of a regulatory region that controls the transcription of a gene or cistron by RNA polymerase II.
sequence-specific double-stranded DNA binding	Binding to double-stranded DNA of a specific nucleotide composition, e.g. GC-rich DNA binding, or with a specific sequence motif or type of DNA, e.g. promotor binding or rDNA binding.

11 GO annotations of biological process

Name	Definition
anatomical structure formation involved in morphogenesis	The developmental process pertaining to the initial formation of an anatomical structure from unspecified parts. This process begins with the specific processes that contribute to the appearance of the discrete structure and ends when the structural rudiment is recognizable. An anatomical structure is any biological entity that occupies space and is distinguished from its surroundings. Anatomical structures can be macroscopic such as a carpel, or microscopic such as an acrosome.
anterior/posterior pattern specification	The regionalization process in which specific areas of cell differentiation are determined along the anterior-posterior axis. The anterior-posterior axis is defined by a line that runs from the head or mouth of an organism to the tail or opposite end of the organism.
embryonic skeletal system morphogenesis	The process in which the anatomical structures of the skeleton are generated and organized during the embryonic phase.
facial nerve structural organization	The process that contributes to the act of creating the structural organization of the facial nerve. This process pertains to the physical shaping of a rudimentary structure. This sensory and motor nerve supplies the muscles of facial expression and the expression and taste at the anterior two-thirds of the tongue. The principal branches are the superficial opthalmic, buccal, palatine and hyomandibular. The main trunk synapses within pterygopalatine ganglion in the parotid gland and this ganglion then gives of nerve branches which supply the lacrimal gland and the mucous secreting glands of the nasal and oral cavities.
facial nucleus development	The process whose specific outcome is the progression of the facial nucleus over time, from its formation to the mature structure.
pattern specification process	Any developmental process that results in the creation of defined areas or spaces within an organism to which cells respond and eventually are instructed to differentiate.
positive regulation of transcription by RNA polymerase II	Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter.
regulation of DNA-templated transcription	Any process that modulates the frequency, rate or extent of cellular DNA-templated transcription.
regulation of transcription by RNA polymerase II	Any process that modulates the frequency, rate or extent of transcription mediated by RNA polymerase II.
rhombomere 4 development	The process whose specific outcome is the progression of rhombomere 4 over time, from its formation to the mature structure. Rhombomeres are transverse segments of the developing rhombencephalon. Rhombomeres are lineage restricted, express different genes from one another, and adopt different developmental fates. Rhombomeres are numbered in anterior to posterior order.
rhombomere 5 development	The process whose specific outcome is the progression of rhombomere 5 over time, from its formation to the mature structure. Rhombomeres are transverse segments of the developing rhombencephalon. Rhombomeres are lineage restricted, express different genes from one another, and adopt different developmental fates. Rhombomeres are numbered in anterior to posterior order.

11 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
P23459	HOXD8	Homeobox protein Hox-D8	Gallus gallus (Chicken)	PR
A2T6Z0	HOXB1	Homeobox protein Hox-B1	Pan troglodytes (Chimpanzee)	SS
P10105	lab	Homeotic protein labial	Drosophila melanogaster (Fruit fly)	EV
P31268	HOXA7	Homeobox protein Hox-A7	Homo sapiens (Human)	SS
P49639	HOXA1	Homeobox protein Hox-A1	Homo sapiens (Human)	SS
P09022	Hoxa1	Homeobox protein Hox-A1	Mus musculus (Mouse)	SS
O08656	Hoxa1	Homeobox protein Hox-A1	Rattus norvegicus (Rat)	SS
A2D649	HOXB1	Homeobox protein Hox-B1	Macaca mulatta (Rhesus macaque)	SS
Q28IU6	hoxd1	Homeobox protein Hox-D1	Xenopus tropicalis (Western clawed frog) (Silurana tropicalis)	SS
Q8JH55	hoxb8b	Homeobox protein Hox-B8b	Danio rerio (Zebrafish) (Brachydanio rerio)	PR
F1Q4R9	meox1	Homeobox protein MOX-1	Danio rerio (Zebrafish) (Brachydanio rerio)	PR

10	20	30	40	50	60
MDYNRMNSFL	EYPLCNRGPS	AYSAHSAPTS	FPPSSAQAVD	SYASEGRYGG	GLSSPAFQQN
70	80	90	100	110	120
SGYPAQQPPS	TLGVPFPSSA	PSGYAPAACS	PSYGPSQYYP	LGQSEGDGGY	FHPSSYGAQL
130	140	150	160	170	180
GGLSDGYGAG	GAGPGPYPPQ	HPPYGNEQTA	SFAPAYADLL	SEDKETPCPS	EPNTPTARTF
190	200	210	220	230	240
DWMKVKRNPP	KTAKVSEPGL	GSPSGLRTNF	TTRQLTELEK	EFHFNKYLSR	ARRVEIAATL
250	260	270	280	290	300
ELNETQVKIW	FQNRRMKQKK	REREEGRVPP	APPGCPKEAA	GDASDQSTCT	SPEASPSSVT

S