AiPD: Autoinhibited Protein Database

Q15475

Gene name	SIX1
Protein name	Homeobox protein SIX1
Names	Sine oculis homeobox homolog 1
Species	Homo sapiens (Human)
KEGG Pathway	hsa:6495
EC number
Protein Class

Descriptions

The autoinhibited protein was predicted that may have potential autoinhibitory elements via cis-regPred.

Autoinhibitory domains (AIDs)

73-284 (Predicted disordered autoinhibitory region) PR

Target domain
Relief mechanism
Assay	cis-regPred

AID

73-284 (Predicted disordered autoinhibitory region)

Target domain

Relief mechanism

Assay

cis-regPred

Accessory elements

No accessory elements

References

Yeon JH et al. (2016) "Systems-wide Identification of cis-Regulatory Elements in Proteins", Cell Systems, 2, 89-100

Autoinhibited structure

Activated structure

2 structures for Q15475

Entry ID	Method	Resolution	Chain	Position	Source
4EGC	X-ray	199 A	A	1-189	PDB
AF-Q15475-F1	Predicted				AlphaFoldDB

247 variants for Q15475

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
RCV001262831 rs1895013419	1	M>L	Branchiootic syndrome 3 [ClinVar]	Yes	ClinVar dbSNP
VAR_064948 rs397515562 CA345039 RCV002477184	17	V>E	Branchiootic syndrome 3 BOS3; crucial for interaction with EYA1 and EYA2 and transcription factor activity [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs1051653507 RCV000512900 RCV000706990 RCV001375398 CA261723226 RCV002524959	64	R>H	Variant assessed as Somatic; 0.0 impact. Branchiootic syndrome 3 Inborn genetic diseases [NCI-TCGA, ClinVar]	Yes	ClinGen ClinVar NCI-TCGA TOPMed dbSNP gnomAD
VAR_064949	73	H>P	BOS3 [UniProt]	Yes	UniProt
VAR_064950 RCV002477182 rs397515560 CA345037	106	V>G	Branchiootic syndrome 3 BOS3; crucial for protein stability, DNA binding and transcription factor activity [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
VAR_064951 rs1064794308 CA16619881 RCV000482613 RCV003223408	110	R>Q	Branchiootic syndrome 3 BOS3 [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt TOPMed dbSNP
rs80356459 RCV002512919 VAR_031024 CA340772 RCV000008807 RCV002262561	110	R>W	Variant assessed as Somatic; impact. Branchiootic syndrome 3 (bos3) Branchiootic syndrome 3 BOS3; crucial for interaction with EYA1, DNA binding and transcription factor activity [NCI-TCGA, Ensembl, ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl NCI-TCGA dbSNP
RCV002477183 VAR_064952 CA345038 rs397515561	112	R>C	Branchiootic syndrome 3 BOS3; crucial for DNA binding and transcription factor activity [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs121909770 CA254384 VAR_064953 RCV000008809	122	W>R	Branchiootic syndrome 3 (bos3) Branchiootic syndrome 3 BOS3 [Ensembl, ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV000190433 RCV002478668 RCV001852527 rs797044960 CA275962	125	E>K	Autosomal dominant nonsyndromic hearing loss 23 Branchiootic syndrome 3 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV000763344 RCV002512918 VAR_031025 RCV000008806 rs104894478 RCV000413341 RCV000679883 CA254381	129	Y>C	Autosomal dominant nonsyndromic hearing loss 23 Branchiootic syndrome 3 (bos3) Branchiootic syndrome 3 BOS3; crucial for interaction with EYA1, DNA binding and transcription factor activity [ClinVar, Ensembl, UniProt]	Yes	ClinGen ClinVar UniProt TOPMed dbSNP gnomAD
RCV001799516 rs104894478 CA389910423 RCV000825046 RCV000857227	129	Y>S	Branchiootic syndrome 3 (bos3) Branchiootic syndrome 1 Branchiootic syndrome 3 [Ensembl, ClinVar]	Yes	ClinGen ClinVar TOPMed dbSNP gnomAD
rs80356460 RCV003162220 RCV002512920 VAR_031026 RCV000008808 RCV000020636	133	E>missing	DFNA23; in addition to deafness the patient had renal anomalies suggesting a branchiootorenal syndrome; crucial for interaction with EYA1, DNA binding and transcription factor activity Autosomal dominant nonsyndromic hearing loss 23 Branchiootic syndrome 3 [UniProt, ClinVar]	Yes	ClinVar UniProt dbSNP
rs80356460 VAR_031026	133	E>del	DFNA23; in addition to deafness the patient had renal anomalies suggesting a branchiootorenal syndrome; crucial for interaction with EYA1, DNA binding and transcription factor activity [UniProt]	Yes	UniProt dbSNP
RCV001250998 rs1895001312	139	L>R	Branchiootic syndrome 3 [ClinVar]	Yes	ClinVar dbSNP
RCV000477918 rs1060499595 CA16616927	154	K>*	Branchiootic syndrome 3 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV000313323 CA7212757 RCV001718645 RCV000276902 rs142301715 RCV002520905	193	N>I	Autosomal dominant nonsyndromic hearing loss 23 Branchiootic syndrome 3 [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
rs1894944353 RCV001331501	207	E>A	Branchiootic syndrome 3 [ClinVar]	Yes	ClinVar dbSNP
CA389909850 RCV000528335 rs540778343	215	S>I	Branchiootic syndrome 3 [ClinVar]	Yes	ClinGen ClinVar 1000Genomes dbSNP
CA261720668 rs149265761 RCV001114978 RCV001772329 RCV001114979	227	D>E	Autosomal dominant nonsyndromic hearing loss 23 Branchiootic syndrome 3 [ClinVar]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
rs144481204 CA7212741 RCV000782257 RCV001109337 RCV001114980	227	D>Y	Autosomal dominant nonsyndromic hearing loss 23 Branchiootic syndrome 3 (bos3) Branchiootic syndrome 3 [ClinVar, Ensembl]	Yes	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
CA7212731 rs747474509 CA389909720 RCV001002755	235	Q>H	Autosomal dominant nonsyndromic hearing loss 23 [ClinVar]	Yes	ClinGen ExAC TOPMed gnomAD ClinVar dbSNP
RCV001114976 RCV002556255 rs368974927 RCV001563359 RCV001114977 CA7212719 VAR_064954	249	P>L	Autosomal dominant nonsyndromic hearing loss 23 Branchiootic syndrome 3 (bos3) Branchiootic syndrome 3 BOR; uncertain pathological significance [ClinVar, Ensembl, UniProt]	Yes	ClinGen ClinVar UniProt 1000Genomes ExAC TOPMed dbSNP gnomAD
rs368974927 RCV002066828 RCV000613496 RCV001591374 CA7212718	249	P>Q	Branchiootic syndrome 3 (bos3) Branchiootic syndrome 3 [Ensembl, ClinVar]	Yes	ClinGen ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
CA7212873 rs759906473	5	P>A		No	ClinGen ExAC gnomAD
rs771057416 CA7212871	5	P>L		No	ClinGen ExAC TOPMed gnomAD
rs771057416 CA7212872	5	P>Q		No	ClinGen ExAC TOPMed gnomAD
rs749690789 CA7212870	6	S>A		No	ClinGen ExAC gnomAD
rs778375446 CA7212869	8	G>A		No	ClinGen ExAC gnomAD
CA389911212 rs778375446	8	G>V		No	ClinGen ExAC gnomAD
rs1417956063 CA389911198	10	T>M		No	ClinGen gnomAD
CA389911189 rs1167753630	12	E>K		No	ClinGen gnomAD
rs1480942237 CA389911181	13	Q>K		No	ClinGen gnomAD
rs1197458982 CA389911153	17	V>M		No	ClinGen gnomAD
CA389911140 rs1490210309	19	E>K		No	ClinGen gnomAD
rs1233578721 CA389911128	20	V>A		No	ClinGen gnomAD
CA389911123 rs1206708089	21	L>P		No	ClinGen gnomAD
rs1177617020 CA389911116	22	Q>L		No	ClinGen TOPMed
CA7212866 rs781574148	23	Q>P		No	ClinGen ExAC gnomAD
rs754869969 CA261723399	24	G>S		No	ClinGen Ensembl
rs1009804624 CA261723395	25	G>*		No	ClinGen Ensembl
CA261723394 rs867031506	25	G>E		No	ClinGen gnomAD
CA389911090 rs1375481520	26	N>K		No	ClinGen TOPMed
CA7212863 rs146357380	28	E>D		No	ClinGen ESP ExAC TOPMed gnomAD
CA7212860 rs764103068	33	F>L		No	ClinGen ExAC gnomAD
rs1297503138 CA389911052	33	F>L		No	ClinGen TOPMed
CA261723350 rs1032525136	35	W>*		No	ClinGen Ensembl
rs1001409064 CA389911026	37	L>V		No	ClinGen TOPMed gnomAD
CA7212859 rs760736490	38	P>A		No	ClinGen ExAC gnomAD
rs1431824329 CA389911015	39	A>T		No	ClinGen gnomAD
CA7212857 rs767478646	40	C>G		No	ClinGen ExAC gnomAD
TCGA novel	41	D>N	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1303484853 CA389910994	42	H>Y		No	ClinGen TOPMed
TCGA novel	44	H>A	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs149166341 CA7212856	44	H>Q		No	ClinGen ESP ExAC TOPMed gnomAD
rs1480268855 CA389910979	44	H>R		No	ClinGen gnomAD
CA389910960 rs1223102250	47	E>K		No	ClinGen TOPMed
rs774637636 CA7212855	48	S>N		No	ClinGen ExAC gnomAD
rs770875229 CA7212854	48	S>R		No	ClinGen ExAC gnomAD
CA261723311 rs904273350	49	V>I		No	ClinGen Ensembl
rs1232263034 CA389910939	50	L>F		No	ClinGen gnomAD
rs1258971434 CA389910922	52	A>V		No	ClinGen TOPMed
TCGA novel	53	K>E	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA389910912 rs1261097341	54	A>T		No	ClinGen gnomAD
CA389910904 rs1251187381	55	V>A		No	ClinGen TOPMed
rs770253091 CA7212851	55	V>M		No	ClinGen ExAC gnomAD
CA7212850 rs748718182	56	V>L		No	ClinGen ExAC gnomAD
CA389910897 rs1221612141	57	A>T		No	ClinGen gnomAD
TCGA novel	59	H>Q	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA389910881 rs1371905806	59	H>Y		No	ClinGen gnomAD
rs893019043 CA261723251	60	R>H		No	ClinGen TOPMed gnomAD
CA389910856 rs1335186361	63	F>L		No	ClinGen gnomAD
TCGA novel	64	R>C	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1051653507 CA389910845	64	R>P		No	ClinGen TOPMed gnomAD
CA389910841 rs1463809728	65	E>Q		No	ClinGen TOPMed
rs1161503372 CA389910831	66	L>P		No	ClinGen gnomAD
rs1293880867 CA389910816	68	K>M		No	ClinGen gnomAD
rs751225628 CA261723202	69	I>S		No	ClinGen Ensembl
TCGA novel	70	L>M	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs372978267 CA389910806	70	L>V		No	ClinGen ESP ExAC gnomAD
CA7212846 rs778653697	72	S>R		No	ClinGen ExAC gnomAD
CA7212845 rs756912951	76	S>L		No	ClinGen ExAC gnomAD
rs752695594 CA7212841	79	N>D		No	ClinGen ExAC gnomAD
CA7212840 rs767354178	79	N>S		No	ClinGen ExAC TOPMed gnomAD
CA7212839 rs759405851	81	P>S		No	ClinGen ExAC TOPMed gnomAD
rs766600023 CA7212837	82	K>R	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
CA261723145 CA389910707 rs973266865	84	Q>H		No	ClinGen TOPMed gnomAD
CA389910709 rs1247489566	84	Q>R		No	ClinGen gnomAD
CA261723138 rs941857857	87	W>*		No	ClinGen Ensembl
TCGA novel	89	K>E	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA261723137 rs1045845044	93	V>L		No	ClinGen TOPMed
TCGA novel CA389910641 rs1224396065	94	E>G	Variant assessed as Somatic; impact. [NCI-TCGA]	No	ClinGen TOPMed NCI-TCGA
CA389910637 rs1264228301	95	A>T		No	ClinGen TOPMed
rs200835641 CA7212834	95	A>V	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
TCGA novel	96	E>D	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA389910632 rs1216716466	96	E>K		No	ClinGen TOPMed
rs1451985437 CA389910616	98	L>M		No	ClinGen TOPMed gnomAD
CA389910615 rs1451985437	98	L>V		No	ClinGen TOPMed gnomAD
VAR_067446 CA261723126 rs17850414	99	R>C		No	ClinGen UniProt Ensembl dbSNP
CA389910609 rs1185640236	99	R>H		No	ClinGen TOPMed
TCGA novel	101	R>Q	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1426574416 CA389910593	102	P>S		No	ClinGen gnomAD
rs1555366324 CA658798220 RCV000592334	109	Y>*		No	ClinGen ClinVar Ensembl dbSNP
rs1268579529 CA389910530	113	R>G		No	ClinGen TOPMed gnomAD
TCGA novel	114	K>N	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
TCGA novel	114	K>Q	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
TCGA novel	115	F>C	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs748953823 CA7212827	116	P>A		No	ClinGen ExAC gnomAD
rs777361656 CA7212826	116	P>L		No	ClinGen ExAC TOPMed gnomAD
rs748057221 CA7212824	120	T>S		No	ClinGen ExAC gnomAD
TCGA novel	121	I>F	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1230421981 CA389910483	121	I>V		No	ClinGen TOPMed
CA7212822 rs754918861	128	S>N		No	ClinGen ExAC gnomAD
CA261723014 rs371614639	129	Y>*		No	ClinGen ESP
rs930853232 CA261722975	131	F>L		No	ClinGen TOPMed
CA389910407 rs1212556544	131	F>L		No	ClinGen TOPMed gnomAD
rs975058979 CA261722943	137	G>V		No	ClinGen TOPMed
CA7212819 rs758631109	138	V>L		No	ClinGen ExAC gnomAD
rs776744679 CA7212815	141	E>G		No	ClinGen ExAC TOPMed gnomAD
CA7212816 rs761906849	141	E>K		No	ClinGen ExAC gnomAD
rs1201052250 CA389910332	143	Y>D		No	ClinGen gnomAD
rs988112453 CA389910322	144	A>G		No	ClinGen TOPMed gnomAD
CA261722913 rs988112453	144	A>V		No	ClinGen TOPMed gnomAD
rs764633083 CA7212814	145	H>D		No	ClinGen ExAC gnomAD
rs1195840852 CA389910316 CA389910315	145	H>Q		No	ClinGen TOPMed gnomAD
CA389910313 rs1566722147	146	N>Y		No	ClinGen Ensembl
rs1253548277 CA389910293	148	Y>*		No	ClinGen gnomAD
CA389910297 rs1594673234	148	Y>S		No	ClinGen Ensembl
TCGA novel	151	P>L	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA389910272 rs1331478259	152	R>C		No	ClinGen Ensembl
rs1317609914 CA389910266	153	E>K		No	ClinGen gnomAD
CA7212811 rs772338719	155	R>Q		No	ClinGen ExAC gnomAD
CA7212812 rs775911579	155	R>W		No	ClinGen ExAC gnomAD
rs769379475 CA389910244	156	E>D		No	ClinGen ExAC TOPMed
CA7212809 rs773031458	156	E>K	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
RCV000761879 CA389910242 rs1566722096	157	L>V		No	ClinGen ClinVar Ensembl dbSNP
CA7212807 rs747639845	158	A>V		No	ClinGen ExAC gnomAD
rs1301781969 CA389910233	159	E>K		No	ClinGen TOPMed gnomAD
rs1301781969 CA389910232	159	E>Q		No	ClinGen TOPMed gnomAD
CA261722870 rs1010466700	160	A>D		No	ClinGen TOPMed
rs1010466700 CA261722855	160	A>V		No	ClinGen TOPMed
rs746973450 CA7212804	161	T>A		No	ClinGen ExAC gnomAD
CA7212803 rs779837812	161	T>S		No	ClinGen ExAC TOPMed gnomAD
RCV000215644 rs876658002 CA10576966	163	L>V		No	ClinGen ClinVar Ensembl dbSNP
rs1479289739 CA389910202	164	T>S		No	ClinGen gnomAD
rs143516729 CA261722833	165	T>I		No	ClinGen ESP gnomAD
CA389910188 rs1201459073	167	Q>E		No	ClinGen TOPMed
rs371998997 CA7212801	168	V>I		No	ClinGen ESP ExAC TOPMed gnomAD
rs765427858 CA7212800	169	S>G		No	ClinGen ExAC gnomAD
CA389910162 RCV000520421 rs1555366309	170	N>K		No	ClinGen ClinVar Ensembl dbSNP
CA261722804 rs1033334195	172	F>C		No	ClinGen TOPMed
CA389910106 rs1236315675	178	R>K		No	ClinGen TOPMed
CA389910093 rs1264219816	180	R>W		No	ClinGen gnomAD
CA16619880 RCV000483984 rs1064793268	183	E>G		No	ClinGen ClinVar Ensembl dbSNP
CA389910070 rs1274431236	184	A>T		No	ClinGen TOPMed gnomAD
rs1239894490 CA389910065	184	A>V		No	ClinGen TOPMed gnomAD
rs1337543986 CA389910056	186	E>K		No	ClinGen gnomAD
rs1594673095 CA389910048	187	R>G		No	ClinGen Ensembl
rs760121808 CA7212762	188	E>G		No	ClinGen ExAC gnomAD
rs775109837 CA7212761	189	N>S		No	ClinGen ExAC TOPMed gnomAD
CA389910011 rs1440228225	190	T>I	Variant assessed as Somatic; impact. [NCI-TCGA]	No	ClinGen NCI-TCGA TOPMed
CA7212760 rs771994916	191	E>K	Variant assessed as Somatic; 0.0002225 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
rs574181095 CA7212759	193	N>D		No	ClinGen ExAC TOPMed gnomAD
rs142301715 CA7212758	193	N>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA389909986 rs1594671817	194	N>T		No	ClinGen Ensembl
CA7212756 rs749472807	196	S>F		No	ClinGen ExAC gnomAD
CA389909970 rs1411016799	197	S>P		No	ClinGen TOPMed
CA389909950 rs1168903423	199	K>N		No	ClinGen TOPMed gnomAD
rs756406449 CA7212753	201	N>K		No	ClinGen ExAC gnomAD
TCGA novel	201	N>S	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs912522508 CA261720732	202	Q>H		No	ClinGen Ensembl
CA389909925 rs1304541108	203	L>F		No	ClinGen TOPMed
TCGA novel	203	L>V	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs752687781 CA7212752	204	S>C		No	ClinGen ExAC TOPMed gnomAD
rs752687781 CA389909918	204	S>Y		No	ClinGen ExAC TOPMed gnomAD
CA389909912 rs781397777	205	P>H		No	ClinGen ExAC gnomAD
rs781397777 CA7212751	205	P>L		No	ClinGen ExAC gnomAD
CA389909908 rs1594671774	206	L>R		No	ClinGen Ensembl
rs543609416 CA389909910	206	L>V		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA7212747 rs758861510	209	G>A		No	ClinGen ExAC gnomAD
CA389909892 rs1286824463	209	G>S		No	ClinGen TOPMed
CA7212745 rs374638294	211	P>L		No	ClinGen ESP ExAC TOPMed gnomAD
rs1337123501 CA389909872	212	L>F		No	ClinGen gnomAD
rs1481960266 CA389909861	213	M>I		No	ClinGen TOPMed
CA389909868 rs1277192666	213	M>L		No	ClinGen gnomAD
rs1223807292 CA389909865	213	M>T		No	ClinGen gnomAD
rs560990241 CA7212744	215	S>G		No	ClinGen 1000Genomes ExAC gnomAD
CA261720691 rs540778343	215	S>N	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen 1000Genomes NCI-TCGA
TCGA novel	216	S>L	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs146129487 CA261720686	217	E>K		No	ClinGen Ensembl
CA389909819 rs1435096818	219	E>D		No	ClinGen gnomAD
rs1349841820 CA389909806	221	S>*		No	ClinGen gnomAD
rs767030543 CA7212742	222	P>S		No	ClinGen ExAC gnomAD
CA389909789 rs1412013227	224	Q>R		No	ClinGen gnomAD
CA7212739 rs770666125	228	Q>E		No	ClinGen ExAC gnomAD
CA7212738 rs749015316	228	Q>H		No	ClinGen ExAC gnomAD
CA261720658 rs918862160	230	S>L		No	ClinGen TOPMed
CA7212736 rs769901336	231	V>F		No	ClinGen ExAC gnomAD
rs1179637997 CA389909739	232	L>F		No	ClinGen TOPMed
CA7212734 rs781362403	233	L>M		No	ClinGen ExAC gnomAD
CA7212730 rs780726681	236	G>R		No	ClinGen ExAC gnomAD
CA389909714 rs1204025083	237	N>H		No	ClinGen gnomAD
CA389909703 rs915194188	238	M>K		No	ClinGen TOPMed
rs915194188 CA261720615	238	M>T		No	ClinGen TOPMed
CA261720608 rs759290962	240	H>Q		No	ClinGen ExAC TOPMed gnomAD
rs750752374 CA7212728	241	A>T		No	ClinGen ExAC TOPMed gnomAD
CA7212726 rs755668042	242	R>G		No	ClinGen ExAC gnomAD
CA7212725 rs752399991	242	R>K		No	ClinGen ExAC gnomAD
CA389909677 rs766975120	242	R>S		No	ClinGen ExAC TOPMed
rs1445078561 CA389909662	244	S>L	Variant assessed as Somatic; 4.619e-05 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
CA7212722 rs773902181	245	N>S		No	ClinGen ExAC gnomAD
TCGA novel	246	Y>C	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA389909642 rs766271672	247	S>F		No	ClinGen ExAC TOPMed gnomAD
rs1470481678 CA389909646	247	S>P		No	ClinGen gnomAD
CA7212721 rs766271672	247	S>Y	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
rs763012848 CA7212720	249	P>S		No	ClinGen ExAC
CA261720514 rs200205240	252	T>A		No	ClinGen ExAC TOPMed gnomAD
rs200205240 CA7212715	252	T>S		No	ClinGen ExAC TOPMed gnomAD
rs747061363 CA7212714	254	S>L		No	ClinGen ExAC gnomAD
rs758821559 CA389909595	256	P>A		No	ClinGen ExAC TOPMed gnomAD
rs758821559 CA7212712	256	P>S		No	ClinGen ExAC TOPMed gnomAD
CA7212711 rs779084301	259	G>C		No	ClinGen ExAC TOPMed gnomAD
rs779084301 CA7212710	259	G>R		No	ClinGen ExAC TOPMed gnomAD
rs779084301 CA261720476	259	G>S	Variant assessed as Somatic; impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
CA7212708 rs370259896	260	L>Q		No	ClinGen ESP ExAC TOPMed gnomAD
rs370259896 CA7212709	260	L>R		No	ClinGen ESP ExAC TOPMed gnomAD
CA389909566 rs780802037	261	Q>P		No	ClinGen ExAC gnomAD
CA7212707 rs780802037	261	Q>R		No	ClinGen ExAC gnomAD
CA261720415 rs922456534	263	H>Y		No	ClinGen Ensembl
rs751062848 CA7212705	264	Q>E		No	ClinGen ExAC gnomAD
rs1375362861 CA389909537	265	H>Q		No	ClinGen gnomAD
CA389909540 rs1475558927	265	H>R		No	ClinGen gnomAD
rs997323109 CA261720409	265	H>Y		No	ClinGen TOPMed
rs765929697 CA7212704	267	L>F		No	ClinGen ExAC gnomAD
TCGA novel	268	Q>H	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1385361246 CA389909510	269	D>G		No	ClinGen gnomAD
CA389909513 rs1453838313	269	D>H		No	ClinGen gnomAD
CA261720400 rs901741650	270	S>C		No	ClinGen TOPMed
CA389909506 rs1301445039	270	S>T		No	ClinGen gnomAD
CA389909489 rs764896733	273	G>C		No	ClinGen ExAC TOPMed gnomAD
TCGA novel	273	G>D	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA7212700 rs764896733	273	G>S		No	ClinGen ExAC TOPMed gnomAD
rs1446357667 CA389909458	278	S>N		No	ClinGen gnomAD
rs577150755 CA7212697	281	D>E		No	ClinGen 1000Genomes ExAC gnomAD
rs1043747885 CA261720370	283	G>R		No	ClinGen TOPMed
rs775655341 CA7212695	284	S>P		No	ClinGen ExAC gnomAD
TCGA novel	284	S>V	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA

3 associated diseases with Q15475

[MIM: 605192]: Deafness, autosomal dominant, 23 (DFNA23)

A form of non-syndromic deafness characterized by prelingual, bilateral, symmetric hearing loss with a conductive component present in some but not all patients. {ECO:0000269|PubMed:15141091, ECO:0000269|PubMed:19497856, ECO:0000269|PubMed:23435380}. Note=The disease is caused by variants affecting the gene represented in this entry.

[MIM: 608389]: Branchiootic syndrome 3 (BOS3)

A syndrome characterized by usually bilateral branchial cleft fistulas or cysts, sensorineural and/or conductive hearing loss, pre-auricular pits, and structural defects of the outer, middle or inner ear. Otic defects include malformed and hypoplastic pinnae, a narrowed external ear canal, bulbous internal auditory canal, stapes fixation, malformed and hypoplastic cochlea. Branchial and otic anomalies overlap with those seen in individuals with the branchiootorenal syndrome. However renal anomalies are absent in branchiootic syndrome patients. {ECO:0000269|PubMed:15141091, ECO:0000269|PubMed:17637804, ECO:0000269|PubMed:18330911, ECO:0000269|PubMed:19497856, ECO:0000269|PubMed:21280147, ECO:0000269|PubMed:23435380}. Note=The disease is caused by variants affecting the gene represented in this entry.

Without disease ID

A form of non-syndromic deafness characterized by prelingual, bilateral, symmetric hearing loss with a conductive component present in some but not all patients. {ECO:0000269|PubMed:15141091, ECO:0000269|PubMed:19497856, ECO:0000269|PubMed:23435380}. Note=The disease is caused by variants affecting the gene represented in this entry.
A syndrome characterized by usually bilateral branchial cleft fistulas or cysts, sensorineural and/or conductive hearing loss, pre-auricular pits, and structural defects of the outer, middle or inner ear. Otic defects include malformed and hypoplastic pinnae, a narrowed external ear canal, bulbous internal auditory canal, stapes fixation, malformed and hypoplastic cochlea. Branchial and otic anomalies overlap with those seen in individuals with the branchiootorenal syndrome. However renal anomalies are absent in branchiootic syndrome patients. {ECO:0000269|PubMed:15141091, ECO:0000269|PubMed:17637804, ECO:0000269|PubMed:18330911, ECO:0000269|PubMed:19497856, ECO:0000269|PubMed:21280147, ECO:0000269|PubMed:23435380}. Note=The disease is caused by variants affecting the gene represented in this entry.

2 regional properties for Q15475

Type	Name	Position	InterPro Accession
domain	Homeobox domain	154 - 218	IPR001356
domain	Homeobox protein SIX1, N-terminal SD domain	37 - 150	IPR031701

Functions

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

6 GO annotations of cellular component

Name	Definition
chromatin	The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome.
cytoplasm	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
nucleolus	A small, dense body one or more of which are present in the nucleus of eukaryotic cells. It is rich in RNA and protein, is not bounded by a limiting membrane, and is not seen during mitosis. Its prime function is the transcription of the nucleolar DNA into 45S ribosomal-precursor RNA, the processing of this RNA into 5.8S, 18S, and 28S components of ribosomal RNA, and the association of these components with 5S RNA and proteins synthesized outside the nucleolus. This association results in the formation of ribonucleoprotein precursors; these pass into the cytoplasm and mature into the 40S and 60S subunits of the ribosome.
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.
transcription regulator complex	A protein complex that is capable of associating with DNA by direct binding, or via other DNA-binding proteins or complexes, and regulating transcription.

10 GO annotations of molecular function

Name	Definition
chromatin binding	Binding to chromatin, the network of fibers of DNA, protein, and sometimes RNA, that make up the chromosomes of the eukaryotic nucleus during interphase.
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	A transcription regulator activity that modulates transcription of gene sets via selective and non-covalent binding to a specific double-stranded genomic DNA sequence (sometimes referred to as a motif) within a cis-regulatory region. Regulatory regions include promoters (proximal and distal) and enhancers. Genes are transcriptional units, and include bacterial operons.
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.
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.
sequence-specific DNA binding	Binding to 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.
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.
transcription cis-regulatory region binding	Binding to a specific sequence of DNA that is part of a regulatory region that controls transcription of that section of the DNA. The transcribed region might be described as a gene, cistron, or operon.
transcription coactivator binding	Binding to a transcription coactivator, a protein involved in positive regulation of transcription via protein-protein interactions with transcription factors and other proteins that positively regulate transcription. Transcription coactivators do not bind DNA directly, but rather mediate protein-protein interactions between activating transcription factors and the basal transcription machinery.

60 GO annotations of biological process

Name	Definition
aorta morphogenesis	The process in which the anatomical structures of an aorta are generated and organized. An aorta is an artery that carries blood from the heart to other parts of the body.
apoptotic process	A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died.
branching involved in ureteric bud morphogenesis	The process in which the branching structure of the ureteric bud is generated and organized. The ureteric bud is an epithelial tube that grows out from the metanephric duct. The bud elongates and branches to give rise to the ureter and kidney collecting tubules.
cellular response to 3,3',5-triiodo-L-thyronine	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a 3,3',5-triiodo-L-thyronine stimulus.
cochlea morphogenesis	The process in which the cochlea is generated and organized.
embryonic cranial skeleton morphogenesis	The process in which the anatomical structures of the cranial skeleton are generated and organized during the embryonic phase.
embryonic skeletal system morphogenesis	The process in which the anatomical structures of the skeleton are generated and organized during the embryonic phase.
endothelin receptor signaling pathway	A G protein-coupled receptor signaling pathway initiated by endothelin binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
epithelial cell differentiation	The process in which a relatively unspecialized cell acquires specialized features of an epithelial cell, any of the cells making up an epithelium.
facial nerve morphogenesis	The process in which the anatomical structure of the facial nerve is generated and organized. 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.
fungiform papilla morphogenesis	The process in which the anatomical structures of the fungiform papilla are generated and organized. The fungiform papilla is a mushroom-shaped papilla of the tongue.
generation of neurons	The process in which nerve cells are generated. This includes the production of neuroblasts and their differentiation into neurons.
inner ear development	The process whose specific outcome is the progression of the inner ear over time, from its formation to the mature structure.
inner ear morphogenesis	The process in which the anatomical structures of the inner ear are generated and organized. The inner ear is the structure in vertebrates that contains the organs of balance and hearing. It consists of soft hollow sensory structures (the membranous labyrinth) containing fluid (endolymph) surrounded by fluid (perilymph) and encased in a bony cavity (the bony labyrinth). It consists of two chambers, the sacculus and utriculus, from which arise the cochlea and semicircular canals respectively.
kidney development	The process whose specific outcome is the progression of the kidney over time, from its formation to the mature structure. The kidney is an organ that filters the blood and/or excretes the end products of body metabolism in the form of urine.
mesenchymal cell proliferation involved in ureter development	The multiplication or reproduction of cells, resulting in the expansion of a mesenchymal cell population of the ureter, that contributes to ureter development.
mesonephric tubule formation	The developmental process pertaining to the initial formation of a mesonephric tubule from unspecified parts. A mesonephric tubule is an epithelial tube that is part of the mesonephros.
metanephric mesenchyme development	The biological process whose specific outcome is the progression of a metanephric mesenchyme from an initial condition to its mature state. This process begins with the formation of metanephric mesenchyme and ends with the mature structure. Metanephric mesenchyme is the tissue made up of loosely connected mesenchymal cells in the metanephros.
middle ear morphogenesis	The process in which the anatomical structures of the middle ear are generated and organized. The middle ear is the air-filled cavity within the skull of vertebrates that lies between the outer ear and the inner ear. It is linked to the pharynx (and therefore to outside air) via the Eustachian tube and in mammals contains the three ear ossicles, which transmit auditory vibrations from the outer ear (via the tympanum) to the inner ear (via the oval window).
myoblast migration	The orderly movement of a myoblast from one site to another, often during the development of a multicellular organism. A myoblast is a cell type that, by fusion with other myoblasts, gives rise to the myotubes that eventually develop into skeletal muscle fibers.
myoblast proliferation	The multiplication or reproduction of myoblasts, resulting in the expansion of a myoblast cell population. A myoblast is a mononucleate cell type that, by fusion with other myoblasts, gives rise to the myotubes that eventually develop into skeletal muscle fibers.
myotome development	The progression of the myotome over time, from its formation to the mature structure. The myotome is the portion of the somite that will give rise to muscle.
negative regulation of neuron apoptotic process	Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process in neurons.
negative regulation of transcription by RNA polymerase II	Any process that stops, prevents, or reduces the frequency, rate or extent of transcription mediated by RNA polymerase II.
neural crest cell differentiation	The process in which a relatively unspecialized cell acquires specialized features of a neural crest cell.
neuron fate specification	The process in which a cell becomes capable of differentiating autonomously into a neuron in an environment that is neutral with respect to the developmental pathway. Upon specification, the cell fate can be reversed.
Notch signaling pathway	The series of molecular signals initiated by an extracellular ligand binding to the receptor Notch on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
olfactory placode formation	The formation of a thickening of the neural ectoderm in the head region of the vertebrate embryo which develops into the olfactory region of the nasal cavity.
organ induction	The interaction of two or more cells or tissues that causes them to change their fates and specify the development of an organ.
otic vesicle development	The process whose specific outcome is the progression of the otic vesicle over time, from its formation to the mature structure. The otic vesicle is a transient embryonic structure formed during development of the vertebrate inner ear.
outflow tract morphogenesis	The process in which the anatomical structures of the outflow tract are generated and organized. The outflow tract is the portion of the heart through which blood flows into the arteries.
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.
pharyngeal system development	The process whose specific outcome is the progression of the pharyngeal system over time, from its formation to the mature structure. The pharyngeal system is a transient embryonic complex that is specific to vertebrates. It comprises the pharyngeal arches, bulges of tissues of mesoderm and neural crest derivation through which pass nerves and pharyngeal arch arteries. The arches are separated internally by pharyngeal pouches, evaginations of foregut endoderm, and externally by pharyngeal clefts, invaginations of surface ectoderm. The development of the system ends when the stucture it contributes to are forming: the thymus, thyroid, parathyroids, maxilla, mandible, aortic arch, cardiac outflow tract, external and middle ear.
positive regulation of branching involved in ureteric bud morphogenesis	Any process that increases the rate, frequency or extent of branching involved in ureteric bud morphogenesis, the process in which the branching structure of the ureteric bud is generated and organized. The ureteric bud is an epithelial tube that grows out from the metanephric duct. The bud elongates and branches to give rise to the ureter and kidney collecting tubules.
positive regulation of brown fat cell differentiation	Any process that increases the rate, frequency, or extent of brown fat cell differentiation. Brown fat cell differentiation is the process in which a relatively unspecialized cell acquires specialized features of a brown adipocyte, an animal connective tissue cell involved in adaptive thermogenesis. Brown adipocytes contain multiple small droplets of triglycerides and a high number of mitochondria.
positive regulation of DNA-templated transcription	Any process that activates or increases the frequency, rate or extent of cellular DNA-templated transcription.
positive regulation of mesenchymal cell proliferation involved in ureter development	Any process that activates or increases the frequency, rate or extent of mesenchymal cell proliferation involved in ureter development.
positive regulation of myoblast proliferation	Any process that activates or increases the frequency, rate or extent of myoblast proliferation.
positive regulation of secondary heart field cardioblast proliferation	Any process that activates or increases the frequency, rate or extent of cardioblast proliferation in the second heart field. A cardioblast is a cardiac precursor cell. It is a cell that has been committed to a cardiac fate, but will undergo more cell division rather than terminally differentiating. The secondary heart field is the region of the heart that will form the majority of the mesodermal component of the right ventricle, the arterial pole (outflow tract) and the venous pole (inflow tract).
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.
positive regulation of ureteric bud formation	Any process that increases the rate or extent of the developmental process pertaining to the initial formation of the ureteric bud from the Wolffian duct.
protein localization to nucleus	A process in which a protein transports or maintains the localization of another protein to the nucleus.
regulation of branch elongation involved in ureteric bud branching	Any process that modulates the frequency, rate or extent of branch elongation involved in ureteric bud branching, the growth of a branch of the ureteric bud along its axis.
regulation of DNA-templated transcription	Any process that modulates the frequency, rate or extent of cellular DNA-templated transcription.
regulation of epithelial cell proliferation	Any process that modulates the frequency, rate or extent of epithelial cell proliferation.
regulation of neuron differentiation	Any process that modulates the frequency, rate or extent of neuron differentiation.
regulation of protein localization	Any process that modulates the frequency, rate or extent of any process in which a protein is transported to, or maintained in, a specific location.
regulation of skeletal muscle cell differentiation	Any process that modulates the frequency, rate or extent of skeletal muscle cell differentiation.
regulation of skeletal muscle cell proliferation	Any process that modulates the frequency, rate or extent of skeletal muscle cell proliferation.
regulation of skeletal muscle satellite cell proliferation	Any process that modulates the frequency, rate or extent of skeletal muscle satellite cell proliferation.
regulation of synaptic assembly at neuromuscular junction	Any process that modulates the frequency, rate or extent of synaptic assembly at neuromuscular junctions.
regulation of transcription by RNA polymerase II	Any process that modulates the frequency, rate or extent of transcription mediated by RNA polymerase II.
sensory perception of sound	The series of events required for an organism to receive an auditory stimulus, convert it to a molecular signal, and recognize and characterize the signal. Sonic stimuli are detected in the form of vibrations and are processed to form a sound.
skeletal muscle fiber development	The process whose specific outcome is the progression of the skeletal muscle fiber over time, from its formation to the mature structure. Muscle fibers are formed by the maturation of myotubes. They can be classed as slow, intermediate/fast or fast.
skeletal muscle tissue development	The developmental sequence of events leading to the formation of adult skeletal muscle tissue. The main events are: the fusion of myoblasts to form myotubes that increase in size by further fusion to them of myoblasts, the formation of myofibrils within their cytoplasm and the establishment of functional neuromuscular junctions with motor neurons. At this stage they can be regarded as mature muscle fibers.
thymus development	The process whose specific outcome is the progression of the thymus over time, from its formation to the mature structure. The thymus is a symmetric bi-lobed organ involved primarily in the differentiation of immature to mature T cells, with unique vascular, nervous, epithelial, and lymphoid cell components.
thyroid gland development	The process whose specific outcome is the progression of the thyroid gland over time, from its formation to the mature structure. The thyroid gland is an endoderm-derived gland that produces thyroid hormone.
trigeminal ganglion development	The process whose specific outcome is the progression of a trigeminal ganglion over time, from its formation to the mature structure.
ureter smooth muscle cell differentiation	The process in which a relatively unspecialized cell acquires specialized features of a smooth muscle cell in the ureter.
ureteric bud development	The process whose specific outcome is the progression of the ureteric bud over time, from its formation to the mature structure.

12 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
O93307	SIX6	Homeobox protein SIX6	Gallus gallus (Chicken)	PR
Q95RW8	Optix	Protein Optix	Drosophila melanogaster (Fruit fly)	PR
O95343	SIX3	Homeobox protein SIX3	Homo sapiens (Human)	PR
O95475	SIX6	Homeobox protein SIX6	Homo sapiens (Human)	PR
Q9NPC8	SIX2	Homeobox protein SIX2	Homo sapiens (Human)	PR
Q9QZ28	Six6	Homeobox protein SIX6	Mus musculus (Mouse)	PR
Q62232	Six2	Homeobox protein SIX2	Mus musculus (Mouse)	PR
Q62233	Six3	Homeobox protein SIX3	Mus musculus (Mouse)	PR
Q62231	Six1	Homeobox protein SIX1	Mus musculus (Mouse)	PR
Q94165	ceh-34	Homeobox protein ceh-34	Caenorhabditis elegans	PR
Q6DHF9	six1a	Homeobox protein six1a	Danio rerio (Zebrafish) (Brachydanio rerio)	PR
Q6NZ04	six1b	Homeobox protein six1b	Danio rerio (Zebrafish) (Brachydanio rerio)	PR

10	20	30	40	50	60
MSMLPSFGFT	QEQVACVCEV	LQQGGNLERL	GRFLWSLPAC	DHLHKNESVL	KAKAVVAFHR
70	80	90	100	110	120
GNFRELYKIL	ESHQFSPHNH	PKLQQLWLKA	HYVEAEKLRG	RPLGAVGKYR	VRRKFPLPRT
130	140	150	160	170	180
IWDGEETSYC	FKEKSRGVLR	EWYAHNPYPS	PREKRELAEA	TGLTTTQVSN	WFKNRRQRDR
190	200	210	220	230	240
AAEAKERENT	ENNNSSSNKQ	NQLSPLEGGK	PLMSSSEEEF	SPPQSPDQNS	VLLLQGNMGH
250	260	270	280
ARSSNYSLPG	LTASQPSHGL	QTHQHQLQDS	LLGPLTSSLV	DLGS