CleftGeneDB-Search

Gene: SIX3

Basic information

Tag	Content
Uniprot ID	O95343; D6W5A5; Q53T42;
Entrez ID	6496
Genbank protein ID	AAD15753.1; AAD51091.1; EAX00268.1; EAX00267.1; CAB42539.1; AAD11939.1; AAX93283.1;
Genbank nucleotide ID	NM_005413.3
Ensembl protein ID	ENSP00000260653
Ensembl nucleotide ID	ENSG00000138083
Gene name	Homeobox protein SIX3
Gene symbol	SIX3
Organism	Homo sapiens
NCBI taxa ID	9606
Cleft type
Developmental stage
Data sources	Homology search
Reference
Functional description	Transcriptional regulator which can act as both a transcriptional repressor and activator by binding a ATTA homeodomain core recognition sequence on these target genes. During forebrain development represses WNT1 expression allowing zona limitans intrathalamica formation and thereby ensuring proper anterio-posterior patterning of the diencephalon and formation of the rostral diencephalon. Acts as a direct upstream activator of SHH expression in the rostral diencephalon ventral midline and that in turn SHH maintains its expression. In addition, Six3 activity is required for the formation of the telencephalon. During postnatal stages of brain development is necessary for ependymal cell maturation by promoting the maturation of radial glia into ependymal cells through regulation of neuroblast proliferation and migration. Acts on the proliferation and differentiation of neural progenitor cells through activating transcription of CCND1 AND CCND2. During early lens formation plays a role in lens induction and specification by activating directly PAX6 in the presumptive lens ectoderm. In turn PAX6 activates SIX3 resulting in activation of PDGFRA and CCND1 promoting cell proliferation. Also is required for the neuroretina development by directly suppressing WNT8B expression in the anterior neural plate territory. Its action during retina development and lens morphogenesis is TLE5 and TLE4-dependent manner. Furthermore, during eye development regulates several genes expression. Before and during early lens development represses the CRYGF promoter by binding a SIX repressor element. Directly activates RHO transcription, or cooperates with CRX or NRL. Six3 functions also in the formation of the proximodistal axis of the optic cup, and promotes the formation of optic vesicles-like structures. During pituitary development, acts in parallel or alternatively with HESX1 to control cell proliferation through Wnt/beta-catenin pathway (By similarity). Plays a role in eye development by suppressing WNT1 expression and in dorsal-ventral patterning by repressing BMP signaling pathway.
Sequence	MVFRSPLDLY SSHFLLPNFA DSHHRSILLA SSGGGNGAGG GGGAGGGSGG GNGAGGGGAG 60 GAGGGGGGGS RAPPEELSMF QLPTLNFSPE QVASVCETLE ETGDIERLGR FLWSLPVAPG 120 ACEAINKHES ILRARAVVAF HTGNFRDLYH ILENHKFTKE SHGKLQAMWL EAHYQEAEKL 180 RGRPLGPVDK YRVRKKFPLP RTIWDGEQKT HCFKERTRSL LREWYLQDPY PNPSKKRELA 240 QATGLTPTQV GNWFKNRRQR DRAAAAKNRL QHQAIGPSGM RSLAEPGCPT HGSAESPSTA 300 ASPTTSVSSL TERADTGTSI LSVTSSDSEC DV 332

Abbreviation :
CLO : cleft lip only. CPO : cleft palate only. CLP : cleft lip and palate. CL/P : cleft lip with/without cleft palate.
For humans: CL/P, CLO, CPO, and CLP. For mice: CLO, CLP, and CPO.

Gene expression information

Gene expression in different tissues (GTEx V7)

Protein structural annotations

3D structure in PDB database

There is no related protein structure for this gene.

Protein disorder information

Orthologous information

Relation	Gene symbol	Entrez ID	UniProt ID	Cleft type	Species	Evidence	Details
1:1 ortholog	SIX3	616756	E1BMT1		Bos taurus	Prediction	More>>
1:1 ortholog	SIX3	102179678	A0A452E3R7		Capra hircus	Prediction	More>>
1:1 ortholog	SIX3	6496	O95343		Homo sapiens	Prediction	More>>
1:1 ortholog	Six3	20473	Q62233	CPO	Mus musculus	Publication	More>>
1:1 ortholog	SIX3	470367	H2QHU7		Pan troglodytes	Prediction	More>>
1:1 ortholog	Six3		A0A0G2K2C0		Rattus norvegicus	Prediction	More>>
1:1 ortholog	six3a		Q6PCA5		Danio rerio	Prediction	More>>

Other genetic variants/mutations

ID	Variant	Type	Disease	Chromosome\Coordinate	Evidence
RCV000599004	p.Met1Val	missense variant	-	NC_000002.12:g.44942105A>G	ClinVar
rs766767053	p.Val2Ile	missense variant	-	NC_000002.12:g.44942108G>A	ExAC,gnomAD
NCI-TCGA novel	p.Arg4His	missense variant	-	NC_000002.12:g.44942115G>A	NCI-TCGA
rs775115929	p.Ser5Phe	missense variant	-	NC_000002.12:g.44942118C>T	ExAC,gnomAD
rs775115929	p.Ser5Tyr	missense variant	-	NC_000002.12:g.44942118C>A	ExAC,gnomAD
rs775115929	p.Ser5Cys	missense variant	-	NC_000002.12:g.44942118C>G	ExAC,gnomAD
rs528794855	p.Pro6Leu	missense variant	-	NC_000002.12:g.44942121C>T	1000Genomes,ExAC,TOPMed,gnomAD
rs528794855	p.Pro6Arg	missense variant	-	NC_000002.12:g.44942121C>G	1000Genomes,ExAC,TOPMed,gnomAD
NCI-TCGA novel	p.Leu7Ter	frameshift	-	NC_000002.12:g.44942118C>-	NCI-TCGA
rs1490771348	p.Leu7Ile	missense variant	-	NC_000002.12:g.44942123C>A	gnomAD
rs756113841	p.Asp8Glu	missense variant	-	NC_000002.12:g.44942128C>A	ExAC,gnomAD
rs779829905	p.Leu9Val	missense variant	-	NC_000002.12:g.44942129C>G	ExAC,gnomAD
rs1479578284	p.Leu9Pro	missense variant	-	NC_000002.12:g.44942130T>C	gnomAD
rs749405556	p.Ser12Thr	missense variant	-	NC_000002.12:g.44942138T>A	ExAC,gnomAD
rs1443510881	p.His13Tyr	missense variant	-	NC_000002.12:g.44942141C>T	gnomAD
rs1410141912	p.His13Arg	missense variant	-	NC_000002.12:g.44942142A>G	TOPMed
rs772181424	p.Phe14Leu	missense variant	-	NC_000002.12:g.44942146C>G	ExAC,TOPMed,gnomAD
rs748430037	p.Phe14Cys	missense variant	-	NC_000002.12:g.44942145T>G	ExAC,gnomAD
rs773668631	p.Leu15Phe	missense variant	-	NC_000002.12:g.44942149G>T	ExAC,gnomAD
NCI-TCGA novel	p.Pro17Thr	missense variant	-	NC_000002.12:g.44942153C>A	NCI-TCGA
COSM1021108	p.Asn18Lys	missense variant	Variant assessed as Somatic; MODERATE impact.	NC_000002.12:g.44942158C>A	NCI-TCGA Cosmic
rs551637040	p.Asn18Asp	missense variant	-	NC_000002.12:g.44942156A>G	1000Genomes,TOPMed
rs551637040	p.Asn18Tyr	missense variant	-	NC_000002.12:g.44942156A>T	1000Genomes,TOPMed
rs199595730	p.Asn18Lys	missense variant	-	NC_000002.12:g.44942158C>G	TOPMed,gnomAD
rs200575650	p.Ala20Ser	missense variant	-	NC_000002.12:g.44942162G>T	1000Genomes,ExAC,TOPMed,gnomAD
COSM1240203	p.Asp21Asn	missense variant	Variant assessed as Somatic; MODERATE impact.	NC_000002.12:g.44942165G>A	NCI-TCGA Cosmic
rs537643024	p.Asp21Tyr	missense variant	-	NC_000002.12:g.44942165G>T	1000Genomes,ExAC,gnomAD
rs968579804	p.His24Gln	missense variant	-	NC_000002.12:g.44942176C>G	TOPMed,gnomAD
rs1269327293	p.Arg25Cys	missense variant	-	NC_000002.12:g.44942177C>T	TOPMed
NCI-TCGA novel	p.Ser26LeuPheSerTerUnk	frameshift	-	NC_000002.12:g.44942178_44942179insT	NCI-TCGA
rs1305570509	p.Ile27Thr	missense variant	-	NC_000002.12:g.44942184T>C	gnomAD
rs761622084	p.Ile27Met	missense variant	-	NC_000002.12:g.44942185A>G	ExAC,gnomAD
rs773982749	p.Ile27Val	missense variant	-	NC_000002.12:g.44942183A>G	ExAC,gnomAD
rs181010373	p.Leu29Pro	missense variant	-	NC_000002.12:g.44942190T>C	1000Genomes,ESP,ExAC,TOPMed,gnomAD
rs536278475	p.Ser31Arg	missense variant	-	NC_000002.12:g.44942195A>C	1000Genomes
COSM4094353	p.Ser32Asn	missense variant	Variant assessed as Somatic; MODERATE impact.	NC_000002.12:g.44942199G>A	NCI-TCGA Cosmic
rs753721024	p.Gly33Cys	missense variant	-	NC_000002.12:g.44942201G>T	ExAC,TOPMed,gnomAD
rs754899804	p.Gly33Asp	missense variant	-	NC_000002.12:g.44942202G>A	ExAC,gnomAD
rs753721024	p.Gly33Ser	missense variant	-	NC_000002.12:g.44942201G>A	ExAC,TOPMed,gnomAD
rs1401728465	p.Gly34Arg	missense variant	-	NC_000002.12:g.44942204G>C	gnomAD
rs1018692851	p.Gly35Arg	missense variant	-	NC_000002.12:g.44942207G>C	TOPMed,gnomAD
rs1018692851	p.Gly35Arg	missense variant	-	NC_000002.12:g.44942207G>A	TOPMed,gnomAD
rs199823175	p.Gly37Cys	missense variant	-	NC_000002.12:g.44942213G>T	1000Genomes,ESP,ExAC,TOPMed,gnomAD
rs199823175	p.Gly37Cys	missense variant	Holoprosencephaly 2 (hpe2)	NC_000002.12:g.44942213G>T	1000Genomes,ESP,ExAC,TOPMed,gnomAD
rs199823175	p.Gly37Cys	missense variant	-	NC_000002.12:g.44942213G>T	UniProt,dbSNP
VAR_071335	p.Gly37Cys	missense variant	-	NC_000002.12:g.44942213G>T	UniProt
RCV000713302	p.Gly37Cys	missense variant	-	NC_000002.12:g.44942213G>T	ClinVar
rs777810054	p.Ala38Val	missense variant	-	NC_000002.12:g.44942217C>T	ExAC,gnomAD
NCI-TCGA novel	p.Gly40Cys	missense variant	-	NC_000002.12:g.44942222G>T	NCI-TCGA
rs1216159686	p.Gly42Arg	missense variant	-	NC_000002.12:g.44942228G>C	gnomAD
RCV000594169	p.Gly43Cys	missense variant	-	NC_000002.12:g.44942231G>T	ClinVar
RCV000764416	p.Gly43Cys	missense variant	Holoprosencephaly 2 (HPE2)	NC_000002.12:g.44942231G>T	ClinVar
rs1436891421	p.Gly43Cys	missense variant	-	NC_000002.12:g.44942231G>T	TOPMed,gnomAD
rs920270639	p.Gly45Glu	missense variant	-	NC_000002.12:g.44942238G>A	TOPMed
rs771134581	p.Ser48Gly	missense variant	-	NC_000002.12:g.44942246A>G	ExAC,gnomAD
rs1264399264	p.Gly49Asp	missense variant	-	NC_000002.12:g.44942250G>A	gnomAD
rs1191977510	p.Gly50Ser	missense variant	-	NC_000002.12:g.44942252G>A	TOPMed,gnomAD
rs777289787	p.Gly50Val	missense variant	-	NC_000002.12:g.44942253G>T	ExAC,gnomAD
rs1191977510	p.Gly50Arg	missense variant	-	NC_000002.12:g.44942252G>C	TOPMed,gnomAD
rs558809633	p.Gly51Arg	missense variant	-	NC_000002.12:g.44942255G>C	1000Genomes,ExAC,TOPMed,gnomAD
rs558809633	p.Gly51Trp	missense variant	-	NC_000002.12:g.44942255G>T	1000Genomes,ExAC,TOPMed,gnomAD
rs558809633	p.Gly51Arg	missense variant	-	NC_000002.12:g.44942255G>A	1000Genomes,ExAC,TOPMed,gnomAD
rs770418171	p.Gly51Glu	missense variant	-	NC_000002.12:g.44942256G>A	ExAC,gnomAD
rs761202592	p.Gly53Cys	missense variant	-	NC_000002.12:g.44942261G>T	ExAC,TOPMed,gnomAD
rs771774953	p.Gly53Ala	missense variant	-	NC_000002.12:g.44942262G>C	ExAC,gnomAD
rs761202592	p.Gly53Arg	missense variant	-	NC_000002.12:g.44942261G>C	ExAC,TOPMed,gnomAD
rs1321033933	p.Ala54Glu	missense variant	-	NC_000002.12:g.44942265C>A	TOPMed
rs772677168	p.Gly55Glu	missense variant	-	NC_000002.12:g.44942268G>A	ExAC,TOPMed,gnomAD
rs1386445319	p.Gly55Arg	missense variant	-	NC_000002.12:g.44942267G>C	TOPMed
RCV000656534	p.Gly57Cys	missense variant	Holoprosencephaly 2 (HPE2)	NC_000002.12:g.44942273G>T	ClinVar
rs1344650194	p.Gly57Cys	missense variant	-	NC_000002.12:g.44942273G>T	gnomAD
rs753628024	p.Gly58Cys	missense variant	-	NC_000002.12:g.44942276G>T	ExAC,TOPMed,gnomAD
rs1281686738	p.Gly61Glu	missense variant	-	NC_000002.12:g.44942286G>A	gnomAD
rs575387114	p.Gly61Ter	stop gained	-	NC_000002.12:g.44942285G>T	1000Genomes,ExAC,TOPMed,gnomAD
rs575387114	p.Gly61Arg	missense variant	-	NC_000002.12:g.44942285G>A	1000Genomes,ExAC,TOPMed,gnomAD
rs1448442591	p.Ala62Thr	missense variant	-	NC_000002.12:g.44942288G>A	gnomAD
NCI-TCGA novel	p.Ala62Ser	missense variant	-	NC_000002.12:g.44942288G>T	NCI-TCGA
rs1216076593	p.Gly63Asp	missense variant	-	NC_000002.12:g.44942292G>A	gnomAD
rs1216076593	p.Gly63Ala	missense variant	-	NC_000002.12:g.44942292G>C	gnomAD
rs752797098	p.Gly64Asp	missense variant	-	NC_000002.12:g.44942295G>A	ExAC,gnomAD
rs778060809	p.Gly66Ser	missense variant	-	NC_000002.12:g.44942300G>A	ExAC,TOPMed,gnomAD
NCI-TCGA novel	p.Gly67Cys	missense variant	-	NC_000002.12:g.44942303G>T	NCI-TCGA
RCV000812876	p.Gly69Asp	missense variant	Holoprosencephaly 2 (HPE2)	NC_000002.12:g.44942310G>A	ClinVar
rs121917881	p.Gly69Asp	missense variant	Holoprosencephaly 2 (HPE2)	NC_000002.12:g.44942310G>A	UniProt,dbSNP
VAR_038418	p.Gly69Asp	missense variant	Holoprosencephaly 2 (HPE2)	NC_000002.12:g.44942310G>A	UniProt
rs121917881	p.Gly69Asp	missense variant	Holoprosencephaly 2 (hpe2)	NC_000002.12:g.44942310G>A	ExAC,TOPMed,gnomAD
rs1314811261	p.Ser70Pro	missense variant	-	NC_000002.12:g.44942312T>C	TOPMed
rs1402606672	p.Arg71Ser	missense variant	-	NC_000002.12:g.44942317G>T	gnomAD
rs1382884542	p.Arg71Lys	missense variant	-	NC_000002.12:g.44942316G>A	gnomAD
rs757487016	p.Ala72Ser	missense variant	-	NC_000002.12:g.44942318G>T	ExAC,gnomAD
rs781731500	p.Ala72Val	missense variant	-	NC_000002.12:g.44942319C>T	ExAC,TOPMed,gnomAD
rs889069929	p.Pro73Thr	missense variant	-	NC_000002.12:g.44942321C>A	TOPMed,gnomAD
rs889069929	p.Pro73Ser	missense variant	-	NC_000002.12:g.44942321C>T	TOPMed,gnomAD
rs747721596	p.Pro74Ser	missense variant	-	NC_000002.12:g.44942324C>T	ExAC,gnomAD
rs771429347	p.Pro74Arg	missense variant	-	NC_000002.12:g.44942325C>G	ExAC,TOPMed,gnomAD
rs771429347	p.Pro74Leu	missense variant	-	NC_000002.12:g.44942325C>T	ExAC,TOPMed,gnomAD
rs763853335	p.Pro74ArgPheSerTerUnkUnkUnk	frameshift	-	NC_000002.12:g.44942319C>-	NCI-TCGA,NCI-TCGA Cosmic
rs776461044	p.Glu76Asp	missense variant	-	NC_000002.12:g.44942332G>C	ExAC,gnomAD
rs760315707	p.Glu76Ter	stop gained	-	NC_000002.12:g.44942330G>T	ExAC
rs770543339	p.Glu76Val	missense variant	-	NC_000002.12:g.44942331A>T	ExAC,TOPMed,gnomAD
rs893527638	p.Leu77Val	missense variant	-	NC_000002.12:g.44942333T>G	gnomAD
rs1290628704	p.Ser78Phe	missense variant	-	NC_000002.12:g.44942337C>T	gnomAD
VAR_071336	p.Met79Val	Missense	Holoprosencephaly 2 (HPE2) [MIM:157170]	-	UniProt
rs759280002	p.Phe80Leu	missense variant	-	NC_000002.12:g.44942344C>G	ExAC,gnomAD
rs763108303	p.Leu85Val	missense variant	-	NC_000002.12:g.44942357C>G	ExAC,gnomAD
rs533412798	p.Ser88Leu	missense variant	-	NC_000002.12:g.44942367C>T	1000Genomes,ExAC,TOPMed,gnomAD
VAR_023797	p.Val92Gly	Missense	Holoprosencephaly 2 (HPE2) [MIM:157170]	-	UniProt
rs751652441	p.Ala93Val	missense variant	-	NC_000002.12:g.44942382C>T	ExAC,gnomAD
VAR_071337	p.Ala93Asp	Missense	Holoprosencephaly 2 (HPE2) [MIM:157170]	-	UniProt
rs757457966	p.Cys96Ser	missense variant	-	NC_000002.12:g.44942391G>C	ExAC,gnomAD
rs1553337648	p.Cys96Ter	stop gained	-	NC_000002.12:g.44942392T>A	-
RCV000578945	p.Cys96Ter	nonsense	-	NC_000002.12:g.44942392T>A	ClinVar
rs1304803510	p.Thr98Met	missense variant	-	NC_000002.12:g.44942397C>T	gnomAD
rs1326804162	p.Gly103Arg	missense variant	-	NC_000002.12:g.44942411G>C	TOPMed,gnomAD
rs1197341218	p.Asp104Asn	missense variant	-	NC_000002.12:g.44942414G>A	TOPMed,gnomAD
COSM6158558	p.Ile105Met	missense variant	Variant assessed as Somatic; MODERATE impact.	NC_000002.12:g.44942419C>G	NCI-TCGA Cosmic
VAR_023798	p.Ile105Val	Missense	Holoprosencephaly 2 (HPE2) [MIM:157170]	-	UniProt
rs1336980946	p.Glu106Asp	missense variant	-	NC_000002.12:g.44942422G>C	TOPMed,gnomAD
rs1267045983	p.Arg110His	missense variant	-	NC_000002.12:g.44942433G>A	TOPMed
rs137853021	p.Trp113Cys	missense variant	Holoprosencephaly 2 (HPE2)	NC_000002.12:g.44942443G>T	UniProt,dbSNP
VAR_071338	p.Trp113Cys	missense variant	Holoprosencephaly 2 (HPE2)	NC_000002.12:g.44942443G>T	UniProt
rs137853021	p.Trp113Cys	missense variant	Holoprosencephaly 2 (hpe2)	NC_000002.12:g.44942443G>T	-
RCV000506131	p.Trp113Cys	missense variant	-	NC_000002.12:g.44942443G>T	ClinVar
RCV000006472	p.Trp113Cys	missense variant	Holoprosencephaly 2 (HPE2)	NC_000002.12:g.44942443G>T	ClinVar
COSM4094357	p.Ser114Leu	missense variant	Variant assessed as Somatic; MODERATE impact.	NC_000002.12:g.44942445C>T	NCI-TCGA Cosmic
VAR_071339	p.Ser114Leu	Missense	Holoprosencephaly 2 (HPE2) [MIM:157170]	-	UniProt
rs1267545533	p.Val117Leu	missense variant	-	NC_000002.12:g.44942453G>C	gnomAD
rs1195691730	p.Ala121Glu	missense variant	-	NC_000002.12:g.44942466C>A	TOPMed,gnomAD
rs1195691730	p.Ala121Val	missense variant	-	NC_000002.12:g.44942466C>T	TOPMed,gnomAD
RCV000351427	p.Ala121Ter	frameshift	-	NC_000002.12:g.44942461del	ClinVar
rs746508020	p.Glu123Lys	missense variant	-	NC_000002.12:g.44942471G>A	ExAC,gnomAD
rs1242759851	p.Ala124Thr	missense variant	-	NC_000002.12:g.44942474G>A	gnomAD
COSM721772	p.Ile125Thr	missense variant	Variant assessed as Somatic; MODERATE impact.	NC_000002.12:g.44942478T>C	NCI-TCGA Cosmic
rs372100479	p.Lys127Gln	missense variant	-	NC_000002.12:g.44942483A>C	ESP
RCV000023328	p.Glu129Ter	nonsense	Holoprosencephaly 2 (HPE2)	NC_000002.12:g.44942489G>T	ClinVar
rs387906867	p.Glu129Ter	stop gained	Holoprosencephaly 2 (hpe2)	NC_000002.12:g.44942489G>T	-
RCV000023329	p.Glu129Ter	nonsense	SCHIZENCEPHALY	NC_000002.12:g.44942489G>T	ClinVar
rs914092830	p.Arg133Ser	missense variant	-	NC_000002.12:g.44942501C>A	TOPMed
rs1335408489	p.Ala134Gly	missense variant	-	NC_000002.12:g.44942505C>G	gnomAD
NCI-TCGA novel	p.Ala134Val	missense variant	-	NC_000002.12:g.44942505C>T	NCI-TCGA
rs775341543	p.Ala134Ser	missense variant	-	NC_000002.12:g.44942504G>T	ExAC,gnomAD
NCI-TCGA novel	p.Arg135His	missense variant	-	NC_000002.12:g.44942508G>A	NCI-TCGA
rs1379956535	p.Arg135Gly	missense variant	-	NC_000002.12:g.44942507C>G	gnomAD
rs762864110	p.Ala136Ser	missense variant	-	NC_000002.12:g.44942510G>T	ExAC
RCV000520730	p.Ala136Ter	frameshift	-	NC_000002.12:g.44942500_44942501GC[5]	ClinVar
rs753473749	p.Ala136ArgPheSerTerUnkUnk	frameshift	-	NC_000002.12:g.44942500_44942501GC>-	NCI-TCGA,NCI-TCGA Cosmic
RCV000006470	p.Val137Ter	frameshift	Holoprosencephaly 2 (HPE2)	NC_000002.12:g.44942500_44942501GC[7]	ClinVar
VAR_071340	p.Val138Asp	Missense	Holoprosencephaly 2 (HPE2) [MIM:157170]	-	UniProt
NCI-TCGA novel	p.Ala139Thr	missense variant	-	NC_000002.12:g.44942519G>A	NCI-TCGA
rs1250116628	p.Thr142Met	missense variant	-	NC_000002.12:g.44942529C>T	gnomAD
rs761932777	p.Gly143Asp	missense variant	-	NC_000002.12:g.44942532G>A	ExAC,gnomAD
rs1460056891	p.Asn144Asp	missense variant	-	NC_000002.12:g.44942534A>G	gnomAD
rs756395470	p.Arg146Cys	missense variant	-	NC_000002.12:g.44942540C>T	ExAC,TOPMed,gnomAD
rs766724439	p.Arg146Leu	missense variant	-	NC_000002.12:g.44942541G>T	ExAC
rs1427686682	p.Asp147Asn	missense variant	-	NC_000002.12:g.44942543G>A	gnomAD
RCV000656533	p.Leu148Ter	frameshift	Holoprosencephaly 2 (HPE2)	NC_000002.12:g.44942545_44942555del	ClinVar
rs754202682	p.Leu148Phe	missense variant	-	NC_000002.12:g.44942546C>T	ExAC,gnomAD
rs1403214451	p.Ile151Val	missense variant	-	NC_000002.12:g.44942555A>G	gnomAD
NCI-TCGA novel	p.Leu152His	missense variant	-	NC_000002.12:g.44942559T>A	NCI-TCGA
NCI-TCGA novel	p.Glu153Gly	missense variant	-	NC_000002.12:g.44942562A>G	NCI-TCGA
VAR_071341	p.His155del	inframe_deletion	Holoprosencephaly 2 (HPE2) [MIM:157170]	-	UniProt
rs1303045479	p.Lys156Thr	missense variant	-	NC_000002.12:g.44942571A>C	gnomAD
VAR_071342	p.Phe157Ile	Missense	Holoprosencephaly 2 (HPE2) [MIM:157170]	-	UniProt
COSM1306821	p.His162Tyr	missense variant	Variant assessed as Somatic; MODERATE impact.	NC_000002.12:g.44942588C>T	NCI-TCGA Cosmic
rs746533848	p.His162Gln	missense variant	-	NC_000002.12:g.44942590C>A	ExAC,gnomAD
rs756689465	p.Gly163Val	missense variant	-	NC_000002.12:g.44942592G>T	ExAC,gnomAD
rs756689465	p.Gly163Asp	missense variant	-	NC_000002.12:g.44942592G>A	ExAC,gnomAD
rs745577214	p.Ala167Gly	missense variant	-	NC_000002.12:g.44942604C>G	ExAC,gnomAD
NCI-TCGA novel	p.Ala167Asp	missense variant	-	NC_000002.12:g.44942604C>A	NCI-TCGA
RCV000023332	p.Ala167Ser	missense variant	SCHIZENCEPHALY	NC_000002.12:g.44942603G>T	ClinVar
rs387906868	p.Ala167Ser	missense variant	-	NC_000002.12:g.44942603G>T	ExAC,TOPMed,gnomAD
rs387906868	p.Ala167Ser	missense variant	Schizencephaly (SCHZC)	NC_000002.12:g.44942603G>T	UniProt,dbSNP
VAR_071343	p.Ala167Ser	missense variant	Schizencephaly (SCHZC)	NC_000002.12:g.44942603G>T	UniProt
RCV000702708	p.Trp169Ter	nonsense	Holoprosencephaly 2 (HPE2)	NC_000002.12:g.44942611G>A	ClinVar
rs769431310	p.Glu171Gln	missense variant	-	NC_000002.12:g.44942615G>C	ExAC,gnomAD
NCI-TCGA novel	p.Ala172Thr	missense variant	-	NC_000002.12:g.44942618G>A	NCI-TCGA
VAR_071344	p.Ala172Val	Missense	Holoprosencephaly 2 (HPE2) [MIM:157170]	-	UniProt
VAR_023799	p.His173Pro	Missense	Holoprosencephaly 2 (HPE2) [MIM:157170]	-	UniProt
VAR_071345	p.Tyr174His	Missense	Holoprosencephaly 2 (HPE2) [MIM:157170]	-	UniProt
NCI-TCGA novel	p.Glu176Lys	missense variant	-	NC_000002.12:g.44942630G>A	NCI-TCGA
rs768497950	p.Ala177Val	missense variant	-	NC_000002.12:g.44942634C>T	ExAC,gnomAD
rs768497950	p.Ala177Asp	missense variant	-	NC_000002.12:g.44942634C>A	ExAC,gnomAD
rs1434383417	p.Arg181His	missense variant	-	NC_000002.12:g.44942646G>A	gnomAD
rs1176239877	p.Gly182Cys	missense variant	-	NC_000002.12:g.44942648G>T	gnomAD
rs1362713577	p.Pro184Leu	missense variant	-	NC_000002.12:g.44942655C>T	gnomAD
rs773424856	p.Gly186Cys	missense variant	-	NC_000002.12:g.44942660G>T	ExAC,gnomAD
rs773424856	p.Gly186Ser	missense variant	-	NC_000002.12:g.44942660G>A	ExAC,gnomAD
rs761021058	p.Pro187Ala	missense variant	-	NC_000002.12:g.44942663C>G	ExAC,gnomAD
rs1221436387	p.Asp189Gly	missense variant	-	NC_000002.12:g.44942670A>G	gnomAD
rs1288474418	p.Val193Met	missense variant	-	NC_000002.12:g.44942681G>A	gnomAD
NCI-TCGA novel	p.Arg194Leu	missense variant	-	NC_000002.12:g.44942685G>T	NCI-TCGA
NCI-TCGA novel	p.Arg194His	missense variant	-	NC_000002.12:g.44942685G>A	NCI-TCGA
NCI-TCGA novel	p.Arg194Ser	missense variant	-	NC_000002.12:g.44942684C>A	NCI-TCGA
rs1157864629	p.Lys196Met	missense variant	-	NC_000002.12:g.44942691A>T	TOPMed
rs1221543535	p.Pro198Leu	missense variant	-	NC_000002.12:g.44942697C>T	gnomAD
NCI-TCGA novel	p.Leu199Met	missense variant	-	NC_000002.12:g.44942699C>A	NCI-TCGA
rs1553337714	p.Arg201His	missense variant	-	NC_000002.12:g.44942706G>A	-
COSM5955061	p.Arg201Cys	missense variant	Variant assessed as Somatic; MODERATE impact.	NC_000002.12:g.44942705C>T	NCI-TCGA Cosmic
RCV000658046	p.Arg201His	missense variant	-	NC_000002.12:g.44942706G>A	ClinVar
VAR_023800	p.Thr202Ile	Missense	Holoprosencephaly 2 (HPE2) [MIM:157170]	-	UniProt
RCV000269190	p.Asp205His	missense variant	-	NC_000002.12:g.44942717G>C	ClinVar
rs886044000	p.Asp205His	missense variant	-	NC_000002.12:g.44942717G>C	TOPMed
NCI-TCGA novel	p.Gly206Ser	missense variant	-	NC_000002.12:g.44942720G>A	NCI-TCGA
NCI-TCGA novel	p.Glu207Lys	missense variant	-	NC_000002.12:g.44942723G>A	NCI-TCGA
rs1380586263	p.Gln208Lys	missense variant	-	NC_000002.12:g.44942726C>A	gnomAD
rs780746878	p.Thr210Lys	missense variant	-	NC_000002.12:g.44942733C>A	ExAC,gnomAD
VAR_071346	p.Phe213Val	Missense	Holoprosencephaly 2 (HPE2) [MIM:157170]	-	UniProt
rs779704824	p.Lys214Arg	missense variant	-	NC_000002.12:g.44942745A>G	ExAC,gnomAD
rs768427864	p.Arg216Gln	missense variant	-	NC_000002.12:g.44942751G>A	ExAC,TOPMed,gnomAD
rs1389795579	p.Thr217Ile	missense variant	-	NC_000002.12:g.44942754C>T	gnomAD
rs1311723501	p.Arg218Gln	missense variant	-	NC_000002.12:g.44942757G>A	gnomAD
VAR_071348	p.Arg218Trp	Missense	Holoprosencephaly 2 (HPE2) [MIM:157170]	-	UniProt
VAR_071347	p.Arg218Pro	Missense	Holoprosencephaly 2 (HPE2) [MIM:157170]	-	UniProt
rs748952099	p.Arg222Trp	missense variant	-	NC_000002.12:g.44942768C>T	ExAC,TOPMed,gnomAD
COSM721771	p.Glu223Gln	missense variant	Variant assessed as Somatic; MODERATE impact.	NC_000002.12:g.44942771G>C	NCI-TCGA Cosmic
COSM3839583	p.Glu223Ter	stop gained	Variant assessed as Somatic; HIGH impact.	NC_000002.12:g.44942771G>T	NCI-TCGA Cosmic
RCV000006466	p.Leu226Val	missense variant	Holoprosencephaly 2 (HPE2)	NC_000002.12:g.44942780C>G	ClinVar
rs121917878	p.Leu226Val	missense variant	Holoprosencephaly 2 (HPE2)	NC_000002.12:g.44942780C>G	UniProt,dbSNP
VAR_003771	p.Leu226Val	missense variant	Holoprosencephaly 2 (HPE2)	NC_000002.12:g.44942780C>G	UniProt
rs121917878	p.Leu226Val	missense variant	Holoprosencephaly 2 (hpe2)	NC_000002.12:g.44942780C>G	-
VAR_071349	p.Gln227Pro	Missense	Holoprosencephaly 2 (HPE2) [MIM:157170]	-	UniProt
rs1479362407	p.Pro231Ser	missense variant	-	NC_000002.12:g.44942795C>T	gnomAD
VAR_023801	p.Pro231Arg	Missense	Holoprosencephaly 2 (HPE2) [MIM:157170]	-	UniProt
RCV000055688	p.Asn232Ter	frameshift	Holoprosencephaly 2 (HPE2)	NC_000002.12:g.44942800_44942809del	ClinVar
COSM4624809	p.Arg237His	missense variant	Variant assessed as Somatic; MODERATE impact.	NC_000002.12:g.44942814G>A	NCI-TCGA Cosmic
rs753054738	p.Glu238Lys	missense variant	-	NC_000002.12:g.44942816G>A	ExAC,gnomAD
rs763491194	p.Leu239Met	missense variant	-	NC_000002.12:g.44942819C>A	ExAC,gnomAD
rs1412023322	p.Ala240Val	missense variant	-	NC_000002.12:g.44942823C>T	gnomAD
NCI-TCGA novel	p.Gly244Ser	missense variant	-	NC_000002.12:g.44942834G>A	NCI-TCGA
rs966396323	p.Thr248Ile	missense variant	-	NC_000002.12:g.44942847C>T	gnomAD
RCV000006468	p.Val250Ala	missense variant	Holoprosencephaly 2 (HPE2)	NC_000002.12:g.44942853T>C	ClinVar
rs121917880	p.Val250Ala	missense variant	Holoprosencephaly 2 (HPE2)	NC_000002.12:g.44942853T>C	UniProt,dbSNP
VAR_003772	p.Val250Ala	missense variant	Holoprosencephaly 2 (HPE2)	NC_000002.12:g.44942853T>C	UniProt
rs121917880	p.Val250Ala	missense variant	Holoprosencephaly 2 (hpe2)	NC_000002.12:g.44942853T>C	-
NCI-TCGA novel	p.Trp253TyrPheSerTerUnkUnk	frameshift	-	NC_000002.12:g.44942861_44942862insATCAACAAACACGAGTCGATCCTGC	NCI-TCGA
VAR_071351	p.Phe254Leu	Missense	Holoprosencephaly 2 (HPE2) [MIM:157170]	-	UniProt
RCV000006467	p.Arg257Pro	missense variant	Holoprosencephaly 2 (HPE2)	NC_000002.12:g.44942874G>C	ClinVar
rs121917879	p.Arg257Pro	missense variant	Holoprosencephaly 2 (hpe2)	NC_000002.12:g.44942874G>C	-
rs121917879	p.Arg257Pro	missense variant	Holoprosencephaly 2 (HPE2)	NC_000002.12:g.44942874G>C	UniProt,dbSNP
VAR_003773	p.Arg257Pro	missense variant	Holoprosencephaly 2 (HPE2)	NC_000002.12:g.44942874G>C	UniProt
VAR_023802	p.Arg257Trp	Missense	Holoprosencephaly 2 (HPE2) [MIM:157170]	-	UniProt
VAR_071352	p.Arg257Gly	Missense	Holoprosencephaly 2 (HPE2) [MIM:157170]	-	UniProt
VAR_071353	p.Arg258Leu	Missense	Holoprosencephaly 2 (HPE2) [MIM:157170]	-	UniProt
RCV000489818	p.Gln259His	missense variant	-	NC_000002.12:g.44942881G>T	ClinVar
rs1085307513	p.Gln259His	missense variant	-	NC_000002.12:g.44942881G>T	-
rs1228726729	p.Arg260Cys	missense variant	-	NC_000002.12:g.44942882C>T	gnomAD
NCI-TCGA novel	p.Asp261Tyr	missense variant	-	NC_000002.12:g.44942885G>T	NCI-TCGA
COSM4094361	p.Arg262His	missense variant	Variant assessed as Somatic; MODERATE impact.	NC_000002.12:g.44942889G>A	NCI-TCGA Cosmic
VAR_071354	p.Arg262His	Missense	Holoprosencephaly 2 (HPE2) [MIM:157170]	-	UniProt
NCI-TCGA novel	p.Ala263Thr	missense variant	-	NC_000002.12:g.44942891G>A	NCI-TCGA
NCI-TCGA novel	p.Ala264Thr	missense variant	-	NC_000002.12:g.44942894G>A	NCI-TCGA
rs1460508805	p.Ala266Thr	missense variant	-	NC_000002.12:g.44942900G>A	gnomAD
COSM4094362	p.Arg269Met	missense variant	Variant assessed as Somatic; MODERATE impact.	NC_000002.12:g.44942910G>T	NCI-TCGA Cosmic
VAR_071355	p.Arg269Met	Missense	Holoprosencephaly 2 (HPE2) [MIM:157170]	-	UniProt
VAR_071357	p.Arg269Thr	Missense	Holoprosencephaly 2 (HPE2) [MIM:157170]	-	UniProt
VAR_071356	p.Arg269Ser	Missense	Holoprosencephaly 2 (HPE2) [MIM:157170]	-	UniProt
rs906435288	p.Leu270Ile	missense variant	-	NC_000002.12:g.44944569C>A	TOPMed,gnomAD
rs906435288	p.Leu270Phe	missense variant	-	NC_000002.12:g.44944569C>T	TOPMed,gnomAD
rs1344878849	p.His272Tyr	missense variant	-	NC_000002.12:g.44944575C>T	gnomAD
rs1344878849	p.His272Asn	missense variant	-	NC_000002.12:g.44944575C>A	gnomAD
rs373028825	p.Ile275Val	missense variant	-	NC_000002.12:g.44944584A>G	ESP,ExAC,TOPMed,gnomAD
rs377320521	p.Ile275Thr	missense variant	-	NC_000002.12:g.44944585T>C	1000Genomes,ESP,ExAC,TOPMed,gnomAD
RCV000514708	p.Ile275Thr	missense variant	-	NC_000002.12:g.44944585T>C	ClinVar
rs1345139300	p.Gly276Glu	missense variant	-	NC_000002.12:g.44944588G>A	gnomAD
rs575632344	p.Pro277Gln	missense variant	-	NC_000002.12:g.44944591C>A	1000Genomes,ExAC,TOPMed,gnomAD
rs575632344	p.Pro277Leu	missense variant	-	NC_000002.12:g.44944591C>T	1000Genomes,ExAC,TOPMed,gnomAD
rs1219329090	p.Ser278Asn	missense variant	-	NC_000002.12:g.44944594G>A	gnomAD
rs1264530554	p.Gly279Cys	missense variant	-	NC_000002.12:g.44944596G>T	TOPMed,gnomAD
rs1275748806	p.Met280Ile	missense variant	-	NC_000002.12:g.44944601G>A	TOPMed
rs774682149	p.Arg281Pro	missense variant	-	NC_000002.12:g.44944603G>C	ExAC,TOPMed,gnomAD
rs1197394985	p.Arg281Ser	missense variant	-	NC_000002.12:g.44944602C>A	gnomAD
rs1197394985	p.Arg281Cys	missense variant	-	NC_000002.12:g.44944602C>T	gnomAD
rs774682149	p.Arg281Leu	missense variant	-	NC_000002.12:g.44944603G>T	ExAC,TOPMed,gnomAD
rs1378761400	p.Leu283Pro	missense variant	-	NC_000002.12:g.44944609T>C	gnomAD
rs767891049	p.Ala284Pro	missense variant	-	NC_000002.12:g.44944611G>C	ExAC,TOPMed,gnomAD
rs776232356	p.Ala284Asp	missense variant	-	NC_000002.12:g.44944612C>A	ExAC,TOPMed,gnomAD
rs767891049	p.Ala284Thr	missense variant	-	NC_000002.12:g.44944611G>A	ExAC,TOPMed,gnomAD
rs776232356	p.Ala284Gly	missense variant	-	NC_000002.12:g.44944612C>G	ExAC,TOPMed,gnomAD
rs1384959715	p.Glu285Lys	missense variant	-	NC_000002.12:g.44944614G>A	TOPMed,gnomAD
rs758933447	p.Glu285Asp	missense variant	-	NC_000002.12:g.44944616G>T	ExAC,TOPMed,gnomAD
rs1440905862	p.Gly287Ser	missense variant	-	NC_000002.12:g.44944620G>A	gnomAD
rs1306618159	p.Gly287Asp	missense variant	-	NC_000002.12:g.44944621G>A	gnomAD
rs1355497595	p.Cys288Arg	missense variant	-	NC_000002.12:g.44944623T>C	gnomAD
rs1240433838	p.Cys288Tyr	missense variant	-	NC_000002.12:g.44944624G>A	gnomAD
rs1287126535	p.Pro289Leu	missense variant	-	NC_000002.12:g.44944627C>T	gnomAD
rs1357166419	p.Pro289Thr	missense variant	-	NC_000002.12:g.44944626C>A	TOPMed
rs1460399712	p.Thr290Lys	missense variant	-	NC_000002.12:g.44944630C>A	gnomAD
rs1330614232	p.Gly292Val	missense variant	-	NC_000002.12:g.44944636G>T	TOPMed
rs1017986805	p.Ser293Leu	missense variant	-	NC_000002.12:g.44944639C>T	TOPMed,gnomAD
rs1452238062	p.Ala294Thr	missense variant	-	NC_000002.12:g.44944641G>A	gnomAD
RCV000639734	p.Ser296Trp	missense variant	Holoprosencephaly 2 (HPE2)	NC_000002.12:g.44944648C>G	ClinVar
rs751280287	p.Ser296Trp	missense variant	-	NC_000002.12:g.44944648C>G	ExAC,TOPMed,gnomAD
rs751280287	p.Ser296Leu	missense variant	-	NC_000002.12:g.44944648C>T	ExAC,TOPMed,gnomAD
rs780942050	p.Pro297Leu	missense variant	-	NC_000002.12:g.44944651C>T	ExAC,TOPMed,gnomAD
rs780942050	p.Pro297Leu	missense variant	Holoprosencephaly 2 (HPE2)	NC_000002.12:g.44944651C>T	UniProt,dbSNP
VAR_071358	p.Pro297Leu	missense variant	Holoprosencephaly 2 (HPE2)	NC_000002.12:g.44944651C>T	UniProt
COSM3581802	p.Ala300Thr	missense variant	Variant assessed as Somatic; MODERATE impact.	NC_000002.12:g.44944659G>A	NCI-TCGA Cosmic
rs1456236951	p.Ala301Thr	missense variant	-	NC_000002.12:g.44944662G>A	gnomAD
rs1391438380	p.Pro303Leu	missense variant	-	NC_000002.12:g.44944669C>T	gnomAD
rs1391438380	p.Pro303Arg	missense variant	-	NC_000002.12:g.44944669C>G	gnomAD
rs1328765266	p.Thr304Ile	missense variant	-	NC_000002.12:g.44944672C>T	TOPMed,gnomAD
rs1328765266	p.Thr304Ser	missense variant	-	NC_000002.12:g.44944672C>G	TOPMed,gnomAD
rs768858748	p.Ser308Ala	missense variant	-	NC_000002.12:g.44944683T>G	ExAC,gnomAD
rs1242996743	p.Ser309Gly	missense variant	-	NC_000002.12:g.44944686A>G	gnomAD
rs1286475473	p.Thr311Met	missense variant	-	NC_000002.12:g.44944693C>T	gnomAD
rs1234997319	p.Thr311Pro	missense variant	-	NC_000002.12:g.44944692A>C	TOPMed
rs1286475473	p.Thr311Lys	missense variant	-	NC_000002.12:g.44944693C>A	gnomAD
rs1198557011	p.Glu312Ter	stop gained	-	NC_000002.12:g.44944695G>T	gnomAD
rs1256290558	p.Arg313His	missense variant	-	NC_000002.12:g.44944699G>A	gnomAD
NCI-TCGA novel	p.Ala314GlyPheSerTerUnkUnk	frameshift	-	NC_000002.12:g.44944702_44944703CA>-	NCI-TCGA
rs1459121699	p.Ala314Val	missense variant	-	NC_000002.12:g.44944702C>T	gnomAD
rs1242705846	p.Asp315Asn	missense variant	-	NC_000002.12:g.44944704G>A	gnomAD
RCV000354705	p.Thr316Ile	missense variant	-	NC_000002.12:g.44944708C>T	ClinVar
rs201922529	p.Thr316Ile	missense variant	-	NC_000002.12:g.44944708C>T	ESP,ExAC,TOPMed,gnomAD
rs1368822738	p.Gly317Ala	missense variant	-	NC_000002.12:g.44944711G>C	gnomAD
rs1168416233	p.Ser319Phe	missense variant	-	NC_000002.12:g.44944717C>T	gnomAD
rs370063753	p.Ile320Leu	missense variant	-	NC_000002.12:g.44944719A>C	1000Genomes,ESP,ExAC,TOPMed,gnomAD
rs199795275	p.Leu321Val	missense variant	-	NC_000002.12:g.44944722C>G	1000Genomes,ExAC,gnomAD
rs199795275	p.Leu321Phe	missense variant	-	NC_000002.12:g.44944722C>T	1000Genomes,ExAC,gnomAD
rs199795275	p.Leu321Ile	missense variant	-	NC_000002.12:g.44944722C>A	1000Genomes,ExAC,gnomAD
rs867552132	p.Ser322Leu	missense variant	-	NC_000002.12:g.44944726C>T	gnomAD
rs909085152	p.Thr324Ile	missense variant	-	NC_000002.12:g.44944732C>T	gnomAD
rs909085152	p.Thr324Asn	missense variant	-	NC_000002.12:g.44944732C>A	gnomAD
COSM1306822	p.Ser326Arg	missense variant	Variant assessed as Somatic; MODERATE impact.	NC_000002.12:g.44944739C>G	NCI-TCGA Cosmic
rs775137524	p.Ser326Ile	missense variant	-	NC_000002.12:g.44944738G>T	ExAC,gnomAD
NCI-TCGA novel	p.Glu329Lys	missense variant	-	NC_000002.12:g.44944746G>A	NCI-TCGA
rs762735658	p.Asp331Gly	missense variant	-	NC_000002.12:g.44944753A>G	ExAC,TOPMed,gnomAD
rs762735658	p.Asp331Val	missense variant	-	NC_000002.12:g.44944753A>T	ExAC,TOPMed,gnomAD
rs1320121239	p.Val332Ile	missense variant	-	NC_000002.12:g.44944755G>A	gnomAD

Disease or phenotype associated information

Disease ID	Disease Name	Disease Type	Source
C0000768	Congenital Abnormality	group	BEFREE
C0001418	Adenocarcinoma	group	BEFREE
C0007120	Bronchioloalveolar Adenocarcinoma	disease	BEFREE
C0008479	Chondrosarcoma	disease	BEFREE;LHGDN
C0009363	Congenital ocular coloboma (disorder)	disease	GENOMICS_ENGLAND
C0009806	Constipation	phenotype	HPO
C0010823	Cytomegalovirus Infections	group	BEFREE
C0011848	Diabetes Insipidus	disease	HPO
C0014544	Epilepsy	disease	HPO
C0017636	Glioblastoma	disease	BEFREE
C0020635	Hypopituitarism	disease	BEFREE
C0023903	Liver neoplasms	group	CTD_human
C0025362	Mental Retardation	disease	HPO
C0026010	Microphthalmos	disease	HPO
C0026654	Moyamoya Disease	disease	BEFREE
C0027627	Neoplasm Metastasis	phenotype	BEFREE
C0027651	Neoplasms	group	BEFREE
C0027708	Nephroblastoma	disease	BEFREE
C0032002	Pituitary Diseases	group	BEFREE
C0032927	Precancerous Conditions	group	CTD_human
C0036572	Seizures	phenotype	HPO
C0037932	Curvature of spine	phenotype	HPO
C0078982	Arhinencephaly	disease	CTD_human
C0079541	Holoprosencephaly	disease	BEFREE;CTD_human;GENOMICS_ENGLAND;HPO;LHGDN
C0086543	Cataract	disease	GENOMICS_ENGLAND
C0152013	Adenocarcinoma of lung (disorder)	disease	BEFREE
C0175754	Agenesis of corpus callosum	disease	HPO
C0237326	Dyschezia	phenotype	HPO
C0242343	Panhypopituitarism	disease	BEFREE
C0242379	Malignant neoplasm of lung	disease	BEFREE
C0265740	Arrhinia	disease	HPO
C0266122	Cleft uvula	disease	HPO
C0266470	Cerebellar Hypoplasia	disease	HPO
C0266484	Schizencephaly	disease	BEFREE;CLINVAR;HPO;ORPHANET;UNIPROT
C0266667	Cyclocephaly	disease	BEFREE;HPO
C0278878	Adult Glioblastoma	disease	BEFREE
C0280474	Childhood Glioblastoma	disease	BEFREE
C0282313	Condition, Preneoplastic	phenotype	CTD_human
C0342491	Small adrenal gland	phenotype	HPO
C0345904	Malignant neoplasm of liver	disease	CTD_human
C0423903	Low intelligence	phenotype	HPO
C0424688	Small head	phenotype	HPO
C0424711	Orbital separation diminished	phenotype	HPO
C0431362	Lobar Holoprosencephaly	disease	BEFREE;CTD_human;ORPHANET
C0431363	Alobar Holoprosencephaly	disease	BEFREE;CTD_human;ORPHANET
C0432103	Submucous cleft of hard palate	disease	HPO
C0543888	Epileptic encephalopathy	disease	GENOMICS_ENGLAND
C0557874	Global developmental delay	disease	HPO
C0596263	Carcinogenesis	phenotype	BEFREE
C0684249	Carcinoma of lung	disease	BEFREE
C0685869	Monophthalmos	disease	BEFREE
C0700208	Acquired scoliosis	phenotype	HPO
C0751617	Semilobar Holoprosencephaly	disease	CTD_human;ORPHANET
C0917816	Mental deficiency	disease	HPO
C1275278	Extraskeletal Myxoid Chondrosarcoma	disease	BEFREE
C1304508	Spindle cell hemangioma	disease	BEFREE
C1306460	Primary malignant neoplasm of lung	disease	BEFREE
C1834877	HOLOPROSENCEPHALY 2 (disorder)	disease	BEFREE;CLINVAR;CTD_human;MGD;UNIPROT
C1840235	SOLITARY MEDIAN MAXILLARY CENTRAL INCISOR	disease	BEFREE;HPO
C1843367	Poor school performance	phenotype	HPO
C1846223	Adrenal hypoplasia	phenotype	HPO
C1853242	Midface retrusion	phenotype	HPO
C1858085	Malar flattening	phenotype	HPO
C1858120	Generalized hypotonia	phenotype	HPO
C1864897	Cognitive delay	phenotype	HPO
C2673410	Small midface	phenotype	HPO
C2750604	Median cleft lip and palate	disease	HPO
C2931384	Moyamoya disease 1	disease	BEFREE
C2931870	Familial schizencephaly	disease	CTD_human
C3711749	Nonsyndromic Holoprosencephaly	disease	BEFREE
C3714756	Intellectual Disability	group	GENOMICS_ENGLAND;HPO
C4020875	Mental and motor retardation	phenotype	HPO
C4020876	Dull intelligence	phenotype	HPO
C4020894	Submucous clefting	phenotype	HPO
C4021249	Anterior pituitary agenesis	phenotype	HPO
C4021638	Absent nasal septal cartilage	phenotype	HPO
C4053775	Pituitary stalk interruption syndrome	disease	BEFREE
C4280320	Hypotrophic midface	phenotype	HPO
C4280321	Decreased projection of midface	phenotype	HPO
C4280391	Missing nose	phenotype	HPO
C4280501	Failure of development of nasal septal cartilage	phenotype	HPO
C4280625	Decreased size of eyeball	phenotype	HPO
C4280651	Hypotrophic malar bone	phenotype	HPO
C4280808	Abnormally small eyeball	phenotype	HPO

Gene Ontology (GO)/biological pathways

GO:Molecular Function

GO ID	GO Term	Evidence
GO:0000976	transcription regulatory region sequence-specific DNA binding	IBA
GO:0000978	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA
GO:0000981	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0000981	DNA-binding transcription factor activity, RNA polymerase II-specific	ISM
GO:0000981	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA
GO:0001222	transcription corepressor binding	IPI
GO:0001228	DNA-binding transcription activator activity, RNA polymerase II-specific	IEA
GO:0003700	DNA-binding transcription factor activity	ISS
GO:0003713	transcription coactivator activity	ISS
GO:0005102	signaling receptor binding	IEA
GO:0005515	protein binding	IPI
GO:0042826	histone deacetylase binding	IEA

GO:Biological Process

GO ID	GO Term	Evidence
GO:0001654	eye development	IDA
GO:0001654	eye development	IBA
GO:0002070	epithelial cell maturation	ISS
GO:0002088	lens development in camera-type eye	ISS
GO:0003404	optic vesicle morphogenesis	ISS
GO:0006606	protein import into nucleus	IEA
GO:0007420	brain development	IBA
GO:0007601	visual perception	TAS
GO:0009946	proximal/distal axis specification	ISS
GO:0014016	neuroblast differentiation	ISS
GO:0021537	telencephalon development	ISS
GO:0021797	forebrain anterior/posterior pattern specification	IEA
GO:0021798	forebrain dorsal/ventral pattern formation	IDA
GO:0021846	cell proliferation in forebrain	ISS
GO:0021978	telencephalon regionalization	ISS
GO:0021983	pituitary gland development	ISS
GO:0030178	negative regulation of Wnt signaling pathway	IEA
GO:0042127	regulation of cell population proliferation	ISS
GO:0045665	negative regulation of neuron differentiation	ISS
GO:0045892	negative regulation of transcription, DNA-templated	IDA
GO:0045892	negative regulation of transcription, DNA-templated	IBA
GO:0045944	positive regulation of transcription by RNA polymerase II	IEA
GO:0048512	circadian behavior	IEA
GO:0048856	anatomical structure development	IBA
GO:0060235	lens induction in camera-type eye	IEA
GO:0061074	regulation of neural retina development	ISS
GO:0070306	lens fiber cell differentiation	ISS
GO:0097402	neuroblast migration	ISS
GO:1901987	regulation of cell cycle phase transition	ISS
GO:1902692	regulation of neuroblast proliferation	ISS
GO:1902742	apoptotic process involved in development	ISS
GO:1990086	lens fiber cell apoptotic process	ISS
GO:2000177	regulation of neural precursor cell proliferation	ISS

GO:Cellular Component

GO ID	GO Term	Evidence
GO:0000790	nuclear chromatin	ISA
GO:0005634	nucleus	IBA
GO:0005667	transcription factor complex	IBA

Reactome Pathway

Reactome ID	Reactome Term	Evidence

Drugs and compounds information

ID	Drug Name	Action	PubMed
D015655	1-Methyl-4-phenylpyridinium	1-Methyl-4-phenylpyridinium results in increased expression of SIX3 mRNA	24810058
C459179	4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	[NOG protein co-treated with belinostat co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide] results in decreased expression of SIX3 mRNA	27188386
C459179	4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	[NOG protein co-treated with entinostat co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide] results in decreased expression of SIX3 mRNA	27188386
C459179	4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	[NOG protein co-treated with mercuric bromide co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide] results in decreased expression of SIX3 mRNA	27188386
C459179	4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	[NOG protein co-treated with Panobinostat co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide] results in decreased expression of SIX3 mRNA	27188386
C459179	4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	[NOG protein co-treated with p-Chloromercuribenzoic Acid co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide] results in decreased expression of SIX3 mRNA	27188386
C459179	4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	[NOG protein co-treated with Phenylmercuric Acetate co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide] results in decreased expression of SIX3 mRNA	27188386
C459179	4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	[NOG protein co-treated with trichostatin A co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide] results in decreased expression of SIX3 mRNA	27188386
C459179	4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	[NOG protein co-treated with Valproic Acid co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide] results in decreased expression of SIX3 mRNA	27188386
C459179	4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	[NOG protein co-treated with Vorinostat co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide] results in decreased expression of SIX3 mRNA	27188386
C496492	abrine	abrine results in decreased expression of SIX3 mRNA	31054353
D000643	Ammonium Chloride	Ammonium Chloride affects the expression of SIX3 mRNA	16483693
D018501	Antirheumatic Agents	Antirheumatic Agents results in decreased expression of SIX3 mRNA	24449571
D001280	Atrazine	Atrazine results in decreased expression of SIX3 mRNA	25929836
D001280	Atrazine	Atrazine results in increased expression of SIX3 mRNA	22378314
C487081	belinostat	belinostat results in decreased expression of SIX3 mRNA	26272509
C487081	belinostat	[NOG protein co-treated with belinostat co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide] results in decreased expression of SIX3 mRNA	27188386
C543008	bis(4-hydroxyphenyl)sulfone	bis(4-hydroxyphenyl)sulfone affects the expression of SIX3 mRNA	30951980
C006780	bisphenol A	bisphenol A affects the methylation of SIX3 promoter	27334623
C006780	bisphenol A	bisphenol A results in decreased expression of SIX3 mRNA	25181051
C000611646	bisphenol F	bisphenol F affects the expression of SIX3 mRNA	30951980
C018475	butyraldehyde	butyraldehyde results in increased expression of SIX3 mRNA	26079696
D019256	Cadmium Chloride	Cadmium Chloride results in decreased methylation of SIX3 promoter	22457795
D019256	Cadmium Chloride	Cadmium Chloride results in decreased expression of SIX3 mRNA	21337468
D002220	Carbamazepine	Carbamazepine affects the expression of SIX3 mRNA	25979313
D003300	Copper	Copper deficiency results in increased expression of SIX3 mRNA	26033743
D003471	Cuprizone	Cuprizone results in increased expression of SIX3 mRNA	26577399
D004051	Diethylhexyl Phthalate	Diethylhexyl Phthalate results in decreased expression of SIX3 mRNA	31163220
C516138	dorsomorphin	[NOG protein co-treated with belinostat co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide] results in decreased expression of SIX3 mRNA	27188386
C516138	dorsomorphin	[NOG protein co-treated with entinostat co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide] results in decreased expression of SIX3 mRNA	27188386
C516138	dorsomorphin	[NOG protein co-treated with mercuric bromide co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide] results in decreased expression of SIX3 mRNA	27188386
C516138	dorsomorphin	[NOG protein co-treated with Panobinostat co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide] results in decreased expression of SIX3 mRNA	27188386
C516138	dorsomorphin	[NOG protein co-treated with p-Chloromercuribenzoic Acid co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide] results in decreased expression of SIX3 mRNA	27188386
C516138	dorsomorphin	[NOG protein co-treated with Phenylmercuric Acetate co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide] results in decreased expression of SIX3 mRNA	27188386
C516138	dorsomorphin	[NOG protein co-treated with trichostatin A co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide] results in decreased expression of SIX3 mRNA	27188386
C516138	dorsomorphin	[NOG protein co-treated with Valproic Acid co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide] results in decreased expression of SIX3 mRNA	27188386
C516138	dorsomorphin	[NOG protein co-treated with Vorinostat co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide] results in decreased expression of SIX3 mRNA	27188386
C118739	entinostat	entinostat results in decreased expression of SIX3 mRNA	26272509
C118739	entinostat	[NOG protein co-treated with entinostat co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide] results in decreased expression of SIX3 mRNA	27188386
D004958	Estradiol	Estradiol results in increased expression of SIX3 mRNA	20068009
D000431	Ethanol	Ethanol affects the splicing of SIX3 mRNA	30319688
D006861	Hydrogen Peroxide	Hydrogen Peroxide affects the expression of SIX3 mRNA	21179406
D008070	Lipopolysaccharides	Lipopolysaccharides results in decreased methylation of SIX3 gene	21212295
D008070	Lipopolysaccharides	Lipopolysaccharides results in increased methylation of SIX3 gene	21212295
D008070	Lipopolysaccharides	[Tetrachlorodibenzodioxin co-treated with Lipopolysaccharides] results in decreased methylation of SIX3 gene	21212295
D008070	Lipopolysaccharides	[Tetrachlorodibenzodioxin co-treated with Lipopolysaccharides] results in increased methylation of SIX3 gene	21212295
D018021	Lithium Chloride	Lithium Chloride results in decreased expression of SIX3 mRNA	17506889
D008345	Manganese	Manganese results in increased expression of SIX3 mRNA	17175027
C025340	manganese chloride	manganese chloride results in increased expression of SIX3 mRNA	17175027
C042720	mercuric bromide	[NOG protein co-treated with mercuric bromide co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide] results in decreased expression of SIX3 mRNA	27188386
D008694	Methamphetamine	Methamphetamine results in decreased expression of SIX3 mRNA	29802913
C517284	monomethyl phthalate	monomethyl phthalate affects the expression of SIX3 mRNA	26924002
D000077767	Panobinostat	[NOG protein co-treated with Panobinostat co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide] results in decreased expression of SIX3 mRNA	27188386
D000077767	Panobinostat	Panobinostat results in decreased expression of SIX3 mRNA	26272509
D020245	p-Chloromercuribenzoic Acid	[NOG protein co-treated with p-Chloromercuribenzoic Acid co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide] results in decreased expression of SIX3 mRNA	27188386
D020245	p-Chloromercuribenzoic Acid	p-Chloromercuribenzoic Acid results in decreased expression of SIX3 mRNA	26272509
C046012	pentanal	pentanal results in increased expression of SIX3 mRNA	26079696
D010634	Phenobarbital	Phenobarbital affects the methylation of SIX3 gene	19233941
D010662	Phenylmercuric Acetate	[NOG protein co-treated with Phenylmercuric Acetate co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide] results in decreased expression of SIX3 mRNA	27188386
D010662	Phenylmercuric Acetate	Phenylmercuric Acetate results in decreased expression of SIX3 mRNA	26272509
C006253	pirinixic acid	[pirinixic acid binds to and results in increased activity of PPARA protein] which results in increased expression of SIX3 mRNA	19710929
D013749	Tetrachlorodibenzodioxin	Tetrachlorodibenzodioxin affects the expression of SIX3 mRNA	24058054
D013749	Tetrachlorodibenzodioxin	[Tetrachlorodibenzodioxin co-treated with Lipopolysaccharides] results in decreased methylation of SIX3 gene	21212295
D013749	Tetrachlorodibenzodioxin	[Tetrachlorodibenzodioxin co-treated with Lipopolysaccharides] results in increased methylation of SIX3 gene	21212295
D013749	Tetrachlorodibenzodioxin	Tetrachlorodibenzodioxin results in decreased methylation of SIX3 gene	21212295
D014212	Tretinoin	Tretinoin results in decreased expression of SIX3 mRNA	21934132; 23724009;
D014212	Tretinoin	[Tretinoin co-treated with SIX3 protein] results in increased expression of BMPR1A mRNA	16341014
D014212	Tretinoin	[Tretinoin co-treated with SIX3 protein] results in increased expression of PAX6 mRNA	16341014
D014212	Tretinoin	[Tretinoin co-treated with SIX3 protein] results in increased expression of SIX3 mRNA	16341014; 16341014;
C012589	trichostatin A	[NOG protein co-treated with trichostatin A co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide] results in decreased expression of SIX3 mRNA	27188386
C012589	trichostatin A	trichostatin A results in decreased expression of SIX3 mRNA	24935251; 26272509;
D014635	Valproic Acid	[NOG protein co-treated with Valproic Acid co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide] results in decreased expression of SIX3 mRNA	27188386
D014635	Valproic Acid	Valproic Acid affects the expression of SIX3 mRNA	24849673; 25979313;
D014635	Valproic Acid	Valproic Acid results in decreased expression of SIX3 mRNA	19101580; 23179753; 24383497; 24935251; 26272509; 28001369;
D014635	Valproic Acid	Valproic Acid affects the expression of SIX3 mRNA	17963808
D000077337	Vorinostat	[NOG protein co-treated with Vorinostat co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide] results in decreased expression of SIX3 mRNA	27188386
D000077337	Vorinostat	Vorinostat results in decreased expression of SIX3 mRNA	26272509
D019287	Zinc Sulfate	Zinc Sulfate results in decreased expression of SIX3 mRNA	17506889

Functional annotations

Keywords

Keyword ID	Keyword Term
KW-0217	Developmental protein
KW-0225	Disease mutation
KW-0238	DNA-binding
KW-0370	Holoprosencephaly
KW-0371	Homeobox
KW-0539	Nucleus
KW-1185	Reference proteome
KW-0678	Repressor
KW-0804	Transcription
KW-0805	Transcription regulation

Interpro

InterPro ID	InterPro Term
IPR009057	Homeobox-like_sf
IPR001356	Homeobox_dom
IPR031701	SIX1_SD
IPR032949	SIX3

PROSITE

PROSITE ID	PROSITE Term
PS50071	HOMEOBOX_2

Pfam

Pfam ID	Pfam Term
PF00046	Homeodomain
PF16878	SIX1_SD

Gene: SIX3

Basic information

Gene expression information

Gene expression in different tissues (GTEx V7)

Protein structural annotations

3D structure in PDB database

There is no related protein structure for this gene.

Protein disorder information

Orthologous information

Other genetic variants/mutations

Disease or phenotype associated information

Gene Ontology (GO)/biological pathways

GO:Molecular Function

GO:Biological Process

GO:Cellular Component

Reactome Pathway

Drugs and compounds information

Functional annotations

Keywords

Interpro

PROSITE

Pfam

Protein-protein interaction

Protein-miRNA interaction