CleftGeneDB-Search

Gene: Gli2

Basic information

Tag	Content
Uniprot ID	Q0VGT2; E9PYJ4;
Entrez ID	14633
Genbank protein ID	AAH85190.1
Genbank nucleotide ID	NM_001081125.1
Ensembl protein ID	ENSMUSP00000054837
Ensembl nucleotide ID	ENSMUSG00000048402
Gene name	Zinc finger protein GLI2
Gene symbol	Gli2
Organism	Mus musculus
NCBI taxa ID	10090
Cleft type	CPO
Developmental stage	E11.5, E13.0, E14.5
Data sources	Manually collected
Reference	27802276; 9006072;
Functional description	Functions as transcription regulator in the hedgehog (Hh) pathway (PubMed:9006072). Functions as transcriptional activator (PubMed:10806483). May also function as transcriptional repressor (PubMed:10433919). Requires STK36 for full transcriptional activator activity (PubMed:10806483). Binds to the DNA sequence 5'-GAACCACCCA-3' which is part of the TRE-2S regulatory element (By similarity). Is involved in the smoothened (SHH) signaling pathway (PubMed:10433919). Required for normal skeleton development (PubMed:9006072).
Sequence	METSAPAPAL EKKEAKSGLL EDSSFPDPGK KACPLAVAAA VAAHGVPQQL LPAFHAPLPI 60 DMRHQEGRYH YDPHSVHSVH GPPTLSGSPV ISDISLIRLS PHPAGPGESP FSAHHPYVNP 120 HMEHYLRSVH SSPTLSMISA ARGLSPADVA HEHLKERGLF SLAAPGTNPS DYYHQMTLMA 180 SHPTPYGDLL MQSGGAASAP HLHDYLNPVD ASRFSSPRVT PRLSRKRALS ISPLSDASLD 240 LQRMIRTSPN SLVAYINNSR SSSAASGSYG HLSAGALSPA FTFPHPINPV AYQQILSQQR 300 GLGSAFGHTP PLIQPSPTFL AQQPMTLTSI STMPTQLSSS SSNCLNDANQ NKQNSESAVS 360 STVNPITIHK RSKVKTEAEG LRPASPLGLT QEQLADLKED LDRDDCKQEA EVVIYETNCH 420 WADCTKEYDT QEQLVHHINN EHIHGEKKEF VCRWQACTRE QKPFKAQYML VVHMRRHTGE 480 KPHKCTFEGC SKAYSRLENL KTHLRSHTGE KPYVCEHEGC NKAFSNASDR AKHQNRTHSN 540 EKPYICKIPG CTKRYTDPSS LRKHVKTVHG PDAHVTKKQR NDVHVRAPLL KENGDNEASA 600 EPGGRGPEES VEASSTSHTV EDCLHIKAIK TESSGLCQSS PGAQSSCSSE PSPLGSAPNN 660 DSGMEMPGTG PGSLGDLTAL ADTCPGADTS ALAAPSTGGL QLRKHMSTVH RFEQLKREKL 720 KSLKDSCSWA GPAPHTRNTK LPPLPVNGSV LENFNNTGGG GPAGLLPSQR LPELTEVTML 780 SQLQERRDSS TSTMSSAYTV SRRSSGISPY FSSRRSSEAS PLGGLRPHNA SSADSYDPIS 840 TDASRRSSEA SQCSGGGPGL LNLTPAQQYN LRAKYAAATG GPPPTPLPGL DRVSLRTRLA 900 LLDAPERALP GACPHPLGPR RGSDGPTYSH GHGHGYAGAA PAFPHEGPNS STRRASDPVR 960 RPDPLILPRV QRFHSTHNMN PGSLPPCADR RGLHVQSHPS VDSNLTRNAY SPRPPSINEN 1020 VVMEAVAAGV DGPGLECDLG LVEDELVLPD DVVQYIKAHT GGTLDDGIRQ GYPTEGTGFP 1080 ENSKLPSPGL QGHRRLAAAD SNMGPSAPGL GGCQLSYSPS SNLNKSNMPV QWNEVSSGTV 1140 DALPTQVKPP PFPHSNLAVV QQKPAFGQYP GYNPQSVQSS SGGLDSTQPH LQLRGAPSAS 1200 RGSYTQQPRQ PAAGSQCLGM SAAMSPQASY SQAHPQLSPN IVSGSLNQFS PSCSNMAAKP 1260 SHLGLPQQME VVPNATIMNG HQREHGVPNS SLAAVSQPHP VLSYPQQDSY QQGSNLLSSH 1320 QPGFMESQQN AGFGLMQPRP PLEPNTASRH RGVRSGQQQL YARTTGQAMV TSANQETAEA 1380 MPKGPAGTMV SLAPQPSQDT GRAQDQNTLY YYGQIHMYEQ NGGCPAVQPQ PPQPQACSDS 1440 IQPEPLPSPG VNQVSSTVDS QLLEPPQIDF DAIMDDGDHS SLFSGALSPT LLHNLSQNSS 1500 RLTTPRNSLT LPSIPAGISN MAVGDMSSML TSLAEESKFL NMMT 1544

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 during embryonic days (E11.5~E18.5) ~ adult days (Ps) in the lip and palate tissues. (X-axis: days, Y-axis: tissues)

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	Developmental stage	Species	Evidence	Details
1:1 ortholog	GLI2	102178402	A0A452F0Y2			Capra hircus	Prediction	More>>
1:1 ortholog	GLI2	2736	P10070			Homo sapiens	Publication	More>>
1:1 ortholog	Gli2	14633	Q0VGT2	CPO	E11.5, E13.0, E14.5	Mus musculus	Publication	More>>
1:1 ortholog	GLI2		A0A2I3SWC0			Pan troglodytes	Prediction	More>>
1:1 ortholog	GLI2	100520334	F1RXX4			Sus scrofa	Prediction	More>>
1:1 ortholog	GLI2		G1SDR5			Oryctolagus cuniculus	Prediction	More>>
1:1 ortholog	Gli2	304729	F1M2B7			Rattus norvegicus	Prediction	More>>

Identified variants/mutations related to cleft phenotype

Gene symbol	Significant Variants/SNPS	Methods	PubMed ID
GLI2	c.2125del; p.Leu709Trpfs*15 (heterozygous)	targeted NGS custom gene panel and Sanger sequencing	30583238
GLI2	c.2684C>T; p.Ala895Val; c.4350G>T; p.Gln1450His; and c.4622C>A; p.Ser1541Tyr (triple compound heterozygous)	WES and Sanger sequencing	31386309

Other genetic variants/mutations

ID	Variant	Type	Disease	Chromosome\Coordinate	Evidence
rs30698944	p.His44Gln	missense variant	-	NC_000067.6:g.119002044G>T	UniProt
rs30812533	p.Ala113Thr	missense variant	-	NC_000067.6:g.118868087C>T	UniProt
rs224809238	p.His308Asn	missense variant	-	NC_000067.6:g.118854569G>T	UniProt
rs245497331	p.Ser610Thr	missense variant	-	NC_000067.6:g.118841992C>G	UniProt
rs30729325	p.Ala681Asp	missense variant	-	NC_000067.6:g.118840454G>T	UniProt
rs227651587	p.Ser707Thr	missense variant	-	NC_000067.6:g.118840376C>G	UniProt
rs30729326	p.Val709Met	missense variant	-	NC_000067.6:g.118840371C>T	UniProt
rs30729327	p.Ser726Pro	missense variant	-	NC_000067.6:g.118840320A>G	UniProt
rs249160291	p.Asn753Ser	missense variant	-	NC_000067.6:g.118838162T>C	UniProt
rs241557064	p.Glu776Gln	missense variant	-	NC_000067.6:g.118838094C>G	UniProt
rs252449840	p.Ala912Thr	missense variant	-	NC_000067.6:g.118837686C>T	UniProt
rs215991378	p.Ala937Val	missense variant	-	NC_000067.6:g.118837610G>A	UniProt
rs229290480	p.Ser997Asn	missense variant	-	NC_000067.6:g.118837430C>T	UniProt
rs254231015	p.Cys1037Tyr	missense variant	-	NC_000067.6:g.118837310C>T	UniProt
rs247391032	p.Thr1063Ala	missense variant	-	NC_000067.6:g.118837233T>C	UniProt
rs239819333	p.Arg1402Gln	missense variant	-	NC_000067.6:g.118836215C>T	UniProt

Gene Ontology (GO)/biological pathways

GO:Molecular Function

GO ID	GO Term	Evidence
GO:0000978	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA
GO:0001228	DNA-binding transcription activator activity, RNA polymerase II-specific	IDA
GO:0003682	chromatin binding	IDA
GO:0003700	DNA-binding transcription factor activity	ISO
GO:0003700	DNA-binding transcription factor activity	IDA
GO:0005515	protein binding	IPI
GO:0008134	transcription factor binding	ISO
GO:0008134	transcription factor binding	IPI
GO:0008270	zinc ion binding	ISO
GO:0043565	sequence-specific DNA binding	ISO
GO:0043565	sequence-specific DNA binding	IDA
GO:0044212	transcription regulatory region DNA binding	IDA
GO:1990841	promoter-specific chromatin binding	ISS
GO:1990841	promoter-specific chromatin binding	ISO
GO:1990841	promoter-specific chromatin binding	IDA

GO:Biological Process

GO ID	GO Term	Evidence
GO:0000122	negative regulation of transcription by RNA polymerase II	ISO
GO:0000122	negative regulation of transcription by RNA polymerase II	IGI
GO:0001501	skeletal system development	IMP
GO:0001649	osteoblast differentiation	ISO
GO:0001649	osteoblast differentiation	IGI
GO:0001701	in utero embryonic development	IMP
GO:0001822	kidney development	IGI
GO:0002009	morphogenesis of an epithelium	IMP
GO:0002062	chondrocyte differentiation	IGI
GO:0002076	osteoblast development	IDA
GO:0002076	osteoblast development	IMP
GO:0007224	smoothened signaling pathway	ISO
GO:0007224	smoothened signaling pathway	IMP
GO:0007224	smoothened signaling pathway	IGI
GO:0007389	pattern specification process	IGI
GO:0007389	pattern specification process	IMP
GO:0007411	axon guidance	IMP
GO:0007418	ventral midline development	IGI
GO:0007418	ventral midline development	IMP
GO:0007442	hindgut morphogenesis	IGI
GO:0007442	hindgut morphogenesis	IMP
GO:0007507	heart development	IGI
GO:0008284	positive regulation of cell population proliferation	IGI
GO:0008284	positive regulation of cell population proliferation	IMP
GO:0009913	epidermal cell differentiation	ISO
GO:0009952	anterior/posterior pattern specification	IGI
GO:0009953	dorsal/ventral pattern formation	IGI
GO:0009954	proximal/distal pattern formation	IGI
GO:0021508	floor plate formation	IMP
GO:0021513	spinal cord dorsal/ventral patterning	IMP
GO:0021513	spinal cord dorsal/ventral patterning	IGI
GO:0021517	ventral spinal cord development	IMP
GO:0021522	spinal cord motor neuron differentiation	IMP
GO:0021696	cerebellar cortex morphogenesis	IGI
GO:0021696	cerebellar cortex morphogenesis	IMP
GO:0021775	smoothened signaling pathway involved in ventral spinal cord interneuron specification	IGI
GO:0021776	smoothened signaling pathway involved in spinal cord motor neuron cell fate specification	IGI
GO:0021904	dorsal/ventral neural tube patterning	IMP
GO:0021904	dorsal/ventral neural tube patterning	IDA
GO:0021915	neural tube development	IMP
GO:0021938	smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation	IGI
GO:0021938	smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation	IMP
GO:0021965	spinal cord ventral commissure morphogenesis	IMP
GO:0021983	pituitary gland development	IGI
GO:0030154	cell differentiation	IMP
GO:0030324	lung development	IGI
GO:0030324	lung development	IMP
GO:0030879	mammary gland development	IMP
GO:0030902	hindbrain development	IGI
GO:0030902	hindbrain development	IMP
GO:0031069	hair follicle morphogenesis	ISO
GO:0032331	negative regulation of chondrocyte differentiation	IMP
GO:0035295	tube development	IGI
GO:0042475	odontogenesis of dentin-containing tooth	IGI
GO:0042475	odontogenesis of dentin-containing tooth	IMP
GO:0042733	embryonic digit morphogenesis	IMP
GO:0043066	negative regulation of apoptotic process	IDA
GO:0045666	positive regulation of neuron differentiation	IGI
GO:0045740	positive regulation of DNA replication	ISO
GO:0045879	negative regulation of smoothened signaling pathway	IGI
GO:0045893	positive regulation of transcription, DNA-templated	ISO
GO:0045893	positive regulation of transcription, DNA-templated	IDA
GO:0045893	positive regulation of transcription, DNA-templated	IMP
GO:0045944	positive regulation of transcription by RNA polymerase II	ISO
GO:0045944	positive regulation of transcription by RNA polymerase II	IDA
GO:0045944	positive regulation of transcription by RNA polymerase II	IGI
GO:0048566	embryonic digestive tract development	IMP
GO:0048589	developmental growth	IMP
GO:0048646	anatomical structure formation involved in morphogenesis	IGI
GO:0048666	neuron development	IMP
GO:0048754	branching morphogenesis of an epithelial tube	IMP
GO:0048856	anatomical structure development	IGI
GO:0048856	anatomical structure development	IMP
GO:0060032	notochord regression	IGI
GO:0060322	head development	IMP
GO:0060513	prostatic bud formation	IMP
GO:0060603	mammary gland duct morphogenesis	IMP
GO:0060831	smoothened signaling pathway involved in dorsal/ventral neural tube patterning	IGI
GO:0071407	cellular response to organic cyclic compound	IDA
GO:0090103	cochlea morphogenesis	IMP
GO:0098586	cellular response to virus	ISO

GO:Cellular Component

GO ID	GO Term	Evidence
GO:0005634	nucleus	ISO
GO:0005634	nucleus	IDA
GO:0005654	nucleoplasm	ISO
GO:0005654	nucleoplasm	TAS
GO:0005730	nucleolus	ISO
GO:0005737	cytoplasm	IGI
GO:0005737	cytoplasm	IDA
GO:0005829	cytosol	TAS
GO:0005929	cilium	IDA
GO:0005930	axoneme	IDA
GO:0016020	membrane	IDA
GO:0016607	nuclear speck	IDA
GO:0031514	motile cilium	IDA
GO:0097542	ciliary tip	IDA

Reactome Pathway

Reactome ID	Reactome Term	Evidence
R-MMU-162582	Signal Transduction	IEA
R-MMU-5358351	Signaling by Hedgehog	IEA
R-MMU-5610787	Hedgehog 'off' state	IEA
R-MMU-5632684	Hedgehog 'on' state	IEA

Functional annotations

Keywords

Keyword ID	Keyword Term
KW-0007	Acetylation
KW-0010	Activator
KW-0966	Cell projection
KW-0969	Cilium
KW-0963	Cytoplasm
KW-0217	Developmental protein
KW-0238	DNA-binding
KW-0479	Metal-binding
KW-0539	Nucleus
KW-0597	Phosphoprotein
KW-1185	Reference proteome
KW-0677	Repeat
KW-0678	Repressor
KW-0804	Transcription
KW-0805	Transcription regulation
KW-0862	Zinc
KW-0863	Zinc-finger

Interpro

InterPro ID	InterPro Term
IPR043359	GLI-like
IPR036236	Znf_C2H2_sf
IPR013087	Znf_C2H2_type

PROSITE

PROSITE ID	PROSITE Term
PS00028	ZINC_FINGER_C2H2_1
PS50157	ZINC_FINGER_C2H2_2

Pfam

Pfam ID	Pfam Term
PF00096	zf-C2H2

Gene: Gli2

Basic information

Gene expression information

Gene expression during embryonic days (E11.5~E18.5) ~ adult days (Ps) in the lip and palate tissues. (X-axis: days, Y-axis: tissues)

Protein structural annotations

3D structure in PDB database

There is no related protein structure for this gene.

Protein disorder information

Orthologous information

Identified variants/mutations related to cleft phenotype

Other genetic variants/mutations

Gene Ontology (GO)/biological pathways

GO:Molecular Function

GO:Biological Process

GO:Cellular Component

Reactome Pathway

Functional annotations

Keywords

Interpro

PROSITE

Pfam

Protein-protein interaction

Protein-miRNA interaction