CleftGeneDB-Search

Gene: Sox9

Basic information

Tag	Content
Uniprot ID	Q04887; Q8C7L2; Q91ZK2; Q99KQ0;
Entrez ID	20682
Genbank protein ID	AAH04064.1; AAH23796.1; AAH34264.1; CAA79483.1; BAC34018.1; AAH23808.1; AAH24958.1; BAC26830.1; AAL16093.1; AAH23953.1;
Genbank nucleotide ID	NM_011448.4
Ensembl protein ID	ENSMUSP00000000579
Ensembl nucleotide ID	ENSMUSG00000000567
Gene name	Transcription factor SOX-9
Gene symbol	Sox9
Organism	Mus musculus
NCBI taxa ID	10090
Cleft type	CPO
Developmental stage	E14.5
Data sources	Manually collected
Reference	12878728; 11371614; 11857796;
Functional description	Transcription factor that plays a key role in chondrocytes differentiation and skeletal development (PubMed:10319868, PubMed:11371614, PubMed:12414734, PubMed:15132997, PubMed:18415932, PubMed:20940257, PubMed:28263186). Specifically binds the 5'-ACAAAG-3' DNA motif present in enhancers and super-enhancers and promotes expression of genes important for chondrogenesis, including cartilage matrix protein-coding genes COL2A1, COL4A2, COL9A1, COL11A2 and ACAN, SOX5 and SOX6 (PubMed:9119111, PubMed:10805756, PubMed:12414734, PubMed:15694126, PubMed:17525254, PubMed:26146088, PubMed:26150426, PubMed:26910618, PubMed:28263186). Also binds to some promoter regions (PubMed:20940257). Plays a central role in successive steps of chondrocyte differentiation (PubMed:11371614, PubMed:12414734, PubMed:22421045). Absolutely required for precartilaginous condensation, the first step in chondrogenesis during which skeletal progenitors differentiate into prechondrocytes (PubMed:11371614, PubMed:12414734). Together with SOX5 and SOX6, required for overt chondrogenesis when condensed prechondrocytes differentiate into early stage chondrocytes, the second step in chondrogenesis (PubMed:11371614, PubMed:12414734, PubMed:15529345). Later, required to direct hypertrophic maturation and block osteoblast differentiation of growth plate chondrocytes: maintains chondrocyte columnar proliferation, delays prehypertrophy and then prevents osteoblastic differentiation of chondrocytes by lowering beta-catenin (CTNNB1) signaling and RUNX2 expression (PubMed:22421045, PubMed:31121357). Also required for chondrocyte hypertrophy, both indirectly, by keeping the lineage fate of chondrocytes, and directly, by remaining present in upper hypertrophic cells and transactivating COL10A1 along with MEF2C (PubMed:21367821, PubMed:22421045). Low lipid levels are the main nutritional determinant for chondrogenic commitment of skeletal progenitor cells: when lipids levels are low, FOXO (FOXO1 and FOXO3) transcription factors promote expression of SOX9, which induces chondrogenic commitment and suppresses fatty acid oxidation (PubMed:32103177). Mechanistically, helps, but is not required, to remove epigenetic signatures of transcriptional repression and deposit active promoter and enhancer marks at chondrocyte-specific genes (PubMed:30021842). Acts in cooperation with the Hedgehog pathway-dependent GLI (GLI1 and GLI3) transcription factors (PubMed:29659575). In addition to cartilage development, also acts as a regulator of proliferation and differentiation in epithelial stem/progenitor cells: involved in the lung epithelium during branching morphogenesis, by balancing proliferation and differentiation and regulating the extracellular matrix (PubMed:24191021). Controls epithelial branching during kidney development (PubMed:21212101).
Sequence	MNLLDPFMKM TDEQEKGLSG APSPTMSEDS AGSPCPSGSG SDTENTRPQE NTFPKGEPDL 60 KKESEEDKFP VCIREAVSQV LKGYDWTLVP MPVRVNGSSK NKPHVKRPMN AFMVWAQAAR 120 RKLADQYPHL HNAELSKTLG KLWRLLNESE KRPFVEEAER LRVQHKKDHP DYKYQPRRRK 180 SVKNGQAEAE EATEQTHISP NAIFKALQAD SPHSSSGMSE VHSPGEHSGQ SQGPPTPPTT 240 PKTDVQAGKV DLKREGRPLA EGGRQPPIDF RDVDIGELSS DVISNIETFD VNEFDQYLPP 300 NGHPGVPATH GQVTYTGSYG ISSTAPTPAT AGHVWMSKQQ APPPPPQQPP QAPQAPQAPP 360 QQQAPPQQPQ APQQQQAHTL TTLSSEPGQS QRTHIKTEQL SPSHYSEQQQ HSPQQISYSP 420 FNLPHYSPSY PPITRSQYDY ADHQNSGSYY SHAAGQGSGL YSTFTYMNPA QRPMYTPIAD 480 TSGVPSIPQT HSPQHWEQPV YTQLTRP 507

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

PDB ID
4S2Q

Protein disorder information

Orthologous information

Relation	Gene symbol	Entrez ID	UniProt ID	Cleft type	Developmental stage	Species	Evidence	Details
1:1 ortholog	SOX9	106503295	A0A452FKA9			Capra hircus	Prediction	More>>
1:1 ortholog	SOX9	6662	P48436			Homo sapiens	Publication	More>>
1:1 ortholog	Sox9	20682	Q04887	CPO	E14.5	Mus musculus	Publication	More>>
1:1 ortholog	SOX9		H2QDR6			Pan troglodytes	Prediction	More>>
1:1 ortholog	SOX9	396840	F1RV30			Sus scrofa	Prediction	More>>
1:1 ortholog	Sox9	140586	F1LYL9			Rattus norvegicus	Prediction	More>>
1:1 ortholog	sox9a	60641	Q9DFH2			Danio rerio	Prediction	More>>

Other genetic variants/mutations

ID	Variant	Type	Disease	Chromosome\Coordinate	Evidence
rs217705772	p.Val250Ile	missense variant	-	NC_000077.6:g.112784734G>A	UniProt
rs222636079	p.Pro346Gln	missense variant	-	NC_000077.6:g.112785023C>A	UniProt

Gene Ontology (GO)/biological pathways

GO:Molecular Function

GO ID	GO Term	Evidence
GO:0000976	transcription regulatory region sequence-specific DNA binding	IDA
GO:0000978	RNA polymerase II cis-regulatory region sequence-specific DNA binding	ISS
GO:0000978	RNA polymerase II cis-regulatory region sequence-specific DNA binding	ISO
GO:0000978	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA
GO:0000981	DNA-binding transcription factor activity, RNA polymerase II-specific	ISO
GO:0000981	DNA-binding transcription factor activity, RNA polymerase II-specific	IDA
GO:0000987	cis-regulatory region sequence-specific DNA binding	IDA
GO:0001228	DNA-binding transcription activator activity, RNA polymerase II-specific	ISS
GO:0001228	DNA-binding transcription activator activity, RNA polymerase II-specific	ISO
GO:0001228	DNA-binding transcription activator activity, RNA polymerase II-specific	IDA
GO:0001228	DNA-binding transcription activator activity, RNA polymerase II-specific	IBA
GO:0003682	chromatin binding	ISS
GO:0003682	chromatin binding	ISO
GO:0003700	DNA-binding transcription factor activity	ISO
GO:0003700	DNA-binding transcription factor activity	IMP
GO:0003700	DNA-binding transcription factor activity	IDA
GO:0005515	protein binding	IPI
GO:0008013	beta-catenin binding	IPI
GO:0034236	protein kinase A catalytic subunit binding	ISO
GO:0035326	cis-regulatory region binding	ISO
GO:0035326	cis-regulatory region binding	IDA
GO:0043425	bHLH transcription factor binding	ISO
GO:0043565	sequence-specific DNA binding	IDA
GO:0044212	transcription regulatory region DNA binding	IDA
GO:0097157	pre-mRNA intronic 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	IBA
GO:0000122	negative regulation of transcription by RNA polymerase II	IMP
GO:0001501	skeletal system development	ISS
GO:0001501	skeletal system development	ISO
GO:0001502	cartilage condensation	ISS
GO:0001502	cartilage condensation	IMP
GO:0001503	ossification	IEP
GO:0001658	branching involved in ureteric bud morphogenesis	IEP
GO:0001708	cell fate specification	IMP
GO:0001837	epithelial to mesenchymal transition	IMP
GO:0001894	tissue homeostasis	IMP
GO:0001934	positive regulation of protein phosphorylation	IDA
GO:0001934	positive regulation of protein phosphorylation	IMP
GO:0001942	hair follicle development	IMP
GO:0002009	morphogenesis of an epithelium	IBA
GO:0002053	positive regulation of mesenchymal cell proliferation	IMP
GO:0002062	chondrocyte differentiation	ISS
GO:0002062	chondrocyte differentiation	IBA
GO:0002062	chondrocyte differentiation	IEP
GO:0002063	chondrocyte development	IMP
GO:0002683	negative regulation of immune system process	IMP
GO:0003170	heart valve development	IMP
GO:0003179	heart valve morphogenesis	IMP
GO:0003180	aortic valve morphogenesis	ISO
GO:0003188	heart valve formation	IMP
GO:0003203	endocardial cushion morphogenesis	IMP
GO:0003413	chondrocyte differentiation involved in endochondral bone morphogenesis	ISS
GO:0003413	chondrocyte differentiation involved in endochondral bone morphogenesis	ISO
GO:0003415	chondrocyte hypertrophy	IMP
GO:0006334	nucleosome assembly	ISS
GO:0006334	nucleosome assembly	ISO
GO:0006338	chromatin remodeling	ISS
GO:0006338	chromatin remodeling	ISO
GO:0006355	regulation of transcription, DNA-templated	TAS
GO:0006357	regulation of transcription by RNA polymerase II	IDA
GO:0007010	cytoskeleton organization	IMP
GO:0007165	signal transduction	IMP
GO:0007173	epidermal growth factor receptor signaling pathway	IDA
GO:0007219	Notch signaling pathway	IDA
GO:0007283	spermatogenesis	IGI
GO:0007417	central nervous system development	IBA
GO:0007417	central nervous system development	IEP
GO:0007507	heart development	IMP
GO:0007507	heart development	IBA
GO:0008284	positive regulation of cell population proliferation	ISO
GO:0008284	positive regulation of cell population proliferation	IMP
GO:0008285	negative regulation of cell population proliferation	IMP
GO:0008584	male gonad development	ISO
GO:0008584	male gonad development	IMP
GO:0008584	male gonad development	IEP
GO:0008584	male gonad development	IGI
GO:0010468	regulation of gene expression	IDA
GO:0010564	regulation of cell cycle process	ISS
GO:0010564	regulation of cell cycle process	ISO
GO:0010628	positive regulation of gene expression	ISO
GO:0010628	positive regulation of gene expression	IGI
GO:0010629	negative regulation of gene expression	IMP
GO:0010634	positive regulation of epithelial cell migration	ISO
GO:0010634	positive regulation of epithelial cell migration	ISS
GO:0010634	positive regulation of epithelial cell migration	IMP
GO:0014032	neural crest cell development	IMP
GO:0014036	neural crest cell fate specification	ISS
GO:0014068	positive regulation of phosphatidylinositol 3-kinase signaling	IMP
GO:0019100	male germ-line sex determination	IMP
GO:0019933	cAMP-mediated signaling	ISS
GO:0019933	cAMP-mediated signaling	ISO
GO:0030154	cell differentiation	IMP
GO:0030155	regulation of cell adhesion	IMP
GO:0030198	extracellular matrix organization	IMP
GO:0030238	male sex determination	IGI
GO:0030279	negative regulation of ossification	ISO
GO:0030279	negative regulation of ossification	IMP
GO:0030502	negative regulation of bone mineralization	IMP
GO:0030850	prostate gland development	IEP
GO:0030857	negative regulation of epithelial cell differentiation	IMP
GO:0030858	positive regulation of epithelial cell differentiation	IMP
GO:0030879	mammary gland development	IEP
GO:0030903	notochord development	IEP
GO:0030916	otic vesicle formation	IMP
GO:0031018	endocrine pancreas development	IMP
GO:0032331	negative regulation of chondrocyte differentiation	IMP
GO:0032332	positive regulation of chondrocyte differentiation	ISO
GO:0032332	positive regulation of chondrocyte differentiation	IDA
GO:0032332	positive regulation of chondrocyte differentiation	IMP
GO:0032332	positive regulation of chondrocyte differentiation	IBA
GO:0032808	lacrimal gland development	IMP
GO:0034504	protein localization to nucleus	IDA
GO:0035019	somatic stem cell population maintenance	IMP
GO:0035622	intrahepatic bile duct development	IMP
GO:0042127	regulation of cell population proliferation	IMP
GO:0043066	negative regulation of apoptotic process	ISO
GO:0043066	negative regulation of apoptotic process	IMP
GO:0043491	protein kinase B signaling	IMP
GO:0045165	cell fate commitment	IGI
GO:0045595	regulation of cell differentiation	IMP
GO:0045662	negative regulation of myoblast differentiation	IDA
GO:0045732	positive regulation of protein catabolic process	IDA
GO:0045892	negative regulation of transcription, DNA-templated	ISO
GO:0045892	negative regulation of transcription, DNA-templated	IDA
GO:0045892	negative regulation of transcription, DNA-templated	IMP
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	IMP
GO:0045944	positive regulation of transcription by RNA polymerase II	IGI
GO:0045944	positive regulation of transcription by RNA polymerase II	IBA
GO:0046533	negative regulation of photoreceptor cell differentiation	IGI
GO:0048709	oligodendrocyte differentiation	IMP
GO:0048709	oligodendrocyte differentiation	IBA
GO:0048873	homeostasis of number of cells within a tissue	IMP
GO:0050679	positive regulation of epithelial cell proliferation	IMP
GO:0050680	negative regulation of epithelial cell proliferation	IMP
GO:0051216	cartilage development	IMP
GO:0060008	Sertoli cell differentiation	IMP
GO:0060009	Sertoli cell development	IGI
GO:0060018	astrocyte fate commitment	IGI
GO:0060041	retina development in camera-type eye	IGI
GO:0060174	limb bud formation	IEP
GO:0060221	retinal rod cell differentiation	IGI
GO:0060350	endochondral bone morphogenesis	IMP
GO:0060441	epithelial tube branching involved in lung morphogenesis	IGI
GO:0060441	epithelial tube branching involved in lung morphogenesis	IMP
GO:0060487	lung epithelial cell differentiation	IMP
GO:0060512	prostate gland morphogenesis	IMP
GO:0060517	epithelial cell proliferation involved in prostatic bud elongation	IMP
GO:0060532	bronchus cartilage development	IMP
GO:0060534	trachea cartilage development	IMP
GO:0060729	intestinal epithelial structure maintenance	IMP
GO:0060784	regulation of cell proliferation involved in tissue homeostasis	IMP
GO:0061036	positive regulation of cartilage development	ISO
GO:0061036	positive regulation of cartilage development	IDA
GO:0061046	regulation of branching involved in lung morphogenesis	IMP
GO:0061138	morphogenesis of a branching epithelium	IGI
GO:0061138	morphogenesis of a branching epithelium	IMP
GO:0061145	lung smooth muscle development	IMP
GO:0065003	protein-containing complex assembly	ISS
GO:0065003	protein-containing complex assembly	ISO
GO:0070168	negative regulation of biomineral tissue development	ISO
GO:0070168	negative regulation of biomineral tissue development	IMP
GO:0070371	ERK1 and ERK2 cascade	IDA
GO:0070384	Harderian gland development	IMP
GO:0071260	cellular response to mechanical stimulus	IDA
GO:0071300	cellular response to retinoic acid	IDA
GO:0071347	cellular response to interleukin-1	IEA
GO:0071364	cellular response to epidermal growth factor stimulus	IDA
GO:0071504	cellular response to heparin	IDA
GO:0071560	cellular response to transforming growth factor beta stimulus	ISO
GO:0071560	cellular response to transforming growth factor beta stimulus	IEP
GO:0071599	otic vesicle development	IEP
GO:0071773	cellular response to BMP stimulus	ISS
GO:0072034	renal vesicle induction	IMP
GO:0072170	metanephric tubule development	IEP
GO:0072189	ureter development	IGI
GO:0072190	ureter urothelium development	IEP
GO:0072193	ureter smooth muscle cell differentiation	IMP
GO:0072197	ureter morphogenesis	IGI
GO:0072289	metanephric nephron tubule formation	IGI
GO:0090090	negative regulation of canonical Wnt signaling pathway	IDA
GO:0090103	cochlea morphogenesis	IMP
GO:0090184	positive regulation of kidney development	IGI
GO:0090190	positive regulation of branching involved in ureteric bud morphogenesis	IMP
GO:0097065	anterior head development	IMP
GO:0098609	cell-cell adhesion	IMP
GO:1901203	positive regulation of extracellular matrix assembly	IMP
GO:1902732	positive regulation of chondrocyte proliferation	ISO
GO:1902894	negative regulation of pri-miRNA transcription by RNA polymerase II	ISO
GO:2000020	positive regulation of male gonad development	ISS
GO:2000020	positive regulation of male gonad development	ISO
GO:2000138	positive regulation of cell proliferation involved in heart morphogenesis	IMP
GO:2000741	positive regulation of mesenchymal stem cell differentiation	ISS
GO:2000741	positive regulation of mesenchymal stem cell differentiation	ISO
GO:2000794	regulation of epithelial cell proliferation involved in lung morphogenesis	IMP
GO:2001054	negative regulation of mesenchymal cell apoptotic process	IMP

GO:Cellular Component

GO ID	GO Term	Evidence
GO:0005634	nucleus	ISO
GO:0005634	nucleus	IDA
GO:0005654	nucleoplasm	ISO
GO:0005667	transcription factor complex	ISO
GO:0005667	transcription factor complex	IPI
GO:0032991	protein-containing complex	ISS
GO:0032991	protein-containing complex	ISO
GO:0044798	nuclear transcription factor complex	IDA

Reactome Pathway

Reactome ID	Reactome Term	Evidence
R-MMU-162582	Signal Transduction	IEA
R-MMU-195721	Signaling by WNT	IEA
R-MMU-201681	TCF dependent signaling in response to WNT	IEA
R-MMU-212436	Generic Transcription Pathway	IEA
R-MMU-3769402	Deactivation of the beta-catenin transactivating complex	IEA
R-MMU-73857	RNA Polymerase II Transcription	IEA
R-MMU-74160	Gene expression (Transcription)	IEA
R-MMU-8878166	Transcriptional regulation by RUNX2	IEA

Functional annotations

Keywords

Keyword ID	Keyword Term
KW-0002	3D-structure
KW-0007	Acetylation
KW-0010	Activator
KW-0221	Differentiation
KW-0238	DNA-binding
KW-1017	Isopeptide bond
KW-0539	Nucleus
KW-0597	Phosphoprotein
KW-1185	Reference proteome
KW-0804	Transcription
KW-0805	Transcription regulation
KW-0832	Ubl conjugation

Interpro

InterPro ID	InterPro Term
IPR009071	HMG_box_dom
IPR036910	HMG_box_dom_sf
IPR029548	SOX-9
IPR022151	Sox_N

PROSITE

PROSITE ID	PROSITE Term
PS50118	HMG_BOX_2

Pfam

Pfam ID	Pfam Term
PF00505	HMG_box
PF12444	Sox_N

Gene: Sox9

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

Protein disorder information

Orthologous information

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