SOX9 Gene: Master Regulator of Chondrogenesis and Sex Determination
Comprehensive guide to SOX9 (SRY-box transcription factor 9): genomic data, expression, mutations, and clinical significance in campomelic dysplasia and cancers.
Gene Information Card
| Symbol | SOX9 |
|---|---|
| Full Name | SRY-box transcription factor 9 |
| Gene Type | protein-coding |
| Chromosomal Location | 17q24.3 |
| NCBI Gene ID | 6662 ncbi.nlm.nih.gov/gene/6662 |
| Ensembl ID | ENSG00000125398 |
| UniProt ID | P48436 |
| OMIM ID | 608160 |
| HGNC ID | 11206 |
| Aliases | CMPD1, SRA1, SRXX4, SRXY1, TFG |
Description
SOX9 (SRY-box transcription factor 9) is a member of the SOX (SRY-related HMG-box) family of transcription factors. It plays a critical role in skeletal development, particularly chondrogenesis, and is essential for male sex determination. SOX9 regulates the expression of genes involved in cartilage formation, such as COL2A1, and is also implicated in several cancers and developmental disorders. Mutations in SOX9 cause campomelic dysplasia, a severe skeletal malformation syndrome often accompanied by sex reversal in XY individuals.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Campomelic dysplasia | Haploinsufficiency or dominant-negative mutations in SOX9 disrupt chondrocyte differentiation and skeletal development. | OMIM #114290; ClinVar |
| Sex reversal (46,XY) | Loss-of-function mutations in SOX9 impair testis determination, leading to male-to-female sex reversal. | OMIM #608160; ClinVar |
| Colorectal cancer | SOX9 overexpression promotes tumor progression and metastasis via Wnt/β-catenin signaling. | COSMIC; PubMed studies |
| Chondrosarcoma | SOX9 is overexpressed and maintains the undifferentiated phenotype of chondrosarcoma cells. | COSMIC; PubMed studies |
| Prostate cancer | SOX9 contributes to tumor growth and invasion through regulation of androgen receptor signaling. | COSMIC; PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.4 | Medium |
| Cartilage | High | High |
| Lung | 8.2 | Low |
| Colon | 6.5 | Low |
| Kidney | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SW1353 (chondrosarcoma) | High | Chondrocytic cell line |
| HCT116 (colorectal carcinoma) | Medium | SOX9 expression linked to Wnt pathway |
| MCF7 (breast cancer) | Low | Minimal expression |
| A549 (lung carcinoma) | Low | Low expression |
| PC3 (prostate cancer) | Medium | Androgen-independent line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1043G>A (p.Arg348Gln) | Missense | Rare | Dominant-negative effect; associated with campomelic dysplasia |
| c.1081C>T (p.Arg361Ter) | Nonsense | Rare | Loss-of-function; causes haploinsufficiency |
| c.507delC (p.Leu170SerfsTer14) | Frameshift | Rare | Loss-of-function; severe phenotype |
| c.1A>G (p.Met1?) | Start codon loss | Rare | Loss-of-function; no protein produced |
| c.1180G>A (p.Gly394Ser) | Missense | Rare | Dominant-negative; campomelic dysplasia |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., nonsense, frameshift) reduce SOX9 protein levels, leading to haploinsufficiency. This is the primary mechanism for campomelic dysplasia and sex reversal.
Gain of Function (GOF)
Gain-of-function mutations are rare but have been reported in some cancers, leading to increased SOX9 activity and oncogenic transformation.
Dominant Negative (DN)
Dominant-negative mutations (e.g., missense in HMG domain) produce a mutant protein that interferes with the wild-type SOX9 function, often causing more severe phenotypes.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • chromatin binding | • protein dimerization activity |
| • regulation of transcription by RNA polymerase II | • chondrocyte differentiation |
| • male gonad development | • skeletal system development |
| • cell fate commitment | • positive regulation of transcription by RNA polymerase II |
Pathways
• Chondrocyte differentiation (KEGG: hsa04550)
• Wnt signaling pathway (KEGG: hsa04310)
• TGF-beta signaling pathway (KEGG: hsa04350)
• Sex determination (Reactome: R-HSA-5619507)
Protein Summary
SOX9 is a 509-amino acid transcription factor containing a high-mobility group (HMG) DNA-binding domain. It binds to the consensus sequence (A/T)(A/T)CAA(A/T)G and regulates target genes such as COL2A1, COL9A1, and AMH. SOX9 forms dimers and interacts with other transcription factors (e.g., SF1, WT1) to control tissue-specific gene expression. It is essential for chondrocyte differentiation and testis development. Post-translational modifications include phosphorylation and acetylation, which modulate its activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SOX9 Knockout HEK293 Cell Line | EDJ-KQ928 | Human | 6662 | Details Get a Quote |
| SOX9 Knockout A-549 Cell Line | EDJ-KQ19903 | Human | 6662 | Details Get a Quote |
| SOX9 Knockout HCT 116 Cell Line | EDJ-KQ19904 | Human | 6662 | Details Get a Quote |
| SOX9 Knockout HeLa Cell Line | EDJ-KQ19905 | Human | 6662 | Details Get a Quote |
| Sox9 Knockout HBZY-1 Cell Line | EDJ-KZ489 | Rat | 140586 | Details Get a Quote |
| SOX9 Knock-in H1 Cell Line | EDC90736 | Human | 6662 | Details Get a Quote |
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