Details for: SOX9

Gene ID: 6662

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: SOX9

Ensembl ID: ENSG00000125398

Description: SRY-box transcription factor 9

Cell Significance Landscape

Associated with

  • Deactivation of the beta-catenin transactivating complex
    (R-HSA-3769402)
  • Developmental biology
    (R-HSA-1266738)
  • Gene expression (transcription)
    (R-HSA-74160)
  • Generic transcription pathway
    (R-HSA-212436)
  • Mitf-m-regulated melanocyte development
    (R-HSA-9730414)
  • Rna polymerase ii transcription
    (R-HSA-73857)
  • Signaling by wnt
    (R-HSA-195721)
  • Tcf dependent signaling in response to wnt
    (R-HSA-201681)
  • Transcriptional and post-translational regulation of mitf-m expression and activity
    (R-HSA-9856649)
  • Transcriptional regulation by runx2
    (R-HSA-8878166)
  • Transcriptional regulation of testis differentiation
    (R-HSA-9690406)
  • Anterior head development
    (GO:0097065)
  • Aortic valve morphogenesis
    (GO:0003180)
  • Astrocyte fate commitment
    (GO:0060018)
  • Beta-catenin binding
    (GO:0008013)
  • Bhlh transcription factor binding
    (GO:0043425)
  • Bone mineralization
    (GO:0030282)
  • Branching involved in ureteric bud morphogenesis
    (GO:0001658)
  • Bronchus cartilage development
    (GO:0060532)
  • Camp-mediated signaling
    (GO:0019933)
  • Canonical wnt signaling pathway
    (GO:0060070)
  • Cartilage condensation
    (GO:0001502)
  • Cartilage development
    (GO:0051216)
  • Cell-cell adhesion
    (GO:0098609)
  • Cell fate specification
    (GO:0001708)
  • Cell proliferation involved in heart morphogenesis
    (GO:0061323)
  • Cellular response to bmp stimulus
    (GO:0071773)
  • Cellular response to epidermal growth factor stimulus
    (GO:0071364)
  • Cellular response to heparin
    (GO:0071504)
  • Cellular response to interleukin-1
    (GO:0071347)
  • Cellular response to mechanical stimulus
    (GO:0071260)
  • Cellular response to retinoic acid
    (GO:0071300)
  • Cellular response to transforming growth factor beta stimulus
    (GO:0071560)
  • Chondrocyte differentiation
    (GO:0002062)
  • Chondrocyte differentiation involved in endochondral bone morphogenesis
    (GO:0003413)
  • Chondrocyte hypertrophy
    (GO:0003415)
  • Chromatin
    (GO:0000785)
  • Chromatin binding
    (GO:0003682)
  • Chromatin remodeling
    (GO:0006338)
  • Cis-regulatory region sequence-specific dna binding
    (GO:0000987)
  • Cochlea morphogenesis
    (GO:0090103)
  • Cytoskeleton organization
    (GO:0007010)
  • Dna-binding transcription activator activity, rna polymerase ii-specific
    (GO:0001228)
  • Dna-binding transcription factor activity
    (GO:0003700)
  • Dna-binding transcription factor activity, rna polymerase ii-specific
    (GO:0000981)
  • Endocardial cushion morphogenesis
    (GO:0003203)
  • Endocrine pancreas development
    (GO:0031018)
  • Epidermal growth factor receptor signaling pathway
    (GO:0007173)
  • Epithelial cell proliferation involved in prostatic bud elongation
    (GO:0060517)
  • Epithelial to mesenchymal transition
    (GO:0001837)
  • Epithelial tube branching involved in lung morphogenesis
    (GO:0060441)
  • Erk1 and erk2 cascade
    (GO:0070371)
  • Extracellular matrix assembly
    (GO:0085029)
  • Glandular epithelial cell differentiation
    (GO:0002067)
  • Glial cell fate specification
    (GO:0021780)
  • Growth plate cartilage chondrocyte growth
    (GO:0003430)
  • Hair follicle development
    (GO:0001942)
  • Harderian gland development
    (GO:0070384)
  • Heart development
    (GO:0007507)
  • Heart valve development
    (GO:0003170)
  • Heart valve formation
    (GO:0003188)
  • Heart valve morphogenesis
    (GO:0003179)
  • Intestinal epithelial cell differentiation
    (GO:0060575)
  • Intestinal epithelial structure maintenance
    (GO:0060729)
  • Intrahepatic bile duct development
    (GO:0035622)
  • Lacrimal gland development
    (GO:0032808)
  • Limb bud formation
    (GO:0060174)
  • Lung smooth muscle development
    (GO:0061145)
  • Male germ-line sex determination
    (GO:0019100)
  • Male gonad development
    (GO:0008584)
  • Mammary gland development
    (GO:0030879)
  • Mesenchymal cell apoptotic process
    (GO:0097152)
  • Mesenchymal cell proliferation
    (GO:0010463)
  • Metanephric nephron tubule formation
    (GO:0072289)
  • Morphogenesis of a branching epithelium
    (GO:0061138)
  • Morphogenesis of an epithelium
    (GO:0002009)
  • Negative regulation of apoptotic process
    (GO:0043066)
  • Negative regulation of beta-catenin-tcf complex assembly
    (GO:1904864)
  • Negative regulation of biomineral tissue development
    (GO:0070168)
  • Negative regulation of bone mineralization
    (GO:0030502)
  • Negative regulation of canonical wnt signaling pathway
    (GO:0090090)
  • Negative regulation of chondrocyte differentiation
    (GO:0032331)
  • Negative regulation of dna-templated transcription
    (GO:0045892)
  • Negative regulation of epithelial cell differentiation
    (GO:0030857)
  • Negative regulation of epithelial cell proliferation
    (GO:0050680)
  • Negative regulation of fatty acid oxidation
    (GO:0046322)
  • Negative regulation of gene expression
    (GO:0010629)
  • Negative regulation of immune system process
    (GO:0002683)
  • Negative regulation of mesenchymal cell apoptotic process
    (GO:2001054)
  • Negative regulation of mirna transcription
    (GO:1902894)
  • Negative regulation of myoblast differentiation
    (GO:0045662)
  • Negative regulation of ossification
    (GO:0030279)
  • Negative regulation of osteoblast differentiation
    (GO:0045668)
  • Negative regulation of photoreceptor cell differentiation
    (GO:0046533)
  • Negative regulation of transcription by rna polymerase ii
    (GO:0000122)
  • Neural crest cell development
    (GO:0014032)
  • Neural crest cell fate specification
    (GO:0014036)
  • Neuron fate specification
    (GO:0048665)
  • Notch signaling pathway
    (GO:0007219)
  • Notochord development
    (GO:0030903)
  • Nucleoplasm
    (GO:0005654)
  • Nucleosome assembly
    (GO:0006334)
  • Nucleus
    (GO:0005634)
  • Oligodendrocyte differentiation
    (GO:0048709)
  • Otic vesicle formation
    (GO:0030916)
  • Positive regulation of branching involved in ureteric bud morphogenesis
    (GO:0090190)
  • Positive regulation of cartilage development
    (GO:0061036)
  • Positive regulation of cell population proliferation
    (GO:0008284)
  • Positive regulation of cell proliferation involved in heart morphogenesis
    (GO:2000138)
  • Positive regulation of chondrocyte differentiation
    (GO:0032332)
  • Positive regulation of chondrocyte proliferation
    (GO:1902732)
  • Positive regulation of dna-templated transcription
    (GO:0045893)
  • Positive regulation of epithelial cell differentiation
    (GO:0030858)
  • Positive regulation of epithelial cell migration
    (GO:0010634)
  • Positive regulation of epithelial cell proliferation
    (GO:0050679)
  • Positive regulation of extracellular matrix assembly
    (GO:1901203)
  • Positive regulation of gene expression
    (GO:0010628)
  • Positive regulation of kidney development
    (GO:0090184)
  • Positive regulation of male gonad development
    (GO:2000020)
  • Positive regulation of mesenchymal cell proliferation
    (GO:0002053)
  • Positive regulation of mesenchymal stem cell differentiation
    (GO:2000741)
  • Positive regulation of protein catabolic process
    (GO:0045732)
  • Positive regulation of stem cell proliferation
    (GO:2000648)
  • Positive regulation of transcription by rna polymerase ii
    (GO:0045944)
  • Pre-mrna intronic binding
    (GO:0097157)
  • Prostate gland development
    (GO:0030850)
  • Protein-containing complex
    (GO:0032991)
  • Protein-containing complex assembly
    (GO:0065003)
  • Protein binding
    (GO:0005515)
  • Protein kinase a catalytic subunit binding
    (GO:0034236)
  • Protein localization to nucleus
    (GO:0034504)
  • Regulation of apoptotic process
    (GO:0042981)
  • Regulation of branching involved in lung morphogenesis
    (GO:0061046)
  • Regulation of cell adhesion
    (GO:0030155)
  • Regulation of cell cycle process
    (GO:0010564)
  • Regulation of cell population proliferation
    (GO:0042127)
  • Regulation of cell proliferation involved in tissue homeostasis
    (GO:0060784)
  • Regulation of epithelial cell proliferation involved in lung morphogenesis
    (GO:2000794)
  • Renal vesicle induction
    (GO:0072034)
  • Response to fatty acid
    (GO:0070542)
  • Response to organic cyclic compound
    (GO:0014070)
  • Retina development in camera-type eye
    (GO:0060041)
  • Retinal rod cell differentiation
    (GO:0060221)
  • Rna polymerase ii cis-regulatory region sequence-specific dna binding
    (GO:0000978)
  • Sequence-specific dna binding
    (GO:0043565)
  • Sequence-specific double-stranded dna binding
    (GO:1990837)
  • Sertoli cell development
    (GO:0060009)
  • Sertoli cell differentiation
    (GO:0060008)
  • Signal transduction
    (GO:0007165)
  • Skeletal system development
    (GO:0001501)
  • Somatic stem cell population maintenance
    (GO:0035019)
  • Spermatogenesis
    (GO:0007283)
  • Stem cell proliferation
    (GO:0072089)
  • Tissue homeostasis
    (GO:0001894)
  • Trachea cartilage development
    (GO:0060534)
  • Transcription by rna polymerase ii
    (GO:0006366)
  • Transcription regulator complex
    (GO:0005667)
  • Type i pneumocyte differentiation
    (GO:0060509)
  • Ureter morphogenesis
    (GO:0072197)
  • Ureter smooth muscle cell differentiation
    (GO:0072193)
  • Ureter urothelium development
    (GO:0072190)

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • intestinal tuft cell CL0019032
    CSI 17.7
    rCSI 27.05%
    PRS 94.34
  • mucous neck cell CL0000651
    CSI 16.24
    rCSI 23.4%
    PRS 95.25
  • epithelial cell of lower respiratory tract CL0002632
    CSI 13.77
    rCSI 10.67%
    PRS 95.09
  • forebrain radial glial cell CL0013000
    CSI 11.09
    rCSI 35.58%
    PRS 93.01
  • intrahepatic cholangiocyte CL0002538
    CSI 10.35
    rCSI 24.84%
    PRS 93.04
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 10.23
    rCSI 27.57%
    PRS 94.73
  • ciliated epithelial cell CL0000067
    CSI 9.97
    rCSI 8.76%
    PRS 86.08
  • pancreatic ductal cell CL0002079
    CSI 9.13
    rCSI 17.76%
    PRS 94.38
  • tuft cell of colon CL0009041
    CSI 7.94
    rCSI 18.5%
    PRS 94.29
  • conjunctival epithelial cell CL1000432
    CSI 7.04
    rCSI 10.75%
    PRS 92.43
  • neural crest cell CL0011012
    CSI 7.01
    rCSI 5.54%
    PRS 87.87
  • bronchus fibroblast of lung CL2000093
    CSI 6.89
    rCSI 5.6%
    PRS 92.83
  • respiratory basal cell CL0002633
    CSI 6.58
    rCSI 6.82%
    PRS 94.53
  • colon goblet cell CL0009039
    CSI 6.35
    rCSI 15.1%
    PRS 94.32
  • stem cell CL0000034
    CSI 5.42
    rCSI 5.22%
    PRS 90.29
  • mucus secreting cell CL0000319
    CSI 5.39
    rCSI 8.56%
    PRS 96.46
  • glioblast CL0000030
    CSI 5.33
    rCSI 8.5%
    PRS 87.08
  • mammary gland epithelial cell CL0002327
    CSI 5.25
    rCSI 18.43%
    PRS 96.16
  • goblet cell CL0000160
    CSI 5.04
    rCSI 4.76%
    PRS 91.3
  • epithelial cell CL0000066
    CSI 4.94
    rCSI 7.59%
    PRS 82.65
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 4.65
    rCSI 5.97%
    PRS 90.1
  • enterocyte of epithelium of large intestine CL0002071
    CSI 4.47
    rCSI 23.45%
    PRS 94.45
  • lung secretory cell CL1000272
    CSI 4.31
    rCSI 10.68%
    PRS 94.54
  • intestinal crypt stem cell of colon CL0009043
    CSI 4.27
    rCSI 32.09%
    PRS 96.36
  • brush cell CL0002204
    CSI 4.24
    rCSI 8.39%
    PRS 94.96
  • radial glial cell CL0000681
    CSI 4.19
    rCSI 5.83%
    PRS 91.88
  • glial cell CL0000125
    CSI 3.88
    rCSI 14.76%
    PRS 87.93
  • intestine goblet cell CL0019031
    CSI 3.7
    rCSI 3.29%
    PRS 91.33
  • basal-myoepithelial cell of mammary gland CL0002324
    CSI 3.65
    rCSI 6.9%
    PRS 97.06
  • mature astrocyte CL0002627
    CSI 3.59
    rCSI 15.24%
    PRS 87.9
  • paneth cell CL0000510
    CSI 3.44
    rCSI 5.08%
    PRS 96.71
  • colon epithelial cell CL0011108
    CSI 3.39
    rCSI 3.55%
    PRS 91.36
  • multi-ciliated epithelial cell CL0005012
    CSI 3.27
    rCSI 3.27%
    PRS 88.49
  • macroglial cell CL0000126
    CSI 3.14
    rCSI 8.08%
    PRS 90.08
  • ependymal cell CL0000065
    CSI 3.1
    rCSI 6.28%
    PRS 78.43
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 3.08
    rCSI 3.55%
    PRS 86.86
  • lung ciliated cell CL1000271
    CSI 3.08
    rCSI 3.56%
    PRS 88.94
  • epithelial cell of lung CL0000082
    CSI 3.01
    rCSI 2.5%
    PRS 94.23
  • Mueller cell CL0000636
    CSI 2.98
    rCSI 6.81%
    PRS 88.1
  • paneth cell of epithelium of small intestine CL1000343
    CSI 2.95
    rCSI 8.27%
    PRS 95.11
  • keratocyte CL0002363
    CSI 2.92
    rCSI 7.01%
    PRS 93.91
  • chondrocyte CL0000138
    CSI 2.84
    rCSI 4.52%
    PRS 89.74
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 2.81
    rCSI 8.31%
    PRS 92.89
  • acinar cell CL0000622
    CSI 2.78
    rCSI 4.08%
    PRS 96.82
  • pancreatic acinar cell CL0002064
    CSI 2.71
    rCSI 3.6%
    PRS 95.38
  • retinal pigment epithelial cell CL0002586
    CSI 2.67
    rCSI 5.31%
    PRS 90.59
  • ionocyte CL0005006
    CSI 2.67
    rCSI 2.86%
    PRS 94.24
  • enteroendocrine cell CL0000164
    CSI 2.59
    rCSI 3.54%
    PRS 91.48
  • duct epithelial cell CL0000068
    CSI 2.55
    rCSI 3.74%
    PRS 95.92
  • myoepithelial cell CL0000185
    CSI 2.54
    rCSI 6.42%
    PRS 94.91
  • fallopian tube secretory epithelial cell CL4030006
    CSI 2.48
    rCSI 2.39%
    PRS 92.19
  • basal cell CL0000646
    CSI 2.44
    rCSI 3.26%
    PRS 90.96
  • BEST4+ enteroycte CL4030026
    CSI 2.4
    rCSI 2.98%
    PRS 92.77
  • choroid plexus epithelial cell CL0000706
    CSI 2.4
    rCSI 3.92%
    PRS 87.86
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 2.38
    rCSI 6.14%
    PRS 91.61
  • colonocyte CL1000347
    CSI 2.37
    rCSI 3.39%
    PRS 91.6
  • luminal epithelial cell of mammary gland CL0002326
    CSI 2.34
    rCSI 4.25%
    PRS 96.51
  • transit amplifying cell of colon CL0009011
    CSI 2.33
    rCSI 2.74%
    PRS 93.36
  • pulmonary ionocyte CL0017000
    CSI 2.28
    rCSI 2.77%
    PRS 95.68
  • foveolar cell of stomach CL0002179
    CSI 2.27
    rCSI 4.83%
    PRS 94.64
  • pancreatic epsilon cell CL0005019
    CSI 2.17
    rCSI 10.14%
    PRS 95.53
  • M cell of gut CL0000682
    CSI 2.01
    rCSI 2.14%
    PRS 94.83
  • Bergmann glial cell CL0000644
    CSI 1.95
    rCSI 2.66%
    PRS 87.35
  • neural progenitor cell CL0011020
    CSI 1.91
    rCSI 8.4%
    PRS 84.05
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.86
    rCSI 4.23%
    PRS 87.26
  • intestinal epithelial cell CL0002563
    CSI 1.85
    rCSI 1.93%
    PRS 91.3
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.7
    rCSI 3.01%
    PRS 82.56
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.66
    rCSI 3.72%
    PRS 83.5
  • squamous epithelial cell CL0000076
    CSI 1.63
    rCSI 3.87%
    PRS 90.31
  • transit amplifying cell of small intestine CL0009012
    CSI 1.61
    rCSI 7.09%
    PRS 95.41
  • small intestine goblet cell CL1000495
    CSI 1.58
    rCSI 3.46%
    PRS 94.74
  • glandular epithelial cell CL0000150
    CSI 1.55
    rCSI 4.08%
    PRS 97.7
  • enterocyte CL0000584
    CSI 1.54
    rCSI 2.48%
    PRS 90.61
  • basal cell of prostate epithelium CL0002341
    CSI 1.49
    rCSI 4.31%
    PRS 94.87
  • corneal epithelial cell CL0000575
    CSI 1.49
    rCSI 4.25%
    PRS 94.16
  • transit amplifying cell CL0009010
    CSI 1.36
    rCSI 2.08%
    PRS 95.71
  • P/D1 enteroendocrine cell CL0002268
    CSI 1.32
    rCSI 7.18%
    PRS 94.86
  • acinar cell of salivary gland CL0002623
    CSI 1.16
    rCSI 26.94%
    PRS 96.83
  • mesenchymal cell CL0008019
    CSI 1.13
    rCSI 2.88%
    PRS 89.38
  • luminal cell of prostate epithelium CL0002340
    CSI 0.83
    rCSI 4.44%
    PRS 95.99
  • peptic cell CL0000155
    CSI 0.72
    rCSI 7.1%
    PRS 95.95
  • tracheobronchial serous cell CL0019001
    CSI 0.59
    rCSI 2.54%
    PRS 95.01
  • respiratory goblet cell CL0002370
    CSI 0.36
    rCSI 3.92%
    PRS 95.38
  • enterocyte of epithelium of small intestine CL1000334
    CSI 0.35
    rCSI 5.41%
    PRS 94.65

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.

Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [SOX9](/details-gene/6662) (SRY-box transcription factor 9) is a master regulatory transcription factor essential for the development and homeostasis of numerous tissues. As a member of the SOX (SRY-related HMG-box) family, it plays a pivotal role in chondrogenesis, skeletal development, and male sex determination. Clinically, mutations in [SOX9](/details-gene/6662) are associated with campomelic dysplasia ([114290](https://omim.org/entry/114290)), a severe skeletal malformation syndrome that is often accompanied by 46,XY disorder of sex development ([Link](https://doi.org/10.1038/372525a0)). Expression analysis reveals that **Overall**, [SOX9](/details-gene/6662) is a highly significant marker in a variety of specialized epithelial and progenitor cell populations, including [intestinal tuft cell](/details-cell/CL0019032), [mucous neck cell](/details-cell/CL0000651), and [intestinal crypt stem cell of small intestine](/details-cell/CL0009017), underscoring its broad importance in tissue maintenance and cell fate specification. ## Cellular Roles and Expression Landscape The expression profile of [SOX9](/details-gene/6662) highlights its fundamental role in governing progenitor cell populations and specialized epithelial linings across diverse organ systems. **Overall**, the gene shows exceptionally high significance in cells responsible for secretion, sensory functions, and tissue renewal. It is a top marker for [intestinal tuft cell](/details-cell/CL0019032) (CSI: 17.70) and [mucous neck cell](/details-cell/CL0000651) (CSI: 16.24), indicating a key function in the gastrointestinal tract's specialized epithelial cell identity. Its prominence in various stem and progenitor cells, such as [forebrain radial glial cell](/details-cell/CL0013000) (CSI: 11.09), [intestinal crypt stem cell of small intestine](/details-cell/CL0009017) (CSI: 10.23), [neural crest cell](/details-cell/CL0011012) (CSI: 7.01), and [respiratory basal cell](/details-cell/CL0002633) (CSI: 6.58), is consistent with its established role as a master regulator of cell fate and differentiation during development. Furthermore, significant expression in [epithelial cell of lower respiratory tract](/details-cell/CL0002632), [intrahepatic cholangiocyte](/details-cell/CL0002538), and [pancreatic ductal cell](/details-cell/CL0002079) reinforces its importance in the maintenance and function of ductal and glandular structures. This widespread yet specific expression pattern suggests that [SOX9](/details-gene/6662) is a conserved transcriptional regulator essential for establishing and maintaining epithelial barriers and progenitor niches in multiple organs. ## Pathways and Molecular Function [SOX9](/details-gene/6662) functions as a sequence-specific [DNA-binding transcription factor](/details-cell/GO:0003700) ([GO:0000981](https://www.ebi.ac.uk/QuickGO/term/GO:0000981)) that localizes to the [nucleus](/details-cell/GO:0005634) and binds to [chromatin](/details-cell/GO:0000785) to regulate target gene expression. Its functional annotations reveal an extensive involvement in developmental biology ([R-HSA-1266738](https://reactome.org/content/detail/R-HSA-1266738)). The most well-characterized role of [SOX9](/details-gene/6662) is in skeletal formation, as evidenced by its connection to processes like [skeletal system development](/details-cell/GO:0001501), [cartilage development](/details-cell/GO:0051216), and [chondrocyte differentiation](/details-cell/GO:0002062). Its critical function in this context is underscored by its ability to associate with co-activators to drive chondrocyte-specific gene expression ([Link](https://doi.org/10.1074/jbc.m303471200)) and its regulation by pathways such as [transcriptional regulation by RUNX2](/details-cell/R-HSA-8878166) ([R-HSA-8878166](https://reactome.org/content/detail/R-HSA-8878166)). Equally important is its function as a key determinant of male sex, where it participates in [male gonad development](/details-cell/GO:0008584) and the [transcriptional regulation of testis differentiation](/details-cell/R-HSA-9690406) ([R-HSA-9690406](https://reactome.org/content/detail/R-HSA-9690406)), a role confirmed by the sex reversal phenotype observed in patients with [SOX9](/details-gene/6662) mutations ([Link](https://doi.org/10.1016/0092-8674(94)90041-8)). [SOX9](/details-gene/6662) acts as a crucial node integrating multiple major signaling pathways. It is a component of the [canonical Wnt signaling pathway](/details-cell/GO:0060070) ([GO:0060070](https://www.ebi.ac.uk/QuickGO/term/GO:0060070)) and is involved in the [deactivation of the beta-catenin transactivating complex](/details-cell/R-HSA-3769402) ([R-HSA-3769402](https://reactome.org/content/detail/R-HSA-3769402)). It also responds to BMP, EGF, and TGF-beta stimuli, placing it at the convergence of signals that control cell proliferation, differentiation, and processes like [epithelial to mesenchymal transition](/details-cell/GO:0001837) ([GO:0001837](https://www.ebi.ac.uk/QuickGO/term/GO:0001837)). ## Research Directions The central role of [SOX9](/details-gene/6662) in regulating stem cells and epithelial biology suggests it is a critical factor in both normal tissue repair and pathological conditions like cancer and fibrosis. ### Proposed Hypotheses: 1. **Role in Gastrointestinal Cancer:** Given its high expression in [intestinal crypt stem cell of small intestine](/details-cell/CL0009017) and its documented function in promoting cell proliferation ([GO:0008284](https://www.ebi.ac.uk/QuickGO/term/GO:0008284)), dysregulation of [SOX9](/details-gene/6662) may be a key event in the initiation and progression of colorectal cancer by locking intestinal progenitors in a proliferative, undifferentiated state. 2. **Driver of Liver Fibrosis:** The high significance of [SOX9](/details-gene/6662) in [intrahepatic cholangiocyte](/details-cell/CL0002538) and its involvement in the response to TGF-beta and EMT suggest that during chronic liver injury, [SOX9](/details-gene/6662) may drive the pathological activation and proliferation of cholangiocytes, contributing to biliary fibrosis. ### Experimental Approach: To test the hypothesis that [SOX9](/details-gene/6662) is a driver of liver fibrosis (Hypothesis 2), a conditional knockout mouse model could be utilized. Mice with a floxed *Sox9* allele (*Sox9*fl/fl) could be crossed with a cholangiocyte-specific Cre-driver line (e.g., Krt19-CreERT2). Following induction of liver fibrosis via a model such as bile duct ligation (BDL) or carbon tetrachloride (CCl4) administration, the effects of cholangiocyte-specific *Sox9* deletion could be assessed. Endpoints would include histological quantification of fibrosis (Sirius Red staining), analysis of hepatic function markers, and single-cell RNA sequencing of liver non-parenchymal cells to define how the loss of [SOX9](/details-gene/6662) in cholangiocytes alters their transcriptional state and their crosstalk with hepatic stellate cells, the primary collagen-producing cells. ### Therapeutic Potential: As a transcription factor, [SOX9](/details-gene/6662) presents a challenging therapeutic target for direct small-molecule inhibition. However, its role as a driver of proliferation and cell fate plasticity in various cancers and fibrotic diseases makes it a high-value target. The therapeutic strategy would focus on **inhibition** rather than activation. Given its critical role in the homeostasis of healthy tissues like the intestine, systemic inhibition would likely cause severe toxicity. Therefore, therapeutic approaches would require targeted delivery, such as lipid nanoparticle-encapsulated siRNAs directed to specific cell types (e.g., tumor cells or activated fibroblasts), or focus on inhibiting key upstream regulators or essential downstream effectors of [SOX9](/details-gene/6662) that are more amenable to drug development.

Genular Protein ID: 3595952783

Symbol: SOX9_HUMAN

Name: N/A

UniProtKB Accession Codes:

Database IDs:

Citations:

PubMed ID: 7990924

Title: Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene.

PubMed ID: 7990924

DOI: 10.1038/372525a0

PubMed ID: 8001137

Title: Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9.

PubMed ID: 8001137

DOI: 10.1016/0092-8674(94)90041-8

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 8640233

Title: Sex reversal by loss of the C-terminal transactivation domain of human SOX9.

PubMed ID: 8640233

DOI: 10.1038/ng0696-230

PubMed ID: 12732631

Title: Transcriptional co-activators CREB-binding protein and p300 regulate chondrocyte-specific gene expression via association with Sox9.

PubMed ID: 12732631

DOI: 10.1074/jbc.m303471200

PubMed ID: 21208124

Title: A SOX9 duplication and familial 46,XX developmental testicular disorder.

PubMed ID: 21208124

DOI: 10.1056/nejmc1010311

PubMed ID: 25604083

Title: Copy number variation of two separate regulatory regions upstream of SOX9 causes isolated 46,XY or 46,XX disorder of sex development.

PubMed ID: 25604083

DOI: 10.1136/jmedgenet-2014-102864

PubMed ID: 28263186

Title: Loss of DDRGK1 modulates SOX9 ubiquitination in spondyloepimetaphyseal dysplasia.

PubMed ID: 28263186

DOI: 10.1172/jci90193

PubMed ID: 31382142

Title: SOX9 in cartilage development and disease.

PubMed ID: 31382142

DOI: 10.1016/j.ceb.2019.07.008

PubMed ID: 31194875

Title: The SOXE transcription factors-SOX8, SOX9 and SOX10-share a bi-partite transactivation mechanism.

PubMed ID: 31194875

DOI: 10.1093/nar/gkz523

PubMed ID: 34342803

Title: The 9aaTAD Activation Domains in the Yamanaka Transcription Factors Oct4, Sox2, Myc, and Klf4.

PubMed ID: 34342803

DOI: 10.1007/s12015-021-10225-8

PubMed ID: 9143916

Title: Mutations in SRY and SOX9: testis-determining genes.

PubMed ID: 9143916

DOI: 10.1002/(sici)1098-1004(1997)9:5<388::aid-humu2>3.0.co;2-0

PubMed ID: 7485151

Title: Mutations in SOX9, the gene responsible for Campomelic dysplasia and autosomal sex reversal.

PubMed ID: 7485151

PubMed ID: 9002675

Title: Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations.

PubMed ID: 9002675

DOI: 10.1093/hmg/6.1.91

PubMed ID: 9452059

Title: Novel missense mutation in the HMG box of SOX9 gene in a Japanese XY male resulted in campomelic dysplasia and severe defect in masculinization.

PubMed ID: 9452059

DOI: 10.1002/humu.1380110138

PubMed ID: 10446171

Title: Functional and structural studies of wild type SOX9 and mutations causing campomelic dysplasia.

PubMed ID: 10446171

DOI: 10.1074/jbc.274.34.24023

PubMed ID: 10951468

Title: Acampomelic campomelic dysplasia with SOX9 mutation.

PubMed ID: 10951468

DOI: 10.1002/1096-8628(20000828)93:5<421::aid-ajmg14>3.3.co;2-x

PubMed ID: 11754051

Title: Acampomelic campomelic syndrome.

PubMed ID: 11754051

DOI: 10.1002/ajmg.10033

PubMed ID: 11323423

Title: Compound effects of point mutations causing campomelic dysplasia/autosomal sex reversal upon SOX9 structure, nuclear transport, DNA binding, and transcriptional activation.

PubMed ID: 11323423

DOI: 10.1074/jbc.m101278200

PubMed ID: 12783851

Title: Loss of DNA-dependent dimerization of the transcription factor SOX9 as a cause for campomelic dysplasia.

PubMed ID: 12783851

DOI: 10.1093/hmg/ddg158

PubMed ID: 19033726

Title: Campomelic dysplasia: echographic suspicion in the first trimester of pregnancy and final diagnosis of two cases.

PubMed ID: 19033726

DOI: 10.1159/000176299

PubMed ID: 19921652

Title: Mutation analysis of SOX9 and single copy number variant analysis of the upstream region in eight patients with campomelic dysplasia and acampomelic campomelic dysplasia.

PubMed ID: 19921652

DOI: 10.1002/ajmg.a.33107

PubMed ID: 20513132

Title: Heterozygous SOX9 mutations allowing for residual DNA-binding and transcriptional activation lead to the acampomelic variant of campomelic dysplasia.

PubMed ID: 20513132

DOI: 10.1002/humu.21238

PubMed ID: 24038782

Title: A novel SOX9 H169Q mutation in a family with overlapping phenotype of mild campomelic dysplasia and small patella syndrome.

PubMed ID: 24038782

DOI: 10.1002/ajmg.a.36134

Sequence Information:

  • Length: 509
  • Mass: 56137
  • Checksum: 9289CFBB8D6631A2
  • Sequence:
  • MNLLDPFMKM TDEQEKGLSG APSPTMSEDS AGSPCPSGSG SDTENTRPQE NTFPKGEPDL 
    KKESEEDKFP VCIREAVSQV LKGYDWTLVP MPVRVNGSSK NKPHVKRPMN AFMVWAQAAR 
    RKLADQYPHL HNAELSKTLG KLWRLLNESE KRPFVEEAER LRVQHKKDHP DYKYQPRRRK 
    SVKNGQAEAE EATEQTHISP NAIFKALQAD SPHSSSGMSE VHSPGEHSGQ SQGPPTPPTT 
    PKTDVQPGKA DLKREGRPLP EGGRQPPIDF RDVDIGELSS DVISNIETFD VNEFDQYLPP 
    NGHPGVPATH GQVTYTGSYG ISSTAATPAS AGHVWMSKQQ APPPPPQQPP QAPPAPQAPP 
    QPQAAPPQQP AAPPQQPQAH TLTTLSSEPG QSQRTHIKTE QLSPSHYSEQ QQHSPQQIAY 
    SPFNLPHYSP SYPPITRSQY DYTDHQNSSS YYSHAAGQGT GLYSTFTYMN PAQRPMYTPI 
    ADTSGVPSIP QTHSPQHWEQ PVYTQLTRP