SOX9 - dismech genes

Normal function · from ai-gene-review (P48436, commit 79fe13b38970) · AI-generated, not KB evidence

SOX9 is a SOXE-family transcription factor that plays dual core roles in development. First, SOX9 is the master regulator of chondrogenesis, cooperating with SOX5 and SOX6 to drive cartilage matrix gene expression (COL2A1, ACAN) and promoting chondrocyte differentiation while antagonizing osteoblast differentiation via beta-catenin inhibition. Second, SOX9 is critical for oligodendrocyte differentiation and glial fate specification, promoting glial over neuronal fates in the CNS. SOX9 binds AACAAT-centered DNA motifs via its HMG-box domain, bends DNA, and recruits co-activators CBP/p300 and TIP60. It functions exclusively in the nucleus with nuclear localization and export signals. Post-translational modifications including phosphorylation, acetylation, and sumoylation regulate its activity. While SOX9 has additional developmental roles in sex determination, heart valve, kidney, and other epithelial programs, its core molecular functions center on transcriptional activation in cartilage and glial lineages.

Nuclear transcriptional activation of the chondrogenic program, driving chondrocyte differentiation and cartilage development.

molecular function: DNA-binding transcription activator activity, RNA polymerase II-specific · directly involved in: chondrocyte differentiation; cartilage development · locations: nucleus

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
46,XX testicular disorder of sex development	causative germline	mechanism: SOX9 enhancer dosage gain subtype: SRXX2 scoped to subtype: SRXX2
46,XY complete gonadal dysgenesis	causative germline	mechanism: SRY-SOX9-SOX8-DMRT1 transcriptional network failure subtype: SOX9-regulatory deletion complete gonadal dysgenesis
Campomelic Dysplasia	causative germline	mechanism: Disrupted 46,XY Sex Determination; SOX9-Mediated Chondrogenesis Disruption
Isolated Pierre Robin Syndrome	untyped Regulatory target of pathogenic noncoding deletions in a subset of isolated Robin sequence	mechanism: Modular Loss of SOX9 Expression in Cranial Neural Crest subtype: SOX9 regulatory scoped to subtype: SOX9 regulatory
Fetal Valproate Syndrome	no genetic record	mechanism: Disturbed Cranial Neural Crest Formation and Migration

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
Cooks syndrome MONDO:0007134	AD	Limited 2020-09-16	Cooks Syndrome not named
campomelic dysplasia MONDO:0007251	AD	Definitive 2020-06-01	Campomelic Dysplasia causative
isolated Pierre-Robin syndrome MONDO:0009869	AD	Limited 2024-08-06	Isolated Pierre Robin Syndrome untyped