SOX10 Gene: Function, Mutations, and Associated Diseases | NCBI, UniProt, OMIM

SOX10 (SRY-Box Transcription Factor 10) is a protein-coding gene located on chromosome 22q13.1. It encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and cell fate determination. SOX10 is essential for neural crest cell survival, migration, and differentiation, particularly in melanocytes, glial cells, and enteric neurons. Mutations in SOX10 are associated with Waardenburg syndrome types 2E and 4C, PCWH (peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease), and isolated Hirschsprung disease.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Neural crest differentiation (WP2064)

• Melanogenesis (KEGG hsa04916)

• Signaling pathways regulating pluripotency of stem cells (KEGG hsa04550)

• Transcriptional regulation of white adipocyte differentiation (WP287)

SOX10 is a 466-amino-acid transcription factor containing a conserved HMG (high-mobility group) DNA-binding domain and a C-terminal transactivation domain. It forms homodimers or heterodimers with other SOX proteins (e.g., SOX9, SOX8) to regulate target genes such as MITF, TYR, and EDNRB. SOX10 is critical for neural crest cell specification, melanocyte survival, and myelination in the peripheral nervous system. Post-translational modifications include phosphorylation and sumoylation, which modulate its transcriptional activity. Mutations in SOX10 cause a spectrum of neurocristopathies, with dominant-negative variants leading to more severe phenotypes.