SOX9

SRY-box transcription factor 9

Ensembl:
ENSG00000125398
UniProt:
P48436
OMIM:
608160
Synonyms:
CMD1, CMPD1, SRA1

Cilia effects upon perturbation of SOX9

Ciliogenesis screen results (5 screens)

  • Kim2016: Not Reported
  • Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-5.68) PMID:26167766
  • Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
  • Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381
  • Pusapati et al. 2018 (CRISPR) [CRISPR]: Negative Regulator (Hh signaling, pos_rank=832, lfc=0.52) PMID:30270045

Ciliopathy associations

  • Birt-Hogg-Dubé Syndrome
  • Nephronophthisis

Subcellular localization

cilia associated gene, nucleoplasm

Functional category

  • Metabolism; Signaling (Hedgehog, GPCRs, ion channels)

Function

Expression levels of SOX9, a known substrate of FBW7, and WNT4, a potent pro-fibrotic factor and downstream effector of SOX9, were elevated upon loss of FBW7. Heterozygous deletion of Sox9 in compound mutant mice led to the normalization of WNT4 levels, reduced fibrosis, and preservation of kidney function without significant effects on cystic dilatation and tubular degeneration. These data suggest that FBW7-SOX9-WNT4-induced fibrosis drives kidney function decline in NPHP and, possibly, other forms of autosomal recessive kidney disorders. Heightened expression of SOX9 was seen in a human biopsy of a patient with NPHP1 mutations and in cystic epithelia of Ift88-null mouse kidneys with ciliary defects. (PMID: 40211043).

Model organism evidence

Mus musculus (2 references)

These proteins function in a cilia-dependent cyst activation (CDCA) pathway-one that requires cilia for its pro-cystic function-yet the molecular driver(s) of this pathway are unknown.

In the brain of furin cKO mice, impaired ciliogenesis and the derangement of microtubule structures appeared along with the down-regulated expression of RAB28, a ciliary vesicle protein.

PMIDs: 41332619, 38292192