ClinGen Dosage Sensitivity Curation Page

SIX1

  • Curation Status: Complete

Location Information

Select assembly: (NC_000014.8) (NC_000014.9)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

There are multiple reports of missense mutations in individuals with branchio-oto-renal syndrome (BOR) and branchio-oto syndrome (BOS), PMIDs: 21280147, 18330911, 21700001, 17637804, 16652090, and 16652090. Functional studies suggest that these mutations interfere with protein-protein interactions with EYA1 or DNA binding, depending on the domain involved, PMID: 16652090 and 19497856. Nolen et al (2006), PMID: 16835935, report one patient with anophalmia, pituitary hypoplasia, and ear anomalies who had a de novo t(3;14)(q28;q23.2) with a deletion at the 14q breakpoint that includes SIX1 and many other genes.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

Ou et al (2008), PMID: 18666230, report a family with clinical features of BOR and oculoauriculvertebral spectrum in which affected members had a 11.79 Mb duplication at 14q22.3q23.3 that contained 51 genes, including SIX1 and also a 4.38 Mb deletion at 13q21.31q21.32.