ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000007.13) (NC_000007.14)
Evidence for haploinsufficiency phenotype
PubMed ID Description
15739154 A 2005 genotype-phenotype correlation study of GLI3 mutations uncovered many types of alterations, including translocations, large deletions, and sequence-level mutations predicted to result in a loss-of-function, in patients with Greig cephalopolysyndactyly syndrome (GCPS).
21326280 2011 report of 3 probands with GCPS and large de novo deletions encompassing GLI3, detected by array CGH.

Haploinsufficiency phenotype comments:

~70% of GCPS patients have heterozygous sequence-level GLI3 mutations. While all currently reported GLI3 deletions include nearby genes, phenotypic overlap and functional data indicate that focal GLI3 deletion would also increase the risk for GCPS. In addition to GCPS, certain heterozygous sequence-level GLI3 mutations are associated with Pallister-Hall syndrome (146510), polydactyly, postaxial, types A1 and B (174200), and polydactyly, preaxial, type IV (174700). As discussed in the GeneReviews link, GCPS is generally caused by haploinsufficiency for GLI3.

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