ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000001.10) (NC_000001.11)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

Mutations (specifically, splice site mutations resulting in deletion of exon 3) in COL9A2 have been associated with autosomal dominant epiphyseal dysplasia, multiple, 2 (phenotype 600204). At this time, no whole gene deletions (or duplications) of COL9A2 have been reported in association with this phenotype. From GeneReviews: "The pathologic effect of mutations in COL9A1, COL9A2, and COL9A3 is not well understood and a number of mechanisms have been proposed for these mutations including the degradation of mRNA from the mutant allele [Holden et al 1999, Spayde et al 2000], an accumulation of abnormal type IX collagen ?-chains in the rER of chondrocytes [Bonnemann et al 2000], and/or the degradation of abnormal ?-chains [van Mourik et al 1998]. However, the remarkable clustering of all COL9A1, COL9A2, and COL9A3 MED-causing mutations, which result in the in-frame deletion of equivalent regions of the COL3 domain of type IX collagen, led to the hypothesis that the deletion of these specific amino acids was a significant contributing factor to the development of the disease [Briggs & Chapman 2002]. Recent studies have confirmed that a COL9A3 mutation indeed abolishes binding of type IX collagen to matrilin-3 and type II collagen, thus identifying for the first time a molecular consequence of these mutations [Fresquet et al 2007]."

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

Triplosensitivity phenotype comment:

There is no evidence to suggest a copy number gain of this gene causes an abnormal phenotype.