ClinGen Dosage Sensitivity Curation Page

MATN3

  • Curation Status: Complete

Location Information

Select assembly: (NC_000002.11) (NC_000002.12)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

Variation within MATN3 has been associated with multiple epiphyseal dysplasia (MED). To date, most MATN3 mutations identified amongst individuals with MED have been missense changes within exon 2. These changes are thought to act in a dominant-negative manner. From GeneReviews: "MATN3 mutations appear to delay the folding of the A-domain, which elicits an unfolded protein response and results in the retention of mutant matrilin-3 in the rER both in vitro [Cotterill et al 2005, Otten et al 2005] and in vivo [Leighton et al 2007, Nundlall et al 2010]." See full GeneReviews article (http://www.ncbi.nlm.nih.gov/books/NBK1123/#edm-ad.MATN3_2) for more comprehensive information. Additionally, Borochowitz et al. (PMID: 15121775) report a large consanguineous family with recessive spondyloepimetaphyseal dysplasia (SEMD) and homozygosity for a missense mutation in MATN3.

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