ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000016.9) (NC_000016.10)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

MEFV (Mediterranean Fever gene) is associated with Familial Mediterranean fever (FMF), an autosomal recessive/autosomal dominant hereditary periodic fever syndrome. FMF is usually inherited in an autosomal recessive manner although heterozygous carriers of pathogenic MEVF variants are also sometimes affected by classical or mild FMF. Whole gene deletions and nonsense variants in MEVF have not been reported as a cause of FMF. Pathogenic MEVF variants are usually missense, although some small deletions and insertions have also been reported (MEFV database, HGMD). Two of these variants are predicted to cause a frameshift (Oztuzcu et al. 2014, Dogan et al. 2014); although one of these variants is near the end of the protein and the encoded product is unlikely to be targeted for nonsense-mediated decay. It has been proposed that the periodic nature of inflammatory attacks in FMF is consistent with a protein that functions adequately at steady state but decompensates under stress (International FMF Consortium 1997), acting via a gain-of-function type mechanism of pathogenicity.

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