ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000006.11) (NC_000006.12)
  • Haploinsufficiency score: Gene associated with autosomal recessive phenotype
  • Strength of Evidence (disclaimer): Gene associated with autosomal recessive phenotype
  • Haploinsufficiency Phenotype: HEMOCHROMATOSIS, TYPE 1; HFE1
Evidence for haploinsufficiency phenotype
PubMed ID Description
18809761 Homozygous deletion of the HFE gene resulting in hemochromatosis type 1 is a founder effect mutation in Sardinia.

Haploinsufficiency phenotype comments:

HFE gene mutations are associated with adult-onset autosomal recessive hemochromatosis type 1 [MIM 235200 ]. Various homozygous or compound heterozygous mutations, including missense (most common), nonsense, splice-site, small deletions and complete gene deletion (only detected in Sardinia) have been described in the literature. Although various mutations of HFE cause hemochromatosis, most of the affected individuals of European descent have either homozygous p.Cys282Tyr (p.282C>Y) mutation or compound heterozygous p.Cys282Tyr (p.282C>Y) and p.His63Asp (p.63H>D) mutations. However, entire gene deletion of HFE has been reported to be the common cause of hemochromatosis in affected individuals of Sardinian descent (PMID: 20007136).

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity
Evidence for triplosensitivity phenotype
PubMed ID Description
Not reported