See Table A. Genes and Databases for chromosome locus and protein.

See Molecular Genetics for information on alleles detected in this gene.

Sequence analysis detects alleles that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Alleles may include missense, nonsense, and splice site alleles and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

Individuals of European ancestry; approximately 60%-90% of individuals of European ancestry with HFE-related hemochromatosis (HFE HC) are homozygous for allele p.Cys282Tyr, 1% are homozygous for p.His63Asp, and 3%-8% are p.Cys282Tyr/p.His63Asp compound heterozygotes [Feder et al 1996, Morrison et al 2003, Barton et al 2015]. Additional population-specific pathogenic alleles have been described, including p.Glu168Ter and p.Trp169Ter, with allele frequencies of 25% and 8.4%, respectively, in individuals with HFE HC in two northern regions of Italy [Piperno et al 2000]. The prevalence of HFE p.Ser65Cys is greatest in French populations. The HFE splice site allele c.1006+1G>A occurs in Vietnamese populations with and without phenotypic evidence of iron overload [Barton et al 2015].

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.

Alu-mediated HFE whole-gene deletion is the most common cause of HFE HC in the Sardinian population [Le Gac et al 2010].