HFE (haemochromatosis)

rs1800562 · rs1799945

HFE variants can affect iron regulation. C282Y homozygosity is an important genetic basis of HFE haemochromatosis, but it does not lead to clinically significant iron overload in everyone. Blood measurements and medical context are essential to assessment.

Key points

C282Y homozygosity raises risk; by itself it does not predict whether iron overload will develop.
H63D and the C282Y/H63D combination do not by themselves establish iron overload.
Clinical expression varies. Assessment includes measures such as ferritin and transferrin saturation.

#The two variants

C282Y (rs1800562) changes a disulfide bond in the HFE protein and affects its function. H63D (rs1799945) causes a different amino acid substitution. Clinical significance depends on genotype, iron measurements and other factors; a variant alone does not show iron overload.

#How the result is assessed

An HFE variant from a genotype file does not establish iron overload. Clinicians assess it alongside iron measurements, symptoms, family history and, when needed, further tests. Whether treatment is appropriate depends on that full assessment.

#Context

The genotype is not a diagnosis. Blood measurements and medical context are needed for assessment. Genome displays technical variant information and does not derive a diagnosis or treatment recommendation from it.

What Genome measures. The genotypes at rs1800562 (C282Y) and rs1799945 (H63D) and the resulting haemochromatosis risk constellation.

Sources

1Feder et al., 1996 A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nature Genetics 13:399-408. doi.org/10.1038/ng0896-399
2EASL, 2022 EASL Clinical Practice Guidelines on haemochromatosis. Journal of Hepatology 77:479-502. doi.org/10.1016/j.jhep.2022.03.033