HFE |
Gene Facts External Data Attribution
- HGNC Symbol
- HFE (HGNC:4886) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- homeostatic iron regulator
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- No previous names found
- Alias symbols
- HLA-H, HFE1
- %HI
- 74.41(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 0(Read more about gnomAD pLI score)
- LOEUF
- 1.19(Read more about gnomAD LOEUF score)
- Cytoband
- 6p22.2
- Genomic Coordinates
-
GRCh37/hg19: chr6:26087657-26098571 NCBI Ensembl UCSC GRCh38/hg38: chr6:26087429-26098343 NCBI Ensembl UCSC - MANE Select Transcript
- NM_000410.4 ENST00000357618.10 (Read more about MANE Select)
- Function
- Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin. {ECO:0000269|PubMed:9465039}. (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Dosage ID:
ISCA-36616
Curation Status:
Reopened
Issue Type:
Dosage Curation -
Gene
Haploinsufficiency:
Reopened
Triplosensitivity:
Reopened
Assoc. with Reduced Penetrance:
Reopened
Schmidtke et al. (PMID: 36140790) reviewed previous studies aiming to address the issues of population screening of Hereditary Hemochromatosis (HH). It was found that the biochemical penetrance (elevated levels of serum ferritin and transferrin saturation) is 40 -60% for female p.Cys282Tyr/p.Cys282Tyr homozygotes and 75-100% for male homozygotes. If use serum ferritin levels of 1000 ug/L as the cut-off, the penetrance of individuals with homozygous p.Cys282Tyr/p.Cys282Tyr is 35% for males and 6% for females at a median age of 65 years. The clinical penetrance varies from different studies. If use full-blown clinical phenotype as the evaluation criteria (i.e. a combination of liver disease, heart failure, diabetes mellitus and bronze skin), the penetrance of homozygous p.Cys282Tyr/p.Cys282Tyr for clinical HH is less than 1%. A cross-sectional study using liver disease as a proxy demonstrated a penetrance of 1.4% for newly diagnosed homozygous p.Cys282Tyr/p.Cys282Tyr individuals. If using life-time incidence as a way of evaluation, it is estimated that roughly 1 in 10 male homozygous p.Cys282Tyr/p.Cys282Tyr individuals will develop liver disease if untreated and the overall clinical penetrance in terms of iron overload related symptoms is around 28% in males.
For p.Cys282Tyr/p.His63Asp compound heterozygotes, it is estimated that 0.5 – 2% of such individuals develop clinical evidence of iron overload. The penetrance for homozygous p.His63Asp/p.His63Asp is lower than p.Cys282Tyr/p.His63Asp compound heterozygotes, while biochemical iron overload may presence, clinical presentation is rare.
(references cited in the review: PMID: 10471457; PMID: 28771247; PMID:15858186; PMID: 11812557; PMID: 15070663; PMID: 16039334; PMID: 19554541; PMID: 11874997)
Last Evaluated:
Reopened
Haploinsufficiency (HI) Score Details
Review not yet complete.
Triplosensitivity (TS) Score Details
Review not yet complete.
Genomic View
Select assembly:
(NC_000006.11)
(NC_000006.12)