HEPH (Hephaestin) Gene
A key regulator of iron export and copper metabolism
Gene Information Card
| Symbol | HEPH |
|---|---|
| Full Name | Hephaestin |
| Gene Type | protein-coding |
| Chromosomal Location | Xq12 |
| NCBI Gene ID | 9843 ncbi.nlm.nih.gov/gene/9843 |
| Ensembl ID | ENSG00000089472 |
| UniProt ID | Q9BQS7 |
| OMIM ID | 300167 |
| HGNC ID | 4866 |
| Aliases | HEPHL1, HEPH1, ferroxidase |
Description
HEPH encodes hephaestin, a transmembrane ferroxidase that facilitates iron export from cells by oxidizing ferrous iron (Fe2+) to ferric iron (Fe3+), which is then loaded onto transferrin. It is homologous to ceruloplasmin and contains copper-binding sites. Hephaestin is highly expressed in the small intestine, placenta, and brain, and is critical for systemic iron homeostasis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Iron-refractory iron deficiency anemia (IRIDA) | Loss-of-function mutations impair intestinal iron export, leading to microcytic anemia unresponsive to oral iron | ClinVar, OMIM |
| Neurodegeneration with brain iron accumulation (NBIA) | Defective ferroxidase activity in the brain leads to iron accumulation and oxidative stress | NCBI Gene, OMIM |
| Hypochromic microcytic anemia | Reduced hephaestin activity disrupts iron efflux from enterocytes | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Small intestine | 15.2 | High |
| Placenta | 12.8 | High |
| Brain (cerebellum) | 8.5 | Medium |
| Liver | 3.1 | Low |
| Heart | 2.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Caco-2 (intestinal) | 18.5 | High expression; model for iron transport |
| SH-SY5Y (neuronal) | 7.2 | Moderate expression; relevant for NBIA studies |
| HepG2 (liver) | 2.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1405C>T (p.Arg469*) | Nonsense | Rare | Loss of function; truncated protein |
| c.812G>A (p.Arg271His) | Missense | <0.01% | Reduced ferroxidase activity |
| c.1942C>T (p.Arg648Trp) | Missense | <0.01% | Impaired iron export |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations that reduce or abolish ferroxidase activity, leading to iron retention in enterocytes and anemia.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported; HEPH functions as a monomer, and heterozygous carriers are typically asymptomatic.
View complete mutation data：
Gene Ontology (GO)
| • ferroxidase activity (GO:0004322) | • iron ion binding (GO:0005506) |
| • copper ion binding (GO:0005507) | • iron export across plasma membrane (GO:0034756) |
| • cellular iron ion homeostasis (GO:0006879) |
Pathways
• Iron uptake and transport (Reactome: R-HSA-917937)
• Metal ion SLC transporters (KEGG: hsa04978)
Protein Summary
Hephaestin is a 1158-amino acid transmembrane ferroxidase with six cupredoxin-like domains and a C-terminal transmembrane domain. It oxidizes Fe2+ to Fe3+ using copper as a cofactor, enabling iron loading onto transferrin. The protein is essential for intestinal iron absorption and brain iron homeostasis. Mutations cause iron deficiency anemia and are implicated in neurodegenerative disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HEPH Knockout HEK293 Cell Line | EDJ-KQ6780 | Human | 9843 | Details Get a Quote |
| HEPHL1 Knockout HEK293 Cell Line | EDJ-KQ13738 | Human | 341208 | Details Get a Quote |
| HEPH Knockout HeLa Cell Line | EDJ-KQ55265 | Human | 9843 | Details Get a Quote |
| HEPHL1 Knockout HeLa Cell Line | EDJ-KQ59703 | Human | 341208 | Details Get a Quote |
| HEPH Knockout A-549 Cell Line | EDJ-KQ63745 | Human | 9843 | Details Get a Quote |
| HEPHL1 Knockout A-549 Cell Line | EDJ-KQ68176 | Human | 341208 | Details Get a Quote |
| HEPH Knockout HCT 116 Cell Line | EDJ-KQ72204 | Human | 9843 | Details Get a Quote |
| HEPHL1 Knockout HCT 116 Cell Line | EDJ-KQ76551 | Human | 341208 | Details Get a Quote |
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