FECH Gene: Ferrochelatase
Key enzyme in heme biosynthesis; mutations cause erythropoietic protoporphyria
Gene Information Card
| Symbol | FECH |
|---|---|
| Full Name | Ferrochelatase |
| Gene Type | Protein coding |
| Chromosomal Location | 18q21.31 |
| NCBI Gene ID | 2235 ncbi.nlm.nih.gov/gene/2235 |
| Ensembl ID | ENSG00000066926 |
| UniProt ID | P22830 |
| OMIM ID | 612386 |
| HGNC ID | 3647 |
| Aliases | EPP, MFE, Heme synthase, Protoheme ferro-lyase |
Description
The FECH gene encodes ferrochelatase, the terminal enzyme of the heme biosynthetic pathway. It catalyzes the insertion of ferrous iron into protoporphyrin IX to form heme. This mitochondrial enzyme is essential for hemoglobin, cytochromes, and other heme proteins. Mutations in FECH are primarily associated with erythropoietic protoporphyria (EPP), a disorder of porphyrin metabolism.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Erythropoietic protoporphyria (EPP) | Reduced ferrochelatase activity leads to accumulation of protoporphyrin IX, causing photosensitivity and liver damage. | OMIM, ClinVar |
| Liver disease (in EPP) | Protoporphyrin accumulation in bile causes cholestatic liver injury and cirrhosis. | OMIM, PubMed |
| Gallstones | Protoporphyrin precipitates in bile, contributing to gallstone formation. | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | High | High |
| Liver | High | High |
| Spleen | Medium | Medium |
| Kidney | Low | Low |
| Brain | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | High | Erythroid lineage |
| HepG2 (liver) | Medium | Hepatic expression |
| HeLa (cervical) | Low | Non-erythroid |
| A549 (lung) | Low | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.315C>T (p.Leu105Phe) | Missense | Common in EPP (allelic frequency varies) | Reduced enzyme activity |
| c.636G>A (p.Trp212Ter) | Nonsense | Rare | Truncated protein, loss of function |
| IVS1-23C>T (intronic) | Splice site | Common in EPP (hypomorphic allele) | Reduced mRNA expression |
| c.1078G>A (p.Gly360Ser) | Missense | Rare | Impaired iron binding |
Mutation functional classification
Loss of Function (LOF)
Most FECH mutations cause partial loss of enzyme activity, leading to protoporphyrin accumulation.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with dimerization, but most EPP cases are due to compound heterozygosity with a null allele and a low-expression allele.
View complete mutation data：
Gene Ontology (GO)
| • ferrochelatase activity | • iron ion binding |
| • protoporphyrinogen oxidase activity | • mitochondrial inner membrane |
| • heme biosynthetic process | • response to oxidative stress |
Pathways
• Heme biosynthesis
• Porphyrin metabolism
• Metabolic pathways
Protein Summary
Ferrochelatase is a homodimeric mitochondrial inner membrane protein. It catalyzes the final step of heme synthesis, inserting ferrous iron into protoporphyrin IX. The enzyme requires iron-sulfur clusters for activity. Defects lead to protoporphyria.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FECH Knockout HEK293 Cell Line | EDJ-KQ2362 | Human | 2235 | Details Get a Quote |
| FECH Knockout A-549 Cell Line | EDJ-KQ22802 | Human | 2235 | Details Get a Quote |
| FECH Knockout HCT 116 Cell Line | EDJ-KQ22803 | Human | 2235 | Details Get a Quote |
| FECH Knockout HeLa Cell Line | EDJ-KQ22804 | Human | 2235 | Details Get a Quote |
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