GFER (Growth Factor, Augmenter of Liver Regeneration)
Mitochondrial FAD-linked sulfhydryl oxidase involved in redox regulation, mitochondrial import, and liver regeneration.
Gene Information Card
| Symbol | GFER |
|---|---|
| Full Name | Growth Factor, Augmenter of Liver Regeneration |
| Gene Type | Protein coding |
| Chromosomal Location | 16p13.3 |
| NCBI Gene ID | 2671 ncbi.nlm.nih.gov/gene/2671 |
| Ensembl ID | ENSG00000103197 |
| UniProt ID | P55789 |
| OMIM ID | 600924 |
| HGNC ID | 4236 |
| Aliases | ALR, HPO, HSS, HSSA, ERV1 |
Description
GFER encodes a FAD-dependent sulfhydryl oxidase localized to the mitochondrial intermembrane space. It functions as an essential component of the mitochondrial import and assembly machinery (MIA pathway), catalyzing disulfide bond formation in imported proteins. GFER also acts as a growth factor augmenting liver regeneration and protects against oxidative stress.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mitochondrial complex deficiency (combined) | Impaired disulfide relay in IMS leads to defective assembly of respiratory chain complexes | ClinVar, OMIM #600924 |
| Hepatocellular carcinoma | Overexpression of GFER/ALR promotes cell proliferation and anti-apoptotic signaling | COSMIC, PMID: 23454719 |
| Myopathy with lactic acidosis | Missense mutations disrupt oxidase activity and mitochondrial protein import | ClinVar, PMID: 19251978 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 32.5 | High |
| Kidney | 18.2 | Medium |
| Heart | 15.8 | Medium |
| Skeletal Muscle | 12.1 | Medium |
| Brain | 6.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 28.7 | Hepatocellular carcinoma cell line |
| HEK293 | 22.3 | Embryonic kidney cells |
| K562 | 14.5 | Leukemia cell line |
| HeLa | 11.9 | Cervical carcinoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.236C>T (p.Pro79Leu) | Missense | <0.01% | Impaired oxidase activity; associated with mitochondrial myopathy |
| c.370G>A (p.Gly124Arg) | Missense | <0.01% | Reduced protein stability; linked to combined oxidative phosphorylation deficiency |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Loss of translation initiation; severe mitochondrial disease |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Pro79Leu) reduce or abolish sulfhydryl oxidase activity, impairing mitochondrial import and causing combined respiratory chain deficiency.
Gain of Function (GOF)
Not reported in germline; overexpression in hepatocellular carcinoma may confer proliferative advantage.
Dominant Negative (DN)
No evidence for dominant-negative effects; all pathogenic variants are recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Mitochondrial disulfide relay (MIA pathway)
• Reactive oxygen species (ROS) metabolism
• Liver regeneration signaling
Protein Summary
GFER (ALR) is a 23 kDa FAD-dependent sulfhydryl oxidase predominantly located in the mitochondrial intermembrane space. It catalyzes disulfide bond formation in substrate proteins during mitochondrial import, a process essential for respiratory chain assembly. The protein also exhibits growth factor activity, particularly in liver regeneration, and protects cells from oxidative stress. Mutations in GFER cause autosomal recessive mitochondrial disease with combined respiratory chain deficiency.
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