GFM1 Gene - Elongation Factor G1, Mitochondrial
Essential mitochondrial translation factor implicated in combined oxidative phosphorylation deficiency and neurodegenerative disorders
Gene Information Card
| Symbol | GFM1 |
|---|---|
| Full Name | G elongation factor mitochondrial 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 3q25.32 |
| NCBI Gene ID | 85476 ncbi.nlm.nih.gov/gene/85476 |
| Ensembl ID | ENSG00000171227 |
| UniProt ID | Q96RP9 |
| OMIM ID | 606639 |
| HGNC ID | 13793 |
| Aliases | EFG1, EFGM, COXPD1, mtEF-G1, hEFG1 |
Description
The GFM1 gene encodes mitochondrial elongation factor G1 (mtEF-G1), a GTPase essential for the translocation step during mitochondrial protein synthesis. It catalyzes the movement of peptidyl-tRNA from the A-site to the P-site on the mitochondrial ribosome, enabling elongation of the nascent polypeptide chain. Mutations in GFM1 cause combined oxidative phosphorylation deficiency 1 (COXPD1), a severe multisystem disorder with early-onset encephalopathy, liver failure, and lactic acidosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Combined oxidative phosphorylation deficiency 1 (COXPD1) | Loss-of-function mutations impair mitochondrial translation, reducing the synthesis of mtDNA-encoded respiratory chain subunits, leading to defective oxidative phosphorylation. | ClinVar, OMIM |
| Hepatic failure, infantile | Severe GFM1 mutations cause early-onset liver failure due to mitochondrial dysfunction in hepatocytes. | OMIM, PubMed |
| Leigh syndrome | Some GFM1 variants present with Leigh-like neuropathology, including bilateral basal ganglia lesions. | ClinVar, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Heart | 10.2 | Medium |
| Skeletal muscle | 8.9 | Medium |
| Brain | 6.3 | Low |
| Kidney | 7.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 14.0 | Hepatocellular carcinoma cell line |
| K-562 | 9.5 | Myelogenous leukemia cell line |
| HeLa | 8.2 | Cervical adenocarcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1399C>T (p.Arg467*) | Nonsense | Rare | Loss of function; truncation of mtEF-G1, abolishing GTPase activity |
| c.745C>T (p.Arg249Trp) | Missense | Rare | Impaired mitochondrial translation; associated with COXPD1 |
| c.1A>G (p.Met1?) | Start loss | Rare | Complete loss of protein expression |
Mutation functional classification
Loss of Function (LOF)
Most GFM1 mutations are loss-of-function, leading to reduced mitochondrial translation and respiratory chain deficiency.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activity | • translation elongation factor activity |
| • mitochondrial translation | • ribosome translocation |
| • mitochondrion |
Pathways
• Mitochondrial translation elongation
• Oxidative phosphorylation
• Organelle biogenesis and maintenance
Protein Summary
Mitochondrial elongation factor G1 (mtEF-G1) is a nuclear-encoded GTPase that localizes to the mitochondrial matrix. It binds to the mitochondrial ribosome and promotes the GTP-dependent translocation of peptidyl-tRNA from the A-site to the P-site, a critical step in mitochondrial protein synthesis. The protein is essential for the production of 13 mtDNA-encoded subunits of the oxidative phosphorylation system. Defects in GFM1 lead to combined oxidative phosphorylation deficiency, manifesting as severe neonatal encephalopathy, liver failure, and lactic acidosis.
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