GFM1

Chr 3AR

G elongation factor mitochondrial 1

NCBI Gene: 85476ENSG00000168827UniProt: Q96RP9

Mitochondrial GTPase that catalyzes the GTP-dependent ribosomal translocation step during translation elongation. During this step, the ribosome changes from the pre-translocational (PRE) to the post-translocational (POST) state as the newly formed A-site-bound peptidyl-tRNA and P-site-bound deacylated tRNA move to the P and E sites, respectively. Catalyzes the coordinated movement of the two tRNA molecules, the mRNA and conformational changes in the ribosome. Does not mediate the disassembly of ribosomes from messenger RNA at the termination of mitochondrial protein biosynthesis

Primary Disease Associations & Inheritance

Combined oxidative phosphorylation deficiency 1MIM #609060
AR
589
ClinVar variants
112
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— GFM1
🧬
Gene-Disease Validity (ClinGen)
Leigh syndrome · ARModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
112 Pathogenic / Likely Pathogenic· 190 VUS of 589 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.80LOEUF
pLI 0.000
Z-score 2.65
OE 0.58 (0.43–0.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.28Z-score
OE missense 0.82 (0.75–0.90)
339 obs / 412.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.58 (0.43–0.80)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.75–0.90)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.07
0≤1.21.6
LoF obs/exp: 27 / 46.5Missense obs/exp: 339 / 412.1Syn Z: -0.61

ClinVar Variant Classifications

589 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic77
VUS190
Likely Benign271
Benign9
Conflicting7
35
Pathogenic
77
Likely Pathogenic
190
VUS
271
Likely Benign
9
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
14
0
21
0
35
Likely Pathogenic
60
1
16
0
77
VUS
0
161
21
8
190
Likely Benign
1
3
142
125
271
Benign
0
0
9
0
9
Conflicting
—7
Total75165209133589

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GFM1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

GFM1-related combined oxidative phosphorylation deficiency

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Combined oxidative phosphorylation deficiency 1

MIM #609060

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — GFM1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical, neuroimaging and biochemical findings in patients and patient fibroblasts expressing ten novel GFM1 mutations.
Barcia G et al.·Hum Mutat
2020Cohort
Evaluation of GFM1 mutations pathogenicity through in silico tools, RNA sequencing and mitophagy pahtway in GFM1 knockout cells.
Ahmad B et al.·Int J Biol Macromol
2025
Whole exome sequencing identifies a novel compound heterozygous GFM1 variant underlying developmental delay, dystonia, polymicrogyria, and severe intellectual disability in a Pakhtun family.
Khan AU et al.·Am J Med Genet A
2022
The Bacterial ClpXP-ClpB Family Is Enriched with RNA-Binding Protein Complexes.
Auburger G et al.·Cells
2022Review
Polydatin and Nicotinamide Rescue the Cellular Phenotype of Mitochondrial Diseases by Mitochondrial Unfolded Protein Response (mtUPR) Activation.
Cilleros-Holgado P et al.·Biomolecules
2024
Activation of a cryptic splice site in the mitochondrial elongation factor GFM1 causes combined OXPHOS deficiency.
Simon MT et al.·Mitochondrion
2017Case report
The first case of combined oxidative phosphorylation deficiency-1 due to a GFM1 mutation in the Serbian population: a case report and literature review.
Aleksic D et al.·Turk J Pediatr
2023Case report
Multi-omics analysis untangles the crosstalk between intratumor microbiome, lactic acid metabolism and immune status in lung squamous cell carcinoma.
Qiu X et al.·Front Immunol
2025
Toward genotype phenotype correlations in GFM1 mutations.
Galmiche L et al.·Mitochondrion
2012Case report
[Analysis of GFM1 gene mutations in a family with combined oxidative phosphorylation deficiency 1].
Shen Y et al.·Zhejiang Da Xue Xue Bao Yi Xue Ban
2020Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools