GFM2

Chr 5AR

GTP dependent ribosome recycling factor mitochondrial 2

Also known as: EF-G2mt, EFG2, MRRF2, MST027, MSTP027, RRF, RRF2, RRF2mt

This gene encodes a mitochondrial translation elongation factor that functions as a GTPase to mediate ribosome disassembly from mRNA during termination of mitochondrial protein synthesis. Biallelic mutations cause combined oxidative phosphorylation deficiency 39, inherited in an autosomal recessive pattern. The pathogenic mechanism involves impaired mitochondrial translation leading to respiratory chain dysfunction and defective maintenance of mitochondrial DNA.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 1.041 OMIM phenotype
Clinical SummaryGFM2
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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.
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GeneReview available — GFM2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.04LOEUF
pLI 0.000
Z-score 1.35
OE 0.78 (0.591.04)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.80Z-score
OE missense 0.89 (0.810.97)
363 obs / 408.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.78 (0.591.04)
00.351.4
Missense OE0.89 (0.810.97)
00.61.4
Synonymous OE0.81
01.21.6
LoF obs/exp: 33 / 42.5Missense obs/exp: 363 / 408.3Syn Z: 1.77
DN
0.6357th %ile
GOF
0.5367th %ile
LOF
0.3940th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GFM2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found