GFM1

Chr 3AR

G elongation factor mitochondrial 1

Also known as: COXPD1, EFG, EFG1, EFGM, EGF1, GFM, hEFG1, mtEF-G1

NCBI Gene: 85476 ENSG00000168827 UniProt: Q96RP9 OMIM: 606639

The protein functions as a mitochondrial translation elongation factor essential for protein synthesis within mitochondria. Mutations cause combined oxidative phosphorylation deficiency 1, an autosomal recessive disorder resulting from impaired mitochondrial respiratory chain function. The pathogenic mechanism involves dominant-negative effects that disrupt normal mitochondrial protein translation.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

Eukaryotes contain two protein translational systems, one in the cytoplasm and one in the mitochondria. Mitochondrial translation is crucial for maintaining mitochondrial function and mutations in this system lead to a breakdown in the respiratory chain-oxidative phosphorylation system and to impaired maintenance of mitochondrial DNA. This gene encodes one of the mitochondrial translation elongation factors. Its role in the regulation of normal mitochondrial function and in different disease states attributed to mitochondrial dysfunction is not known. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.801 OMIM phenotype

Clinical Summary— GFM1

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Gene-Disease Validity (ClinGen)

Leigh syndrome · ARModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

211 unique Pathogenic / Likely Pathogenic· 253 VUS of 1053 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — GFM1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.80LOEUF

pLI 0.000

Z-score 2.65

OE 0.58 (0.43–0.80)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.28Z-score

OE missense 0.82 (0.75–0.90)

339 obs / 412.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.58 (0.43–0.80)

0≤0.351.4

Missense OE?0.82 (0.75–0.90)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 27 / 46.5Missense obs/exp: 339 / 412.1Syn Z: -0.61

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveGFM1-related combined oxidative phosphorylation deficiencyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.74top 25%

GOF

0.7127th %ile

LOF

0.2969th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

1053 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic64

Likely Pathogenic147

VUS253

Likely Benign470

Benign62

Conflicting46

Pathogenic

147

Likely Pathogenic

253

VUS

470

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	51	4	9	0	64
Likely Pathogenic	133	12	2	0	147
VUS	4	202	37	10	253
Likely Benign	2	14	210	244	470
Benign	0	6	52	4	62
Conflicting	—				46
Total	190	238	310	258	1,042

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

View in ClinVar →

20 pathogenic / likely-pathogenic (of 33) ClinVar copy-number / structural variants overlap GFM1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →