GFM1

Chr 3AR

G elongation factor mitochondrial 1

Also known as: COXPD1, EF-G1mt, EFG, EFG1, EFGM, EGF1, GFM, hEFG1

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…

Primary Disease Associations & Inheritance

Combined oxidative phosphorylation deficiency 1MIM #609060

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · Leigh syndrome · AR · ClinGen 2019

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.80

LOEUF

LOF

Mechanism· G2P

📖

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

Background carrier burden — how many people carry a rare variant somewhere in GFM1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 86

945 rare PASS variants

Rare truncating (LoF)

1 in 550

191 rare PASS variants

Rare synonymous (reference)

1 in 130

314 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GFM1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 120	1 in 510
South Asian	~43k	1 in 94	1 in 490
Remaining (unassigned)	~30k	1 in 75	1 in 760
European (Finnish)	~27k	1 in 210	1 in 950
Admixed American	~22k	1 in 75	1 in 1,500
African / African American	~21k	1 in 77	1 in 640
East Asian	~20k	1 in 75	1 in 850
Ashkenazi Jewish	~13k	1 in 140	≈ 1 in 4,400
Middle Eastern	~2,884	1 in 64	≈ 1 in 960

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 15 of 18 coding exons well covered in gnomAD exomes; exons 5, 8, 11 marginal. Genomes: all 18.? see exons ↓