MTFMT

Chr 15AR

mitochondrial methionyl-tRNA formyltransferase

Also known as: COXPD15, FMT1, MC1DN27

NCBI Gene: 123263 ENSG00000103707 UniProt: Q96DP5 OMIM: 611766

The protein catalyzes the formylation of methionyl-tRNA within mitochondria, a critical step in mitochondrial protein synthesis. Mutations cause combined oxidative phosphorylation deficiency 15 and mitochondrial complex I deficiency through autosomal recessive inheritance. The pathogenic mechanism involves de novo mutations that disrupt mitochondrial translation and respiratory chain function.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this nuclear gene localizes to the mitochondrion, where it catalyzes the formylation of methionyl-tRNA. [provided by RefSeq, Jun 2011]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.012 OMIM phenotypes

Clinical Summary— MTFMT

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Gene-Disease Validity (ClinGen)

Leigh syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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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

34 unique Pathogenic / Likely Pathogenic· 114 VUS of 313 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — MTFMT

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?

1.01LOEUF

pLI 0.000

Z-score 1.53

OE 0.64 (0.42–1.01)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.46Z-score

OE missense 1.09 (0.98–1.22)

214 obs / 195.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.64 (0.42–1.01)

0≤0.351.4

Missense OE?1.09 (0.98–1.22)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 14 / 21.7Missense obs/exp: 214 / 195.8Syn Z: -0.38

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveMTFMT-related mitochondrial disease with regression and lactic acidosisLOFAR

This gene — mechanism propensity

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

0.6258th %ile

GOF

0.4973th %ile

LOF

0.3261th %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

313 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20

Likely Pathogenic14

VUS114

Likely Benign91

Benign41

Conflicting16

Pathogenic

Likely Pathogenic

114

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	16	4	0	0	20
Likely Pathogenic	12	2	0	0	14
VUS	3	107	4	0	114
Likely Benign	0	8	42	41	91
Benign	0	5	32	4	41
Conflicting	—				16
Total	31	126	78	45	296

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

View in ClinVar →

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