MTFMT

Chr 15AR

mitochondrial methionyl-tRNA formyltransferase

NCBI Gene: 123263ENSG00000103707UniProt: Q96DP5

Methionyl-tRNA formyltransferase that formylates methionyl-tRNA in mitochondria and is crucial for translation initiation

Primary Disease Associations & Inheritance

Combined oxidative phosphorylation deficiency 15MIM #614947
AR
Mitochondrial complex I deficiency, nuclear type 27MIM #618248
AR
329
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MTFMT
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
329 total variants — no pathogenic classifications of 329 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.
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?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.
-0.46Z-score
OE missense 1.09 (0.98–1.22)
214 obs / 195.8 exp
Tolerant

Tolerant to missense variation

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.0.64 (0.42–1.01)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.09 (0.98–1.22)
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.1.06
0≤1.21.6
LoF obs/exp: 14 / 21.7Missense obs/exp: 214 / 195.8Syn Z: -0.38

ClinVar Variant Classifications

329 submitted variants in ClinVar

ClinVar

Classification Summary

Protein Context — Lollipop Plot

MTFMT · protein map & ClinVar variants

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

Gene2Phenotype Curations

MTFMT-related mitochondrial disease with regression and lactic acidosis

definitive
ARLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. Disorders
G2P ↗
splice region variantframeshift variantstop gainedmissense variant

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Combined oxidative phosphorylation deficiency 15

MIM #614947

Molecular basis of disorder known

Autosomal recessive

Mitochondrial complex I deficiency, nuclear type 27

MIM #618248

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
New perspective in diagnostics of mitochondrial disorders: two years' experience with whole-exome sequencing at a national paediatric centre.
Pronicka E et al.·J Transl Med
2016
Phenotypic spectrum of eleven patients and five novel MTFMT mutations identified by exome sequencing and candidate gene screening.
Haack TB et al.·Mol Genet Metab
2014Cohort
Identifying Genetic Susceptibility in Neonates With Hypoxic-Ischemic Encephalopathy: A Retrospective Case Series.
Woodward KE et al.·J Child Neurol
2023Review
Leigh syndrome caused by mutations in MTFMT is associated with a better prognosis.
Hayhurst H et al.·Ann Clin Transl Neurol
2019
Clinical and functional characterisation of the combined respiratory chain defect in two sisters due to autosomal recessive mutations in MTFMT.
Neeve VC et al.·Mitochondrion
2013Case report
Identification and functional characterization of a novel MTFMT mutation associated with selective vulnerability of the visual pathway and a mild neurological phenotype.
La Piana R et al.·Neurogenetics
2017Case report
An N-terminal formyl methionine on COX 1 is required for the assembly of cytochrome c oxidase.
Hinttala R et al.·Hum Mol Genet
2015
Methionyl-tRNA Formyltransferase (MTFMT) Deficiency Mimicking Acquired Demyelinating Disease.
Pena JA et al.·J Child Neurol
2016Case report
Construction and validation of a folate metabolism-related gene signature for predicting prognosis in HNSCC.
Wang L et al.·J Cancer Res Clin Oncol
2024
Serine Catabolism by SHMT2 Is Required for Proper Mitochondrial Translation Initiation and Maintenance of Formylmethionyl-tRNAs.
Minton DR et al.·Mol Cell
2018
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