TUFM

Chr 16AR

Tu translation elongation factor, mitochondrial

Also known as: COXPD4, EF-TuMT, EFTU, P43

NCBI Gene: 7284ENSG00000178952UniProt: P49411

This gene encodes a protein which participates in protein translation in mitochondria. Mutations in this gene have been associated with combined oxidative phosphorylation deficiency resulting in lactic acidosis and fatal encephalopathy. A pseudogene has been identified on chromosome 17. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Combined oxidative phosphorylation deficiency 4MIM #610678
AR
387
ClinVar variants
121
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TUFM
🧬
Gene-Disease Validity (ClinGen)
mitochondrial disease · 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.
📋
ClinVar Variants
121 Pathogenic / Likely Pathogenic· 148 VUS of 387 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.
0.74LOEUF
pLI 0.004
Z-score 2.37
OE 0.39 (0.22–0.74)
Tolerant

Typical tolerance to LoF variation

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.
1.40Z-score
OE missense 0.76 (0.68–0.85)
205 obs / 269.5 exp
Tolerant

Mild missense constraint

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.0.39 (0.22–0.74)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.76 (0.68–0.85)
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.0.99
0≤1.21.6
LoF obs/exp: 7 / 17.8Missense obs/exp: 205 / 269.5Syn Z: 0.09

ClinVar Variant Classifications

387 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic108
Likely Pathogenic13
VUS148
Likely Benign87
Benign10
Conflicting21
108
Pathogenic
13
Likely Pathogenic
148
VUS
87
Likely Benign
10
Benign
21
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
106
0
108
Likely Pathogenic
0
3
10
0
13
VUS
2
84
59
3
148
Likely Benign
0
1
44
42
87
Benign
0
0
9
1
10
Conflicting
—21
Total38922846387

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

View in ClinVar →

Protein Context — Lollipop Plot

TUFM · protein map & ClinVar variants

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

Gene2Phenotype Curations

TUFM-related combined oxidative phosphorylation deficiency

strong
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Combined oxidative phosphorylation deficiency 4

MIM #610678

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Mapping the immune-genetic architecture of aging: A single-cell causal framework for biomarker discovery and therapeutic targeting.
Hong Y et al.·Ageing Res Rev
2025
A very rare presentation of mitochondrial elongation factor Tu deficiency-TUFM mutation and literature review.
Gokalp S et al.·J Pediatr Endocrinol Metab
2024Review
MRG15 promotes cell apoptosis through inhibition of mitophagy in hyperlipidemic acute pancreatitis.
Gu B et al.·Apoptosis
2025
TUFM variants lead to white matter abnormalities mimicking multiple sclerosis.
Chen S et al.·Eur J Neurol
2023Case report
Novel Tu translation elongation factor, mitochondrial (TUFM) homozygous variant in a consanguineous family with premature ovarian insufficiency.
Zhang J et al.·Clin Genet
2023
Mitochondrial dysfunction and onset of type 2 diabetes along with its complications: a multi-omics Mendelian randomization and colocalization study.
Li Y et al.·Front Endocrinol (Lausanne)
2024
A zebrafish tufm mutant model for the COXPD4 syndrome of aberrant mitochondrial function.
Li T et al.·J Genet Genomics
2024Functional
Activation of mitochondrial TUFM ameliorates metabolic dysregulation through coordinating autophagy induction.
Kim D et al.·Commun Biol
2021
The Bacterial ClpXP-ClpB Family Is Enriched with RNA-Binding Protein Complexes.
Auburger G et al.·Cells
2022Review
Vitamin D disrupts NS1-TUFM interaction to suppress pathogenic mitophagy in RSV-induced mitochondrial injury of bronchial epithelial cells.
Peng L et al.·J Microbiol
2026
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