TUFM

Chr 16AR

Tu translation elongation factor, mitochondrial

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

NCBI Gene: 7284 ENSG00000178952 UniProt: P49411 OMIM: 602389

This gene encodes a mitochondrial elongation factor that facilitates protein synthesis within mitochondria by promoting translocation of aminoacyl-tRNA during translation. Mutations cause combined oxidative phosphorylation deficiency 4, an autosomal recessive disorder characterized by lactic acidosis and fatal encephalopathy due to impaired mitochondrial respiratory chain function. The pathogenic mechanism involves dominant-negative effects where mutant proteins interfere with normal mitochondrial protein synthesis.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 0.741 OMIM phenotype

Clinical Summary— TUFM

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Gene-Disease Validity (ClinGen)

mitochondrial disease · 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

7 unique Pathogenic / Likely Pathogenic· 112 VUS of 243 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.74LOEUF

pLI 0.004

Z-score 2.37

OE 0.39 (0.22–0.74)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.40Z-score

OE missense 0.76 (0.68–0.85)

205 obs / 269.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.39 (0.22–0.74)

0≤0.351.4

Missense OE?0.76 (0.68–0.85)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 7 / 17.8Missense obs/exp: 205 / 269.5Syn Z: 0.09

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongTUFM-related combined oxidative phosphorylation deficiencyOTHERAR

This gene — mechanism propensity

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

0.7036th %ile

GOF

0.6638th %ile

LOF

0.3453th %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

243 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic3

VUS112

Likely Benign86

Benign10

Conflicting19

Pathogenic

Likely Pathogenic

112

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	1	1	0	4
Likely Pathogenic	0	3	0	0	3
VUS	2	86	21	3	112
Likely Benign	0	1	43	42	86
Benign	0	0	9	1	10
Conflicting	—				19
Total	4	91	74	46	234

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

View in ClinVar →

114 pathogenic / likely-pathogenic (of 155) ClinVar copy-number / structural variants overlap TUFM — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →