TSFM

Chr 12AR

Ts translation elongation factor, mitochondrial

Also known as: EFTS, EFTSMT

NCBI Gene: 10102ENSG00000123297UniProt: P43897

This gene encodes a mitochondrial translation elongation factor. The encoded protein is an enzyme that catalyzes the exchange of guanine nucleotides on the translation elongation factor Tu during the elongation step of mitchondrial protein translation. Mutations in this gene are associated with combined oxidative phosphorylation deficiency-3 syndrome. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Mar 2010]

Primary Disease Associations & Inheritance

Combined oxidative phosphorylation deficiency 3MIM #610505
AR
495
ClinVar variants
74
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TSFM
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Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
74 Pathogenic / Likely Pathogenic· 181 VUS of 495 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

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.
1.45LOEUF
pLI 0.000
Z-score 0.25
OE 0.93 (0.61–1.45)
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.
-0.22Z-score
OE missense 1.05 (0.93–1.19)
177 obs / 169.1 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.0.93 (0.61–1.45)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.05 (0.93–1.19)
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.1.08
0≤1.21.6
LoF obs/exp: 14 / 15.0Missense obs/exp: 177 / 169.1Syn Z: -0.52

ClinVar Variant Classifications

495 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic34
Likely Pathogenic40
VUS181
Likely Benign221
Benign12
Conflicting7
34
Pathogenic
40
Likely Pathogenic
181
VUS
221
Likely Benign
12
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
17
0
17
0
34
Likely Pathogenic
27
2
11
0
40
VUS
3
165
9
4
181
Likely Benign
2
6
81
132
221
Benign
0
3
9
0
12
Conflicting
—7
Total49176127136495

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

View in ClinVar →

Protein Context — Lollipop Plot

TSFM · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Combined oxidative phosphorylation deficiency 3

MIM #610505

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Integrated multi-omics insight into the molecular networks of oxidative stress in triggering multiple sclerosis.
Xu Y et al.·Neurobiol Dis
2025
Novel homozygous TSFM pathogenic variant associated with encephalocardiomyopathy with sensorineural hearing loss and peculiar neuroradiologic findings.
Scala M et al.·Neurogenetics
2019Case report
Short-term regulation of TSFM level does not alter amyloidogenesis and mitochondrial function in type-specific cells.
Li XY et al.·Mol Biol Rep
2024
Molecular-genetic characterization and rescue of a TSFM mutation causing childhood-onset ataxia and nonobstructive cardiomyopathy.
Emperador S et al.·Eur J Hum Genet
2016Case report
Novel compound mutations in the mitochondrial translation elongation factor (TSFM) gene cause severe cardiomyopathy with myocardial fibro-adipose replacement.
Perli E et al.·Sci Rep
2019
Extensive clinical and genetic workup is worthwhile in patients with Leigh-like syndrome due to the TSFM variant c.547G>A.
Finsterer J·Neurogenetics
2019Cohort
Identification of extremely rare mitochondrial disorders by whole exome sequencing.
Seo GH et al.·J Hum Genet
2019
KIF2C affects sperm cell differentiation in patients with Klinefelter syndrome, as revealed by RNA-Seq and scRNA-Seq data.
He H et al.·FEBS Open Bio
2022Cohort
The splice site variant rs11078928 may be associated with a genotype-dependent alteration in expression of GSDMB transcripts.
Morrison FS et al.·BMC Genomics
2013
Mitochondrial EFTs defects in juvenile-onset Leigh disease, ataxia, neuropathy, and optic atrophy.
Ahola S et al.·Neurology
2014Case report
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