MTRFR

Chr 12

mitochondrial translation release factor in rescue

Also known as: C12orf65, COXPD7, SPG55, mtRF-R

The protein contributes to peptide chain termination in mitochondrial translation machinery and functions as part of a mitoribosome-associated quality control pathway that ejects unfinished nascent chains from stalled ribosomes. Mutations cause combined oxidative phosphorylation deficiency 7 and spastic paraplegia 55 through autosomal recessive inheritance, resulting in decreased mitochondrial translation and reduced levels of oxidative phosphorylation complexes that lead to encephalomyopathy.

GeneReviewsResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismLOEUF 0.91
Clinical SummaryMTRFR
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Gene-Disease Validity (ClinGen)
Leigh syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
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ClinVar Variants
47 unique Pathogenic / Likely Pathogenic· 104 VUS of 213 total submissions
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GeneReview available — MTRFR
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.91LOEUF
pLI 0.209
Z-score 1.74
OE 0.29 (0.120.91)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.43Z-score
OE missense 1.13 (0.961.33)
102 obs / 90.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.29 (0.120.91)
00.351.4
Missense OE1.13 (0.961.33)
00.61.4
Synonymous OE0.77
01.21.6
LoF obs/exp: 2 / 6.9Missense obs/exp: 102 / 90.4Syn Z: 1.13
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveMTRFR-related combined oxidative phosphorylation deficiencyLOFAR

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

DN
0.7132th %ile
GOF
0.7126th %ile
LOF
0.3259th %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

213 submitted variants in ClinVar

Classification Summary

Pathogenic34
Likely Pathogenic13
VUS104
Likely Benign43
Benign9
Conflicting9
34
Pathogenic
13
Likely Pathogenic
104
VUS
43
Likely Benign
9
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
14
0
20
0
34
Likely Pathogenic
8
1
4
0
13
VUS
3
60
41
0
104
Likely Benign
0
0
15
28
43
Benign
0
1
7
1
9
Conflicting
9
Total25628729212

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

View in ClinVar →

Protein Context — Lollipop Plot

MTRFR · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC