MTRF1L

Chr 6

mitochondrial translation release factor 1 like

Also known as: HMRF1L, MRF1L, mtRF1a

NCBI Gene: 54516ENSG00000112031UniProt: Q9UGC7

The protein encoded by this gene plays a role in mitochondrial translation termination, and is thought to be a release factor that is involved in the dissociation of the complete protein from the final tRNA, the ribosome, and the cognate mRNA. This protein acts upon UAA and UAG stop codons, but has no in vitro activity against UGA, which encodes tryptophan in human mitochondrion, or, the mitochondrial non-cognate stop codons, AGA and AGG. This protein shares sequence similarity to bacterial release factors. Pseudogenes of this gene are found on chromosomes 4, 8, and 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2014]

83
ClinVar variants
23
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MTRF1L
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 51 VUS of 83 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.
1.48LOEUF
pLI 0.000
Z-score 0.14
OE 0.96 (0.64–1.48)
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.
-0.54Z-score
OE missense 1.11 (0.99–1.24)
212 obs / 191.0 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.0.96 (0.64–1.48)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.11 (0.99–1.24)
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.1.01
0≤1.21.6
LoF obs/exp: 15 / 15.6Missense obs/exp: 212 / 191.0Syn Z: -0.10

ClinVar Variant Classifications

83 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic1
VUS51
22
Pathogenic
1
Likely Pathogenic
51
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
22
0
22
Likely Pathogenic
0
0
1
0
1
VUS
0
49
2
0
51
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total04925074

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

View in ClinVar →

Protein Context — Lollipop Plot

MTRF1L · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Mendelian Randomization Analysis of Mitochondria-Related Genes and Screening of Prognostic Genes in Colorectal Cancer.
Zhu L et al.·Cancer Med
2025
Molecular basis of translation termination at noncanonical stop codons in human mitochondria.
Saurer M et al.·Science
2023
Mammalian HEMK1 methylates glutamine residue of the GGQ motif of mitochondrial release factors.
Fang Q et al.·Sci Rep
2022
Human mitochondrial protein complexes revealed by large-scale coevolution analysis and deep learning-based structure modeling.
Pei J et al.·Bioinformatics
2022Functional
Integrative bioinformatics analysis for identifying the mitochondrial-related gene associated with immune infiltration in sarcopenia.
Yan H et al.·Medicine (Baltimore)
2025
Mitochondrial proteomics profile points oxidative phosphorylation as main target for beauvericin and enniatin B mixture.
Alonso-Garrido M et al.·Food Chem Toxicol
2020
Bioinformatic, structural, and functional analyses support release factor-like MTRF1 as a protein able to decode nonstandard stop codons beginning with adenine in vertebrate mitochondria.
Young DJ et al.·RNA
2010Functional
Human mitochondria require mtRF1 for translation termination at non-canonical stop codons.
Krüger A et al.·Nat Commun
2023
Human mtRF1 terminates COX1 translation and its ablation induces mitochondrial ribosome-associated quality control.
Nadler F et al.·Nat Commun
2022
Structural basis of translation termination, rescue, and recycling in mammalian mitochondria.
Kummer E et al.·Mol Cell
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

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