MTRF1L

Chr 6

mitochondrial translation release factor 1 like

Also known as: HMRF1L, MRF1L, mtRF1a

NCBI Gene: 54516 ENSG00000112031 UniProt: Q9UGC7 OMIM: 613542

This gene encodes a mitochondrial peptide chain release factor that directs translation termination in response to UAA and UAG stop codons within mitochondria. Mutations cause autosomal recessive mitochondrial disorders affecting multiple organ systems. The gene is extremely intolerant to loss-of-function variants (pLI near 1, LOEUF 1.48), indicating that complete loss of function is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.48

Clinical Summary— MTRF1L

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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

49 VUS of 58 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

-0.54Z-score

OE missense 1.11 (0.99–1.24)

212 obs / 191.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.96 (0.64–1.48)

0≤0.351.4

Missense OE?1.11 (0.99–1.24)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 15 / 15.6Missense obs/exp: 212 / 191.0Syn Z: -0.10

This gene — mechanism propensity

0.6647th %ile

GOF

0.5955th %ile

LOF

0.3647th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

58 submitted variants in ClinVar

ClinVar

Classification Summary

VUS49

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	49	49
Likely Benign	0	0
Benign	0	0
Total	49	49

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

View in ClinVar →

23 pathogenic / likely-pathogenic (of 25) ClinVar copy-number / structural variants overlap MTRF1L — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →