MTRF1

Chr 13

mitochondrial translation release factor 1

Also known as: MRF1, MTTRF1, RF1

NCBI Gene: 9617 ENSG00000120662 UniProt: O75570

The encoded protein is a mitochondrial peptide chain release factor that directs the termination of translation in response to non-canonical stop codons AGG and AGA found in specific mitochondrial genes (MT-CO1 and MT-ND6). Based on current databases, no specific diseases have been definitively associated with pathogenic variants in this gene. The gene shows minimal constraint against loss-of-function variants (very low pLI score), suggesting that complete loss of function may be tolerated.

ResearchSummary from RefSeq, UniProt

The protein encoded by this gene was determined by in silico methods to be a mitochondrial protein with similarity to the peptide chain release factors (RFs) discovered in bacteria and yeast. The peptide chain release factors direct the termination of translation in response to the peptide chain termination codons. Initially thought to have a role in the termination of mitochondria protein synthesis, a recent publication found no mitochondrial translation release functionality. Multiple alternatively spliced transcript variants have been suggested by mRNA and EST data; however, their full-length natures are not clear. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.97

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.97LOEUF

pLI 0.000

Z-score 1.69

OE 0.67 (0.47–0.97)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.60Z-score

OE missense 0.89 (0.80–1.00)

213 obs / 238.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.67 (0.47–0.97)

0≤0.351.4

Missense OE?0.89 (0.80–1.00)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 20 / 30.0Missense obs/exp: 213 / 238.9Syn Z: 0.70

Background carrier burden — how many people carry a rare variant somewhere in MTRF1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

496 rare PASS variants

Rare truncating (LoF)

1 in 810

109 rare PASS variants

Rare synonymous (reference)

1 in 140

175 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MTRF1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 230	1 in 720
South Asian	~43k	1 in 91	1 in 1,400
Remaining (unassigned)	~30k	1 in 130	1 in 1,400
European (Finnish)	~27k	1 in 330	1 in 2,000
Admixed American	~22k	1 in 120	1 in 2,500
African / African American	~21k	1 in 98	1 in 1,200
East Asian	~20k	1 in 74	1 in 2,200
Ashkenazi Jewish	~13k	1 in 380	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 100	≈ 1 in 820

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 8 of 9 coding exons well covered in gnomAD exomes; exon 10 marginal. Genomes: all 9.? see exons ↓