MTIF3

Chr 13

mitochondrial translational initiation factor 3

Also known as: IF3mt

NCBI Gene: 219402 ENSG00000122033 UniProt: Q9H2K0

This gene encodes a translation initiation factor that binds to the 28S ribosomal subunit and regulates the equilibrium between assembled 55S ribosomes and their free subunits to facilitate mitochondrial protein synthesis initiation. Mutations cause Combined Oxidative Phosphorylation Deficiency 4, an autosomal recessive mitochondrial disorder with infantile onset characterized by severe neurodegeneration and cardiomyopathy. The gene is extremely intolerant to loss-of-function variants, reflecting its critical role in mitochondrial function.

ResearchSummary from RefSeq, UniProt

This gene encodes a translation initiation factor that is involved in mitochondrial protein synthesis. Polymorphism in this gene is associated with the onset of Parkinson's disease. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 5. [provided by RefSeq, Oct 2009]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.61

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?

1.61LOEUF

pLI 0.000

Z-score 0.10

OE 0.97 (0.59–1.61)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.35Z-score

OE missense 0.92 (0.79–1.06)

130 obs / 141.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.97 (0.59–1.61)

0≤0.351.4

Missense OE?0.92 (0.79–1.06)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 10 / 10.3Missense obs/exp: 130 / 141.8Syn Z: 0.00

Background carrier burden — how many people carry a rare variant somewhere in MTIF3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

316 rare PASS variants

Rare truncating (LoF)

1 in 1,500

54 rare PASS variants

Rare synonymous (reference)

1 in 600

122 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MTIF3. 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 170	1 in 1,600
South Asian	~43k	1 in 130	1 in 1,200
Remaining (unassigned)	~30k	1 in 130	1 in 2,200
European (Finnish)	~27k	1 in 1,600	none seen
Admixed American	~22k	1 in 190	1 in 2,000
African / African American	~21k	1 in 230	1 in 940
East Asian	~20k	1 in 380	1 in 2,200
Ashkenazi Jewish	~13k	1 in 1,900	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 200	≈ 1 in 940

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): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓