MIPEP

Chr 13

mitochondrial intermediate peptidase

Also known as: COXPD31, HMIP, MIP

NCBI Gene: 4285 ENSG00000027001 UniProt: Q99797

The protein cleaves imported mitochondrial proteins to their mature size, representing the final processing step for nuclear-encoded proteins targeted to the mitochondrial matrix or inner membrane, particularly those involved in oxidative phosphorylation. Mutations cause combined oxidative phosphorylation deficiency 31 with autosomal recessive inheritance. The gene shows minimal constraint against loss-of-function variants (pLI near zero), which is consistent with recessive disease requiring biallelic mutations.

ResearchSummary from RefSeq, OMIM, UniProt

The product of this gene performs the final step in processing a specific class of nuclear-encoded proteins targeted to the mitochondrial matrix or inner membrane. This protein is primarily involved in the maturation of oxidative phosphorylation (OXPHOS)-related proteins. This gene may contribute to the functional effects of frataxin deficiency and the clinical manifestations of Friedreich ataxia. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCombined oxidative phosphorylation deficiency 31

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · mitochondrial disease · AR · ClinGen 2023

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.03

LOEUF

—

Mechanism

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?

1.03LOEUF

pLI 0.000

Z-score 1.38

OE 0.76 (0.56–1.03)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.22Z-score

OE missense 0.97 (0.89–1.05)

366 obs / 378.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.76 (0.56–1.03)

0≤0.351.4

Missense OE?0.97 (0.89–1.05)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 28 / 37.1Missense obs/exp: 366 / 378.1Syn Z: 0.30

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 36

1,009 rare PASS variants

Rare truncating (LoF)

1 in 670

176 rare PASS variants

Rare synonymous (reference)

1 in 90

354 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MIPEP. 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 55	1 in 640
South Asian	~43k	1 in 40	1 in 390
Remaining (unassigned)	~30k	1 in 38	1 in 1,300
European (Finnish)	~27k	1 in 210	1 in 2,700
Admixed American	~22k	1 in 37	1 in 850
African / African American	~21k	1 in 55	1 in 880
East Asian	~20k	1 in 55	1 in 410
Ashkenazi Jewish	~13k	1 in 330	≈ 1 in 3,200
Middle Eastern	~2,884	1 in 42	1 in 480

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): 14 of 19 coding exons well covered in gnomAD exomes; exons 1, 4, 8, 9, 14 marginal. Genomes: all 19.? see exons ↓