MIPEP

Chr 13

mitochondrial intermediate peptidase

ENSG00000027001UniProt: Q99797

Cleaves proteins, imported into the mitochondrion, to their mature size

Primary Disease Associations & Inheritance

UniProtCombined oxidative phosphorylation deficiency 31
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MIPEP
🧬
Gene-Disease Validity (ClinGen)
mitochondrial disease · ARModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (2)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

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?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.
1.03LOEUF
pLI 0.000
Z-score 1.38
OE 0.76 (0.56–1.03)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?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.
0.22Z-score
OE missense 0.97 (0.89–1.05)
366 obs / 378.1 exp
Tolerant

Mild missense constraint

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.0.76 (0.56–1.03)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.89–1.05)
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.0.97
0≤1.21.6
LoF obs/exp: 28 / 37.1Missense obs/exp: 366 / 378.1Syn Z: 0.30

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

MIPEP · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genotype-phenotype correlation and interaction of 4q25, 15q14 and MIPEP variants with myopia in southern Chinese population.
Liu J et al.·Br J Ophthalmol
2021
Mitochondrial Protein Homeostasis and Cardiomyopathy.
Wachoski-Dark E et al.·Int J Mol Sci
2022Review
Variants in the MIPEP gene presenting with complex neurological phenotype without cardiomyopathy, impair OXPHOS protein maturation and lead to a reduced OXPHOS abundance in patient cells.
Pulman J et al.·Mol Genet Metab
2021Case report
MIPEP recessive variants cause a syndrome of left ventricular non-compaction, hypotonia, and infantile death.
Eldomery MK et al.·Genome Med
2016Case report
Lessons learned from additional research analyses of unsolved clinical exome cases.
Eldomery MK et al.·Genome Med
2017Cohort
Randomized controlled trial of the tolerability and completion of maraviroc compared with Kaletra® in combination with Truvada® for HIV post-exposure prophylaxis (MiPEP Trial).
Milinkovic A et al.·J Antimicrob Chemother
2017
Functional and genomic analysis of the human mitochondrial intermediate peptidase, a putative protein partner of frataxin.
Chew A et al.·Genomics
2000Functional
Genetic variants at 13q12.12 are associated with high myopia in the Han Chinese population.
Shi Y et al.·Am J Hum Genet
2011
Imipridone Anticancer Compounds Ectopically Activate the ClpP Protease and Represent a New Scaffold for Antibiotic Development.
Jacques S et al.·Genetics
2020
Corneal curvature-associated MTOR variant differentiates mild myopia from high myopia in Han Chinese population.
Yuan XL et al.·Ophthalmic Genet
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Identification of a novel MIPEP splice variant with altered substrate-binding properties.
Otani Y et al.·Biochem Biophys Rep
2025🔓 Open Access
Co-overexpression of the caloric restriction-induced mitochondrial factors PGC-1α and MIPEP upregulates Phospho1 expression in adipocytes.
Ishimatsu M et al.·FEBS Open Bio
2025🔓 Open Access
Mipep deficiency in adipocytes impairs mitochondrial protein maturation and leads to systemic inflammation and metabolic dysfunctions.
Nozaki Y et al.·Sci Rep
2025🔓 Open Access
ESF1 and MIPEP proteins promote estrogen receptor-positive breast cancer proliferation and are associated with patient prognosis.
Yu Q et al.·Clin Proteomics
2024🔓 Open Access
Deletion of miPEP in adipocytes protects against obesity and insulin resistance by boosting muscle metabolism.
Diaz-Vegas A et al.·Mol Metab
2024🔓 Open Access
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