MIPEP

Chr 13AR

mitochondrial intermediate peptidase

Also known as: COXPD31, HMIP, MIP

NCBI Gene: 4285 ENSG00000027001 UniProt: Q99797 OMIM: 602241

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.

OMIM 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]

OMIM ResearchGenerating clinical summary…

ARLOEUF 1.031 OMIM phenotype

Clinical Summary— MIPEP

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Gene-Disease Validity (ClinGen)

mitochondrial disease · ARModerate

Moderate evidence — consider for supplementary testing

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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

19 unique Pathogenic / Likely Pathogenic· 154 VUS of 341 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?

1.03LOEUF

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

ClinVar Variant Classifications

341 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7

Likely Pathogenic12

VUS154

Likely Benign84

Benign46

Conflicting13

Pathogenic

Likely Pathogenic

154

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	7	0	0	0	7
Likely Pathogenic	8	3	1	0	12
VUS	1	147	5	1	154
Likely Benign	0	8	34	42	84
Benign	0	9	33	4	46
Conflicting	—				13
Total	16	167	73	47	316

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

View in ClinVar →

44 pathogenic / likely-pathogenic (of 91) ClinVar copy-number / structural variants overlap MIPEP — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →