PMPCB

Chr 7AR

peptidase, mitochondrial processing subunit beta

Also known as: Beta-MPP, MAS1, MPP11, MPPB, MPPP52, P-52

The protein functions as the catalytic subunit of mitochondrial processing protease, which cleaves leader peptides from newly imported mitochondrial precursor proteins and is required for PINK1 turnover. Mutations cause multiple mitochondrial dysfunctions syndrome 6, inherited in an autosomal recessive pattern. The pathogenic mechanism appears to be dominant negative, where mutant proteins likely interfere with the essential mitochondrial protein processing function.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
DNmechanismARLOEUF 0.901 OMIM phenotype
Clinical SummaryPMPCB
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.90LOEUF
pLI 0.000
Z-score 1.96
OE 0.59 (0.400.90)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.22Z-score
OE missense 1.04 (0.941.15)
279 obs / 269.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.59 (0.400.90)
00.351.4
Missense OE1.04 (0.941.15)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 16 / 27.0Missense obs/exp: 279 / 269.0Syn Z: -0.25
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongPMPCB-related neurodegeneration in early childhoodOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7325th %ile
GOF
0.5366th %ile
LOF
0.3357th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PMPCB · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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