PMPCB

Chr 7AR

peptidase, mitochondrial processing subunit beta

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

NCBI Gene: 9512 ENSG00000105819 UniProt: O75439 OMIM: 603131

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene is a member of the peptidase M16 family and encodes a protein with a zinc-binding motif. This protein is located in the mitochondrial matrix and catalyzes the cleavage of the leader peptides of precursor proteins newly imported into the mitochondria, though it only functions as part of a heterodimeric complex. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 0.901 OMIM phenotype

Clinical Summary— PMPCB

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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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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.90LOEUF

pLI 0.000

Z-score 1.96

OE 0.59 (0.40–0.90)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.22Z-score

OE missense 1.04 (0.94–1.15)

279 obs / 269.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.59 (0.40–0.90)

0≤0.351.4

Missense OE?1.04 (0.94–1.15)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

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

This gene — mechanism propensity

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

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.