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…

Primary Disease Associations & Inheritance

Multiple mitochondrial dysfunctions syndrome 6MIM #617954

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Multiple mitochondrial dysfunctions syndrome 6; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.90

LOEUF

Mechanism· predicted

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

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

652 rare PASS variants

Rare truncating (LoF)

1 in 1,400

125 rare PASS variants

Rare synonymous (reference)

1 in 240

210 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PMPCB. 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 110	1 in 1,300
South Asian	~43k	1 in 90	1 in 1,700
Remaining (unassigned)	~30k	1 in 86	1 in 1,500
European (Finnish)	~27k	1 in 240	≈ 1 in 27,000
Admixed American	~22k	1 in 100	1 in 1,200
African / African American	~21k	1 in 79	1 in 700
East Asian	~20k	1 in 110	1 in 880
Ashkenazi Jewish	~13k	1 in 550	1 in 1,400
Middle Eastern	~2,884	1 in 130	≈ 1 in 710

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): 10 of 13 coding exons well covered in gnomAD exomes; exons 3, 6, 7 marginal. Genomes: all 13.? see exons ↓