PMPCA

Chr 9AR

peptidase, mitochondrial processing subunit alpha

The protein functions as the substrate recognition and binding subunit of the mitochondrial processing protease, which cleaves transit peptides from newly imported nuclear-encoded mitochondrial proteins. Mutations cause spinocerebellar ataxia, autosomal recessive 2, which primarily affects cerebellar function leading to progressive ataxia. The gene follows autosomal recessive inheritance and is highly constrained against loss-of-function variants.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 1.071 OMIM phenotype
Clinical SummaryPMPCA
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Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.07LOEUF
pLI 0.000
Z-score 1.27
OE 0.74 (0.521.07)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.16Z-score
OE missense 0.97 (0.891.07)
324 obs / 332.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.74 (0.521.07)
00.351.4
Missense OE0.97 (0.891.07)
00.61.4
Synonymous OE1.14
01.21.6
LoF obs/exp: 20 / 27.2Missense obs/exp: 324 / 332.3Syn Z: -1.31
DN
0.6258th %ile
GOF
0.5268th %ile
LOF
0.3939th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PMPCA · 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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