PCCA

Chr 13AR

propionyl-CoA carboxylase subunit alpha

The protein encoded by this gene is the alpha subunit of the heterodimeric mitochondrial enzyme Propionyl-CoA carboxylase. PCCA encodes the biotin-binding region of this enzyme. Mutations in either PCCA or PCCB (encoding the beta subunit) lead to an enzyme deficiency resulting in propionic acidemia. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]

GeneReviewsOMIMResearchGenerating clinical summary…
LOFmechanismARLOEUF 0.911 OMIM phenotype
Clinical SummaryPCCA
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Gene-Disease Validity (ClinGen)
propionic acidemia · 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.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — PCCA
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.91LOEUF
pLI 0.000
Z-score 2.06
OE 0.67 (0.500.91)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.19Z-score
OE missense 0.97 (0.901.06)
387 obs / 397.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.67 (0.500.91)
00.351.4
Missense OE?0.97 (0.901.06)
00.61.4
Synonymous OE?0.90
01.21.6
LoF obs/exp: 30 / 44.9Missense obs/exp: 387 / 397.4Syn Z: 0.91
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePCCA-related propionic acidemiaLOFAR

This gene — mechanism propensity

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

DN
0.6938th %ile
GOF
0.5856th %ile
LOF
0.3259th %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

PCCA · protein map & ClinVar variants

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