PCCA

Chr 13AR

propionyl-CoA carboxylase subunit alpha

The protein is the alpha subunit of propionyl-CoA carboxylase, a mitochondrial enzyme that contains the biotin-binding region and is essential for catabolism of certain amino acids and odd-chain fatty acids. Mutations cause propionicacidemia, an autosomal recessive disorder characterized by accumulation of toxic metabolites leading to metabolic acidosis, developmental delay, and multisystem complications. The pathogenic mechanism involves enzyme deficiency resulting from loss of normal protein function.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
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
1 active or recruiting trial — 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 OE0.67 (0.500.91)
00.351.4
Missense OE0.97 (0.901.06)
00.61.4
Synonymous OE0.90
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

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.

3D Protein StructureAlphaFold
Clinical Literature
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