PCCB

Chr 3AR

propionyl-CoA carboxylase subunit beta

NCBI Gene: 5096 ENSG00000114054 UniProt: P05166 OMIM: 232050

The protein is the beta subunit of propionyl-CoA carboxylase, a mitochondrial enzyme that catabolizes propionyl-CoA and functions as a dodecamer of six alpha and six beta subunits. Mutations cause propionic acidemia, inherited in an autosomal recessive pattern. Loss-of-function mutations result in deficient enzyme activity leading to accumulation of toxic metabolites.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene is a subunit of the propionyl-CoA carboxylase (PCC) enzyme, which is involved in the catabolism of propionyl-CoA. PCC is a mitochondrial enzyme that probably acts as a dodecamer of six alpha subunits and six beta subunits. This gene encodes the beta subunit of PCC. Defects in this gene are a cause of propionic acidemia type II (PA-2). Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.891 OMIM phenotype

Clinical Summary— PCCB

🧬

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.

📋

ClinVar Variants

286 unique Pathogenic / Likely Pathogenic· 396 VUS of 1376 total submissions

Explore recent and relevant literature in Research Assistant →

📖

GeneReview available — PCCB

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.89LOEUF

pLI 0.000

Z-score 2.00

OE 0.60 (0.41–0.89)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.87Z-score

OE missense 1.14 (1.04–1.24)

353 obs / 310.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.60 (0.41–0.89)

0≤0.351.4

Missense OE?1.14 (1.04–1.24)

0≤0.61.4

Synonymous OE?1.20

0≤1.21.6

LoF obs/exp: 17 / 28.5Missense obs/exp: 353 / 310.0Syn Z: -1.67

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitivePCCB-related propionic acidemiaLOFAR

This gene — mechanism propensity

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

0.79top 25%

GOF

0.5563th %ile

LOF

0.2774th %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

1376 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic121

Likely Pathogenic165

VUS396

Likely Benign590

Benign27

Conflicting58

121

Pathogenic

165

Likely Pathogenic

396

VUS

590

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	78	26	16	1	121
Likely Pathogenic	103	55	7	0	165
VUS	5	348	32	11	396
Likely Benign	3	4	290	293	590
Benign	0	0	27	0	27
Conflicting	—				58
Total	189	433	372	305	1,357

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

21 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap PCCB — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →