PCCB

Chr 3AR

propionyl-CoA carboxylase subunit beta

NCBI Gene: 5096ENSG00000114054UniProt: P05166

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]

Primary Disease Associations & Inheritance

PropionicacidemiaMIM #606054
AR
UniProtPropionic acidemia type II
282
ClinVar variants
50
Pathogenic / LP
0.00
pLI score
0
Active trials
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
50 Pathogenic / Likely Pathogenic· 97 VUS of 282 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.89LOEUF
pLI 0.000
Z-score 2.00
OE 0.60 (0.41–0.89)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.87Z-score
OE missense 1.14 (1.04–1.24)
353 obs / 310.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.60 (0.41–0.89)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.14 (1.04–1.24)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.20
0≤1.21.6
LoF obs/exp: 17 / 28.5Missense obs/exp: 353 / 310.0Syn Z: -1.67

ClinVar Variant Classifications

282 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic26
VUS97
Likely Benign129
Benign3
Conflicting3
24
Pathogenic
26
Likely Pathogenic
97
VUS
129
Likely Benign
3
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
13
2
8
1
24
Likely Pathogenic
16
7
3
0
26
VUS
2
80
7
8
97
Likely Benign
0
0
83
46
129
Benign
0
0
3
0
3
Conflicting
—3
Total318910455282

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

View in ClinVar →

Protein Context — Lollipop Plot

PCCB · protein map & ClinVar variants

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

Gene2Phenotype Curations

PCCB-related propionic acidemia

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Propionicacidemia

MIM #606054

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — PCCB
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Pathophysiological mechanisms of complications associated with propionic acidemia.
Marchuk H et al.·Pharmacol Ther
2023Review
Prevalence of propionic acidemia in China.
Zhang Y et al.·Orphanet J Rare Dis
2023Review
Overview of mutations in the PCCA and PCCB genes causing propionic acidemia.
Ugarte M et al.·Hum Mutat
1999Review
Novel compound heterozygous variants in the PCCB gene causing adult-onset propionic acidemia presenting with neuropsychiatric symptoms: a case report and literature review.
Li Y et al.·BMC Med Genomics
2022Review
Propionic acidemia in the Arab World.
Zayed H·Gene
2015Review
Propionic acidemia: mutation update and functional and structural effects of the variant alleles.
Desviat LR et al.·Mol Genet Metab
2004Review
A common benign intronic deletion masking a pathogenic deep intronic PCCB variant - genome sequencing and RNA studies to the rescue.
Kurolap A et al.·Mol Genet Metab
2023
Clinical and laboratory characteristics of propionic acidemia in a Turkish cohort.
Akar HT et al.·J Pediatr Endocrinol Metab
2025Cohort
Functional analysis of PCCB mutations causing propionic acidemia based on expression studies in deficient human skin fibroblasts.
Pérez-Cerdá C et al.·Biochim Biophys Acta
2003Functional
Seventeen Novel Mutations in PCCA and PCCB Genes in Indian Propionic Acidemia Patients, and Their Outcomes.
Gupta D et al.·Genet Test Mol Biomarkers
2016Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Identification of novel compound heterozygote variants in the PCCB gene in a fetus with undetectable fetal phenotype.
Feng X et al.·BMC Med Genomics
2026
Novel CRISPR-Cas9 iPSC knockouts for PCCA and PCCB genes: advancing propionic acidemia research.
García-Tenorio EM et al.·Hum Cell
2025🔓 Open Access
PPDPF promotes esophageal squamous cell carcinoma progression by blocking PCCA binding to PCCB and inhibiting methionine catabolism.
Li M et al.·Cancer Lett
2024
Establishment of a non-integrated iPSC line (SDQLCHi043-A) from a male infant with propionic acidemia carrying compound heterozygote mutations in PCCB gene.
Li Z et al.·Stem Cell Res
2024
Functional analysis of novel variants identified in cis in the PCCB gene in a patient with propionic acidemia.
Martínez-Pizarro A et al.·Gene
2024Functional
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools