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.

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

PropionicacidemiaMIM #606054

UniProtPropionic acidemia type II

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · propionic acidemia · AR · ClinGen 2018

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.89

LOEUF

LOF

Mechanism· G2P

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

Background carrier burden — how many people carry a rare variant somewhere in PCCB?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 53

972 rare PASS variants

Rare truncating (LoF)

1 in 200

170 rare PASS variants

Rare synonymous (reference)

1 in 220

348 rare PASS variants

Rare missense and truncating variants are carried at similar rates in PCCB; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 66	1 in 260
South Asian	~43k	1 in 58	1 in 810
Remaining (unassigned)	~30k	1 in 42	1 in 420
European (Finnish)	~27k	1 in 140	1 in 1,700
Admixed American	~22k	1 in 45	1 in 510
African / African American	~21k	1 in 41	1 in 970
East Asian	~20k	1 in 52	1 in 700
Ashkenazi Jewish	~13k	1 in 400	≈ 1 in 4,400
Middle Eastern	~2,884	1 in 53	1 in 450

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.