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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
PCCA
propionyl-CoA carboxylase subunit alpha
Chromosome 13 Β· 13q32.3
NCBI Gene: 5095Ensembl: ENSG00000175198.18HGNC: HGNC:8653UniProt: P05165
143PubMed Papers
21Diseases
0Drugs
303Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
succinyl-CoA biosynthetic processpropionyl-CoA carboxylase activitymitochondrial matrixprotein bindingpropionic acidemiagenetic disorderdilated cardiomyopathyneurodegenerative disease
✦AI Summary

PCCA (propionyl-CoA carboxylase subunit alpha) is the catalytic alpha subunit of the biotin-dependent mitochondrial enzyme propionyl-CoA carboxylase (PCC). This enzyme catalyzes the ATP-dependent carboxylation of biotin, which is subsequently transferred to propionyl-CoA to form methylmalonyl-CoA 1. PCCA functions in the catabolism of odd-chain fatty acids, branched-chain amino acids (isoleucine, threonine, methionine, valine), and other metabolites 1. The enzyme also acts on alternative substrates including butyryl-CoA at lower rates. Propionyl-CoA carboxylase is essential for feeding propionyl-CoA into the tricarboxylic acid cycle for energy metabolism 1. Mutations in PCCA cause propionic acidemia (PA), a genetic metabolic disorder characterized by impaired propionyl-CoA conversion and subsequent accumulation of propionyl-CoA and its metabolites 1. This accumulation leads to life-threatening complications including cardiac diseases and metabolic dysfunction through mitochondrial energy impairment and oxidative stress induction 1. Recent evidence demonstrates that PCCA activity can be enhanced by isoflavone biochanin-A binding, which promotes protective glutathione synthesis and ameliorates acetaminophen-induced liver injury 2. Reduced PCCA expression has been documented in liver failure patients, highlighting its clinical significance in hepatic function 2.

Sources cited
1
PCCA is a mitochondrial enzyme responsible for converting propionyl-CoA to methylmalonyl-CoA; mutations cause propionic acidemia with complications including cardiac disease; propionyl-CoA and metabolites impair mitochondrial energy metabolism and cause oxidative stress
PMID: 37482098
2
PCCA binds isoflavone biochanin-A to augment the tricarboxylic acid cycle and promote glutathione synthesis; PCCA expression is reduced in liver failure patients
PMID: 40318624
⚠Limited data available β€” This gene has 2 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜21
propionic acidemiaOpen Targets
0.85Strong
genetic disorderOpen Targets
0.45Moderate
dilated cardiomyopathyOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.36Weak
pontocerebellar hypoplasia type 2DOpen Targets
0.34Weak
risk-taking behaviourOpen Targets
0.33Weak
mathematical abilityOpen Targets
0.33Weak
male reproductive organ cancerOpen Targets
0.33Weak
attention deficit hyperactivity disorderOpen Targets
0.31Weak
substance abuseOpen Targets
0.31Weak
refractive errorOpen Targets
0.30Weak
Abdominal painOpen Targets
0.28Weak
HeadacheOpen Targets
0.28Weak
androgenetic alopeciaOpen Targets
0.27Weak
Limb painOpen Targets
0.26Weak
placenta praeviaOpen Targets
0.26Weak
post-operative sign or symptomOpen Targets
0.26Weak
ovarian neoplasmOpen Targets
0.23Weak
SplenomegalyOpen Targets
0.20Weak
smoking behaviorOpen Targets
0.17Weak
Propionic acidemia type IUniProt
Pathogenic Variants303
NM_000282.4(PCCA):c.2041-2A>GPathogenic
Propionic acidemia
β˜…β˜…β˜†β˜†2026
NM_000282.4(PCCA):c.1168del (p.Arg390fs)Pathogenic
Propionic acidemia
β˜…β˜…β˜†β˜†2026β†’ Residue 390
NM_000282.4(PCCA):c.2002G>A (p.Gly668Arg)Pathogenic
Propionic acidemia|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 668
NM_000282.4(PCCA):c.69_78del (p.Gln23fs)Pathogenic
Propionic acidemia
β˜…β˜…β˜†β˜†2026β†’ Residue 23
NM_000282.4(PCCA):c.183+2T>CPathogenic
Propionic acidemia
β˜…β˜…β˜†β˜†2026
NM_000282.4(PCCA):c.183+1G>APathogenic
Propionic acidemia
β˜…β˜…β˜†β˜†2026
NM_000282.4(PCCA):c.1937del (p.Glu645_Leu646insTer)Likely pathogenic
Propionic acidemia
β˜…β˜…β˜†β˜†2026β†’ Residue 645
NM_000282.4(PCCA):c.889C>T (p.Gln297Ter)Likely pathogenic
Propionic acidemia
β˜…β˜…β˜†β˜†2026β†’ Residue 297
NM_000282.4(PCCA):c.2119-9A>GPathogenic
Propionic acidemia
β˜…β˜…β˜†β˜†2026
NM_000282.4(PCCA):c.1593_1595del (p.Leu532del)Likely pathogenic
Propionic acidemia|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 532
NM_000282.4(PCCA):c.866_867del (p.Glu289fs)Pathogenic
Propionic acidemia|Inborn genetic diseases|PCCA-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 289
NM_000282.4(PCCA):c.1284+1G>APathogenic
not provided|Propionic acidemia|PCCA-related disorder|Cervical cancer|Malignant tumor of urinary bladder
β˜…β˜…β˜†β˜†2025
NM_000282.4(PCCA):c.775_779del (p.Leu259fs)Pathogenic
Propionic acidemia|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 259
NM_000282.4(PCCA):c.1117A>G (p.Met373Val)Likely pathogenic
Propionic acidemia
β˜…β˜…β˜†β˜†2025β†’ Residue 373
NM_000282.4(PCCA):c.231+1G>CPathogenic
Propionic acidemia
β˜…β˜…β˜†β˜†2025
NM_000282.4(PCCA):c.229C>T (p.Arg77Trp)Pathogenic
Propionic acidemia
β˜…β˜…β˜†β˜†2025β†’ Residue 77
NM_000282.4(PCCA):c.1195C>T (p.Arg399Trp)Pathogenic
Propionic acidemia
β˜…β˜…β˜†β˜†2025β†’ Residue 399
NM_000282.4(PCCA):c.2103del (p.Thr704fs)Pathogenic
Propionic acidemia
β˜…β˜…β˜†β˜†2025β†’ Residue 704
NM_000282.4(PCCA):c.497del (p.Pro166fs)Pathogenic
Propionic acidemia
β˜…β˜…β˜†β˜†2025β†’ Residue 166
NM_000282.4(PCCA):c.722del (p.Gly241fs)Pathogenic
Propionic acidemia
β˜…β˜…β˜†β˜†2025β†’ Residue 241
View on ClinVar β†—
Related Genes
CYP4B1Shared pathway100%ACBD7Shared pathway100%AASDHShared pathway100%ACBD4Shared pathway100%ECHDC3Shared pathway100%ACAA2Protein interaction100%
Tissue Expression6 tissues
Liver
100%
Heart
50%
Brain
42%
Ovary
29%
Lung
16%
Bone Marrow
12%
Gene Interaction Network
Click a node to explore
PCCACYP4B1ACBD7AASDHACBD4ECHDC3ACAA2
PROTEIN STRUCTURE
Preparing viewer…
PDB2JKU Β· 1.50 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.99LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.67 [0.47–0.99]
RankingsWhere PCCA stands among ~20K protein-coding genes
  • #3,201of 20,598
    Most Researched143 Β· top quartile
  • #201of 5,498
    Most Pathogenic Variants303 Β· top 5%
  • #9,438of 17,882
    Most Constrained (LOEUF)0.99
Genes detectedPCCA
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Epidemiology of cholangiocarcinoma.
PMID: 37709624
Eur J Surg Oncol Β· 2025
1.00
2
Pathogenesis, diagnosis, and management of cholangiocarcinoma.
PMID: 24140396
Gastroenterology Β· 2013
0.90
3
Clinical treatment of cholangiocarcinoma: an updated comprehensive review.
PMID: 35809836
Ann Hepatol Β· 2022
0.80
4
Pathophysiological mechanisms of complications associated with propionic acidemia.
PMID: 37482098
Pharmacol Ther Β· 2023
0.70
5
A Review of Immunotherapy for Head and Neck Cancer.
PMID: 39370694
J Dent Res Β· 2024
0.60