PCCA Gene

Name	propionyl CoA carboxylase, alpha polypeptide
Description	The protein encoded by this gene is the alpha subunit of the heterodimeric mitochondrial enzyme Propionyl-CoA carboxylase. PCCA encodes the biotin-binding region of this enzyme. Mutations in either PCCA or PCCB (encoding the beta subunit) lead to an enzyme deficiency resulting in propionic acidemia. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPropionyl‐CoA carboxylase (PCC) is a mitochondrial, biotin‐dependent enzyme that catalyzes the carboxylation of propionyl–CoA to D–methylmalonyl–CoA—a critical step in the catabolism of branched chain amino acids (threonine, valine, isoleucine, and methionine), odd–chain fatty acids, and cholesterol. The PCCA gene encodes the alpha subunit of PCC, which contains the biotin carboxylase and biotin–carboxyl carrier protein domains and is responsible for the formation and transfer of carboxybiotin during the reaction cycle. This structural organization has been elucidated by crystallographic and electron microscopy studies that also reveal the spatial separation of the active sites within the holoenzyme."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDefects in PCCA function—arising from a heterogeneous spectrum of mutations including missense changes, small insertions or deletions, and aberrant splicing events—impair PCC activity and lead to propionic acidemia, an autosomal recessive metabolic disorder. Detailed mutational analyses have revealed that many patients harbor unique or compound–heterozygous changes in the PCCA gene, and innovative therapeutic approaches, such as the use of antisense morpholino oligonucleotides, have been employed to correct aberrant pre–mRNA splicing and rescue PCC enzyme function. Studies in diverse patient populations, including those from Europe, Asia, and the Americas, have contributed to our understanding of genotype–phenotype correlations and the molecular basis for enzyme deficiency in propionic acidemia."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "12"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its canonical role in intermediary metabolism, emerging evidence suggests that PCCA may influence host–pathogen interactions. Recent investigations have demonstrated that PCCA interacts with bacterial factors—specifically the phospholipase PlcB of Listeria monocytogenes—and that increased PCCA expression correlates with reduced bacterial proliferation in host cells, indicating a novel, non–metabolic role in moderating intracellular infection."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Christine S Huang, Kianoush Sadre-Bazzaz, Yang Shen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Crystal structure of the alpha(6)beta(6) holoenzyme of propionyl-coenzyme A carboxylase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature09302"}], "href": "https://doi.org/10.1038/nature09302"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20725044"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20725044"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hua Jiang, K Sudhindra Rao, Vivien C Yee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of four variant forms of human propionyl-CoA carboxylase expressed in Escherichia coli."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M413281200"}], "href": "https://doi.org/10.1074/jbc.M413281200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15890657"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15890657"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sonia Clavero, Maria Angeles Martínez, Belén Pérez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional characterization of PCCA mutations causing propionic acidemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0925-4439(02)00155-2"}], "href": "https://doi.org/10.1016/s0925-4439(02"}, {"type": "t", "text": "00155-2) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12385775"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12385775"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "B Pérez, L R Desviat, P Rodríguez-Pombo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Propionic acidemia: identification of twenty-four novel mutations in Europe and North America."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Metab (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s1096-7192(02)00197-x"}], "href": "https://doi.org/10.1016/s1096-7192(02"}, {"type": "t", "text": "00197-x) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12559849"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12559849"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "A Rincón, C Aguado, L R Desviat, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Propionic and methylmalonic acidemia: antisense therapeutics for intronic variations causing aberrantly spliced messenger RNA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/522376"}], "href": "https://doi.org/10.1086/522376"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17966092"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17966092"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Lourdes R Desviat, Rocío Sanchez-Alcudia, Belén Pérez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High frequency of large genomic deletions in the PCCA gene causing propionic acidemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Metab (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymgme.2008.12.009"}], "href": "https://doi.org/10.1016/j.ymgme.2008.12.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19157943"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19157943"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Lourdes R Desviat, Sonia Clavero, Celia Perez-Cerdá, et al. "}, {"type": "b", "children": [{"type": "t", "text": "New splicing mutations in propionic acidemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hum Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10038-006-0068-3"}], "href": "https://doi.org/10.1007/s10038-006-0068-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17051315"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17051315"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Ana Rivera-Barahona, Rosa Navarrete, Raquel García-Rodríguez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of 34 novel mutations in propionic acidemia: Functional characterization of missense variants and phenotype associations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Metab (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymgme.2018.09.008"}], "href": "https://doi.org/10.1016/j.ymgme.2018.09.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30274917"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30274917"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yan Li, Li Zhang, Francesca Polverino, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hedgehog interacting protein (HHIP) represses airway remodeling and metabolic reprogramming in COPD-derived airway smooth muscle cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-021-88434-x"}], "href": "https://doi.org/10.1038/s41598-021-88434-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33907231"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33907231"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Zhanling Chen, Pengqiang Wen, Guobing Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[Analysis of PCCA and PCCB gene mutations in patients with propionic acidemia]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Zhonghua Yi Xue Yi Chuan Xue Za Zhi (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3760/cma.j.issn.1003-9406.2015.01.006"}], "href": "https://doi.org/10.3760/cma.j.issn.1003-9406.2015.01.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25636094"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25636094"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Nithiwat Vatanavicharn, Somporn Liammongkolkul, Osamu Sakamoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical characteristics and mutation analysis of propionic acidemia in Thailand."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "World J Pediatr (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12519-014-0454-4"}], "href": "https://doi.org/10.1007/s12519-014-0454-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24464666"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24464666"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Igor Bychkov, Artur Galushkin, Alexandra Filatova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional Analysis of the "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "PCCA"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " and "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "PCCB"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Gene Variants Predicted to Affect Splicing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms22084154"}], "href": "https://doi.org/10.3390/ijms22084154"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33923806"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33923806"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Jing Wang, Mingzhu Cui, Yucong Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The mitochondrial carboxylase PCCA interacts with "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "Listeria monocytogenes"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " phospholipase PlcB to modulate bacterial survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Appl Environ Microbiol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/aem.02135-23"}], "href": "https://doi.org/10.1128/aem.02135-23"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38727222"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38727222"}]}]}]}
Proteins	PCCA_HUMAN
NCBI Gene ID	5095
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PCCA has 7,066 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 132 datasets.

Click the + buttons to view associations for PCCA from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PCCA Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by PCCA gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PCCA gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of PCCA gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of PCCA gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of PCCA gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PCCA gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of PCCA gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PCCA gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PCCA gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PCCA gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of PCCA gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PCCA protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PCCA gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PCCA gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of PCCA gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with PCCA gene from the curated ClinVar Gene-Phenotype Associations dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of PCCA gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PCCA protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PCCA protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with PCCA protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with PCCA protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of PCCA gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PCCA gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PCCA gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PCCA gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with PCCA gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of PCCA protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by PCCA gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving PCCA gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving PCCA gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with PCCA gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with PCCA gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with PCCA gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with PCCA gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with PCCA gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PCCA gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for PCCA protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at PCCA gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PCCA gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PCCA gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.