PCCA

propionyl-CoA carboxylase subunit alpha

Basic information

Region (hg38): 13:100089015-100530437

Links

ENSG00000175198

∙ NCBI:5095 ∙ OMIM:232000 ∙ HGNC:8653 ∙ Uniprot:P05165 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

propionic acidemia (Definitive), mode of inheritance: AR
propionic acidemia (Definitive), mode of inheritance: AR
propionic acidemia (Strong), mode of inheritance: AR
propionic acidemia (Supportive), mode of inheritance: AR
propionic acidemia (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Propionic acidemia	AR	Biochemical; Cardiovascular	In acute episodes, acidosis and hypoglycemia correction, with IV carnitine are beneficial (hemodialysis may be required); Dietary (including protein restriction, to decrease propiogenic substrates) and medical (eg, l-carnitine, metronidazole, N-carbamoylglutamate) therapy may be beneficial; Liver transplant may be required in some individuals; Fasting should be avoided, and care should be taken in the setting of acute stressors; Individuals are at risk for manifestations such as cardiovascular aberrations, and surveillance may be beneficial; mRNA therapy has shown promise in trials	Allergy/Immunology/Infectious; Biochemical; Cardiovascular; Hematologic; Neurologic	4815259; 10502773; 17051315; 19157943; 20301313; 22033733; 22593918 ; 23053474; 30879957; 36395710; 38570682

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PCCA gene.

Propionic_acidemia (1325 variants)
not_provided (130 variants)
Inborn_genetic_diseases (83 variants)
not_specified (50 variants)
PCCA-related_disorder (25 variants)
Pontocerebellar_hypoplasia_type_2D (1 variants)
See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PCCA gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000282.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous		2 clinvar	19 clinvar	323 clinvar	1 clinvar	345
missense	9 clinvar	47 clinvar	368 clinvar	16 clinvar	3 clinvar	443
nonsense	25 clinvar	18 clinvar	2 clinvar			45
start loss	1	1	2			4
frameshift	51 clinvar	61 clinvar	2 clinvar			114
splice donor/acceptor (+/-2bp)	14 clinvar	61 clinvar			1 clinvar	76
Total	100	190	393	339	5

Highest pathogenic variant AF is 0.0000902916

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PCCA	protein_coding	protein_coding	ENST00000376285	24	441418

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.13e-15	0.864	125628	0	120	125748	0.000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.185	387	397	0.974	0.0000212	4736
Missense in Polyphen		99	136.3	0.72634		1604
Synonymous	0.911	127	141	0.902	0.00000793	1375
Loss of Function	2.06	30	44.9	0.668	0.00000225	551

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000855	0.000854
Ashkenazi Jewish	0.000795	0.000794
East Asian	0.000381	0.000381
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000458	0.000457
Middle Eastern	0.000381	0.000381
South Asian	0.000752	0.000752
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

Disease: DISEASE: Propionic acidemia type I (PA-1) [MIM:606054]: Life- threatening disease characterized by episodic vomiting, lethargy and ketosis, neutropenia, periodic thrombocytopenia, hypogammaglobulinemia, developmental retardation, and intolerance to protein. {ECO:0000269|PubMed:10101253, ECO:0000269|PubMed:10329019, ECO:0000269|PubMed:12559849, ECO:0000269|PubMed:15059621}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Propanoate metabolism - Homo sapiens (human);Valine, leucine and isoleucine degradation - Homo sapiens (human);Glyoxylate and dicarboxylate metabolism - Homo sapiens (human);3-Methylglutaconic Aciduria Type I;Valine, Leucine and Isoleucine Degradation;2-Methyl-3-Hydroxybutryl CoA Dehydrogenase Deficiency;Malonyl-coa decarboxylase deficiency;Malonic Aciduria;Isovaleric Aciduria;3-Methylcrotonyl Coa Carboxylase Deficiency Type I;Propionic Acidemia;Maple Syrup Urine Disease;Propanoate Metabolism;3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency;Isobutyryl-coa dehydrogenase deficiency;3-hydroxyisobutyric aciduria;3-hydroxyisobutyric acid dehydrogenase deficiency;Isovaleric acidemia;Methylmalonate Semialdehyde Dehydrogenase Deficiency;Methylmalonic Aciduria;Methylmalonic Aciduria Due to Cobalamin-Related Disorders;3-Methylglutaconic Aciduria Type IV;3-Methylglutaconic Aciduria Type III;Threonine and 2-Oxobutanoate Degradation;Beta-Ketothiolase Deficiency;Biotin transport and metabolism;Metabolism of lipids;propionyl-CoA degradation;Propionyl-CoA catabolism;Mitochondrial Fatty Acid Beta-Oxidation;Metabolism;Fatty acid metabolism;Propanoate metabolism;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors;Valine, leucine and isoleucine degradation;Propanoate metabolism;Valine Leucine Isoleucine degradation;2-oxobutanoate degradation;superpathway of methionine degradation (Consensus)

Recessive Scores

pRec: 0.427

Intolerance Scores

loftool: 0.116
rvis_EVS: 0.09
rvis_percentile_EVS: 60.65

Haploinsufficiency Scores

pHI: 0.675
hipred: N
hipred_score: 0.274
ghis: 0.483

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.860

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Pcca
Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); renal/urinary system phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan);

Gene ontology

Biological process: biotin metabolic process
Cellular component: mitochondrial matrix;cytosol
Molecular function: propionyl-CoA carboxylase activity;protein binding;ATP binding;biotin binding;enzyme binding;metal ion binding