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	Allergy/Immunology/Infectious; Biochemical; Cardiovascular; Hematologic; Neurologic	4815259; 10502773; 17051315; 19157943; 20301313; 22033733; 22593918 ; 23053474; 30879957; 36395710

ClinVar

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

• Propionic acidemia (80 variants)
• not provided (5 variants)
• PCCA-related disorder (2 variants)
• Pontocerebellar hypoplasia type 2D (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	282	2	286
missense	8	20	298	6	2	334
nonsense	22	17	1			40
start loss			2			2
frameshift	38	55	1			94
inframe indel	1		3			4
splice donor/acceptor (+/-2bp)	12	56			1	69
splice region	1	5	16	73	4	99
non coding		1	12	243	51	307
Total	81	149	319	531	56

Highest pathogenic variant AF is 0.0000460

Variants in PCCA

This is a list of pathogenic ClinVar variants found in the PCCA region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
13-100089052-T-G			Likely benign (Feb 24, 2019)
13-100089061-C-T		Propionic acidemia	Uncertain significance (Jun 14, 2016)
13-100089101-G-A		Propionic acidemia • not specified	Conflicting classifications of pathogenicity (Jan 13, 2018)
13-100089107-C-T		not specified	Likely benign (Aug 03, 2016)
13-100089116-C-T		Propionic acidemia	Uncertain significance (Jan 13, 2018)
13-100089117-A-C		Propionic acidemia	Uncertain significance (Apr 17, 2020)
13-100089121-A-G		Propionic acidemia	Uncertain significance (May 04, 2022)
13-100089121-A-AT		Propionic acidemia	Conflicting classifications of pathogenicity (May 01, 2022)
13-100089122-T-A		Propionic acidemia	Pathogenic (May 08, 2019)
13-100089122-T-C		Propionic acidemia • not specified	Uncertain significance (Jun 09, 2023)
13-100089124-G-C		Inborn genetic diseases • Propionic acidemia	Uncertain significance (Jun 15, 2022)
13-100089126-G-A		Propionic acidemia	Likely benign (Nov 17, 2023)
13-100089126-G-T		Propionic acidemia	Likely benign (Jul 17, 2023)
13-100089129-G-A		Propionic acidemia	Likely benign (Feb 26, 2023)
13-100089129-G-C		Propionic acidemia	Likely benign (Nov 29, 2023)
13-100089132-C-G		Propionic acidemia	Uncertain significance (Sep 21, 2021)
13-100089132-C-T		Propionic acidemia	Likely benign (Dec 26, 2022)
13-100089133-TG-T		Propionic acidemia	Pathogenic (Nov 25, 2023)
13-100089135-G-A		Propionic acidemia	Uncertain significance (Jun 05, 2018)
13-100089137-T-C		Inborn genetic diseases	Uncertain significance (Jun 21, 2022)
13-100089138-C-G		Propionic acidemia	Likely benign (Feb 11, 2022)
13-100089138-C-T		Propionic acidemia	Likely benign (Jan 04, 2024)
13-100089138-CG-C		Propionic acidemia	Likely pathogenic (May 15, 2019)
13-100089139-G-C		Propionic acidemia	Uncertain significance (Jul 24, 2022)
13-100089140-G-C		Propionic acidemia	Uncertain significance (Jan 22, 2024)

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