PCCB

propionyl-CoA carboxylase subunit beta

Basic information

Region (hg38): 3:136250340-136337896

Links

ENSG00000114054

∙ NCBI:5096 ∙ OMIM:232050 ∙ HGNC:8654 ∙ Uniprot:P05166 ∙ 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 (Definitive), mode of inheritance: AR
propionic acidemia (Supportive), mode of inheritance: AR
propionic acidemia (Strong), 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	10502773; 17051315; 19238581; 20301313; 22593918; 22033733; 23053474; 30879957; 36395710; 38570682

ClinVar

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

Propionic_acidemia (1160 variants)
not_provided (129 variants)
Inborn_genetic_diseases (69 variants)
not_specified (57 variants)
PCCB-related_disorder (27 variants)
Hyperammonemia (2 variants)
Global_developmental_delay (2 variants)
Abnormality_of_metabolism/homeostasis (1 variants)
Hypertrophic_cardiomyopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PCCB gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000532.5. 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	1 clinvar	1 clinvar	11 clinvar	285 clinvar		298
missense	23 clinvar	74 clinvar	321 clinvar	17 clinvar		435
nonsense	23 clinvar	12 clinvar	1 clinvar			36
start loss	5	1				6
frameshift	50 clinvar	36 clinvar	2 clinvar			88
splice donor/acceptor (+/-2bp)	13 clinvar	47 clinvar	1 clinvar			61
Total	115	171	336	302	0

Highest pathogenic variant AF is 0.00019144507

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PCCB	protein_coding	protein_coding	ENST00000469217	16	87591

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.53e-8	0.955	125672	0	76	125748	0.000302

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.867	353	310	1.14	0.0000172	3623
Missense in Polyphen		137	136.23	1.0056		1609
Synonymous	-1.67	139	116	1.20	0.00000658	1118
Loss of Function	2.00	17	28.5	0.596	0.00000159	331

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00147	0.00146
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000327	0.000326
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000275	0.000273
Middle Eastern	0.000327	0.000326
South Asian	0.000164	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Disease: DISEASE: Propionic acidemia type II (PA-2) [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:10447268, ECO:0000269|PubMed:11749052, ECO:0000269|PubMed:12189489, ECO:0000269|PubMed:12559849, ECO:0000269|PubMed:15059621, ECO:0000269|PubMed:2154743, ECO:0000269|PubMed:8411997, ECO:0000269|PubMed:9683601}. 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;Valine Leucine Isoleucine degradation;2-oxobutanoate degradation;superpathway of methionine degradation (Consensus)

Recessive Scores

pRec: 0.542

Intolerance Scores

loftool: 0.0993
rvis_EVS: 0.11
rvis_percentile_EVS: 62

Haploinsufficiency Scores

pHI: 0.166
hipred: Y
hipred_score: 0.694
ghis: 0.522

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.994

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Pccb
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);

Gene ontology

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