CA5A

carbonic anhydrase 5A, the group of Carbonic anhydrases

Basic information

Region (hg38): 16:87881546-87936580

Previous symbols: [ "CA5" ]

Links

ENSG00000174990 ∙ NCBI:763 ∙ OMIM:114761 ∙ HGNC:1377 ∙ Uniprot:P35218 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency (Strong), mode of inheritance: AR
• hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency (Moderate), mode of inheritance: AR
• hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency (Supportive), mode of inheritance: AR
• hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Carbonic anhydrase VA deficiency	AR	Biochemical	Medical treatment (eg, with N-carbamyl-L-glutamate (NCG) alone or with other treatments) has been reported as resolving hyperammonemia in affected individuals	Biochemical	24530203; 26913920

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CA5A gene.

• Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CA5A 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				40	4	44
missense		1	84	6	2	93
nonsense	2	1	1			4
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region			1	7		8
non coding				11	5	16
Total	2	3	85	57	11

Highest pathogenic variant AF is 0.0000132

Variants in CA5A

This is a list of pathogenic ClinVar variants found in the CA5A region.

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

Position	Type	Phenotype	Significance	ClinVar
16-87881815-T-C		Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency	Uncertain significance (Feb 14, 2023)
16-87888119-C-T		CA5A-related disorder	Likely benign (Nov 25, 2019)
16-87888130-T-C		Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency	Uncertain significance (Jan 20, 2025)
16-87888162-G-A		Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency	Likely benign (Sep 10, 2024)
16-87888165-C-T		Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency	Benign (Dec 26, 2024)
16-87888166-G-A		Inborn genetic diseases	Uncertain significance (Aug 12, 2021)
16-87888178-C-T			Uncertain significance (Jan 09, 2024)
16-87888179-G-A		Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency	Uncertain significance (May 09, 2023)
16-87888180-G-A		Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency	Likely benign (Oct 05, 2023)
16-87888195-A-C		Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency	Likely benign (Aug 16, 2022)
16-87888198-T-C		Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency	Likely benign (Oct 14, 2020)
16-87888199-GG-TC		Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency	Uncertain significance (Sep 16, 2021)
16-87888201-G-A		Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency	Likely benign (Oct 24, 2022)
16-87888203-G-A		Inborn genetic diseases	Uncertain significance (Oct 26, 2021)
16-87888228-C-T		Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency	Likely benign (May 18, 2019)
16-87888240-T-A		not specified • Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency	Benign (Feb 03, 2025)
16-87888248-A-G			Uncertain significance (Aug 01, 2017)
16-87888259-C-T		Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency	Conflicting classifications of pathogenicity (Dec 02, 2024)
16-87888260-G-A		Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency	Uncertain significance (Jun 09, 2022)
16-87888265-G-A		Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency • Inborn genetic diseases	Uncertain significance (Jan 04, 2024)
16-87888270-G-C		Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency	Likely benign (Jun 09, 2024)
16-87888271-A-G		Inborn genetic diseases	Uncertain significance (Mar 15, 2024)
16-87888272-G-C		Inborn genetic diseases	Uncertain significance (Feb 06, 2023)
16-87888282-A-T		Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency	Likely benign (Feb 02, 2023)
16-87888292-G-A		Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency	Likely benign (Feb 02, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CA5A	protein_coding	protein_coding	ENST00000309893	7	48511

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000791	0.929	125737	0	11	125748	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.20	222	177	1.25	0.0000108	1952
Missense in Polyphen		72	63.855	1.1275		741
Synonymous	-1.53	90	73.3	1.23	0.00000491	583
Loss of Function	1.65	9	16.2	0.556	7.75e-7	171

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.000163	0.000163
South Asian	0.0000985	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Reversible hydration of carbon dioxide. Low activity.
• Disease: DISEASE: Hyperammonemia due to carbonic anhydrase VA deficiency (CA5AD) [MIM:615751]: An autosomal recessive inborn error of metabolism, clinically characterized by infantile hyperammonemic encephalopathy. Metabolic abnormalities include hypoglycemia, hyperlactatemia, metabolic acidosis and respiratory alkalosis. {ECO:0000269|PubMed:24530203}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Nitrogen metabolism - Homo sapiens (human);Metabolism;Reversible hydration of carbon dioxide (Consensus)

Recessive Scores

• pRec: 0.109

Intolerance Scores

• loftool: 0.482
• rvis_EVS: 0
• rvis_percentile_EVS: 53.85

Haploinsufficiency Scores

• pHI: 0.112
• hipred: N
• hipred_score: 0.172

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.512

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Car5a
• Phenotype: growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism 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)

Zebrafish Information Network

• Gene name: ca5a
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: necrotic

Gene ontology

• Biological process: bicarbonate transport
• Cellular component: mitochondrion;mitochondrial matrix
• Molecular function: carbonate dehydratase activity;zinc ion binding