CA8

carbonic anhydrase 8, the group of Carbonic anhydrases

Basic information

Region (hg38): 8:60185412-60281400

Previous symbols: [ "CALS" ]

Links

ENSG00000178538 ∙ NCBI:767 ∙ OMIM:114815 ∙ HGNC:1382 ∙ Uniprot:P35219 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cerebellar ataxia (Moderate), mode of inheritance: AR
• cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 3 (Strong), mode of inheritance: AR
• cerebellar ataxia, intellectual disability, and dysequilibrium (Supportive), mode of inheritance: AR
• cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 3 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spinocerebellar ataxia, autosomal recessive 34	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	19461874; 21937992

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CA8 gene.

• Inborn_genetic_diseases (30 variants)
• not_provided (22 variants)
• Cerebellar_ataxia,_intellectual_disability,_and_dysequilibrium_syndrome_3 (11 variants)
• not_specified (8 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CA8 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004056.6. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	9	3	13
missense	4	2	30		1	37
nonsense	1	1				2
start loss						0
frameshift		1				1
splice donor/acceptor (+/-2bp)		1	1			2
Total	5	5	32	9	4

Highest pathogenic variant AF is 0.0000047884005

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CA8	protein_coding	protein_coding	ENST00000317995	8	94066

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125735	0	13	125748	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.24	115	159	0.723	0.00000809	1880
Missense in Polyphen		22	48.089	0.45748		582
Synonymous	-0.0688	63	62.3	1.01	0.00000332	554
Loss of Function	2.64	7	19.6	0.357	0.00000107	207

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000940	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000547	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000796	0.0000791
Middle Eastern	0.0000547	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Does not have a carbonic anhydrase catalytic activity.
• Disease: DISEASE: Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 3 (CMARQ3) [MIM:613227]: A congenital cerebellar ataxia associated with dysarthia, quadrupedal gait and mental retardation. {ECO:0000269|PubMed:19461874}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Nitrogen metabolism - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.136

Intolerance Scores

• loftool: 0.514
• rvis_EVS: -0.01
• rvis_percentile_EVS: 53.19

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.910

Gene Damage Prediction

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

Zebrafish Information Network

• Gene name: ca8
• Affected structure: neuron
• Phenotype tag: abnormal
• Phenotype quality: apoptotic

Gene ontology

• Biological process: phosphatidylinositol-mediated signaling
• Cellular component: cytoplasm
• Molecular function: carbonate dehydratase activity;protein binding;zinc ion binding