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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cerebellar ataxia, impaired intellectual development and dysequilibrium syndrome 3	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.

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.

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				6	4	10
missense			15		1	16
nonsense		1				1
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			4	1		5
non coding					29	29
Total	0	2	15	6	34

Variants in CA8

This is a list of pathogenic ClinVar variants found in the CA8 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-60189993-C-CA		not specified	Benign/Likely benign (-)
8-60208863-G-T		not specified • Inborn genetic diseases	Likely benign (Jan 01, 2024)
8-60208884-C-T			Likely benign (Jun 01, 2024)
8-60209160-T-C			Benign (Jun 18, 2021)
8-60209224-G-A			Benign (Jun 19, 2021)
8-60222337-CAG-C			Benign (Jun 19, 2021)
8-60222436-G-A			Benign (Jun 18, 2021)
8-60222656-T-TG		Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 3	Likely pathogenic (Jan 01, 2016)
8-60222663-T-C		Inborn genetic diseases	Uncertain significance (Oct 14, 2017)
8-60222677-C-T		Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 3	Pathogenic (Sep 21, 2011)
8-60222745-A-G			Likely benign (Mar 29, 2018)
8-60222749-C-T		Inborn genetic diseases	Uncertain significance (Nov 27, 2023)
8-60226591-T-C			Benign (Jun 18, 2021)
8-60226721-C-T			Benign (Jun 18, 2021)
8-60226760-C-T			Benign (Jun 18, 2021)
8-60226868-C-T		Inborn genetic diseases	Benign/Likely benign (Dec 31, 2019)
8-60227048-T-C			Benign (Jun 19, 2021)
8-60227088-G-A			Benign (Jun 18, 2021)
8-60227104-C-A			Benign (Jun 18, 2021)
8-60232231-G-T			Benign (Jun 19, 2021)
8-60232277-C-T		not specified	Uncertain significance (Sep 28, 2017)
8-60232278-G-A			Uncertain significance (May 01, 2016)
8-60232307-C-A		Inborn genetic diseases	Uncertain significance (Nov 29, 2017)
8-60232313-C-T		Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 3	Pathogenic (Aug 05, 2024)
8-60232318-G-A			Uncertain significance (Nov 01, 2022)

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
0.00825	0.989	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

Haploinsufficiency Scores

• pHI: 0.435
• hipred: Y
• hipred_score: 0.783
• ghis: 0.528

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

Mouse Genome Informatics

• Gene name: Car8
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

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