CA2

carbonic anhydrase 2, the group of Carbonic anhydrases

Basic information

Region (hg38): 8:85463968-85481493

Links

ENSG00000104267 ∙ NCBI:760 ∙ OMIM:611492 ∙ HGNC:1373 ∙ Uniprot:P00918 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive osteopetrosis 3 (Definitive), mode of inheritance: AR
• autosomal recessive osteopetrosis 3 (Strong), mode of inheritance: AR
• autosomal recessive osteopetrosis 3 (Supportive), mode of inheritance: AR
• autosomal recessive osteopetrosis 3 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Osteopetrosis, autosomal recessive 3	AR	Musculoskeletal; Renal	Identification and treatment of renal tubular acidosis may be beneficial; Awareness of multi-organ system complications of osteopetrosis may allow surveillance and prompt management	Audiologic/Otolaryngologic; Craniofacial; Dental; Musculoskeletal; Neurologic; Ophthalmologic; Renal	5041390; 7386510; 7312081; 3925334; 3081869; 2107079; 1928091; 1301935; 1542674; 8127074; 7627193; 8834238; 9143915; 12566520

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CA2 gene.

• Osteopetrosis with renal tubular acidosis (3 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CA2 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			3	22	1	26
missense		1	43	2	1	47
nonsense	2	2				4
start loss		1				1
frameshift		2				2
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1	1				2
splice region			3	3		6
non coding			9	25	20	54
Total	3	7	56	49	22

Highest pathogenic variant AF is 0.00000657

Variants in CA2

This is a list of pathogenic ClinVar variants found in the CA2 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-85463997-A-ACCC		Osteopetrosis with renal tubular acidosis	Uncertain significance (Jun 14, 2016)
8-85464029-G-T		Osteopetrosis with renal tubular acidosis	Uncertain significance (Jan 12, 2018)
8-85464039-G-C		Osteopetrosis with renal tubular acidosis	Uncertain significance (Jan 13, 2018)
8-85464083-T-G		Neurodevelopmental delay	Likely pathogenic (-)
8-85464097-G-C			Uncertain significance (May 23, 2023)
8-85464102-C-A		Osteopetrosis with renal tubular acidosis	Pathogenic (Dec 03, 2017)
8-85464133-C-A			Likely benign (Oct 29, 2023)
8-85464134-C-T			Likely benign (May 29, 2022)
8-85465108-A-C			Likely benign (Sep 21, 2020)
8-85465253-CAT-C			Likely benign (Jan 22, 2024)
8-85465265-C-A		CA2-related disorder	Conflicting classifications of pathogenicity (Oct 22, 2023)
8-85465267-C-G			Uncertain significance (Nov 30, 2021)
8-85465268-C-T			Likely benign (Jun 14, 2023)
8-85465277-G-A		Osteopetrosis with renal tubular acidosis • Inborn genetic diseases	Uncertain significance (Feb 17, 2023)
8-85465289-A-C			Benign (Mar 22, 2023)
8-85465289-A-G		CARBONIC ANHYDRASE II VARIANT	Pathogenic (Oct 01, 1982)
8-85465295-T-C		Inborn genetic diseases	Uncertain significance (Jan 06, 2023)
8-85465311-G-A		Osteopetrosis with renal tubular acidosis	Uncertain significance (Jan 13, 2018)
8-85465324-C-T		Osteopetrosis with renal tubular acidosis	Uncertain significance (Jan 13, 2018)
8-85465333-C-T			Likely benign (Dec 25, 2022)
8-85465352-A-C			Uncertain significance (Jun 02, 2022)
8-85465357-T-G		Osteopetrosis with renal tubular acidosis	Pathogenic (Jan 01, 1995)
8-85465361-C-A		Inborn genetic diseases	Uncertain significance (Oct 25, 2023)
8-85465362-C-T			Uncertain significance (Nov 08, 2022)
8-85465366-C-T			Likely benign (Aug 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CA2	protein_coding	protein_coding	ENST00000285379	7	17642

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000169	0.437	125729	0	19	125748	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.359	128	140	0.914	0.00000751	1709
Missense in Polyphen		42	57.159	0.73479		713
Synonymous	0.434	49	53.0	0.924	0.00000299	488
Loss of Function	0.615	10	12.3	0.811	5.26e-7	153

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000264	0.000264
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000528	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.000163	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption. Stimulates the chloride-bicarbonate exchange activity of SLC26A6. {ECO:0000250, ECO:0000269|PubMed:10550681, ECO:0000269|PubMed:11831900, ECO:0000269|PubMed:15990874}.
• Disease: DISEASE: Osteopetrosis, autosomal recessive 3 (OPTB3) [MIM:259730]: A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Recessive osteopetrosis commonly manifests in early infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves. OPTB3 is associated with renal tubular acidosis, cerebral calcification (marble brain disease) and in some cases with mental retardation. {ECO:0000269|PubMed:15300855, ECO:0000269|PubMed:1542674, ECO:0000269|PubMed:1928091, ECO:0000269|PubMed:8834238, ECO:0000269|PubMed:9143915}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Bile secretion - Homo sapiens (human);Gastric acid secretion - Homo sapiens (human);Proximal tubule bicarbonate reclamation - Homo sapiens (human);Collecting duct acid secretion - Homo sapiens (human);Pancreatic secretion - Homo sapiens (human);Nitrogen metabolism - Homo sapiens (human);Metabolism;O2/CO2 exchange in erythrocytes;Transport of small molecules;Erythrocytes take up oxygen and release carbon dioxide;Erythrocytes take up carbon dioxide and release oxygen;Reversible hydration of carbon dioxide (Consensus)

Recessive Scores

• pRec: 0.372

Intolerance Scores

• loftool: 0.466
• rvis_EVS: -0.14
• rvis_percentile_EVS: 43.29

Haploinsufficiency Scores

• pHI: 0.230
• hipred: Y
• hipred_score: 0.708
• ghis: 0.454

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.913

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Car2
• Phenotype: respiratory system phenotype; reproductive 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); 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); digestive/alimentary phenotype; renal/urinary system phenotype; homeostasis/metabolism phenotype; immune system phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: cahz
• Affected structure: respiratory gaseous exchange
• Phenotype tag: abnormal
• Phenotype quality: process quality

Gene ontology

• Biological process: kidney development;morphogenesis of an epithelium;response to pH;response to zinc ion;carbon dioxide transport;bicarbonate transport;positive regulation of synaptic transmission, GABAergic;positive regulation of cellular pH reduction;angiotensin-activated signaling pathway;odontogenesis of dentin-containing tooth;response to estrogen;regulation of anion transport;positive regulation of osteoclast differentiation;positive regulation of bone resorption;secretion;response to steroid hormone;regulation of intracellular pH;cellular response to fluid shear stress;positive regulation of dipeptide transmembrane transport;regulation of chloride transport
• Cellular component: cytoplasm;cytosol;plasma membrane;microvillus;basolateral plasma membrane;axon;myelin sheath;apical part of cell;extracellular exosome
• Molecular function: arylesterase activity;carbonate dehydratase activity;protein binding;zinc ion binding