CA12

protein-coding

carbonic anhydrase 12, the group of Carbonic anhydrases

Gene summary

Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. This gene product is a type I membrane protein that is highly expressed in normal tissues, such as kidney, colon and pancreas, and has been found to be overexpressed in 10% of clear cell renal carcinomas. Three transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jun 2014]

MANE transcript

NM_001218.5

Inheritance

ClinVar variants

P:7U:75B:20

Top phenotype

Hyperchlorhidrosis, isolated

gnomAD constraint

pLI —, LoF o/e 0.89

Max pathogenic AF

—

Genomic locus

chr15:63,321,378-63,381,846

External References & Databases

Ensembl (ENSG00000074410)

Transcript & Mutation Effects

hg38 • Region Span ~60.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

isolated hyperchlorhidrosisSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0007747

Submitter: Labcorp Genetics (formerly Invitae)

isolated hyperchlorhidrosisSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0007747

Submitter: Orphanet

isolated hyperchlorhidrosisLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0007747

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Hyperchlorhidrosis, isolatedAR

Manifestation: Renal

Intervention: Renal

Rationale: In infancy, salt wasting can lead to severe hyponatremic dehydration/hyperkalemia, and precautionary measures (eg, sodium supplementation) can be beneficial

Refs: 21035102; 21184099

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CA12 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 62

not providedTotal: 16

Isolated hyperchlorhidrosisTotal: 11

CA12-related disorderTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001218.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	9 clinvar	4 clinvar	14
missense	1 clinvar	1 clinvar	61 clinvar	5 clinvar	2 clinvar	70
nonsense		1 clinvar				1
start loss						0
frameshift	1 clinvar	2 clinvar	1 clinvar			4
splice donor/acceptor (+/-2bp)		1 clinvar	12 clinvar			13
Total	2	5	75	14	6	102

Highest pathogenic variant AF is 0.00078296545

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001218.5	RefSeq	NP_001209.1	11	MANE Select
ENST00000178638.8	Ensembl	ENSP00000178638.3	11	MANE Select
NM_001293642.2	RefSeq	NP_001280571.1	9	Standard
NM_206925.3	RefSeq	NP_996808.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Nitrogen metabolism - Homo sapiens (human)
Celecoxib Pathway, Pharmacodynamics
miR-targeted genes in epithelium - TarBase
miR-targeted genes in leukocytes - TarBase
miR-targeted genes in muscle cell - TarBase

Biological Process

bicarbonate transport
chloride ion homeostasis

Molecular Function

carbonate dehydratase activity
zinc ion binding

Cellular Component

plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000178638
Coding exons: 11
Length: 60784
Individuals with no LoFs: 125477
Homozygous LoFs: 0
Heterozygous LoFs: 271
Defined: 125748
p: 0.00108

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.184	203	196	1.04	0.0000118	2296
Missense (PolyPhen)		75	75.806	0.98937		871
Synonymous	-0.920	99	88.0	1.12	0.00000635	697
Loss of Function	0.437	18	20.1	0.895	9.65e-7	229

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.0023	0.0023	notable
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00033	0.00033	rare
Finnish	0.00033	0.00032	rare
European (Non-Finnish)	0.0014	0.0014	notable
South Asian	0.00016	0.00016	rare
Other	0.00098	0.00098	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Reversible hydration of carbon dioxide.;

Recessive Scores

pRec: 0.128

Intolerance Scores

LoFtool: 0.901
RVIS EVS: -0.62
RVIS percentile EVS: 17.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.996

Gene Damage Prediction

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