CA9

protein-coding

carbonic anhydrase 9, 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. They show extensive diversity in tissue distribution and in their subcellular localization. CA IX is a transmembrane protein and is one of only two tumor-associated carbonic anhydrase isoenzymes known. It is expressed in all clear-cell renal cell carcinoma, but is not detected in normal kidney or most other normal tissues. It may be involved in cell proliferation and transformation. This gene was mapped to 17q21.2 by fluorescence in situ hybridization, however, radiation hybrid mapping localized it to 9p13-p12. [provided by RefSeq, Jun 2014]

MANE transcript

NM_001216.3

Inheritance

—

ClinVar variants

U:74B:12

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.73

Max pathogenic AF

—

Genomic locus

chr9:35,673,928-35,681,159

External References & Databases

Ensembl (ENSG00000107159)

Transcript & Mutation Effects

hg38 • Region Span ~7.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CA9 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 82

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001216.3. 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	1
missense			71 clinvar	11 clinvar		82
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	74	11	1	86

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001216.3	RefSeq	NP_001207.2	11	MANE Select
ENST00000378357.9	Ensembl	ENSP00000367608.4	11	MANE Select
ENST00000903366.1	Ensembl	ENSP00000573425.1	10	Standard
ENST00000903366.2	Ensembl	ENSP00000573425.1	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
Regulation of Hypoxia-inducible Factor (HIF) by oxygen
Vitamin D Receptor Pathway
Metabolism

Biological Process

morphogenesis of an epithelium
bicarbonate transport
response to testosterone
response to drug
secretion

Molecular Function

carbonate dehydratase activity
protein binding
zinc ion binding

Cellular Component

nucleolus
plasma membrane
integral component of membrane
basolateral plasma membrane
microvillus membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000378357
Coding exons: 11
Length: 7304
Individuals with no LoFs: 125667
Homozygous LoFs: 0
Heterozygous LoFs: 81
Defined: 125748
p: 0.000322

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.110	258	263	0.981	0.0000137	2901
Missense (PolyPhen)		73	79.894	0.91371		926
Synonymous	0.401	108	113	0.952	0.00000597	1008
Loss of Function	1.21	17	23.3	0.729	0.00000117	246

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0015	0.0015	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.00034	0.00033	rare
South Asian	0.00026	0.00026	rare
Other	0.00034	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Reversible hydration of carbon dioxide. Participates in pH regulation. May be involved in the control of cell proliferation and transformation. Appears to be a novel specific biomarker for a cervical neoplasia. {ECO:0000269|PubMed:18703501}.;

Recessive Scores

pRec: 0.163

Intolerance Scores

LoFtool: 0.903
RVIS EVS: 0.09
RVIS percentile EVS: 60.47

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.987

Gene Damage Prediction

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