CA9

Chr 9

carbonic anhydrase 9

Also known as: CAIX, MN

CA9 encodes a transmembrane carbonic anhydrase that catalyzes the interconversion between carbon dioxide and water and the dissociated ions of carbonic acid (bicarbonate and hydrogen ions). Mutations cause autosomal recessive cerebral ataxia, mental retardation, and disequilibrium syndrome 4 (CAMRQ4), characterized by early-onset cerebellar dysfunction and intellectual disability. This gene is highly tolerant to loss-of-function variants in the general population (low constraint), which is consistent with its autosomal recessive inheritance pattern.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.09
Clinical SummaryCA9
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.09LOEUF
pLI 0.000
Z-score 1.21
OE 0.73 (0.501.09)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.11Z-score
OE missense 0.98 (0.891.09)
258 obs / 263.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.73 (0.501.09)
00.351.4
Missense OE0.98 (0.891.09)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 17 / 23.3Missense obs/exp: 258 / 263.0Syn Z: 0.40
DN
0.7131th %ile
GOF
0.7029th %ile
LOF
0.2582th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CA9 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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