CA8

Chr 8AR

carbonic anhydrase 8 (inactive)

Also known as: CA-RP, CA-VIII, CALS, CAMRQ3, CARP, SCAR34

The protein encoded by this gene was initially named CA-related protein because of sequence similarity to other known carbonic anhydrase genes. However, the gene product lacks carbonic anhydrase activity (i.e., the reversible hydration of carbon dioxide). The gene product continues to carry a carbonic anhydrase designation based on clear sequence identity to other members of the carbonic anhydrase gene family. The absence of CA8 gene transcription in the cerebellum of the lurcher mutant in mice with a neurologic defect suggests an important role for this acatalytic form. Mutations in this gene are associated with cerebellar ataxia, mental retardation, and dysequilibrium syndrome 3 (CMARQ3). Polymorphisms in this gene are associated with osteoporosis, and overexpression of this gene in osteosarcoma cells suggests an oncogenic role. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

OMIMResearchGenerating clinical summary…
LOFmechanismARLOEUF 0.671 OMIM phenotype
Clinical SummaryCA8
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Gene-Disease Validity (ClinGen)
cerebellar ataxia · ARModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.67LOEUF
pLI 0.008
Z-score 2.64
OE 0.36 (0.200.67)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.24Z-score
OE missense 0.72 (0.620.84)
115 obs / 159.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.36 (0.200.67)
00.351.4
Missense OE?0.72 (0.620.84)
00.61.4
Synonymous OE?1.01
01.21.6
LoF obs/exp: 7 / 19.6Missense obs/exp: 115 / 159.0Syn Z: -0.07
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCA8-related cerebellar ataxia, intellectual developmental disorder, and dysequilibrium syndromeLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.74top 25%
GOF
0.5954th %ile
LOF
0.2190th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CA8 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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