CA5B

Chr X

carbonic anhydrase 5B

Also known as: CA-VB, CAVB

NCBI Gene: 11238 ENSG00000169239 UniProt: Q9Y2D0

The protein is a mitochondrial carbonic anhydrase that catalyzes the reversible conversion of carbon dioxide to bicarbonate, participating in cellular acid-base balance and metabolic processes. Currently, no Mendelian diseases have been definitively associated with CA5B mutations in humans. The gene shows low constraint against loss-of-function variants (pLI = 0.0003, LOEUF = 1.2), suggesting tolerance to complete gene loss.

ResearchSummary from RefSeq, UniProt

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. This gene encodes carbonic anhydrase 5B. CA5B, and the related CA5A gene, has its expression localized in the mitochondria though CA5B has a wider tissue distribution than CA5A, which is restricted to the liver, kidneys, and skeletal muscle. A carbonic anhydrase pseudogene (CA5BP1) is adjacent to the CA5B gene and these two loci produce CA5BP1-CA5B readthrough transcripts. [provided by RefSeq, Jan 2019]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.20

Clinical Summary— CA5B

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.20LOEUF

pLI 0.000

Z-score 1.11

OE 0.64 (0.36–1.20)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.05Z-score

OE missense 1.01 (0.88–1.17)

125 obs / 123.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.64 (0.36–1.20)

0≤0.351.4

Missense OE?1.01 (0.88–1.17)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 7 / 11.0Missense obs/exp: 125 / 123.5Syn Z: 0.29

This gene — mechanism propensity

0.7228th %ile

GOF

0.6344th %ile

LOF

0.2873th %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.