CA5B

Chr X

carbonic anhydrase 5B

Also known as: CA-VB, CAVB

NCBI Gene: 11238 ENSG00000169239 UniProt: Q9Y2D0 OMIM: 300230

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.

OMIM 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]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.20

LOEUF

Multiple*

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in CA5B?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 230

262 rare PASS variants

Rare truncating (LoF)

1 in 3,000

33 rare PASS variants

Rare synonymous (reference)

1 in 580

95 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CA5B. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~561k	1 in 320	1 in 4,300
South Asian	~36k	1 in 250	1 in 1,700
Remaining (unassigned)	~31k	1 in 180	1 in 1,900
European (Finnish)	~27k	1 in 4,500	1 in 870
Admixed American	~23k	1 in 210	1 in 1,400
African / African American	~21k	1 in 310	1 in 630
East Asian	~20k	1 in 220	none seen
Ashkenazi Jewish	~13k	≈ 1 in 6,200	none seen
Middle Eastern	~2,758	1 in 300	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓