CA5A

Chr 16AR

carbonic anhydrase 5A

Also known as: CA5, CA5AD, CAV, CAVA, GS1-21A4.1

The carbonic anhydrase VA protein catalyzes the reversible conversion of carbon dioxide to bicarbonate within mitochondria, providing bicarbonate for essential enzymes in the urea and Krebs cycles. Autosomal recessive mutations cause hyperammonemia due to carbonic anhydrase VA deficiency, disrupting ureagenesis and gluconeogenesis primarily in the liver. The pathogenic mechanism involves loss of function of this mitochondrial enzyme.

Summary from RefSeq, OMIM, UniProt, Mechanism

Primary Disease Associations & Inheritance

Hyperammonemia due to carbonic anhydrase VA deficiencyMIM #615751
AR
0
Active trials
6
Pubs (1 yr)
80
P/LP submissions
3%
P/LP missense
0.97
LOEUF
LOF
Mechanism· G2P
Clinical SummaryCA5A
🧬
Gene-Disease Validity (ClinGen)
hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
68 unique Pathogenic / Likely Pathogenic· 128 VUS of 312 total submissions
📖
GeneReview available — CA5A
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.97LOEUF
pLI 0.000
Z-score 1.65
OE 0.56 (0.330.97)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-1.20Z-score
OE missense 1.25 (1.121.40)
222 obs / 177.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.56 (0.330.97)
00.351.4
Missense OE1.25 (1.121.40)
00.61.4
Synonymous OE1.23
01.21.6
LoF obs/exp: 9 / 16.2Missense obs/exp: 222 / 177.0Syn Z: -1.53
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongCA5A-related hyperammonemia due to carbonic anhydrase VA deficiencyLOFAR

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

DN
0.78top 25%
GOF
0.6247th %ile
LOF
0.2678th %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

312 submitted variants in ClinVar

Classification Summary

Pathogenic55
Likely Pathogenic13
VUS128
Likely Benign88
Benign10
Conflicting11
55
Pathogenic
13
Likely Pathogenic
128
VUS
88
Likely Benign
10
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
1
52
0
55
Likely Pathogenic
2
1
10
0
13
VUS
1
103
23
1
128
Likely Benign
0
7
28
53
88
Benign
0
2
5
3
10
Conflicting
11
Total511411857305

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CA5A · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC