AQP12A

Chr 2

aquaporin 12A

Also known as: AQP-12, AQP12, AQPX2

NCBI Gene: 375318ENSG00000184945UniProt: Q8IXF9

The protein is a putative aquaporin that forms homotetrameric transmembrane channels, with each monomer mediating water transport across the plasma membrane along osmotic gradients. Currently, no human diseases have been definitively associated with AQP12A mutations in the medical literature. The gene appears to tolerate loss-of-function variants well, with low constraint scores suggesting it may not be essential for normal human development.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
0
Pubs (1 yr)
101
P/LP submissions
0%
P/LP missense
1.53
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— AQP12A
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
99 unique Pathogenic / Likely Pathogenic· 61 VUS of 171 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.53LOEUF
pLI 0.018
Z-score 0.77
OE 0.62 (0.28–1.53)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.90Z-score
OE missense 1.24 (1.08–1.43)
139 obs / 112.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.62 (0.28–1.53)
0≤0.351.4
Missense OE1.24 (1.08–1.43)
0≤0.61.4
Synonymous OE1.22
0≤1.21.6
LoF obs/exp: 3 / 4.8Missense obs/exp: 139 / 112.1Syn Z: -1.27
DN
0.79top 25%
GOF
0.83top 10%
LOF
0.1895th %ile

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

GOFprediction above median
DNprediction 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

171 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic90
Likely Pathogenic9
VUS61
Likely Benign7
Benign4
90
Pathogenic
9
Likely Pathogenic
61
VUS
7
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
90
0
90
Likely Pathogenic
0
0
9
0
9
VUS
0
49
12
0
61
Likely Benign
0
4
3
0
7
Benign
0
1
1
2
4
Total0541152171

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

View in ClinVar →

Protein Context — Lollipop Plot

AQP12A · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients