AQP3

Chr 9

aquaporin 3 (Gill blood group)

Also known as: AQP-3, GIL

Aquaporin 3 is a transmembrane channel protein that transports water, glycerol, and urea across cell membranes, playing important roles in kidney water reabsorption and skin hydration. Mutations in this gene cause GIL blood group variants, which are inherited in an autosomal pattern. The gene shows moderate tolerance to loss-of-function variants (LOEUF 0.644), suggesting some functional redundancy in its biological pathways.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismLOEUF 0.641 OMIM phenotype
Clinical SummaryAQP3
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
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ClinVar Variants
69 unique Pathogenic / Likely Pathogenic· 26 VUS of 107 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.64LOEUF
pLI 0.134
Z-score 2.51
OE 0.28 (0.140.64)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.58Z-score
OE missense 0.66 (0.570.77)
117 obs / 176.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.28 (0.140.64)
00.351.4
Missense OE0.66 (0.570.77)
00.61.4
Synonymous OE0.87
01.21.6
LoF obs/exp: 4 / 14.2Missense obs/exp: 117 / 176.2Syn Z: 0.94
DN
0.85top 5%
GOF
0.87top 5%
LOF
0.1796th %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

107 submitted variants in ClinVar

Classification Summary

Pathogenic61
Likely Pathogenic8
VUS26
Likely Benign1
Benign3
61
Pathogenic
8
Likely Pathogenic
26
VUS
1
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
61
0
61
Likely Pathogenic
0
0
8
0
8
VUS
0
21
5
0
26
Likely Benign
0
1
0
0
1
Benign
0
0
0
3
3
Total02274399

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

View in ClinVar →

Protein Context — Lollipop Plot

AQP3 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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