AQP7

Chr 9

aquaporin 7

Also known as: AQP7L, AQPap, GLYCQTL

This protein functions as a transmembrane channel that transports water, glycerol, and urea across cell membranes, playing a critical role in energy homeostasis by facilitating glycerol efflux from adipocytes and glycerol reabsorption in the kidney. Mutations cause autosomal recessive inheritance of altered glycerol metabolism, though specific clinical phenotypes beyond quantitative trait effects on glycerol levels have not been well-characterized. The gene shows high tolerance to loss-of-function variants (LOEUF 1.95), suggesting that complete loss of function may be required for clinical manifestations.

ResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismLOEUF 1.95
Clinical SummaryAQP7
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· 9 VUS of 98 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.95LOEUF
pLI 0.000
Z-score -2.13
OE 1.68 (1.131.95)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.20Z-score
OE missense 0.96 (0.851.08)
193 obs / 201.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.68 (1.131.95)
00.351.4
Missense OE0.96 (0.851.08)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 19 / 11.3Missense obs/exp: 193 / 201.1Syn Z: -0.11
DN
0.81top 10%
GOF
0.88top 5%
LOF
0.2385th %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

98 submitted variants in ClinVar

Classification Summary

Pathogenic60
Likely Pathogenic8
VUS9
Likely Benign1
Benign5
Conflicting1
60
Pathogenic
8
Likely Pathogenic
9
VUS
1
Likely Benign
5
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
60
Likely Pathogenic
8
VUS
9
Likely Benign
1
Benign
5
Conflicting
1
Total84

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

AQP7 · 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
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗