AQP1

Chr 7

aquaporin 1 (Colton blood group)

Also known as: AQP-CHIP, CHIP28, CO

NCBI Gene: 358ENSG00000240583UniProt: P29972

This gene encodes a small integral membrane protein with six bilayer spanning domains that functions as a water channel protein. This protein permits passive transport of water along an osmotic gradient. This gene is a possible candidate for disorders involving imbalance in ocular fluid movement. [provided by RefSeq, Aug 2016]

118
ClinVar variants
26
Pathogenic / LP
0.09
pLI score
1
Active trials
Clinical Summary— AQP1
🧬
Gene-Disease Validity (ClinGen)
pulmonary arterial hypertension · ADLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.
📋
ClinVar Variants
26 Pathogenic / Likely Pathogenic· 49 VUS of 118 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.88LOEUF
pLI 0.093
Z-score 1.81
OE 0.34 (0.15–0.88)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.54Z-score
OE missense 0.88 (0.78–1.01)
156 obs / 176.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.34 (0.15–0.88)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.78–1.01)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.12
0≤1.21.6
LoF obs/exp: 3 / 8.8Missense obs/exp: 156 / 176.3Syn Z: -0.85

ClinVar Variant Classifications

118 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic4
VUS49
Likely Benign22
Benign20
Conflicting1
22
Pathogenic
4
Likely Pathogenic
49
VUS
22
Likely Benign
20
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
3
19
0
22
Likely Pathogenic
0
0
4
0
4
VUS
0
38
11
0
49
Likely Benign
0
5
3
14
22
Benign
0
6
10
4
20
Conflicting
—1
Total0524718118

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

View in ClinVar →

Protein Context — Lollipop Plot

AQP1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
AQP1 differentially orchestrates endothelial cell senescence.
Shabanian K et al.·Redox Biol
2024
Identification of rare sequence variation underlying heritable pulmonary arterial hypertension.
Gräf S et al.·Nat Commun
2018
Defining the clinical validity of genes reported to cause pulmonary arterial hypertension.
Welch CL et al.·Genet Med
2023
AQP1 Promoter Variant, Water Transport, and Outcomes in Peritoneal Dialysis.
Morelle J et al.·N Engl J Med
2021
Enhancer of zeste homolog 2 promotes renal fibrosis after acute kidney injury by inducing epithelial-mesenchymal transition and activation of M2 macrophage polarization.
Zhou X et al.·Cell Death Dis
2023
Aquaporins in sepsis- an update.
Rump K et al.·Front Immunol
2024Review
Aquaporins in Urinary System.
Li Y et al.·Adv Exp Med Biol
2017Review
Pathophysiology of leptospirosis.
Seguro AC et al.·Shock
2013
Regulation of brain aquaporins.
Gunnarson E et al.·Neuroscience
2004Review
Aquaporins in the kidney: physiology and pathophysiology.
Su W et al.·Am J Physiol Renal Physiol
2020Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Panax notoginseng saponins protect the blood-brain barrier against oxidative stress by activating the Akap12-PI3K/AKT-AQP1 signaling axis.
Fan L et al.·Int J Biol Macromol
2026
Mechanical and cellular response of lenses to acute ocular hypertension: Implications of AQP1 regulating water transport and lenses opacification.
Zhu J et al.·Exp Eye Res
2026
Engineering AQP1-Deficient DF-1 Suspension Cells for High-Yield IBDV Production and Vaccine Scale-Up.
Dong B et al.·Vaccines (Basel)
2025🔓 Open Access
Disrupting BMP/TGF-β Signaling: Modulation of AQP1 and TGFB1 in Human Pulmonary Microvascular Endothelial Cells.
Keskinidou C et al.·Compr Physiol
2025🔓 Open Access
Dexmedetomidine Dose-Dependent Modulation of Lung Function and AQP1 Expression During One-Lung Ventilation in Adults Undergoing Thoracoscopic Surgery.
Li Y et al.·Med Sci Monit
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Squamous Cell Head and Neck CancerRadiation Induced XerostomiaSalivary Hypofunction

Safety of a Single Administration of AAV2hAQP1, an Adeno-Associated Viral Vector Encoding Human Aquaporin-1 to One Parotid Salivary Gland in People With Irradiation-Induced Parotid Salivary Hypofunction

ACTIVE NOT RECRUITING
NCT02446249Phase PHASE1MeiraGTx, LLCStarted 2015-05-04
AAV2hAQP1

External Resources

Links to major genomics databases and tools