AQP7

Summary

AQP7 (aquaporin 7, HGNC:640) is a protein-coding gene on chromosome 9p13.3, encoding Aquaporin-7 (O14520). Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient. It is a selective cancer dependency (DepMap: 40.0% of cell lines).

This gene encodes a member of the aquaporin family of water-selective membrane channels. The encoded protein localizes to the plasma membrane and allows movement of water, glycerol and urea across cell membranes. This gene is highly expressed in the adipose tissue where the encoded protein facilitates efflux of glycerol. In the proximal straight tubules of kidney, the encoded protein is localized to the apical membrane and prevents excretion of glycerol into urine. The encoded protein is present in spermatids, as well as in the testicular and epididymal spermatozoa suggesting an important role in late spermatogenesis. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. This gene is located adjacent to a related aquaporin gene on chromosome 9. Multiple pseudogenes of this gene have been identified.

Source: NCBI Gene 364 — RefSeq curated summary.

At a glance

• GWAS associations: 51
• Clinical variants (ClinVar): 86 total
• Cancer dependency (DepMap): dependent in 40.0% of screened cell lines
• MANE Select transcript: NM_001170

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:640
Approved symbol	AQP7
Name	aquaporin 7
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Aliases	AQP9, AQPap
Ensembl gene	ENSG00000165269
Ensembl biotype	protein_coding
OMIM	602974
Entrez	364

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 19 protein_coding, 5 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000297988, ENST00000377425, ENST00000379503, ENST00000379506, ENST00000379507, ENST00000439678, ENST00000447660, ENST00000537089, ENST00000623097, ENST00000623519, ENST00000623743, ENST00000624005, ENST00000624075, ENST00000624095, ENST00000624420, ENST00000624432, ENST00000624890, ENST00000625032, ENST00000625109, ENST00000898395, ENST00000898396, ENST00000898397, ENST00000898398, ENST00000898399, ENST00000898400, ENST00000967226, ENST00000967227, ENST00000967228, ENST00000967229

RefSeq mRNA: 7 — MANE Select: NM_001170 NM_001170, NM_001318156, NM_001318157, NM_001318158, NM_001376191, NM_001376192, NM_001376193

CCDS: CCDS6541, CCDS83353, CCDS83354, CCDS83356

Canonical transcript exons

ENST00000297988 — 8 exons

Exon	Start	End
ENSE00001091751	33402373	33402568
ENSE00001644259	33383191	33385290
ENSE00003443413	33385649	33385866
ENSE00003563387	33395078	33395195
ENSE00003583886	33386969	33387092
ENSE00003602351	33401237	33401287
ENSE00003756169	33386404	33386541
ENSE00003759811	33386077	33386195

Expression profiles

Bgee: expression breadth ubiquitous, 139 present calls, max score 99.15.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2286 / max 23.0039, expressed in 63 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100455	0.1287	51
100454	0.0999	37

Top tissues by expression

142 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	99.15	gold quality
omental fat pad	UBERON:0010414	98.59	gold quality
adipose tissue	UBERON:0001013	98.58	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.57	gold quality
heart left ventricle	UBERON:0002084	97.98	gold quality
sural nerve	UBERON:0015488	97.31	gold quality
right atrium auricular region	UBERON:0006631	96.43	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.38	gold quality
heart	UBERON:0000948	95.21	gold quality
mammary gland	UBERON:0001911	93.80	gold quality
thoracic mammary gland	UBERON:0005200	93.80	gold quality
tibial nerve	UBERON:0001323	93.33	gold quality
mucosa of stomach	UBERON:0001199	93.23	gold quality
duodenum	UBERON:0002114	92.19	gold quality
vastus lateralis	UBERON:0001379	91.70	gold quality
quadriceps femoris	UBERON:0001377	91.24	gold quality
right lobe of liver	UBERON:0001114	91.13	gold quality
left testis	UBERON:0004533	91.08	gold quality
right testis	UBERON:0004534	91.05	gold quality
testis	UBERON:0000473	90.51	gold quality
muscle of leg	UBERON:0001383	90.42	gold quality
liver	UBERON:0002107	90.22	gold quality
adult mammalian kidney	UBERON:0000082	90.21	gold quality
gastrocnemius	UBERON:0001388	90.08	gold quality
skeletal muscle tissue	UBERON:0001134	89.95	gold quality
right uterine tube	UBERON:0001302	89.10	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.45	gold quality
small intestine	UBERON:0002108	87.89	gold quality
kidney	UBERON:0002113	86.82	gold quality
muscle tissue	UBERON:0002385	86.54	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.33

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PPARA, PPARG

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 40.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 39)

• determination of genomic structure, promotor analysis and functional mutation (PMID:11952783)
• In summary, our data show that the AQP7 gene is differentially expressed in adipose tissue of lean and obese individuals. (PMID:16325777)
• AQP7 downregulation is pathogenic for obesity and/or type 2 diabetes. (PMID:17351148)
• Dysfunction of AQP7 in the periadventitial fat may trigger the inflammation involved in aatherosclerosis. (PMID:17562358)
• Expression of AQP7 is down-regulated in women with severe obesity. The expression of this glycerol channel is not affected by type 2 diabetes. (PMID:17566090)
• increased gene expression in visceral adipose tissue and liver in morbid obesity (PMID:18401671)
• we found a greater expression found in visceral fat, and between subcutaneous adipose AQP7 and hepatic aquaporin 9 gene expression within the context of human morbid obesity (PMID:19615702)
• these data suggest a subtle regulation between adipose depots of the sole adipose aquaporin, AQP7, which is unbalanced in obesity and T2D. (PMID:20463097)
• Diazoxide may have an impact on myocardial water balance and glycerol energy supply by decreasing relative aquaporin-7 expression during coronary artery bypass grafting. (PMID:21609198)
• In all of the 33 investigated semen samples, we observed AQP7 binding to the sperm sur-face with different intensity and modality. (PMID:22206455)
• There is a coordinated regulation of adipose AQP7 and hepatic AQP9 gene expression that is distorted in metabolic syndrome X. (PMID:22425521)
• The discovery of an association between urine glycerol loss and a platelet secretion defect is a novel one, and our findings imply the involvement of AQPs in platelet secretion. (PMID:22899094)
• AQP7 is regulated in response to physical training in a gender-dependent manner in adipose tissue. (PMID:23001483)
• AQP7 overexpression may be related to insulin sensitivity and glucose homeostasis in women with the polycystic ovary syndrome. (PMID:23235401)
• AQP7 is expressed in human and mouse oocytes and upregulated by cryoprotectants. (PMID:23290745)
• AQP7-specific glycerol transport was furthermore found to be specifically inhibited. (PMID:24334538)
• a direct involvement of AQP7 in water and glycerol transport (PMID:24376702)
• REVIEW: the current knowledge on the role of the glycerol channels AQP7 and AQP9 in controlling glycerol metabolism in adipose tissue and liver (PMID:24463099)
• the human aquaglyceroporins, i.e., AQP3, AQP7, AQP9 and AQP10 can act as silicon transporters in both Xenopus laevis oocytes and HEK-293 cells. (PMID:26313002)
• AQP3 was upregulated, and AQP7 and AQP9 were downregulated in hepatocellular carcinoma. A high expression of AQP3 and low expression of AQP7 was significantly associated with the aggressive features of hepatocellular carcinoma. (PMID:27121567)
• ex vivo studies in human primary adipocytes, demonstrate that perilipin 1 binds to AQP7, and that catecholamine activated protein kinase A phosphorylates the N-terminus of AQP7, thereby reducing complex formation (PMID:27832861)
• Aquaporins AQP3, -7, -8, and -11 proteins were found in sperm cells and localized in the head (AQP7), in the middle piece (AQP8) and in the tail (AQP3 and -11) in both the plasma membrane and in intracellular structures. (PMID:28042826)
• adipose tissue lipolysis. However, in contrast to SAT AQP7, skeletal muscle AQP7 protein abundance is markedly increased in obese T2D men, potentially contributing to the excess lipid accumulation in skeletal muscle in type 2 diabetes (PMID:29783856)
• AQP7 messenger RNA (mRNA) was increased in the younger obese prepubertal children but decreased in the obese adolescents (p=0.014) who also had increased insulin and homeostatic model assessment - insulin resistance. (PMID:30226208)
• Identification of functional estrogen response elements in glycerol channel Aquaporin-7 gene. (PMID:30888885)
• NEAT1 played an important role in the activation of ERalpha to regulate AQP7-mediated hepatic steatosis (PMID:31062612)
• Structural Basis for Glycerol Efflux and Selectivity of Human Aquaporin 7. (PMID:31831212)
• Glucocorticoid gene regulation of aquaporin-7. (PMID:32061341)
• The metabolic implications of aquaporin 7 (AQP7) promoter variants in lean children and children with obesity. (PMID:32146590)
• Aquaporin-7 Regulates the Response to Cellular Stress in Breast Cancer. (PMID:32631905)
• AQP7 mediates post-menopausal lipogenesis in adipocytes through FSH-induced transcriptional crosstalk with AP-1 sites. (PMID:33132060)
• Different expression and localization of aquaporin 7 and aquaporin 9 in granulosa cells, oocytes, and embryos of patients with polycystic ovary syndrome and the negatively correlated relationship with insulin regulation. (PMID:33579525)
• Association of Aquaporin-3, Aquaporin-7, NOS3 and CYBA polymorphisms with hypertensive disorders in women. (PMID:33652340)
• Aquaglyceroporins and orthodox aquaporins in human adipocytes. (PMID:34627746)
• [Association study of single nucleotide polymorphisms of AQP7 and AQP9 genes with type 2 diabetes mellitus among ethnic Han Chinese population]. (PMID:35076928)
• Cholecystokinin promotes functional expression of the aquaglycerol channel aquaporin 7 in adipocytes. (PMID:35366004)
• Cryo-EM structure supports a role of AQP7 as a junction protein. (PMID:36737436)
• Aquaporin-7-Mediated Glycerol Permeability Is Linked to Human Sperm Motility in Asthenozoospermia and during Sperm Capacitation. (PMID:37566082)
• The Important Role of Aquaglyceroporin 7 in Health and Disease. (PMID:39456161)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	aqp7	ENSDARG00000026787
mus_musculus	Aqp7	ENSMUSG00000028427
rattus_norvegicus	Aqp7	ENSRNOG00000009686
drosophila_melanogaster	Eglp1	FBGN0034882
drosophila_melanogaster	Eglp2	FBGN0034883
drosophila_melanogaster	Eglp3	FBGN0034884
drosophila_melanogaster	Eglp4	FBGN0034885
caenorhabditis_elegans		WBGENE00000170

Paralogs (11): AQP6 (ENSG00000086159), AQP8 (ENSG00000103375), AQP9 (ENSG00000103569), MIP (ENSG00000135517), AQP10 (ENSG00000143595), AQP5 (ENSG00000161798), AQP3 (ENSG00000165272), AQP2 (ENSG00000167580), AQP4 (ENSG00000171885), AQP1 (ENSG00000240583), AQP7B (ENSG00000259916)

Protein

Protein identifiers

Aquaporin-7 — O14520 (reviewed: O14520)

Alternative names: Aquaglyceroporin-7, Aquaporin adipose, Aquaporin-7-like

All UniProt accessions (12): A0A096LNK2, A0A096LNN5, A0A096LNU3, A0A096LNV7, A0A096LP23, A0A096LP64, B7Z4U2, O14520, Q5T5L3, Q5T5M0, Q5T5M1, Q6P5T0

UniProt curated annotations — full annotation on UniProt →

Function. Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient. Could also be permeable to urea. Mediates the efflux of glycerol, formed upon triglyceride hydrolysis, to avoid its accumulation in adipocytes and to make it available to other tissues. In the kidney, mediates the reabsorption of glycerol, preventing its loss in urine, again participating to energy homeostasis. In pancreatic beta cells, it also mediates the efflux of glycerol, regulating its intracellular levels.

Subunit / interactions. Homotetramer; each monomer provides an independent glycerol/water pore. Two homotetramers on opposing membranes can dimerize, forming a cell-cell junction. Interacts with PLIN1.

Subcellular location. Cell membrane. Cytoplasmic vesicle membrane. Lipid droplet.

Tissue specificity. Detected in the sperm head (at protein level). Detected in white adipose tissue.

Post-translational modifications. Phosphorylation by PKA could prevent the interaction with PLIN1.

Activity regulation. Glycerol transport is regulated by pH, with the porin being permeable to glycerol at pH 7.4 but not at pH 5.5. Water permeability, however, is not influenced by pH. Inhibited by mercury ions.

Domain organisation. Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro/Ala-Ala/Ser (NPA).

Polymorphism. Genetic variations in AQP7 are responsible for changes in glycerol release during exercise and define the glycerol quantitative trait locus (GLYCQTL) [MIM:614411].

Similarity. Belongs to the MIP/aquaporin (TC 1.A.8) family.

Isoforms (2)

UniProt ID	Names	Canonical?
O14520-1	1	yes
O14520-2	2

RefSeq proteins (7): NP_001161, NP_001305085, NP_001305086, NP_001305087, NP_001363120, NP_001363121, NP_001363122 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000425	MIP	Family
IPR023271	Aquaporin-like	Homologous_superfamily
IPR050363	MIP/Aquaporin	Family

Pfam: PF00230

Catalyzed reactions (Rhea), 3 shown:

• H2O(in) = H2O(out) (RHEA:29667)
• glycerol(in) = glycerol(out) (RHEA:29675)
• urea(in) = urea(out) (RHEA:32799)

UniProt features (56 total): helix 12, topological domain 9, transmembrane region 6, mutagenesis site 6, sequence variant 5, turn 5, site 4, intramembrane region 2, short sequence motif 2, splice variant 2, chain 1, modified residue 1, strand 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
6QZI	X-RAY DIFFRACTION	1.9
6QZJ	X-RAY DIFFRACTION	2.2
8Y8V	ELECTRON MICROSCOPY	2.49
8AMX	ELECTRON MICROSCOPY	2.55
8AMW	ELECTRON MICROSCOPY	3
8C9H	ELECTRON MICROSCOPY	3.2
6KXW	X-RAY DIFFRACTION	3.7
6N1G	X-RAY DIFFRACTION	4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14520-F1	84.81	0.71

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (4): 74 (selectivity filter); 135 (important for permeability to glycerol); 223 (selectivity filter); 229 (selectivity filter)

Post-translational modifications (1): 20

Mutagenesis-validated functional residues (6):

Position	Phenotype
10–11	loss of phosphorylation by pka. increased interaction with plin1.
67	no effect on glycerol channel activity. no effect on water channel activity.
74	no effect on glycerol channel activity. no effect on water channel activity. decreased glycerol channel activity; when a
135	strongly decreased glycerol channel activity. mildly decreased water channel activity.
165	decreased glycerol channel activity. mildly decreased water channel activity.
223	no effect on glycerol channel activity. no effect on water channel activity. decreased glycerol channel activity; when a

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-432030	Transport of glycerol from adipocytes to the liver by Aquaporins
R-HSA-432047	Passive transport by Aquaporins
R-HSA-382551	Transport of small molecules
R-HSA-445717	Aquaporin-mediated transport

MSigDB gene sets: 463 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_CARBOHYDRATE_TRANSPORT, MORF_FLT1, MORF_MSH3, GOLDRATH_IMMUNE_MEMORY, MODULE_45, MODULE_64, MORF_BRCA1, TGACCTY_ERR1_Q2, HNF1_Q6, MORF_ESR1, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, MORF_RAD51L3, GCM_MYCL1, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT

GO Biological Process (4): water transport (GO:0006833), glycerol transmembrane transport (GO:0015793), transmembrane transport (GO:0055085), urea transmembrane transport (GO:0071918)

GO Molecular Function (5): urea transmembrane transporter activity (GO:0015204), water channel activity (GO:0015250), glycerol channel activity (GO:0015254), protein binding (GO:0005515), channel activity (GO:0015267)

GO Cellular Component (8): cytoplasm (GO:0005737), lipid droplet (GO:0005811), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), basolateral plasma membrane (GO:0016323), cytoplasmic vesicle membrane (GO:0030659), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Aquaporin-mediated transport	2
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
channel activity	2
cellular anatomical structure	2
fluid transport	1
polyol transmembrane transport	1
carbohydrate transmembrane transport	1
transport	1
cellular process	1
urea transport	1
transmembrane transport	1
transmembrane transporter activity	1
urea transmembrane transport	1
water transmembrane transporter activity	1
glycerol transmembrane transporter activity	1
binding	1
passive transmembrane transporter activity	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
anchoring junction	1
basal plasma membrane	1
plasma membrane region	1
vesicle membrane	1
cytoplasmic vesicle	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

3112 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AQP7	AQP11	Q8NBQ7	914
AQP7	AQP12A	Q8IXF9	858
AQP7	PLIN1	O60240	617
AQP7	GK2	Q14410	579
AQP7	GK	P32189	578
AQP7	AQP8	O94778	573
AQP7	ADIPOQ	Q15848	557
AQP7	CFTR	P13569	551
AQP7	C14orf180	Q8N912	531
AQP7	AQP12B	A6NM10	523
AQP7	ACSL1	P33121	518
AQP7	AQP6	Q13520	510
AQP7	PROK2	Q9HC23	480
AQP7	TLR2	O60603	458
AQP7	FCGR3B	O75015	449

IntAct

6 interactions, top by confidence:

A	B	Type	Score
AQP7	PLIN1	psi-mi:“MI:0914”(association)	0.570
PLIN1	AQP7	psi-mi:“MI:2364”(proximity)	0.570
PLIN1	AQP7	psi-mi:“MI:0915”(physical association)	0.570
PLIN1	AQP7	psi-mi:“MI:0403”(colocalization)	0.570
MEP1B	AQP7	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (6): AQP7 (Two-hybrid), AQP7 (Two-hybrid), AQP7 (Two-hybrid), ABHD16A (Two-hybrid), AQP7 (Negative Genetic), AQP7 (Affinity Capture-MS)

ESM2 similar proteins: A0A075B734, A1L272, A2IBY8, A8W649, A9Y006, D4A7H1, E7EXX2, F7B113, O14520, O35454, O54794, O62735, O94956, P34080, P35525, P41181, P47862, P47863, P47864, P51789, P51797, P56402, P56403, P79099, Q06495, Q06496, Q08DE6, Q4R691, Q5PQL3, Q62052, Q866S3, Q8BLV3, Q8BXB6, Q8BZ00, Q8IVB4, Q8K078, Q8MIQ9, Q8R2N1, Q8TCT8, Q921R8

Diamond homologs: A0A075B734, A0A384JPP3, A0A384JSZ0, A9Y006, B0D4E4, B0D4J9, B0D4K0, B0DLE4, B1VB61, F9USY3, F9UTW9, F9UUB3, G5CTF9, G5CTG0, G5CTG1, G5CTG4, G5CTG5, G5CTG6, G5CTG7, I1CR68, I1CS06, I1RHJ1, I1RIY3, I1Z8E7, I1Z8E8, I1Z8E9, I1Z8F0, I3W9F7, O14520, O43315, O54794, O62735, O77697, O77714, O77722, O77740, P0A3Q7, P0A3Q8, P0AER0, P0AER1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

86 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	3
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

807 predictions. Top by Δscore:

Variant	Effect	Δscore
15:58173062:TTGCA:T	acceptor_loss	1.0000
15:58173063:TGCAG:T	acceptor_loss	1.0000
15:58173064:GCAG:G	acceptor_loss	1.0000
15:58173065:CA:C	acceptor_loss	1.0000
15:58173066:A:AT	acceptor_loss	1.0000
15:58179346:G:GG	donor_gain	1.0000
15:58166667:TTCCA:T	acceptor_loss	0.9900
15:58166668:TCCAG:T	acceptor_loss	0.9900
15:58166669:CCAGG:C	acceptor_loss	0.9900
15:58166670:CAGGT:C	acceptor_loss	0.9900
15:58166671:A:C	acceptor_loss	0.9900
15:58166795:CTCTG:C	donor_loss	0.9900
15:58166796:TCTGG:T	donor_loss	0.9900
15:58166797:CTGGT:C	donor_loss	0.9900
15:58166799:GGTAA:G	donor_loss	0.9900
15:58166800:G:GG	donor_gain	0.9900
15:58166800:G:T	donor_loss	0.9900
15:58166801:T:A	donor_loss	0.9900
15:58166802:AA:A	donor_loss	0.9900
15:58173066:A:AG	acceptor_gain	0.9900
15:58173066:AGGT:A	acceptor_gain	0.9900
15:58173067:G:GG	acceptor_gain	0.9900
15:58173067:GGT:G	acceptor_gain	0.9900
15:58173067:GGTG:G	acceptor_gain	0.9900
15:58173203:ATGGT:A	donor_loss	0.9900
15:58173204:TG:T	donor_gain	0.9900
15:58173205:GG:G	donor_gain	0.9900
15:58173206:G:GA	donor_loss	0.9900
15:58173206:G:GG	donor_gain	0.9900
15:58173207:T:G	donor_loss	0.9900

AlphaMissense

2220 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:33385714:G:C	N226K	0.996
9:33385714:G:T	N226K	0.996
9:33395093:G:C	S43R	0.995
9:33395093:G:T	S43R	0.995
9:33395095:T:G	S43R	0.995
9:33386128:A:C	F158L	0.994
9:33386128:A:T	F158L	0.994
9:33386130:A:G	F158L	0.994
9:33386528:G:C	N94K	0.994
9:33386528:G:T	N94K	0.994
9:33387015:A:C	F74L	0.992
9:33387015:A:T	F74L	0.992
9:33387017:A:G	F74L	0.992
9:33385706:C:G	R229P	0.991
9:33387013:C:T	G75D	0.990
9:33385691:C:G	R234P	0.989
9:33385668:A:G	W242R	0.988
9:33385668:A:T	W242R	0.988
9:33385703:T:C	D230G	0.988
9:33385703:T:G	D230A	0.988
9:33385704:C:G	D230H	0.988
9:33385692:G:T	R234S	0.987
9:33386433:G:T	A126E	0.986
9:33387007:C:T	G77E	0.986
9:33385666:C:A	W242C	0.985
9:33385666:C:G	W242C	0.985
9:33385752:C:A	G214W	0.985
9:33385772:C:T	G207D	0.985
9:33385773:C:G	G207R	0.985
9:33386445:C:T	G122D	0.985

dbSNP variants (sampled 300 via entrez): RS1000019325 (9:33394171 C>A,T), RS1000235844 (9:33390938 C>G,T), RS1000260940 (9:33396673 G>C), RS1000329908 (9:33386640 C>A,T), RS1000420197 (9:33388642 C>G), RS1000986955 (9:33401126 A>C), RS1001173799 (9:33383849 A>G,T), RS1001226062 (9:33388267 C>T), RS1001708447 (9:33383668 C>T), RS1001731930 (9:33397690 A>G), RS1001929711 (9:33397928 T>C), RS1002030388 (9:33387356 A>T), RS1002107892 (9:33403179 G>A), RS1002515235 (9:33392448 A>G), RS1002582386 (9:33400416 C>G)

Disease associations

OMIM: gene MIM:602974 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

51 associations (top):

Study	Trait	p-value
GCST001639_33	Metabolite levels	3.000000e-27
GCST002987_11	Stroke	4.000000e-08
GCST002987_25	Stroke	4.000000e-08
GCST002988_7	Ischemic stroke	5.000000e-07
GCST002988_9	Ischemic stroke	5.000000e-07
GCST004744_13	Lung adenocarcinoma	9.000000e-07
GCST004746_44	Small cell lung carcinoma	4.000000e-06
GCST006004_5	Low density lipoprotein cholesterol levels	2.000000e-08
GCST006586_23	Urinary albumin excretion	1.000000e-08
GCST007638_47	Glycine levels	3.000000e-09
GCST008070_113	HDL cholesterol levels	2.000000e-06
GCST008070_115	HDL cholesterol levels	6.000000e-64
GCST008070_140	HDL cholesterol levels	3.000000e-09
GCST008070_44	HDL cholesterol levels	5.000000e-124
GCST008070_69	HDL cholesterol levels	2.000000e-50
GCST008074_114	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	6.000000e-15
GCST008074_34	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	8.000000e-34
GCST008074_74	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	8.000000e-17
GCST008075_132	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	6.000000e-14
GCST008075_138	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	3.000000e-294
GCST008075_204	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	3.000000e-97
GCST008075_3	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	4.000000e-186
GCST008075_96	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1.000000e-08
GCST008076_23	Triglyceride levels	4.000000e-24
GCST008076_62	Triglyceride levels	6.000000e-09
GCST008076_87	Triglyceride levels	7.000000e-16
GCST008079_93	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	4.000000e-06
GCST008083_107	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-36
GCST008083_156	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	4.000000e-17
GCST008083_66	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-16

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004723	coronary artery calcification
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004285	albuminuria
EFO:0009767	glycine measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004329	alcohol drinking
EFO:0010367	lysophosphatidylethanolamine 18:0 measurement
EFO:0010410	triacylglycerol 50:3 measurement
EFO:0004736	aspartate aminotransferase measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other ic — Aquaporins

CTD chemical–gene interactions

41 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases mutagenesis, affects cotreatment, increases expression	4
sodium arsenite	increases expression, decreases expression, decreases reaction, increases abundance	3
Acetaminophen	decreases expression, increases expression	3
Dexamethasone	increases expression, affects cotreatment, decreases expression	3
bisphenol S	increases expression, affects cotreatment, decreases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
Particulate Matter	decreases expression, increases abundance, increases expression, affects cotreatment	2
benzo(b)fluoranthene	affects cotreatment, increases expression	1
hydroxyhydroquinone	increases expression	1
arsenite	increases uptake	1
mono-(2-ethylhexyl)phthalate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
benz(a)anthracene	affects cotreatment, increases expression	1
chrysene	increases expression, affects cotreatment	1
tamibarotene	affects expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic Trioxide	affects cotreatment, increases expression, decreases reaction	1
Air Pollutants	increases abundance, increases expression	1
Allergens	decreases expression, increases abundance, affects cotreatment	1
Arsenic	decreases reaction, increases abundance, increases expression	1
Atrazine	increases expression	1
Vehicle Emissions	affects cotreatment, decreases expression, increases abundance	1
Calcitriol	decreases expression, decreases reaction, increases abundance, increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Diazinon	decreases methylation	1
Doxorubicin	decreases expression	1
Glucose	affects cotreatment, increases expression, decreases reaction	1
Glycerol	affects metabolic processing	1
Indomethacin	affects cotreatment, decreases expression, increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.