AQP3

Summary

AQP3 (aquaporin 3 (Gill blood group), HGNC:636) is a protein-coding gene on chromosome 9p13.3, encoding Aquaporin-3 (Q92482). Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient.

This gene encodes the water channel protein aquaporin 3. Aquaporins are a family of small integral membrane proteins related to the major intrinsic protein, also known as aquaporin 0. Aquaporin 3 is localized at the basal lateral membranes of collecting duct cells in the kidney. In addition to its water channel function, aquaporin 3 has been found to facilitate the transport of nonionic small solutes such as urea and glycerol, but to a smaller degree. It has been suggested that water channels can be functionally heterogeneous and possess water and solute permeation mechanisms. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 360 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 34 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_004925

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:636
Approved symbol	AQP3
Name	aquaporin 3 (Gill blood group)
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Aliases	GIL
Ensembl gene	ENSG00000165272
Ensembl biotype	protein_coding
OMIM	600170
Entrez	360

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 3 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay

ENST00000297991, ENST00000463983, ENST00000473153, ENST00000493581, ENST00000494313, ENST00000643650, ENST00000645858, ENST00000969970

RefSeq mRNA: 2 — MANE Select: NM_004925 NM_001318144, NM_004925

CCDS: CCDS6542, CCDS87649

Canonical transcript exons

ENST00000297991 — 6 exons

Exon	Start	End
ENSE00001851895	33447423	33447593
ENSE00001911571	33441160	33442211
ENSE00003321062	33443321	33443458
ENSE00003467346	33442852	33442970
ENSE00003478510	33443766	33443892
ENSE00003643153	33442301	33442518

Expression profiles

Bgee: expression breadth ubiquitous, 271 present calls, max score 99.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.2942 / max 1932.6266, expressed in 1148 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100468	34.8944	1129
100459	0.2623	113
100462	0.2435	46
100469	0.1797	25
100460	0.1743	91
100457	0.1628	87
100465	0.1236	63
100458	0.1119	70
100463	0.0479	17
100466	0.0305	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nasal cavity epithelium	UBERON:0005384	99.96	gold quality
pharyngeal mucosa	UBERON:0000355	99.93	gold quality
gingival epithelium	UBERON:0001949	99.93	gold quality
squamous epithelium	UBERON:0006914	99.93	gold quality
esophagus squamous epithelium	UBERON:0006920	99.93	gold quality
gingiva	UBERON:0001828	99.92	gold quality
epithelium of nasopharynx	UBERON:0001951	99.92	gold quality
cervix squamous epithelium	UBERON:0006922	99.92	gold quality
nasopharynx	UBERON:0001728	99.90	gold quality
tongue squamous epithelium	UBERON:0006919	99.90	gold quality
penis	UBERON:0000989	99.89	gold quality
parotid gland	UBERON:0001831	99.89	gold quality
mammalian vulva	UBERON:0000997	99.85	gold quality
palpebral conjunctiva	UBERON:0001812	99.85	gold quality
nasal cavity mucosa	UBERON:0001826	99.85	gold quality
oral cavity	UBERON:0000167	99.84	gold quality
nipple	UBERON:0002030	99.83	gold quality
trachea	UBERON:0003126	99.81	gold quality
epithelium of bronchus	UBERON:0002031	99.78	gold quality
bronchus	UBERON:0002185	99.78	gold quality
bronchial epithelial cell	CL:0002328	99.77	gold quality
cervix epithelium	UBERON:0004801	99.75	gold quality
lower esophagus mucosa	UBERON:0035834	99.74	gold quality
skin of hip	UBERON:0001554	99.71	gold quality
renal medulla	UBERON:0000362	99.70	gold quality
upper leg skin	UBERON:0004262	99.69	gold quality
body of tongue	UBERON:0011876	99.68	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.67	gold quality
tongue	UBERON:0001723	99.65	gold quality
upper arm skin	UBERON:0004263	99.58	gold quality

Single-cell (SCXA)

Detected in 19 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-HCAD-15	yes	2492.82
E-HCAD-1	yes	2324.55
E-MTAB-3929	yes	864.45
E-CURD-112	yes	350.95
E-GEOD-70580	yes	279.35
E-MTAB-8142	yes	130.26
E-CURD-122	yes	52.37
E-CURD-120	yes	39.96
E-HCAD-10	yes	13.76
E-MTAB-6701	yes	10.24
E-HCAD-31	yes	10.01
E-GEOD-81608	yes	9.42
E-MTAB-6678	yes	5.10
E-MTAB-10137	yes	4.74
E-CURD-114	no	3997.06

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, ESR2, FOXA2, KLF4, PPARA, TP53, TP63, TP73

miRNA regulators (miRDB)

64 targeting AQP3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267

Literature-anchored findings (GeneRIF, showing 40)

• we analyzed the oligomerization of the AQP3 aquaglyceroporin, which presents a mixed selectivity for water, glycerol, and urea. (PMID:11751877)
• the role of aquaporin-3 is to water-clamp viable layers of the epidermis in order to improve the hydration of the epidermis below the stratum corneum. (PMID:11918716)
• Aquaporin-3 protein was detected in the human peritoneal tissue and is upregulated by glucose (PMID:12234316)
• first reported cases of AQP3 deficiency in humans and provide the molecular basis of a new blood group system, GIL, encoded by the AQP3 protein (PMID:12239222)
• analysis of effect of nickel and extracellular acidification on water permeability of human aquaporin-3 in lung epithelial cells (PMID:12773542)
• reduction in the amounts of AQP-2 and AQP-3 expression, especially in lesions with substantial interstitial fibrosis and nephron loss, as compared with a healthy region of normal kidneys. (PMID:14514735)
• results indicate that ANP and BNP up-regulated the expression of AQP3 mRNA and protein, and both PK-A and PK-G dependent pathways mediated this effect (PMID:15375592)
• The distribution and expression levels of AQP3 in normal human tissue. (PMID:15703994)
• analysis of AQP3 expression in human fetal airway epithelial progenitor cells (PMID:16043462)
• AQP3 water channels serve as an essential pathway for volume-regulatory water transport in human epithelial cells. (PMID:16596446)
• provides evidence of AQP3 expression in human fetal membranes and demonstrates that AQP3 expression in primary human amnion cell culture is up-regulated by second-messenger cAMP (PMID:16638588)
• lower expression of AQP3 and enhanced expression of MRP2 are responsible for lower arsenic accumulation in arsenic-resistant cells (PMID:16672223)
• Increased expression and altered cellular distribution of AQP3 is found in atopic eczema, and this may contribute to water loss. (PMID:16918518)
• Lung carcinomas, especially adenocarcinomas, can produce AQP3, possibly in connection with their functional and/or biological nature. (PMID:17056099)
• results suggest that Foxa2 is one of the transcriptional regulators for AQP3 gene expression regulated by insulin (PMID:17471492)
• Data show that AQP-1, 3, 8, 9 mRNA expression was detected in both amnion and chorion and can be associated with intramembranous transport and volume regulation of amniotic fluid. (PMID:17545093)
• all trans retinoic acid increased AQP3 expression and enhanced biological activity in human skin (PMID:17943189)
• Provide evidence for involvement of AQP3-facilitated water transport in epidermal cell migration and for AQP3-facilitated glycerol transport in epidermal cell proliferation. (PMID:17968524)
• The results suggest that water-channel protein may be involved in the preservation of cellular character in the human prostate and prostate cancer is associated with an alteration of water-transporting mechanisms. (PMID:18036046)
• Up-regulated expression of AQP3 in ascending colon and down-regulated expression of AQP9 in descending colon are presented in patients with functional constipation as compared to patients without functional constipation. (PMID:18197497)
• The aim of this study was to use immunohistochemsitry to investigate the expression of aquaporins 1, 2 and 3 within the human intervertebral disc. (PMID:18247144)
• The data suggest potential roles of AQP3 and 5 in the regulation of airway hypersecretion, perhaps ultimately providing a target for treating such diseases (PMID:18280225)
• Although reticulocytes are highly abundant in malarial anemia, low AQP3 expression was observed (PMID:18435676)
• Discuss the role of AQP3 in TNF-alpha-mediated inflammation and the development of periodontitis. (PMID:18543247)
• The trafficking of AQP3 evoked by epinephrine is mediated by protein kinase C in Caco-2 cells. (PMID:18601899)
• differential polarity and selective targeting of AQP3 and AQP10 in the intestinal epithelial cells is influenced by amino acid signal motifs. (PMID:18678926)
• There is little influence of AQP3 on keratinocyte differentiation, but there is support for the proposed involvement of AQP3-facilitated cell proliferation. (PMID:19184071)
• Here the authors show that human aquaporin 3 is internalized into Plasmodium falciparum infected erythrocytes, presumably during or soon after invasion. (PMID:19393693)
• Alteration of aquaporin 1 and aquaporin 3 expression in fetal membranes and placenta may be important in the pathophysiology of isolated oligohydramnios. (PMID:19545896)
• These data indicate that TNF-alpha decreases AQP3 gene expression through p38 and ERK activation, and suggest that the decrease in AQP3 expression caused by TNF-alpha might be related to the phenotypes of skin inflammation, such as dry skin. (PMID:19619514)
• AQP3, 4 & 5 exhibited differential expression between human gastric carcinoma & corresponding normal tissue;AQP3 & AQP5 expression were associated with lymph node metastasis & lymphovascular invasion (PMID:20106632)
• The gene expressions of AQP3 and AQP4 in gastric mucosa are different in patients with various degrees of spleen-stomach dampness-heat syndrome of chronic superficial gastritis. (PMID:20141731)
• The authors conclude that AQP3 plays a critical role in human epidermal growth factor (hEGF) induced cell migration and proliferation in human gastric cancer. (PMID:20364107)
• reduced AQP3 in vitiliginous keratinocytes might be responsible for their reduced survival (PMID:20428189)
• Mucinous colorectal adenocarcinomas displayed 182 upregulated and 135 downregulated genes. The most upregulated genes included those involved in cellular differentiation and mucin metabolism (eg, AQP3). (PMID:20485009)
• AQP3 decreased with increasing age in normal human skin, normal human epidermal keratinocytes, and skin fibroblast samples. (PMID:20546216)
• Found AQP3 is involved in wound healing in human skin keratinocytes. Trans-Zeatin pretreatment also attenuates UV-induced decreased water permeability in HaCaT cells. (PMID:20596606)
• One sequence alteration, homozygous c.105G->C in aquaporin 3 was detected in 11 out of 34 patients but not in 100 control chromosomes. (PMID:21063116)
• aquaporin 3 is an essential membrane pathway for sperm regulatory volume decrease that balances the “trade-off” between sperm motility and cell swelling upon physiological hypotonicity (PMID:21135872)
• involvement of AQP3 in epidermal hyperplasia by a mechanism involving upregulated AQP3 expression and consequent enhancement of keratinocyte proliferation (PMID:21191421)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	aqp3a	ENSDARG00000003808
danio_rerio	aqp3b	ENSDARG00000069518
mus_musculus	Aqp3	ENSMUSG00000028435
rattus_norvegicus	Aqp3	ENSRNOG00000009797
drosophila_melanogaster	Eglp1	FBGN0034882
drosophila_melanogaster	Eglp2	FBGN0034883
drosophila_melanogaster	Eglp3	FBGN0034884
drosophila_melanogaster	Eglp4	FBGN0034885

Paralogs (11): AQP6 (ENSG00000086159), AQP8 (ENSG00000103375), AQP9 (ENSG00000103569), MIP (ENSG00000135517), AQP10 (ENSG00000143595), AQP5 (ENSG00000161798), AQP7 (ENSG00000165269), AQP2 (ENSG00000167580), AQP4 (ENSG00000171885), AQP1 (ENSG00000240583), AQP7B (ENSG00000259916)

Protein

Protein identifiers

Aquaporin-3 — Q92482 (reviewed: Q92482)

Alternative names: Aquaglyceroporin-3

All UniProt accessions (4): A0A2R8Y2R4, A0A2R8YD22, A0A2R8YDV4, Q92482

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. Also participates in cell permeability to H2O2 and H2O2-mediated signaling. In skin, transports glycerol to the epidermis and stratum corneum, where it maintains hydration, elasticity, and supports lipid biosynthesis for barrier repair. In kidney, contributes to the reabsorption of water, helping the body maintain proper fluid balance.

Subunit / interactions. Homotetramer; each monomer provides an independent glycerol/water pore. Could also exist in other oligomeric states.

Subcellular location. Cell membrane. Basolateral cell membrane.

Tissue specificity. Widely expressed in epithelial cells of kidney (collecting ducts) and airways, in keratinocytes, immature dendritic cells and erythrocytes. Isoform 2 is not detectable in erythrocytes at the protein level.

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.

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 (NPA).

Induction. Up-regulated by magnesium.

Polymorphism. AQP3 is responsible for the GIL blood group system. Isoform 2 is detected in GIL-negative individuals that lack functional AQP3.

Miscellaneous. Due to a polymorphism at the 5’-splice donor site of intron 5, leading to exon 5 skipping and premature termination of translation. This is the molecular basis of the GIL blood group.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q92482-1	1	yes
Q92482-2	2, delta5

RefSeq proteins (2): NP_001305073, NP_004916* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000425	MIP	Family
IPR022357	MIP_CS	Conserved_site
IPR023271	Aquaporin-like	Homologous_superfamily
IPR023275	Aquaporin_3	Family
IPR050363	MIP/Aquaporin	Family

Pfam: PF00230

Catalyzed reactions (Rhea), 4 shown:

• H2O(in) = H2O(out) (RHEA:29667)
• glycerol(in) = glycerol(out) (RHEA:29675)
• urea(in) = urea(out) (RHEA:32799)
• H2O2(out) = H2O2(in) (RHEA:74375)

UniProt features (29 total): topological domain 9, transmembrane region 6, site 3, intramembrane region 2, short sequence motif 2, splice variant 2, sequence conflict 2, chain 1, glycosylation site 1, sequence variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9QSZ	ELECTRON MICROSCOPY	3
9QSX	ELECTRON MICROSCOPY	3.2
9QSY	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92482-F1	93.47	0.86

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 (3): 63 (selectivity filter); 212 (selectivity filter); 218 (selectivity filter)

Glycosylation sites (1): 141

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-432040	Vasopressin regulates renal water homeostasis via Aquaporins
R-HSA-432047	Passive transport by Aquaporins
R-HSA-9725554	Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin
R-HSA-1266738	Developmental Biology
R-HSA-382551	Transport of small molecules
R-HSA-445717	Aquaporin-mediated transport
R-HSA-9734767	Developmental Cell Lineages

MSigDB gene sets: 387 (showing top): MODULE_416, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_EPITHELIUM_DEVELOPMENT, MULLIGHAN_NPM1_SIGNATURE_3_UP, KOBAYASHI_EGFR_SIGNALING_24HR_UP, MCLACHLAN_DENTAL_CARIES_UP, GOBP_REGULATION_OF_EPIDERMIS_DEVELOPMENT, JAEGER_METASTASIS_DN, NKX25_02, PEREZ_TP63_TARGETS, MODULE_45, MODULE_64, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN, NAGASHIMA_NRG1_SIGNALING_UP, SHEPARD_BMYB_MORPHOLINO_DN

GO Biological Process (16): positive regulation of immune system process (GO:0002684), response to ischemia (GO:0002931), renal water homeostasis (GO:0003091), water transport (GO:0006833), glycerol transmembrane transport (GO:0015793), response to retinoic acid (GO:0032526), response to vitamin D (GO:0033280), odontogenesis (GO:0042476), regulation of keratinocyte differentiation (GO:0045616), response to calcium ion (GO:0051592), establishment of localization in cell (GO:0051649), renal water absorption (GO:0070295), cellular response to hypoxia (GO:0071456), urea transport (GO:0015840), transmembrane transport (GO:0055085), urea transmembrane transport (GO:0071918)

GO Molecular Function (6): urea transmembrane transporter activity (GO:0015204), water channel activity (GO:0015250), glycerol channel activity (GO:0015254), identical protein binding (GO:0042802), protein binding (GO:0005515), channel activity (GO:0015267)

GO Cellular Component (6): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), membrane (GO:0016020), basolateral plasma membrane (GO:0016323)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Aquaporin-mediated transport	2
Developmental Cell Lineages of the Integumentary System	1
Transport of small molecules	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
response to lipid	2
response to oxygen-containing compound	2
channel activity	2
immune system process	1
regulation of immune system process	1
positive regulation of biological process	1
response to stress	1
renal system process	1
multicellular organismal-level water homeostasis	1
fluid transport	1
polyol transmembrane transport	1
carbohydrate transmembrane transport	1
response to vitamin	1
animal organ morphogenesis	1
keratinocyte differentiation	1
regulation of epidermal cell differentiation	1
response to metal ion	1
establishment of localization	1
cellular localization	1
renal water transport	1
renal absorption	1
response to hypoxia	1
cellular response to stress	1
cellular response to decreased oxygen levels	1
one-carbon compound transport	1
nitrogen compound 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
protein binding	1
binding	1
passive transmembrane transporter activity	1
nuclear lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

3345 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AQP3	AQP11	Q8NBQ7	809
AQP3	AQP12A	Q8IXF9	792
AQP3	GK2	Q14410	722
AQP3	GK	P32189	721
AQP3	AVPR2	P30518	582
AQP3	FLG	P20930	547
AQP3	FLG2	Q5D862	544
AQP3	AQP6	Q13520	538
AQP3	CYBB	P04839	527
AQP3	SLC4A1	P02730	494
AQP3	SLC14A1	Q13336	476
AQP3	CDH1	P12830	474
AQP3	SLC12A1	Q13621	471
AQP3	AVP	P01185	469
AQP3	GJA1	P17302	465

IntAct

217 interactions, top by confidence:

A	B	Type	Score
TMEM86A	AQP3	psi-mi:“MI:0915”(physical association)	0.560
TMEM42	AQP3	psi-mi:“MI:0915”(physical association)	0.560
GIMAP5	AQP3	psi-mi:“MI:0915”(physical association)	0.560
AQP3	AQP3	psi-mi:“MI:0915”(physical association)	0.560
MGST3	AQP3	psi-mi:“MI:0915”(physical association)	0.560
NRAC	AQP3	psi-mi:“MI:0915”(physical association)	0.560
AQP3	VASN	psi-mi:“MI:0915”(physical association)	0.560
ERG28	AQP3	psi-mi:“MI:0915”(physical association)	0.560
STX1A	AQP3	psi-mi:“MI:0915”(physical association)	0.560
AQP3	MFF	psi-mi:“MI:0915”(physical association)	0.560
FAM209A	AQP3	psi-mi:“MI:0915”(physical association)	0.560
MUC1	AQP3	psi-mi:“MI:0915”(physical association)	0.560
AQP3	GIMAP5	psi-mi:“MI:0915”(physical association)	0.560
HIBADH	AQP3	psi-mi:“MI:0915”(physical association)	0.560
GPR152	AQP3	psi-mi:“MI:0915”(physical association)	0.560
LEUTX	AQP3	psi-mi:“MI:0915”(physical association)	0.560
EVI2B	AQP3	psi-mi:“MI:0915”(physical association)	0.560
GPX8	AQP3	psi-mi:“MI:0915”(physical association)	0.560
SGPL1	AQP3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (241): AQP3 (Two-hybrid), AQP3 (Affinity Capture-Western), AQP3 (Affinity Capture-Western), PLD2 (Affinity Capture-Western), CAV1 (Affinity Capture-Western), AQP3 (Two-hybrid), AQP3 (Two-hybrid), AQP3 (Two-hybrid), AQP3 (Two-hybrid), AQP3 (Two-hybrid), AQP3 (Two-hybrid), AQP3 (Two-hybrid), AQP3 (Two-hybrid), AQP3 (Two-hybrid), AQP3 (Two-hybrid)

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

1 interactions.

A	Effect	B	Mechanism
PPARA	“up-regulates quantity by expression”	AQP3	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 104 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	47.6×	3e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	45.3×	3e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	45.3×	3e-06
Dopamine Neurotransmitter Release Cycle	5	41.4×	4e-06
Long-term potentiation	5	39.6×	4e-06
Assembly and cell surface presentation of NMDA receptors	9	38.1×	1e-10
Neurexins and neuroligins	11	36.1×	1e-12
Protein-protein interactions at synapses	7	31.0×	2e-07

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	61.2×	3e-13
protein localization to synapse	6	48.4×	4e-07
receptor clustering	7	46.0×	4e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	6	31.3×	4e-06
protein-containing complex assembly	9	10.8×	1e-05
cell-cell adhesion	10	10.7×	4e-06
protein localization to plasma membrane	6	6.9×	8e-03
chemical synaptic transmission	7	5.7×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	21
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
442112	GRCh37/hg19 9p22.2-13.3(chr9:17132123-35567051)x3	Pathogenic

SpliceAI

580 predictions. Top by Δscore:

Variant	Effect	Δscore
9:33442207:CGGTC:C	acceptor_gain	1.0000
9:33442209:GTCC:G	acceptor_loss	1.0000
9:33442210:TC:T	acceptor_gain	1.0000
9:33442210:TCCTG:T	acceptor_loss	1.0000
9:33442211:CC:C	acceptor_gain	1.0000
9:33442212:C:CC	acceptor_gain	1.0000
9:33442212:CTGGG:C	acceptor_loss	1.0000
9:33442213:T:C	acceptor_loss	1.0000
9:33442295:A:AC	donor_gain	1.0000
9:33442296:C:CC	donor_gain	1.0000
9:33442297:TCAC:T	donor_loss	1.0000
9:33442298:CACGT:C	donor_loss	1.0000
9:33442299:A:AC	donor_gain	1.0000
9:33442299:ACG:A	donor_loss	1.0000
9:33442300:C:CA	donor_gain	1.0000
9:33442300:CG:C	donor_gain	1.0000
9:33442300:CGT:C	donor_gain	1.0000
9:33442300:CGTG:C	donor_gain	1.0000
9:33442300:CGTGA:C	donor_gain	1.0000
9:33442514:ATGAA:A	acceptor_gain	1.0000
9:33442515:TGAA:T	acceptor_gain	1.0000
9:33442516:GAA:G	acceptor_gain	1.0000
9:33442517:AA:A	acceptor_gain	1.0000
9:33442519:C:CC	acceptor_gain	1.0000
9:33442846:CCATA:C	donor_loss	1.0000
9:33442847:CATAC:C	donor_loss	1.0000
9:33442849:TACC:T	donor_loss	1.0000
9:33442850:A:AC	donor_gain	1.0000
9:33442850:ACCTG:A	donor_loss	1.0000
9:33442851:C:CA	donor_loss	1.0000

AlphaMissense

1881 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:33442366:G:C	N215K	0.999
9:33442366:G:T	N215K	0.999
9:33442491:A:G	C174R	0.999
9:33442355:T:G	D219A	0.998
9:33442356:C:G	D219H	0.998
9:33442903:A:C	F147L	0.998
9:33442903:A:T	F147L	0.998
9:33442905:A:G	F147L	0.998
9:33443445:G:C	N83K	0.998
9:33443445:G:T	N83K	0.998
9:33443812:A:C	F63L	0.998
9:33443812:A:T	F63L	0.998
9:33443814:A:G	F63L	0.998
9:33442152:C:T	G257D	0.997
9:33442344:G:T	R223S	0.997
9:33442355:T:A	D219V	0.997
9:33442355:T:C	D219G	0.997
9:33442425:C:G	G196R	0.997
9:33442499:A:G	L171P	0.997
9:33447440:C:A	G31W	0.997
9:33442164:C:T	G253D	0.996
9:33442318:C:A	W231C	0.996
9:33442318:C:G	W231C	0.996
9:33442320:A:G	W231R	0.996
9:33442320:A:T	W231R	0.996
9:33442349:C:T	G221D	0.996
9:33442368:T:C	N215D	0.996
9:33442370:A:T	V214D	0.996
9:33442384:G:C	N209K	0.996
9:33442384:G:T	N209K	0.996

dbSNP variants (sampled 300 via entrez): RS1000243316 (9:33448973 G>A,C,T), RS1000670866 (9:33447747 G>T), RS1001129816 (9:33449322 G>C), RS1001310244 (9:33441456 A>C), RS1001873949 (9:33447804 G>C), RS1003145294 (9:33446346 T>C), RS1003421658 (9:33445039 C>T), RS1003502495 (9:33446614 A>T), RS1003585960 (9:33445934 T>A), RS1003849541 (9:33445436 G>T), RS1003881757 (9:33444695 G>C), RS1004906720 (9:33444207 G>C), RS1005391018 (9:33442023 G>A), RS1005525906 (9:33446866 G>C), RS1005734023 (9:33441170 ATATT>A)

Disease associations

OMIM: gene MIM:600170 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004744_13	Lung adenocarcinoma	9.000000e-07
GCST008836_7	Lung adenocarcinoma	2.000000e-08
GCST010152_16	Neuroblastoma or malignant cutaneous melanoma	3.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6196115 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: other ic — Aquaporins

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
Auphen	Inhibitor	6.1	pIC50
Audien	Inhibitor	4.77	pIC50

ChEMBL bioactivities

1 potent at pChembl≥5 of 2 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.70	IC50	200	nM	CHEMBL6188481

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, affects expression, decreases expression	8
sodium arsenite	increases response to substance, affects expression, decreases expression, increases abundance, increases expression	6
Estradiol	affects expression, affects cotreatment, decreases expression, increases expression	5
Tetrachlorodibenzodioxin	decreases reaction, increases expression, increases activity	5
Air Pollutants	increases expression, decreases expression, increases abundance	4
Mercuric Chloride	decreases reaction, increases transport, increases reaction, decreases activity	3
Quercetin	affects cotreatment, decreases expression, increases expression	3
Smoke	decreases expression, increases abundance, increases expression	3
Tobacco Smoke Pollution	decreases expression, increases expression	3
Cyclosporine	decreases expression, increases expression	3
Aflatoxin B1	affects expression, increases expression	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
methylmercuric chloride	decreases expression	2
sodium arsenate	decreases expression, increases abundance	2
arsenite	increases expression, decreases expression, increases abundance	2
nickel sulfate	decreases expression	2
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases expression	2
4-((3-bromophenyl)amino)-6,7-dimethoxyquinazoline	decreases reaction, increases expression	2
U 0126	increases expression, decreases reaction	2
Resveratrol	decreases reaction, increases expression	2
Arsenic Trioxide	affects response to substance, increases expression	2
Acetaminophen	increases expression	2
Arsenic	decreases expression, increases abundance, affects response to substance	2
Catechin	affects cotreatment, increases expression	2
Nickel	increases expression	2
Valproic Acid	decreases methylation, increases expression	2
Water	increases transport, increases reaction, decreases reaction	2
Antirheumatic Agents	decreases expression, increases expression	2
dicrotophos	decreases expression	1
fenamic acid	increases expression, increases reaction	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL6183213	Binding	Inhibition of AQP3 channel in human erythrocyte assessed as inhibition of glycerol permeability	Distinctive roles of aquaporins and novel therapeutic opportunities against cancer. — RSC Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SD10	HAP1 AQP3 (-) 1	Cancer cell line	Male
CVCL_XL42	HAP1 AQP3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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