AQP9

Summary

AQP9 (aquaporin 9, HGNC:643) is a protein-coding gene on chromosome 15q21.3, encoding Aquaporin-9 (O43315). Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient.

The aquaporins are a family of water-selective membrane channels. This gene encodes a member of a subset of aquaporins called the aquaglyceroporins. This protein allows passage of a broad range of noncharged solutes and also stimulates urea transport and osmotic water permeability. This protein may also facilitate the uptake of glycerol in hepatic tissue . The encoded protein may also play a role in specialized leukocyte functions such as immunological response and bactericidal activity. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 366 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 60 total
• Druggable target: yes
• MANE Select transcript: NM_020980

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:643
Approved symbol	AQP9
Name	aquaporin 9
Location	15q21.3
Locus type	gene with protein product
Status	Approved
Aliases	SSC1, HsT17287
Ensembl gene	ENSG00000103569
Ensembl biotype	protein_coding
OMIM	602914
Entrez	366

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000219919, ENST00000558772, ENST00000559443, ENST00000872424, ENST00000872425, ENST00000872426, ENST00000872427

RefSeq mRNA: 3 — MANE Select: NM_020980 NM_001320635, NM_001320636, NM_020980

CCDS: CCDS10165, CCDS81887

Canonical transcript exons

ENST00000219919 — 6 exons

Exon	Start	End
ENSE00000690847	58173068	58173205
ENSE00000690849	58174918	58175036
ENSE00000690851	58179128	58179345
ENSE00001250659	58183961	58185911
ENSE00002286978	58138381	58138676
ENSE00003604575	58166673	58166799

Expression profiles

Bgee: expression breadth ubiquitous, 183 present calls, max score 98.97.

FANTOM5 (CAGE): breadth broad, TPM avg 53.9905 / max 5703.3487, expressed in 356 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146874	38.1611	226
146871	4.4791	230
146868	4.4712	254
146873	3.2734	161
146872	1.1520	142
146869	1.0445	174
146875	0.6624	107
146870	0.5079	136
207537	0.2390	67

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	98.97	gold quality
monocyte	CL:0000576	97.74	gold quality
right lobe of liver	UBERON:0001114	97.68	gold quality
mononuclear cell	CL:0000842	97.41	gold quality
leukocyte	CL:0000738	97.39	gold quality
liver	UBERON:0002107	96.66	gold quality
periodontal ligament	UBERON:0008266	96.03	gold quality
granulocyte	CL:0000094	94.26	gold quality
caput epididymis	UBERON:0004358	93.90	gold quality
germinal epithelium of ovary	UBERON:0001304	93.03	gold quality
corpus epididymis	UBERON:0004359	92.88	gold quality
bone marrow	UBERON:0002371	90.53	gold quality
right lung	UBERON:0002167	90.30	gold quality
spleen	UBERON:0002106	89.92	gold quality
parietal pleura	UBERON:0002400	87.18	gold quality
upper lobe of left lung	UBERON:0008952	87.15	gold quality
upper lobe of lung	UBERON:0008948	86.32	gold quality
skin of abdomen	UBERON:0001416	86.03	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.88	gold quality
skin of leg	UBERON:0001511	85.11	gold quality
bone marrow cell	CL:0002092	84.81	gold quality
zone of skin	UBERON:0000014	83.99	gold quality
trabecular bone tissue	UBERON:0002483	82.03	gold quality
omental fat pad	UBERON:0010414	81.84	gold quality
peritoneum	UBERON:0002358	81.77	gold quality
upper arm skin	UBERON:0004263	81.47	silver quality
vermiform appendix	UBERON:0001154	81.36	gold quality
adipose tissue of abdominal region	UBERON:0007808	81.31	gold quality
pleura	UBERON:0000977	81.23	gold quality
lung	UBERON:0002048	80.82	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	659.24
E-MTAB-9221	yes	28.37
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

83 targeting AQP9, 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-4455	100.00	65.48	1587
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-4766-5P	99.75	69.23	2662

Literature-anchored findings (GeneRIF, showing 40)

• AQP9 can modulate drug sensitivity in cancer. (PMID:15336539)
• The APQ9 mRNA expression in fetal membranes suggest that APQ9 may be an important water channel in intramembranous amniotic fluid water regulation. (PMID:15592307)
• results provide new evidences that suggest the involvement of AQP9 and UT-A in the urea excretion mechanism across human term placenta from mother to fetus in physiological conditions (PMID:16480766)
• We propose that increased water influx through AQP9 is critically involved in the formation of membrane protrusions, and that AQP9-induced actin polymerization is augmented by activation of Cdc42 and PKC(zeta). (PMID:17346701)
• The expression of AQP9 in glioblastoma was studied. (PMID:17525633)
• 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)
• 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)
• decreased hepatic AQP9 expression observed in obese T2DM subjects suggests a potential role in glycerol release from adipose tissue (PMID:18401671)
• Results indicate that aquaporin-9 may play an important role in the malignant progression of brain astrocytic tumours. (PMID:18652774)
• hAQP9 functions as a facilitative carrier for glycerol. (PMID:18762715)
• The present study strongly suggests that membrane transporters responsible for arsenic uptake, such as AQP9, may play a critical role in development of arsenic resistance in human lung cancer cells. (PMID:19100828)
• CFTR expression decreases in preeclampsia and may thus be implicated in the regulation of AQP9 activity (PMID:19481256)
• we found a greater expression found in visceral fat, and between subcutaneous adipose aquaporin 7 and hepatic AQP9 gene expression within the context of human morbid obesity (PMID:19615702)
• The examination was performed whether aquaporin (AQP) 9 is expressed in normal skeletal muscle at mRNA and protein levels. (PMID:19629726)
• TXA(2) receptor mediates water influx through aquaporins in astrocytoma cells via TXA(2) receptor-mediated activation of G alpha(12/13), Rho A, Rho kinase and Na(+)/H(+)-exchanger. (PMID:19772916)
• The results suggest that in addition to the initial uptake of trivalent inorganic As(III) inside cells, AQP9 plays a dual role in the detoxification of arsenic metabolites by facilitating efflux from cells. (PMID:19802720)
• AQP9 expression in fetal membranes was significantly higher in spontaneous term labor when compared with term-not in labor membranes. (PMID:19916714)
• Elevated serum levels of human chorionic gonadotrophin may be involved in increased aquaporin-9 protein expression in preeclamptic placenta explants via adenosine 3’,5’-cyclic phosphate pathways. (PMID:20220109)
• Hyperandrogenism in follicular fluid of women with polycystic ovary syndrome inhibited AQP-9 in granulosa cells through the PI3K pathway. (PMID:20378617)
• insulin treatment inhibited the expression of AQP9 in normal liver cells (PMID:20587318)
• When polyhydramnios occurs, expression of aquaporin 8 and aquaporin 9 in fetal membranes and placenta is an adaptive change. (PMID:20732771)
• Genetic variation in the AQP9 gene is associated with femoral neck BMD in postmenopausal women, and may represent one of the susceptibility genes for phenotypes related to bone mass (PMID:20960106)
• AQP9 plays an active role in neutrophil volume regulation and migration (PMID:21873454)
• The expression levels of aquaporin 9 were approximately 2 times higher in the chorion cells than those in the amnion cells following arsenite administration. (PMID:21945491)
• Aquaporin 9 is linked to the tumorigenesis of glioblastoma. (PMID:22262958)
• There is a coordinated regulation of adipose AQP7 and hepatic AQP9 gene expression that is distorted in metabolic syndrome X. (Review) (PMID:22425521)
• Multi-tissue gene expression studies reveal SERPINA1 and AQP9 variants as genes for atherosclerosis. (PMID:22916037)
• Reduced expression of AQP9 in human fallopian tube may contribute to aspects of pathophysiology of tubal ectopic pregnancy. (PMID:23238960)
• The identification of novel, high affinity AQP9 inhibitors in an intracellular binding site. (PMID:23448163)
• AQP9, rather than other biomarkers such as cell surface markers and chromosomal alterations, correlate closely with the sensitivity to arsenic trioxide in acute promyelocytic leukemia cell lines. (PMID:23563754)
• The interplay of water fluxes through AQP9 and actin dynamics regulate the cellular protrusive and motile activity of cells. (PMID:23573219)
• AQP9 expression is lower in patients with stage III colorectal cancer who do not respond to adjuvant chemotherapy (PMID:23612070)
• Placental expression of the arsenic transporter AQP9 was positively associated with maternal urinary arsenic levels during pregnancy. AQP9 expression related to phospholipase ENPP2 expression which was positively associated with infant birth weight. (PMID:23866971)
• AQP9 expressing glioma cells were negative for the brain tumor stem cell marker CD15. (PMID:24086629)
• AQP9 downregulation together with the subsequent reduction in hepatic glycerol permeability in insulin-resistant states emerges as a compensatory mechanism whereby the liver counteracts further triacylglycerol accumulation (PMID:24418844)
• 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 genetic polymorphisms in OCT2, AQP2, AQP9 and TMEM205 may contribute to chemotherapy response in lung cancer patients. (PMID:24643204)
• Oleic acid-induced hepatic steatosis in HepG2 cells is associated with the coordinated regulation of aquaporin 3 and aquaporin 9 via activation of p38 signaling (PMID:25105540)
• we suggest that AQP9 is involved in viral tropism and pathogenesis of Herpes simplex encephalitis (PMID:25604497)
• 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)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	aqp10a	ENSDARG00000007086
danio_rerio	aqp10b	ENSDARG00000058678
mus_musculus	Aqp9	ENSMUSG00000032204
rattus_norvegicus	Aqp9	ENSRNOG00000061883
drosophila_melanogaster	Drip	FBGN0015872
drosophila_melanogaster	Eglp1	FBGN0034882
drosophila_melanogaster	Eglp2	FBGN0034883
drosophila_melanogaster	Eglp3	FBGN0034884
drosophila_melanogaster	Eglp4	FBGN0034885

Paralogs (11): AQP6 (ENSG00000086159), AQP8 (ENSG00000103375), MIP (ENSG00000135517), AQP10 (ENSG00000143595), AQP5 (ENSG00000161798), AQP7 (ENSG00000165269), AQP3 (ENSG00000165272), AQP2 (ENSG00000167580), AQP4 (ENSG00000171885), AQP1 (ENSG00000240583), AQP7B (ENSG00000259916)

Protein

Protein identifiers

Aquaporin-9 — O43315 (reviewed: O43315)

Alternative names: Aquaglyceroporin-9, Small solute channel 1

All UniProt accessions (2): O43315, H0YK62

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. AQP9 is the primary route for glycerol uptake in hepatocytes, supporting hepatic gluconeogenesis. It exhibits broad specificity and may transport various small, non-charged solutes, including carbamides, polyols, purines, and pyrimidines. AQP9 may also facilitate hepatic urea extrusion. Due to its permeability to lactate, AQP9 might participate in the astrocyte-to-neuron lactate shuttle, supplying neurons with energy. Additionally, AQP9 is permeable to arsenite, contributing to arsenic excretion by the liver and providing partial protection against arsenic toxicity. It is also permeable to H2O2 in vivo. Could also be permeable to ammonium.

Subunit / interactions. Homotetramer; each monomer provides an independent glycerol/water pore.

Subcellular location. Cell membrane. Basolateral cell membrane.

Tissue specificity. Highly expressed in peripheral leukocytes. Also expressed in liver, lung, and spleen.

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).

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

RefSeq proteins (3): NP_001307564, NP_001307565, NP_066190* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000425	MIP	Family
IPR015685	Aquaporin_9	Family
IPR022357	MIP_CS	Conserved_site
IPR023271	Aquaporin-like	Homologous_superfamily
IPR050363	MIP/Aquaporin	Family

Pfam: PF00230

Catalyzed reactions (Rhea), 12 shown:

• NH4(+)(in) = NH4(+)(out) (RHEA:28747)
• H2O(in) = H2O(out) (RHEA:29667)
• glycerol(in) = glycerol(out) (RHEA:29675)
• urea(in) = urea(out) (RHEA:32799)
• selenite(in) = selenite(out) (RHEA:34891)
• (S)-lactate(in) = (S)-lactate(out) (RHEA:34987)
• uracil(in) = uracil(out) (RHEA:69404)
• adenine(out) = adenine(in) (RHEA:71523)
• H2O2(out) = H2O2(in) (RHEA:74375)
• arsenite(in) = arsenite(out) (RHEA:81347)
• 3-hydroxybutanoate(in) = 3-hydroxybutanoate(out) (RHEA:81351)
• D-mannitol(in) = D-mannitol(out) (RHEA:81355)

UniProt features (21 total): topological domain 9, transmembrane region 6, intramembrane region 2, short sequence motif 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43315-F1	91.15	0.84

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: 337 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_CARBOHYDRATE_TRANSPORT, GOLDRATH_IMMUNE_MEMORY, MODULE_45, MODULE_64, HNF1_Q6, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, CAIRO_HEPATOBLASTOMA_CLASSES_DN, GOBP_WATER_TRANSPORT, MODULE_75, UEDA_PERIFERAL_CLOCK, GOBP_POLYOL_TRANSMEMBRANE_TRANSPORT, GOBP_ONE_CARBON_COMPOUND_TRANSPORT, GOBP_RESPONSE_TO_CAMP

GO Biological Process (12): water transport (GO:0006833), purine nucleobase transport (GO:0006863), glycerol transmembrane transport (GO:0015793), amine transport (GO:0015837), pyrimidine nucleobase transport (GO:0015855), cellular response to cAMP (GO:0071320), detoxification of arsenic-containing substance (GO:0071722), urea transmembrane transport (GO:0071918), transmembrane transport (GO:0055085), pyrimidine-containing compound transmembrane transport (GO:0072531), hydrogen peroxide transmembrane transport (GO:0080170), purine nucleobase transmembrane transport (GO:1904823)

GO Molecular Function (9): purine nucleobase transmembrane transporter activity (GO:0005345), pyrimidine nucleobase transmembrane transporter activity (GO:0005350), urea transmembrane transporter activity (GO:0015204), water channel activity (GO:0015250), glycerol channel activity (GO:0015254), urea channel activity (GO:0015265), channel activity (GO:0015267), hydrogen peroxide channel activity (GO:0140070), protein binding (GO:0005515)

GO Cellular Component (4): plasma membrane (GO:0005886), basolateral plasma membrane (GO:0016323), intracellular membrane-bounded organelle (GO:0043231), membrane (GO:0016020)

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	4
transmembrane transport	3
nucleobase transport	2
nitrogen compound transport	2
nucleobase transmembrane transporter activity	2
fluid transport	1
polyol transmembrane transport	1
carbohydrate transmembrane transport	1
response to cAMP	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
response to arsenic-containing substance	1
detoxification	1
urea transport	1
transport	1
cellular process	1
purine nucleobase transport	1
purine-containing compound transmembrane transport	1
purine nucleobase transmembrane transport	1
pyrimidine nucleobase transport	1
pyrimidine-containing compound transmembrane transport	1
transmembrane transporter activity	1
urea transmembrane transport	1
water transmembrane transporter activity	1
glycerol transmembrane transporter activity	1
urea transmembrane transporter activity	1
passive transmembrane transporter activity	1
hydrogen peroxide transmembrane transport	1
binding	1
membrane	1
cell periphery	1
basal plasma membrane	1
plasma membrane region	1
intracellular anatomical structure	1
membrane-bounded organelle	1
intracellular organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

3623 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AQP9	GK2	Q14410	760
AQP9	GK	P32189	759
AQP9	AQP11	Q8NBQ7	745
AQP9	AQP12A	Q8IXF9	695
AQP9	CFTR	P13569	568
AQP9	PROK2	Q9HC23	501
AQP9	TLR2	O60603	475
AQP9	PPARA	Q07869	475
AQP9	FCGR3B	O75015	470
AQP9	NHERF1	O14745	460
AQP9	AQP1	P29972	458
AQP9	ACSL1	P33121	449
AQP9	XCL2	Q9UBD3	445
AQP9	CALML5	Q9NZT1	441
AQP9	CALML6	Q8TD86	439
AQP9	CALML4	Q96GE6	439

IntAct

73 interactions, top by confidence:

A	B	Type	Score
TF	AQP9	psi-mi:“MI:0915”(physical association)	0.560
AQP9	SGPL1	psi-mi:“MI:0915”(physical association)	0.560
GAST	AQP9	psi-mi:“MI:0915”(physical association)	0.560
CXCL16	AQP9	psi-mi:“MI:0915”(physical association)	0.560
CTXN3	AQP9	psi-mi:“MI:0915”(physical association)	0.560
AQP9	LHFPL5	psi-mi:“MI:0915”(physical association)	0.560
AQP9	CLDN19	psi-mi:“MI:0915”(physical association)	0.560
AQP9	HHLA2	psi-mi:“MI:0915”(physical association)	0.560
AQP9	MIP	psi-mi:“MI:0915”(physical association)	0.560
AQP9	APOD	psi-mi:“MI:0915”(physical association)	0.560
AQP9	CCDC167	psi-mi:“MI:0915”(physical association)	0.560
AQP9	IGFBP5	psi-mi:“MI:0915”(physical association)	0.560
AQP9	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
AQP9	EMC6	psi-mi:“MI:0915”(physical association)	0.560
AQP9	TMED9	psi-mi:“MI:0915”(physical association)	0.560
AQP9	TMEM109	psi-mi:“MI:0915”(physical association)	0.560
AQP9	TF	psi-mi:“MI:0915”(physical association)	0.560
AQP9	FZD7	psi-mi:“MI:0915”(physical association)	0.560
AQP9	FXYD3	psi-mi:“MI:0915”(physical association)	0.560
AQP9	CTXN3	psi-mi:“MI:0915”(physical association)	0.560
AQP9	PAEP	psi-mi:“MI:0915”(physical association)	0.560
AQP9	SLC38A7	psi-mi:“MI:0915”(physical association)	0.560
AQP9	AIG1	psi-mi:“MI:0915”(physical association)	0.560
AQP9	SERINC1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (44): FATE1 (Two-hybrid), VDAC1 (Co-fractionation), AQP9 (Two-hybrid), AQP9 (Two-hybrid), AQP9 (Two-hybrid), TMEM109 (Two-hybrid), SERINC1 (Two-hybrid), HHLA2 (Two-hybrid), IGFBP5 (Two-hybrid), PAEP (Two-hybrid), EMC6 (Two-hybrid), MIP (Two-hybrid), AIG1 (Two-hybrid), ADAM33 (Two-hybrid), FZD7 (Two-hybrid)

ESM2 similar proteins: A2IBY8, A4L9J0, A8W649, A9Y006, G5CTG2, G5CTG4, O43315, O62735, O77750, P06624, P09011, P29972, P29975, P30301, P34080, P41181, P47862, P47863, P47864, P47865, P50501, P51180, P55064, P55087, P55088, P56401, P56402, P56627, P79099, Q02013, Q06019, Q08DE6, Q13520, Q23808, Q5I4F9, Q5R819, Q6J8I9, Q6PQZ1, Q6RZ07, Q866S3

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

2 interactions.

A	Effect	B	Mechanism
PRKCZ	up-regulates	AQP9	phosphorylation
DSCAML1	“up-regulates activity”	AQP9	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1908 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:58179280:C:A	N216K	0.998
15:58179280:C:G	N216K	0.998
15:58173081:C:A	N84K	0.996
15:58173081:C:G	N84K	0.996
15:58173175:G:T	G116W	0.995
15:58179296:A:C	S222R	0.995
15:58179298:T:A	S222R	0.995
15:58179298:T:G	S222R	0.995
15:58179290:G:C	D220H	0.994
15:58179291:A:C	D220A	0.994
15:58173092:C:T	S88F	0.993
15:58173176:G:A	G116E	0.992
15:58174983:T:C	F148L	0.992
15:58174985:T:A	F148L	0.992
15:58174985:T:G	F148L	0.992
15:58184020:G:A	G258E	0.992
15:58179291:A:G	D220G	0.991
15:58183980:T:A	W245R	0.991
15:58183980:T:C	W245R	0.991
15:58173175:G:A	G116R	0.990
15:58173175:G:C	G116R	0.990
15:58179291:A:T	D220V	0.990
15:58179326:T:A	W232R	0.990
15:58179326:T:C	W232R	0.990
15:58166751:T:C	F64L	0.989
15:58166753:T:A	F64L	0.989
15:58166753:T:G	F64L	0.989
15:58179304:A:C	R224S	0.989
15:58179304:A:T	R224S	0.989
15:58138659:G:C	G32R	0.988

dbSNP variants (sampled 300 via entrez): RS1000086486 (15:58141675 C>G,T), RS1000143137 (15:58155482 C>A,G,T), RS1000196460 (15:58138303 A>G), RS1000284371 (15:58184645 G>A,T), RS1000358730 (15:58179436 A>C,G), RS1000515071 (15:58155279 T>C), RS1000585590 (15:58174618 T>C), RS1000599136 (15:58159057 G>A), RS1000696056 (15:58169885 T>C), RS1000751599 (15:58144638 G>A,C), RS1000791401 (15:58164354 G>A,T), RS1000886449 (15:58183239 T>G), RS1001206281 (15:58145372 G>A,T), RS1001319510 (15:58180080 G>A), RS1001381507 (15:58183612 T>C)

Disease associations

OMIM: gene MIM:602914 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6196059 (SINGLE PROTEIN)

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

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1516400	AQP9		0.00	0
rs1554203	AQP9		0.00	0
rs1867380	AQP9		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: other ic — Aquaporins

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	affects cotreatment, affects reaction, increases reaction, increases uptake, increases expression (+7 more)	9
Tretinoin	affects cotreatment, increases expression, affects reaction, decreases expression, increases degradation (+3 more)	5
arsenite	increases abundance, increases expression, increases response to substance, increases uptake, decreases reaction	4
sodium arsenite	decreases reaction, increases abundance, increases expression, decreases expression	4
Arsenic	increases abundance, decreases expression, increases expression, decreases reaction	4
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
sodium arsenate	increases abundance, increases expression, decreases expression	2
Acetaminophen	decreases expression	2
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	2
Cyclosporine	decreases expression, increases expression	2
Aflatoxin B1	affects expression, decreases expression	2
Lactic Acid	decreases expression, increases uptake, decreases reaction	2
TL8-506	affects cotreatment, increases expression	1
tungsten carbide	affects cotreatment, decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
perfluorooctanoic acid	decreases expression	1
arsenic acid	increases transport, increases abundance, increases expression	1
cupric chloride	increases expression	1
nickel sulfate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases expression, decreases reaction	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
monomethylarsonous acid	increases expression	1
abrine	increases expression	1
dimethylmonothioarsinic acid	increases expression	1
Troglitazone	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL6183209	Binding	Inhibition of AQP9 (unknown origin) expressed in xenopus laevis oocytes at 100 uM relative to control	Distinctive roles of aquaporins and novel therapeutic opportunities against cancer. — RSC Med Chem

Clinical trials (associated diseases)

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