AQP1

Summary

AQP1 (aquaporin 1 (Colton blood group), HGNC:633) is a protein-coding gene on chromosome 7p14.3, encoding Aquaporin-1 (P29972). Forms a water channel that facilitates the transport of water across cell membranes, playing a crucial role in water homeostasis in various tissues.

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.

Source: NCBI Gene 358 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pulmonary arterial hypertension (Moderate, GenCC)
• GWAS associations: 18
• Clinical variants (ClinVar): 92 total — 3 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_198098

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:633
Approved symbol	AQP1
Name	aquaporin 1 (Colton blood group)
Location	7p14.3
Locus type	gene with protein product
Status	Approved
Aliases	CHIP28
Ensembl gene	ENSG00000240583
Ensembl biotype	protein_coding
OMIM	107776
Entrez	358

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000311813, ENST00000409611, ENST00000409899, ENST00000441328, ENST00000482461, ENST00000651610, ENST00000652692, ENST00000652696, ENST00000873043, ENST00000873044, ENST00000873045

RefSeq mRNA: 2 — MANE Select: NM_198098 NM_001329872, NM_198098

CCDS: CCDS5431

Canonical transcript exons

ENST00000311813 — 4 exons

Exon	Start	End
ENSE00001372057	30923450	30925516
ENSE00003641952	30922564	30922644
ENSE00003687504	30922066	30922230
ENSE00003841632	30911853	30912293

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 99.64.

FANTOM5 (CAGE): breadth broad, TPM avg 15.0131 / max 630.9639, expressed in 585 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
78014	14.2102	567
78016	0.3122	119
78013	0.2151	113
78018	0.1418	69
78017	0.0846	35
78012	0.0281	10
78015	0.0210	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
descending thoracic aorta	UBERON:0002345	99.64	gold quality
ascending aorta	UBERON:0001496	99.63	gold quality
thoracic aorta	UBERON:0001515	99.63	gold quality
right lung	UBERON:0002167	99.60	gold quality
tendon of biceps brachii	UBERON:0008188	99.58	gold quality
upper lobe of left lung	UBERON:0008952	99.57	gold quality
upper lobe of lung	UBERON:0008948	99.55	gold quality
right coronary artery	UBERON:0001625	99.48	gold quality
pericardium	UBERON:0002407	99.44	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.41	gold quality
lower esophagus	UBERON:0013473	99.39	gold quality
adult mammalian kidney	UBERON:0000082	99.36	gold quality
apex of heart	UBERON:0002098	99.34	gold quality
coronary artery	UBERON:0001621	99.28	gold quality
adult organism	UBERON:0007023	99.28	gold quality
lower lobe of lung	UBERON:0008949	99.28	gold quality
left coronary artery	UBERON:0001626	99.25	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.23	gold quality
mucosa of stomach	UBERON:0001199	99.18	gold quality
renal medulla	UBERON:0000362	99.17	gold quality
left uterine tube	UBERON:0001303	99.16	gold quality
calcaneal tendon	UBERON:0003701	99.11	gold quality
metanephros cortex	UBERON:0010533	99.07	gold quality
synovial joint	UBERON:0002217	99.06	gold quality
peripheral nervous system	UBERON:0000010	99.05	gold quality
nerve	UBERON:0001021	99.05	gold quality
tibial nerve	UBERON:0001323	99.05	gold quality
gall bladder	UBERON:0002110	99.00	gold quality
aorta	UBERON:0000947	98.97	gold quality
tendon	UBERON:0000043	98.96	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-HCAD-15	yes	3075.34
E-CURD-126	yes	2222.76
E-MTAB-8322	yes	1358.27
E-HCAD-1	yes	1308.68
E-MTAB-10287	yes	1129.61
E-MTAB-9841	yes	1065.81
E-ENAD-20	yes	683.74
E-MTAB-8410	yes	27.49
E-MTAB-5061	yes	27.03
E-GEOD-81547	yes	25.86
E-HCAD-9	yes	19.64
E-MTAB-10553	yes	18.99
E-GEOD-125970	yes	18.15
E-MTAB-9388	yes	11.10
E-GEOD-130148	yes	5.61

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ATF3, ESR1, GLI1, HIF1A, NFAT5, NFE2L2, NR1H2, NR5A2, PPARG, RUNX1, TCF3, TFAP2A, TP53, TP73, TTF1, ZBED1, ZBTB17, ZBTB4, ZNF350

miRNA regulators (miRDB)

84 targeting AQP1, 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-4692	100.00	67.32	2066
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-3618	99.69	68.57	1012
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-888-3P	99.53	69.77	1057
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-4325	99.49	72.20	1342
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-657	99.48	66.02	848

Literature-anchored findings (GeneRIF, showing 40)

• transmembrane biogenesis is cotranslational in intact mammalian cells (PMID:11884383)
• A novel role for aquaporin-1 as a gated ion channel reshapes our current views of this ancient family of transmembrane channel proteins. (PMID:11909995)
• These data suggest that the transcription of the AQP1 by hypertonicity in renal cells is upregulated by the interaction with putative DNA binding proteins to a novel HRE located at -54 to -46 in the AQP1 gene. (PMID:11922632)
• This study showed the distinct localization of AQP1 in the mesangial cells of human glomeruli, suggesting its role in water movement through these cells. (PMID:12002613)
• visualization of the water-selective pathway at 3.7A resolution in a three-dimenional density map (REVIEW) (PMID:12027013)
• In astrocytomas, aquaporin 1 expressed in microvessel endothelia and neoplastic astrocytes. In metastatic carcinomas, aquaporin 1 present in microvessel endothelia and reactive astrocytes. Aquaporin 1 may participate in formation of brain tumour oedema. (PMID:12237771)
• Data suggest that variations found in plasma osmolarity during hemodialysis may induce aquaporin 1 expression on the membrane of intact red blood cells. (PMID:12399631)
• Data present a detailed comparison between the cryo-electron microscopy and X-ray crystallography model structures of the human and bovine water channel aquaporin-1 (AQP1). (PMID:12498798)
• Transmembrane helices at the periphery of the hAQP1 tetramer exhibited smaller extraction forces than helices at the interface between hAQP1 monomers. (PMID:12781664)
• substantial and striking upregulation of AQP-1 in the glomeruli of most diseased kidneys. (PMID:14514735)
• presence of AQP-1 in endothelia and water-transporting epithelia and new locations: mammary epithelium, articular chondrocytes, synoviocytes, and synovial microvessels where it may be involved in milk, chondrocyte volume, synovial fluid, and homeostasis. (PMID:14592814)
• lack of significant cyclic guanine nucleotide ion channel activity rules out a secondary role of aquaporin 1 water channels in cellular signal transduction (PMID:14701836)
• Increased expression. Over-expression occurred on astrocytic processes. Induction of AQP1 and AQP4 on reactive astrocytes in subarachnoid hemorrhage. May be involved in brain edema formation or resolution. (PMID:14753493)
• Intense upregulation of AQP1 expression was found in all glioblastomas. Expression of aquaporins in glioblastomas suggests pathologic role. Selective AQP inhibition might be new therapeutic option for tumor-associated cerebral edema. (PMID:14753494)
• AQP1 has a role in the movement of extracellular matrix and metabolic water across the membranes of chondrocytes and synoviocytes (PMID:15024704)
• AQP1 co-localizes with t-tubular and caveolar proteins (PMID:15135660)
• Aquaporin-1 is a reliable marker for clear cell renal cell carcinomas of lower grades but not for higher grades. (PMID:15502805)
• The expression of AQP-1 mRNA was positively correlated with Bcl-2 mRNA expression in nasal polyps. AQP-1 contributes to the survival of eosinophils in nasal polyps. (PMID:15563082)
• AQP-1 may be a possible critical reabsorption factor, acting to reduce abnormal fluid retention in endotubular cells and the extracellular matrix and, to a lesser extent, in Leydig cells. (PMID:15667881)
• increased AQP1 expression in some human adenocarcinomas may be a consequence of angiogenesis and important for the formation or clearance of tumor edema (PMID:15809704)
• AQP1 expression heavely in cystic hemangioblastomas. (PMID:16300893)
• Aquaporin (AQP) 1 is predominantly situated in the apical plasma membrane domain of the human choroid plexus, although distinct basolateral and endothelial immunoreactivity is also observed. (PMID:16481371)
• high AQP1 expression may play an important role in ovarian carcinogenesis, disease progression, and ascites formation. (PMID:16515633)
• AQPs are differentially expressed in the peripheral versus central nervous system and that channel-mediated water transport mechanisms may be involved in peripheral neuronal activity by regulating water homeostasis in nerve plexuses and bundles. (PMID:16534779)
• Review. In Colton (null) RBC ghosts, lack of AQP1 resulted in about 30% reduction of the alkalinization rates. (PMID:16574458)
• aquaporin-1-mediated CO(2) permeation is to be expected only in membranes with a low intrinsic CO(2) permeability (PMID:16698771)
• These results in human fetal brain lend morphological support to the previous findings that aquaporin-1 and aquaporin-4 play different roles in the regulation of the water homeostasis of the brain. (PMID:16814974)
• Significant increased expression levels of AQP1 and AQP4 were seen in Creutzfeldt-Jakob disease, but not in advanced Alzheimer’s disease and diffuse Lewy body disease. (PMID:16871401)
• AQP1 is responsible for 60% of the high P(CO2) of red cells and that another, so far unidentified, CO2 pathway is present in this membrane that may account for at least 30% of total P(CO2). (PMID:17012249)
• In hemangioblastomas, expression of AQP1 was predominantly localized on membranes of stromal cells. The expression level of AQP1 in cystic group of hemangioblastomas is much higher than that of solid group. (PMID:17077939)
• Inhibiting AQP-1 with acetazolamide may significantly induce apoptosis of Hep-2 cells. (PMID:17219999)
• The deregulation of aquaporin-1 in menorrhagia may be involved in abnormal endometrial vascular growth and permeability. (PMID:17273788)
• AQP1 is expressed at the endomysial capillary endothelial cell and further AQP1 may be expressed at the human skeletal myofiber plasma membrane. (PMID:17409744)
• AQP1 mRNA and protein expression level in laryngeal tumor tissues is remarkably stronger than that in normal tissues. (PMID:17511167)
• 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)
• Only the presence of AQP1, but not AQP4, enhanced cell growth and migration, typical properties of gliomas, while AQP4 enhanced cell adhesion suggesting differential biological roles for AQP1 and AQP4 in glioma cell biology. (PMID:17549682)
• In AQP1, Asn49 and Lys51 interact with Asp185 at the C terminus of TM5 to form a polar, quaternary structural motif that influences multiple stages of folding. (PMID:17632520)
• AQP-1 is up-regulated in biliary dysplasia…and down-regulation of AQP-1 is associated with mucin production and aggressive progression of intrahepatic cholangiocarcinoma. (PMID:17854859)
• These results establish the nature and determinants of AQP1 diffusion in cell plasma membranes and demonstrate long-range nonanomalous diffusion of AQP1. (PMID:17890385)
• a detailed mechanism for ion exclusion in aquaporin-1 (AQP1) at an atomistic level is investigated by calculating the free energy for transport of ions in AQP1 (PMID:17894331)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	aqp1a.1	ENSDARG00000023713
danio_rerio	aqp1a.2	ENSDARG00000091027
mus_musculus	Aqp1	ENSMUSG00000004655
rattus_norvegicus	Aqp1	ENSRNOG00000011648
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), AQP3 (ENSG00000165272), AQP2 (ENSG00000167580), AQP4 (ENSG00000171885), AQP7B (ENSG00000259916)

Protein

Protein identifiers

Aquaporin-1 — P29972 (reviewed: P29972)

Alternative names: Aquaporin-CHIP, Channel-like integral membrane protein of 28 kDa, Urine water channel

All UniProt accessions (4): A0A024RA31, A0A494C115, A0A494C1U4, P29972

UniProt curated annotations — full annotation on UniProt →

Function. Forms a water channel that facilitates the transport of water across cell membranes, playing a crucial role in water homeostasis in various tissues. Could also be permeable to small solutes including hydrogen peroxide, glycerol and gases such as amonnia (NH3), nitric oxide (NO) and carbon dioxide (CO2). Recruited to the ankyrin-1 complex, a multiprotein complex of the erythrocyte membrane, it could be part of a CO2 metabolon, linking facilitated diffusion of CO2 across the membrane, anion exchange of Cl(-)/HCO3(-) and interconversion of dissolved CO2 and carbonic acid in the cytosol. In vitro, it shows non-selective gated cation channel activity and may be permeable to cations like K(+) and Na(+) in vivo.

Subunit / interactions. Homotetramer; each monomer provides an independent water pore. Component of the ankyrin-1 complex in the erythrocyte, composed of ANK1, RHCE, RHAG, SLC4A1, EPB42, GYPA, GYPB and AQP1. Interacts with EPHB2; involved in endolymph production in the inner ear. Identified in a complex with STOM. Interacts (via the N-terminal) with ANK1 (via ANK 1-5 repeats). Interacts (via the C-terminal) with EPB42.

Subcellular location. Cell membrane.

Tissue specificity. Detected in erythrocytes (at protein level). Expressed in a number of tissues including erythrocytes, renal tubules, retinal pigment epithelium, heart, lung, skeletal muscle, kidney and pancreas. Weakly expressed in brain, placenta and liver.

Activity regulation. The water channel activity is inhibited by P-choloromercuribenzene sulphonate and diethylpyrocarbonate(DPPC). The glycerol channel activity is inhibited by P-choloromercuribenzene sulphonate, diethylpyrocarbonate(DPPC), phloretin and Cu(2+). Inhibited by mercury.

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).

Polymorphism. AQP1 is responsible for the Colton blood group system [MIM:110450]. Approximately 92% of Caucasians are Co(A+B-) (Ala-45), approximately 8% are Co(A+B+), and only 0.2% are Co(A-B+) (Val-45). Co(A-B-) which is very rare, is due to a complete absence of AQP1.

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

Isoforms (4)

UniProt ID	Names	Canonical?
P29972-1	1	yes
P29972-2	2
P29972-3	3
P29972-4	4

RefSeq proteins (2): NP_001316801, NP_932766* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000425	MIP	Family
IPR022357	MIP_CS	Conserved_site
IPR023271	Aquaporin-like	Homologous_superfamily
IPR023274	Aquaporin_1	Family
IPR034294	Aquaporin_transptr	Family

Pfam: PF00230

Catalyzed reactions (Rhea), 7 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)
• H2O(in) = H2O(out) (RHEA:29667)
• glycerol(in) = glycerol(out) (RHEA:29675)
• Na(+)(in) = Na(+)(out) (RHEA:34963)
• H2O2(out) = H2O2(in) (RHEA:74375)
• CO2(out) = CO2(in) (RHEA:74891)
• nitric oxide(out) = nitric oxide(in) (RHEA:74895)

UniProt features (57 total): helix 11, topological domain 9, transmembrane region 6, splice variant 5, strand 5, modified residue 3, sequence variant 3, mutagenesis site 3, intramembrane region 2, short sequence motif 2, glycosylation site 2, turn 2, initiator methionine 1, chain 1, site 1, sequence conflict 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
9ZCZ	ELECTRON MICROSCOPY	2.3
7UZE	ELECTRON MICROSCOPY	2.4
8CTE	ELECTRON MICROSCOPY	2.9
8CT2	ELECTRON MICROSCOPY	3.1
9ZD2	ELECTRON MICROSCOPY	3.1
4CSK	X-RAY DIFFRACTION	3.28
1H6I	ELECTRON CRYSTALLOGRAPHY	3.54
1IH5	ELECTRON CRYSTALLOGRAPHY	3.7
1FQY	ELECTRON CRYSTALLOGRAPHY	3.8
6POJ	SOLID-STATE NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P29972-F1	90.25	0.81

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 (1): 189 (hg(2+)-sensitive residue)

Post-translational modifications (3): 247, 253, 262

Glycosylation sites (2): 42, 205

Mutagenesis-validated functional residues (3):

Position	Phenotype
180	no effect on water channel activity.
189	no effect on water channel activity.
209	decreased water channel activity.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-1237044	Erythrocytes take up carbon dioxide and release oxygen
R-HSA-1247673	Erythrocytes take up oxygen and release carbon dioxide
R-HSA-432040	Vasopressin regulates renal water homeostasis via Aquaporins
R-HSA-432047	Passive transport by Aquaporins
R-HSA-9925563	Developmental Lineage of Pancreatic Ductal Cells
R-HSA-1480926	O2/CO2 exchange in erythrocytes
R-HSA-382551	Transport of small molecules
R-HSA-445717	Aquaporin-mediated transport

MSigDB gene sets: 443 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, GOBP_POTASSIUM_ION_TRANSPORT, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_6HR_DN, GOBP_DIGESTION, MODULE_416, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_EPITHELIUM_DEVELOPMENT, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_METANEPHROS_DEVELOPMENT, MODULE_571, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_CELLULAR_RESPONSE_TO_UV

GO Biological Process (59): renal water homeostasis (GO:0003091), glomerular filtration (GO:0003094), renal water transport (GO:0003097), potassium ion transport (GO:0006813), water transport (GO:0006833), cell volume homeostasis (GO:0006884), hyperosmotic response (GO:0006972), intracellular water homeostasis (GO:0009992), fibroblast migration (GO:0010761), positive regulation of fibroblast migration (GO:0010763), carbon dioxide transport (GO:0015670), glycerol transmembrane transport (GO:0015793), sensory perception of pain (GO:0019233), cellular homeostasis (GO:0019725), lateral ventricle development (GO:0021670), pancreatic juice secretion (GO:0030157), nitric oxide transport (GO:0030185), establishment or maintenance of actin cytoskeleton polarity (GO:0030950), cerebrospinal fluid secretion (GO:0033326), secretory granule organization (GO:0033363), cellular response to UV (GO:0034644), transepithelial water transport (GO:0035377), carbon dioxide transmembrane transport (GO:0035378), wound healing (GO:0042060), odontogenesis (GO:0042476), negative regulation of apoptotic process (GO:0043066), lipid digestion (GO:0044241), positive regulation of angiogenesis (GO:0045766), positive regulation of saliva secretion (GO:0046878), positive regulation of fibroblast proliferation (GO:0048146), camera-type eye morphogenesis (GO:0048593), defense response to Gram-negative bacterium (GO:0050829), multicellular organismal-level water homeostasis (GO:0050891), corticotropin secretion (GO:0051458), establishment of localization in cell (GO:0051649), renal water absorption (GO:0070295), cellular response to hydrogen peroxide (GO:0070301), cellular response to mechanical stimulus (GO:0071260), cellular response to copper ion (GO:0071280), cellular response to mercury ion (GO:0071288)

GO Molecular Function (15): intracellularly cGMP-activated cation channel activity (GO:0005223), potassium channel activity (GO:0005267), water transmembrane transporter activity (GO:0005372), ammonium channel activity (GO:0008519), potassium ion transmembrane transporter activity (GO:0015079), glycerol transmembrane transporter activity (GO:0015168), water channel activity (GO:0015250), transmembrane transporter activity (GO:0022857), nitric oxide transmembrane transporter activity (GO:0030184), carbon dioxide transmembrane transporter activity (GO:0035379), identical protein binding (GO:0042802), ephrin receptor binding (GO:0046875), hydrogen peroxide channel activity (GO:0140070), protein binding (GO:0005515), channel activity (GO:0015267)

GO Cellular Component (16): nucleus (GO:0005634), cytoplasm (GO:0005737), plasma membrane (GO:0005886), brush border (GO:0005903), basal plasma membrane (GO:0009925), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), axon (GO:0030424), brush border membrane (GO:0031526), nuclear membrane (GO:0031965), sarcolemma (GO:0042383), apical part of cell (GO:0045177), extracellular exosome (GO:0070062), ankyrin-1 complex (GO:0170014), caveola (GO:0005901), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
O2/CO2 exchange in erythrocytes	2
Aquaporin-mediated transport	2
Transport of small molecules	2
Developmental Cell Lineages of the Exocrine Pancreas	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transmembrane transporter activity	3
channel activity	3
cellular anatomical structure	3
plasma membrane region	3
renal system process	2
water transport	2
body fluid secretion	2
secretion by tissue	2
apical part of cell	2
multicellular organismal-level water homeostasis	1
renal filtration	1
renal water homeostasis	1
metal ion transport	1
fluid transport	1
regulation of cell size	1
cellular homeostasis	1
response to osmotic stress	1
cell volume homeostasis	1
intracellular chemical homeostasis	1
ameboidal-type cell migration	1
fibroblast migration	1
regulation of fibroblast migration	1
positive regulation of cell migration	1
gas transport	1
one-carbon compound transport	1
polyol transmembrane transport	1
carbohydrate transmembrane transport	1
sensory perception	1
homeostatic process	1
telencephalon development	1
ventricular system development	1
anatomical structure development	1
digestive system process	1
nitrogen compound transport	1
actin cytoskeleton organization	1
establishment or maintenance of cytoskeleton polarity	1
endomembrane system organization	1
vesicle organization	1
intracellularly cyclic nucleotide-activated monoatomic cation channel activity	1
monoatomic cation channel activity	1

Protein interactions and networks

STRING

3684 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AQP1	STUB1	Q9UNE7	657
AQP1	SLC14A2	Q15849	641
AQP1	AQP11	Q8NBQ7	627
AQP1	RHAG	Q02094	623
AQP1	STOM	P27105	616
AQP1	SLC12A1	Q13621	602
AQP1	SLC16A8	O95907	599
AQP1	LIN7A	O14910	594
AQP1	SCT	P09683	593
AQP1	EPHA8	P29322	592
AQP1	SLC9A3	P48764	566
AQP1	CLIC4	Q9Y696	558
AQP1	AQP12A	Q8IXF9	556
AQP1	SLC2A1	P11166	552
AQP1	ASS1	P00966	547
AQP1	HRH3	Q9Y5N1	547

IntAct

426 interactions, top by confidence:

A	B	Type	Score
MDFI	AQP1	psi-mi:“MI:0915”(physical association)	0.820
TRIP6	AQP1	psi-mi:“MI:0915”(physical association)	0.780
AQP1	TRIP6	psi-mi:“MI:0915”(physical association)	0.780
TRIM23	AQP1	psi-mi:“MI:0915”(physical association)	0.720
KRTAP4-2	AQP1	psi-mi:“MI:0915”(physical association)	0.720
RGS17	AQP1	psi-mi:“MI:0915”(physical association)	0.720
AQP1	IKZF3	psi-mi:“MI:0915”(physical association)	0.720
AQP1	RGS17	psi-mi:“MI:0915”(physical association)	0.720
IKZF3	AQP1	psi-mi:“MI:0915”(physical association)	0.720
AQP1	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.720
AQP1	AQP1	psi-mi:“MI:0915”(physical association)	0.660
AQP1	AQP1	psi-mi:“MI:0407”(direct interaction)	0.660
AQP1	FSD2	psi-mi:“MI:0915”(physical association)	0.560
AQP1		psi-mi:“MI:0915”(physical association)	0.560
AQP1	SPRY2	psi-mi:“MI:0915”(physical association)	0.560
AQP1	RGS20	psi-mi:“MI:0915”(physical association)	0.560
RGS20	AQP1	psi-mi:“MI:0915”(physical association)	0.560
AQP1	TCF4	psi-mi:“MI:0915”(physical association)	0.560
AQP1	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.560
TNK2	AQP1	psi-mi:“MI:0915”(physical association)	0.560
TRAF2	AQP1	psi-mi:“MI:0915”(physical association)	0.560
TRAF1	AQP1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (149): AQP1 (Two-hybrid), TRIM23 (Two-hybrid), FOS (Two-hybrid), KRT31 (Two-hybrid), KRT33B (Two-hybrid), SIAH1 (Two-hybrid), TCF4 (Two-hybrid), TRAF1 (Two-hybrid), TRAF2 (Two-hybrid), TRIP6 (Two-hybrid), RGS20 (Two-hybrid), TNK2 (Two-hybrid), SPRY2 (Two-hybrid), MID2 (Two-hybrid), IKZF3 (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: A0A384J409, A0A384J441, A0A384J983, A0A384JGJ4, A0A384JL97, A0A384JP03, A2IBY8, A4L9J0, A6ZX66, A7A0K7, A8W649, B0DMR6, B3LTC4, C7GNE2, C8ZCS2, C8ZJM1, G5CTG2, I1Z8E5, I3W9F6, O22588, O62735, O64964, O77750, O82316, O82598, P06624, P09011, P0CD89, P0CD91, P0CD92, P0CD98, P0DO54, P21653, P23958, P24422, P25818, P26587, P28238, P29972, P29975

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PRKCA	up-regulates	AQP1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 84 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
Keratinization	14	15.6×	2e-11

GO biological processes:

GO term	Partners	Fold	FDR
epithelial cell differentiation	5	12.5×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	42
Likely benign	22
Benign	20

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
17847	NM_198098.4(AQP1):c.113C>T (p.Pro38Leu)	Pathogenic
3704391	NM_198098.4(AQP1):c.583C>T (p.Arg195Trp)	Pathogenic
4087716	NM_198098.4(AQP1):c.587C>G (p.Ser196Cys)	Pathogenic

SpliceAI

1145 predictions. Top by Δscore:

Variant	Effect	Δscore
7:30912289:ATGAC:A	donor_gain	1.0000
7:30912291:GAC:G	donor_gain	1.0000
7:30912292:ACGTG:A	donor_loss	1.0000
7:30912293:CG:C	donor_loss	1.0000
7:30912294:G:GG	donor_gain	1.0000
7:30922061:TGCA:T	acceptor_loss	1.0000
7:30922062:GCAG:G	acceptor_loss	1.0000
7:30922063:CA:C	acceptor_loss	1.0000
7:30922064:A:AG	acceptor_gain	1.0000
7:30922064:AGCT:A	acceptor_gain	1.0000
7:30922064:AGCTG:A	acceptor_gain	1.0000
7:30922065:G:GA	acceptor_gain	1.0000
7:30922065:GC:G	acceptor_gain	1.0000
7:30922065:GCT:G	acceptor_gain	1.0000
7:30922065:GCTG:G	acceptor_gain	1.0000
7:30922065:GCTGG:G	acceptor_gain	1.0000
7:30922226:TGGCT:T	donor_gain	1.0000
7:30922227:GGCT:G	donor_gain	1.0000
7:30922227:GGCTG:G	donor_gain	1.0000
7:30922228:GCT:G	donor_gain	1.0000
7:30922228:GCTG:G	donor_gain	1.0000
7:30922229:CT:C	donor_gain	1.0000
7:30922230:TG:T	donor_loss	1.0000
7:30922230:TGTG:T	donor_loss	1.0000
7:30922231:G:C	donor_loss	1.0000
7:30922231:G:GG	donor_gain	1.0000
7:30922232:T:G	donor_loss	1.0000
7:30922234:A:AG	donor_gain	1.0000
7:30922235:G:GG	donor_gain	1.0000
7:30922558:TCACA:T	acceptor_loss	1.0000

AlphaMissense

1747 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:30911991:A:C	S28R	0.999
7:30911993:C:A	S28R	0.999
7:30911993:C:G	S28R	0.999
7:30912075:T:C	F56L	0.999
7:30912077:C:A	F56L	0.999
7:30912077:C:G	F56L	0.999
7:30912079:G:A	G57E	0.999
7:30912084:A:C	S59R	0.999
7:30912086:C:A	S59R	0.999
7:30912086:C:G	S59R	0.999
7:30912137:C:A	N76K	0.999
7:30912137:C:G	N76K	0.999
7:30922198:G:C	G173R	0.999
7:30922199:G:A	G173D	0.999
7:30922590:C:A	N192K	0.999
7:30922590:C:G	N192K	0.999
7:30912067:C:G	S53W	0.998
7:30912078:G:A	G57R	0.998
7:30912078:G:C	G57R	0.998
7:30912091:C:A	A61D	0.998
7:30912105:A:C	S66R	0.998
7:30912107:T:A	S66R	0.998
7:30912107:T:G	S66R	0.998
7:30912139:C:A	P77Q	0.998
7:30912148:C:T	T80I	0.998
7:30912219:G:T	G104W	0.998
7:30922127:T:C	L149P	0.998
7:30922135:T:C	C152R	0.998
7:30922223:T:C	L181P	0.998
7:30922607:G:A	G198D	0.998

dbSNP variants (sampled 300 via entrez): RS1000042441 (7:30916195 G>A), RS1000415137 (7:30913062 T>C), RS1000609579 (7:30914998 A>C,G), RS1000826927 (7:30918064 G>A), RS1001031938 (7:30923597 A>G,T), RS1001286114 (7:30917677 G>A), RS1001499691 (7:30915651 C>G,T), RS1001536983 (7:30913575 C>T), RS1001591035 (7:30913389 C>A), RS1001931392 (7:30914310 T>C,G), RS1002048664 (7:30918713 A>G), RS1002441347 (7:30922303 C>A), RS1002490923 (7:30917075 C>T), RS1002513670 (7:30914440 C>T), RS1002664892 (7:30920168 C>T)

Disease associations

OMIM: gene MIM:107776 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
pulmonary arterial hypertension	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
pulmonary arterial hypertension	Limited	AD

Mondo (2): Charcot-Marie-Tooth disease type 2 (MONDO:0018993), pulmonary arterial hypertension (MONDO:0015924)

Orphanet (1): Autosomal dominant Charcot-Marie-Tooth disease type 2 (Orphanet:64746)

HPO phenotypes

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

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST001432_2	Nephrolithiasis	2.000000e-14
GCST004691_13	Huntington’s disease progression	5.000000e-06
GCST005348_105	Total body bone mineral density	7.000000e-14
GCST005348_74	Total body bone mineral density	1.000000e-12
GCST006288_147	Heel bone mineral density	4.000000e-15
GCST006288_642	Heel bone mineral density	2.000000e-34
GCST006288_749	Heel bone mineral density	3.000000e-21
GCST006624_46	Systolic blood pressure	1.000000e-13
GCST006979_344	Heel bone mineral density	2.000000e-89
GCST006980_6	Fracture	3.000000e-55
GCST009598_9	Kidney stones	3.000000e-08
GCST012048_9	Triglyceride levels	8.000000e-07
GCST012126_3	hemolysis of donated blood (osmotic)	5.000000e-08
GCST012135_3	hemolysis of donated blood (osmotic)	4.000000e-10
GCST90020025_749	Waist-to-hip ratio adjusted for BMI	4.000000e-09
GCST90020025_750	Waist-to-hip ratio adjusted for BMI	2.000000e-08
GCST90020027_1352	Waist-hip index	3.000000e-09
GCST90020027_1353	Waist-hip index	2.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0008336	disease progression measurement
EFO:0009270	heel bone mineral density
EFO:0006335	systolic blood pressure
EFO:0004530	triglyceride measurement
EFO:0009473	hemolysis
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D000081029	Pulmonary Arterial Hypertension	C08.381.423.847

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523210 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

5 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1049305	Toxicity	3	cisplatin	Alopecia;Mesothelioma
rs1049305	Toxicity	3	cisplatin	Anemia;Mesothelioma
rs1049305	Toxicity	3	cisplatin	Leukopenia;Mesothelioma
rs1049305	Toxicity	3	cisplatin	Mesothelioma;Thrombocytopenia
rs28362731	Toxicity	3	cisplatin	Thrombocytopenia

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs28362731	AQP1	3	2.50	1	cisplatin
rs1049305	AQP1	3	2.50	4	cisplatin

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
5-Hydroxymethyl-2-furfural	Inhibition	6.37	pIC50
compound 1 [PMID: 23113556]	Inhibition	5.1	pIC50

ChEMBL bioactivities

4 potent at pChembl≥5 of 11 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.57	IC50	2700	nM	CHEMBL195380
5.48	EC50	3300	nM	CHEMBL5268096
5.24	IC50	5800	nM	CHEMBL5280011
5.01	IC50	9800	nM	CHEMBL5266140

PubChem BioAssay actives

8 with measured affinity, of 17 total; 5 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[[4-[[(4-aminoquinazolin-2-yl)amino]methyl]cyclohexyl]methyl]naphthalene-1-sulfonamide	1801571: Stopped-flow Assay from Article 10.1111/cbdd.12713: “Rapid Identification of Novel Inhibitors of the Human Aquaporin-1 Water Channel.”	ic50	2.7000	uM
methyl 5-(benzylsulfamoyl)-4-chloro-2-(furan-2-ylmethylamino)benzoate	1928701: Agonist activity at human AQP1 water channel expressed in Xenopus laevis oocytes assessed as inhibition of AQP1-mediated osmotic swelling	ec50	3.3000	uM
N-[[4-[[(4-aminoquinazolin-2-yl)amino]methyl]cyclohexyl]methyl]naphthalene-2-sulfonamide	1801571: Stopped-flow Assay from Article 10.1111/cbdd.12713: “Rapid Identification of Novel Inhibitors of the Human Aquaporin-1 Water Channel.”	ic50	3.9000	uM
N-[[4-[[(4-aminoquinazolin-2-yl)amino]methyl]cyclohexyl]methyl]-5-chloronaphthalene-1-sulfonamide	1801571: Stopped-flow Assay from Article 10.1111/cbdd.12713: “Rapid Identification of Novel Inhibitors of the Human Aquaporin-1 Water Channel.”	ic50	5.8000	uM
1-[7-(2,4-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]-N-methylmethanamine	1801571: Stopped-flow Assay from Article 10.1111/cbdd.12713: “Rapid Identification of Novel Inhibitors of the Human Aquaporin-1 Water Channel.”	ic50	9.8000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression	3
bisphenol A	decreases methylation, decreases expression	2
SB 203580	decreases reaction, increases expression, decreases expression	2
lipopolysaccharide, E coli O55-B5	decreases expression, decreases reaction	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Lipopolysaccharides	affects response to substance, decreases reaction, increases expression	2
Mercuric Chloride	decreases reaction, increases transport, affects activity	2
Triclosan	increases expression, increases methylation	2
Water	increases transport, decreases reaction	2
Cyclosporine	decreases expression	2
methylmercuric chloride	decreases expression	1
naringenin	decreases expression, decreases reaction, increases abundance	1
kojic acid	increases expression	1
cobaltous chloride	increases expression, decreases reaction	1
butyraldehyde	increases expression	1
2-tert-butylhydroquinone	decreases expression	1
tetrathiomolybdate	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
triadimefon	decreases expression	1
puerarin	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
epigallocatechin gallate	decreases expression, increases expression	1
calphostin C	decreases reaction, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases expression, decreases reaction	1
Roflumilast	decreases expression, decreases reaction, increases abundance	1
pyrazolanthrone	decreases expression, decreases reaction	1
pomiferin	increases expression	1
osajin	increases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4422158	Binding	Inhibition of AQP1 (unknown origin) expressed in CHO cells assessed as reduction in aquaporin-mediated cell Volume shrinkage at 10 uM by light scattering based assay	Novel prodrug salts

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_D1VB	Abcam A-549 AQP1 KO	Cancer cell line	Male
CVCL_D1ZY	Abcam HCT 116 AQP1 KO	Cancer cell line	Male
CVCL_VS01	23C27	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00058929	PHASE4	COMPLETED	A Transition Study From Flolan® to Remodulin® in Patients With Pulmonary Arterial Hypertension
NCT00303459	PHASE4	COMPLETED	Effects of the Combination of Bosentan and Sildenafil Versus Sildenafil Monotherapy on Pulmonary Arterial Hypertension (PAH)
NCT00323297	PHASE4	COMPLETED	Assess the Efficacy and Safety of Sildenafil When Added to Bosentan in the Treatment of Pulmonary Arterial Hypertension
NCT00367770	PHASE4	COMPLETED	BREATHE 5-OL: Tracleer (Bosentan) in Patients With Pulmonary Arterial Hypertension Related to Eisenmenger Physiology
NCT00403650	PHASE4	COMPLETED	Inhaled Iloprost for Sarcoidosis-associated Pulmonary Hypertension
NCT00430716	PHASE4	TERMINATED	To Assess The Efficacy and Safety Of Oral Sildenafil in the Treatment of Pulmonary Arterial Hypertension.
NCT00433329	PHASE4	COMPLETED	Combination Therapy in Pulmonary Arterial Hypertension
NCT00439946	PHASE4	TERMINATED	Safety, Efficacy, and Treatment Satisfaction Switching From Flolan to Remodulin Using the Crono Five Ambulatory Pump in Patients With PAH
NCT00483626	PHASE4	UNKNOWN	Hemodynamic Response After Six Months of Sildenafil
NCT00494533	PHASE4	TERMINATED	Study of Intravenous Remodulin in Patients in India With Pulmonary Arterial Hypertension
NCT00617305	PHASE4	COMPLETED	Study of Add-on Ambrisentan Therapy to Background Phosphodiesterase Type-5 Inhibitor (PDE5i) Therapy in Pulmonary Arterial Hypertension (ATHENA-1)
NCT00625079	PHASE4	WITHDRAWN	Pulmonary Hypertension Secondary to Idiopathic Pulmonary Fibrosis And Treatment With Sildenafil
NCT00625469	PHASE4	WITHDRAWN	Pulmonary Arterial Hypertension Secondary to Idiopathic Pulmonary Fibrosis and Treatment With Bosentan
NCT00705588	PHASE4	UNKNOWN	Long Acting Phosphodiesterase 5 Inhibitors as Add-on Therapy for Patients With Pulmonary Hypertension Treated With Prostanoids.
NCT00741819	PHASE4	COMPLETED	Safety Evaluation of Inhaled Treprostinil Administration Following Transition From Inhaled Ventavis in Pulmonary Arterial Hypertension (PAH) Subjects
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT01105091	PHASE4	COMPLETED	Epoprostenol for Injection in Pulmonary Arterial Hypertension
NCT01105117	PHASE4	COMPLETED	Epoprostenol for Injection in Pulmonary Arterial Hypertension - Extension of AC-066A401
NCT01268553	PHASE4	COMPLETED	Transition From Injectable Prostacyclin Medication to Inhaled Prostacyclin Medication
NCT01302444	PHASE4	TERMINATED	Treprostinil Combined With Tadalafil for Pulmonary Hypertension
NCT01330108	PHASE4	COMPLETED	Safely Change From Bosentan to Ambrisentan in Pulmonary Hypertension
NCT01433328	PHASE4	TERMINATED	Lidocaine Subcutaneous Infusion for Control of Treprostinil Related Site Pain
NCT01508780	PHASE4	WITHDRAWN	Combined Use of Angiography, Optical Coherence Tomography and Intravascular Ultrasound in Evaluation of Pulmonary Vascular Structure and Function in Patients With Pulmonary Arterial Hypertension Treated With Oral Bosentan
NCT01615627	PHASE4	WITHDRAWN	Hypotonic Treprostinil Subcutaneous Infusion for Control of Treprostinil Related Site Pain
NCT01642407	PHASE4	COMPLETED	Safety And Efficacy Of Sildenafil In Children With Pulmonary Arterial Hypertension
NCT01649739	PHASE4	UNKNOWN	Vardenafil as add-on Therapy for Patients With Pulmonary Hypertension Treated With Inhaled Iloprost
NCT02060487	PHASE4	TERMINATED	Effects of Oral Sildenafil on Mortality in Adults With PAH
NCT02253394	PHASE4	TERMINATED	The Combination Ambrisentan Plus Spironolactone in Pulmonary Arterial Hypertension Study
NCT02284737	PHASE4	TERMINATED	A Study to Investigate the Efficacy of PADN to Improved Functional Capacity and Hemodynamics in Patients With PAH
NCT02310672	PHASE4	COMPLETED	REPAIR: Right vEntricular Remodeling in Pulmonary ArterIal hypeRtension
NCT02847260	PHASE4	COMPLETED	Safety and Tolerability of Rapid Dose Titration of Subcutaneous Remodulin® Therapy in PAH Subjects (RAPID)
NCT02882126	PHASE4	WITHDRAWN	An Open Label Extension Study to Evaluate the Safety of Continued Therapy of Subcutanous Remodulin® in Pulmonary Arterial Hypertension
NCT02885012	PHASE4	TERMINATED	Crossover Study From Macitentan or Bosentan Over to Ambrisentan
NCT02891850	PHASE4	COMPLETED	Riociguat rEplacing PDE-5i Therapy evaLuated Against Continued PDE-5i thErapy
NCT02893995	PHASE4	WITHDRAWN	Safety, Tolerability, Pharmacokinetics and Efficacy of Two Different Rates of Subcutanous Remodulin® Dose Titration in Pulmonary Arterial Hypertension
NCT02968901	PHASE4	TERMINATED	Clinical Study Evaluating the Effects of First-line Oral cOmbination theraPy of maciTentan and tadalafIl in Patients With Newly Diagnosed pulMonary Arterial Hypertension (OPTIMA)
NCT03055221	PHASE4	COMPLETED	TRUST-2: Safety and Efficacy of Intravenous Remodulin® in Patients in India With Pulmonary Arterial Hypertension (PAH)
NCT03078907	PHASE4	COMPLETED	Effect of Selexipag on Daily Life Physical Activity of Patients With Pulmonary Arterial Hypertension.
NCT03236818	PHASE4	UNKNOWN	Goal Oriented Strategy to Preserve Ejection Fraction Trial
NCT03344159	PHASE4	COMPLETED	Spironolactone Therapy in Chronic Stable Right HF Trial