AVPR2

Summary

AVPR2 (arginine vasopressin receptor 2, HGNC:897) is a protein-coding gene on chromosome Xq28, encoding Vasopressin V2 receptor (P30518). G protein-coupled receptor for arginine vasopressin, an antidiuretic that promotes renal water reabsorption. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes the vasopressin receptor, type 2, also known as the V2 receptor, which belongs to the seven-transmembrane-domain G protein-coupled receptor (GPCR) superfamily, and couples to Gs thus stimulating adenylate cyclase. The subfamily that includes the V2 receptor, the V1a and V1b vasopressin receptors, the oxytocin receptor, and isotocin and mesotocin receptors in non-mammals, is well conserved, though several members signal via other G proteins. All bind similar cyclic nonapeptide hormones. The V2 receptor is expressed in the kidney tubule, predominantly in the distal convoluted tubule and collecting ducts, where its primary property is to respond to the pituitary hormone arginine vasopressin (AVP) by stimulating mechanisms that concentrate the urine and maintain water homeostasis in the organism. When the function of this gene is lost, the disease Nephrogenic Diabetes Insipidus (NDI) results. The V2 receptor is also expressed outside the kidney although its tissue localization is uncertain. When these ’extrarenal receptors’ are stimulated by infusion of a V2 selective agonist (dDAVP), a variety of clotting factors are released into the bloodstream. The physiologic importance of this property is not known - its absence does not appear to be detrimental in NDI patients. The gene expression has also been described in fetal lung tissue and lung cancer associated with alternative splicing.

Source: NCBI Gene 554 — RefSeq curated summary.

At a glance

• Gene–disease (curated): diabetes insipidus, nephrogenic, X-linked (Definitive, GenCC) — +2 more curated relationships
• Clinical variants (ClinVar): 461 total — 66 pathogenic, 53 likely-pathogenic (top 7% of genes corpus-wide)
• GTEx eGene: eQTL in 4 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 42
• Drug target: yes — 8 curated mechanism-of-action drugs, 4 via a complex or family; 51 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 5 — Conivaptan Hydrochloride, Mozavaptan, Terlipressin, +2 more
• Approved drugs acting on a complex or family including it: 3 — Desmopressin Acetate, Lypressin, Vasopressin (Vasopressin receptor)
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000054

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:897
Approved symbol	AVPR2
Name	arginine vasopressin receptor 2
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	V2R
Ensembl gene	ENSG00000126895
Ensembl biotype	protein_coding
OMIM	300538
Entrez	554

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 12 protein_coding, 2 nonsense_mediated_decay

MANE Select: ENST00000646375

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 5: 1

ENST00000646375, ENST00000337474, ENST00000370049, ENST00000430697, ENST00000434679, ENST00000881289, ENST00000881290, ENST00000881291, ENST00000960389, ENST00001001949, ENST00001123895, ENST00001123896, ENST00001123897, ENST00001123898

RefSeq mRNA: 2 — MANE Select: NM_000054 NM_000054, NM_001146151

CCDS: CCDS14735, CCDS55539

Canonical transcript exons

ENST00000646375 — 4 exons

Exon	Start	End
ENSE00001276810	153905532	153906416
ENSE00001419977	153906523	153907166
ENSE00002231876	153904974	153905170
ENSE00003822128	153904673	153904771

Expression profiles

Bgee: expression breadth ubiquitous, 146 present calls, max score 86.31.

Highest expression (Bgee): apex of heart, type B pancreatic cell, olfactory bulb, omental fat pad, peritoneum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

AVPR2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 4 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

4 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	3.3e-03	-0.60	X:154031965:G:A
Brain Frontal Cortex BA9	eqtl	2.8e-02	-0.27	X:153393480:C:T
Pituitary	eqtl	2.9e-02	-0.18	X:153396773:G:A
Brain Cerebellum	eqtl	3.3e-02	+0.24	X:154240284:T:C

Top tissues by expression

showing 100 of 274 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	86.31	gold quality
type B pancreatic cell	CL:0000169	83.60	gold quality
olfactory bulb	UBERON:0002264	82.82	gold quality
omental fat pad	UBERON:0010414	76.75	gold quality
peritoneum	UBERON:0002358	76.72	gold quality
adipose tissue of abdominal region	UBERON:0007808	76.12	gold quality
subcutaneous adipose tissue	UBERON:0002190	75.94	gold quality
heart left ventricle	UBERON:0002084	74.32	gold quality
cardiac ventricle	UBERON:0002082	73.97	gold quality
adipose tissue	UBERON:0001013	73.11	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	73.10	gold quality
buccal mucosa cell	CL:0002336	72.98	gold quality
metanephros cortex	UBERON:0010533	72.64	gold quality
granulocyte	CL:0000094	72.63	gold quality
vena cava	UBERON:0004087	72.44	silver quality
connective tissue	UBERON:0002384	72.37	gold quality
male germ cell	CL:0000015	71.57	gold quality
triceps brachii	UBERON:0001509	71.45	gold quality
tendon of biceps brachii	UBERON:0008188	71.12	silver quality
gluteal muscle	UBERON:0002000	71.05	gold quality
lower esophagus muscularis layer	UBERON:0035833	70.71	gold quality
lower esophagus	UBERON:0013473	70.58	gold quality
parotid gland	UBERON:0001831	70.28	gold quality
sperm	CL:0000019	70.25	gold quality
heart	UBERON:0000948	69.97	gold quality
adult mammalian kidney	UBERON:0000082	69.61	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	69.49	gold quality
hindlimb stylopod muscle	UBERON:0004252	69.44	gold quality
vastus lateralis	UBERON:0001379	69.42	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	69.12	gold quality
left uterine tube	UBERON:0001303	68.95	gold quality
gastrocnemius	UBERON:0001388	68.90	gold quality
muscle of leg	UBERON:0001383	68.67	gold quality
thymus	UBERON:0002370	68.59	gold quality
muscle organ	UBERON:0001630	68.52	gold quality
tongue squamous epithelium	UBERON:0006919	68.43	gold quality
quadriceps femoris	UBERON:0001377	68.31	gold quality
right atrium auricular region	UBERON:0006631	68.09	gold quality
skeletal muscle tissue	UBERON:0001134	67.42	gold quality
pancreatic ductal cell	CL:0002079	67.29	silver quality
body of uterus	UBERON:0009853	67.21	gold quality
decidua	UBERON:0002450	67.17	gold quality
cardiac atrium	UBERON:0002081	67.15	gold quality
diaphragm	UBERON:0001103	67.11	gold quality
gingival epithelium	UBERON:0001949	67.08	gold quality
mucosa of stomach	UBERON:0001199	66.93	gold quality
biceps brachii	UBERON:0001507	66.93	gold quality
tibial nerve	UBERON:0001323	66.92	gold quality
hair follicle	UBERON:0002073	66.88	gold quality
superficial temporal artery	UBERON:0001614	66.56	gold quality
pericardium	UBERON:0002407	66.55	gold quality
myometrium	UBERON:0001296	66.46	gold quality
right lobe of thyroid gland	UBERON:0001119	66.31	gold quality
cerebellar hemisphere	UBERON:0002245	65.87	gold quality
gingiva	UBERON:0001828	65.86	gold quality
nasal cavity epithelium	UBERON:0005384	65.86	gold quality
cerebellar cortex	UBERON:0002129	65.82	gold quality
trachea	UBERON:0003126	65.81	gold quality
fundus of stomach	UBERON:0001160	65.72	gold quality
endocervix	UBERON:0000458	65.71	gold quality
bone marrow	UBERON:0002371	65.70	gold quality
pons	UBERON:0000988	65.68	silver quality
right coronary artery	UBERON:0001625	65.59	gold quality
right uterine tube	UBERON:0001302	65.53	gold quality
ectocervix	UBERON:0012249	65.51	gold quality
cerebellum	UBERON:0002037	65.40	gold quality
coronary artery	UBERON:0001621	65.39	gold quality
epithelial cell of pancreas	CL:0000083	65.28	gold quality
left coronary artery	UBERON:0001626	65.28	gold quality
endothelial cell	CL:0000115	65.12	gold quality
cervix squamous epithelium	UBERON:0006922	65.04	gold quality
mammary gland	UBERON:0001911	64.83	gold quality
thoracic mammary gland	UBERON:0005200	64.81	gold quality
lymph node	UBERON:0000029	64.69	gold quality
muscle layer of sigmoid colon	UBERON:0035805	64.67	gold quality
muscle tissue	UBERON:0002385	64.66	gold quality
dorsal plus ventral thalamus	UBERON:0001897	64.64	gold quality
pharyngeal mucosa	UBERON:0000355	64.49	gold quality
esophagus	UBERON:0001043	64.40	gold quality
uterine cervix	UBERON:0000002	64.31	gold quality
renal medulla	UBERON:0000362	64.21	gold quality
right hemisphere of cerebellum	UBERON:0014890	64.10	gold quality
smooth muscle tissue	UBERON:0001135	64.08	gold quality
skin of leg	UBERON:0001511	63.98	gold quality
mammary duct	UBERON:0001765	63.91	gold quality
inferior vagus X ganglion	UBERON:0005363	63.88	gold quality
kidney	UBERON:0002113	63.84	gold quality
periodontal ligament	UBERON:0008266	63.84	gold quality
pylorus	UBERON:0001166	63.81	gold quality
epithelium of mammary gland	UBERON:0003244	63.74	gold quality
medulla oblongata	UBERON:0001896	63.55	gold quality
skin of abdomen	UBERON:0001416	63.51	gold quality
ventral tegmental area	UBERON:0002691	63.50	gold quality
sigmoid colon	UBERON:0001159	63.41	gold quality
blood	UBERON:0000178	63.37	gold quality
superior vestibular nucleus	UBERON:0007227	63.04	gold quality
subthalamic nucleus	UBERON:0001906	62.86	gold quality
amniotic fluid	UBERON:0000173	62.74	gold quality
zone of skin	UBERON:0000014	62.72	gold quality
trigeminal ganglion	UBERON:0001675	62.52	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.58

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 68 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Cerebellum	tissue	10.5
Adipose tissue	tissue	4.8
Heart muscle	tissue	3.6
Tongue	tissue	3.6
Skeletal muscle	tissue	2.8
Vagina	tissue	2.2
Kidney	tissue	2.2
Choroid plexus	tissue	1.9
Fallopian tube	tissue	1.5
Skin 1	tissue	1.4
Lung	tissue	1.2
Cervix	tissue	0.9
Lymph node	tissue	0.9
Endometrium 1	tissue	0.9
Gallbladder	tissue	0.9
Locus coeruleus	tissue	0.9
Bone marrow	tissue	0.9
Breast	tissue	0.8
Smooth muscle	tissue	0.7
Thyroid gland	tissue	0.7
Hippocampus	tissue	0.7
Seminal vesicle	tissue	0.6
Esophagus	tissue	0.6
Salivary gland	tissue	0.6
Parathyroid gland	tissue	0.6
Urinary bladder	tissue	0.6
Ovary	tissue	0.5
Duodenum	tissue	0.5
Small intestine	tissue	0.4
Thymus	tissue	0.4
Colon	tissue	0.3
Nucleus accumbens	tissue	0.3
Midbrain	tissue	0.3
Prostate	tissue	0.3
Tonsil	tissue	0.3
Hippocampal formation	tissue	0.3
Pituitary gland	tissue	0.2
Medulla oblongata	tissue	0.2
Superior colliculi	tissue	0.2
Placenta	tissue	0.2
Spleen	tissue	0.2
Adrenal gland	tissue	0.2
Appendix	tissue	0.2
Prefrontal cortex	tissue	0.1
Testis	tissue	0.1
Stomach 1	tissue	0.1
Cerebral cortex	tissue	0.1
Pons	tissue	0.1
Rectum	tissue	0.1
Pancreas	tissue	0.1
Epididymis	tissue	0.1
Motor cortex	tissue	0.1
Basal ganglia	tissue	0.1
Thalamus	tissue	0.1
Hypothalamus	tissue	0.1
Substantia nigra	tissue	0.1
Spinal cord	tissue	0.1
Corpus callosum	tissue	0.1
Postcentral gyrus	tissue	0.1
Entorhinal cortex	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 187; highest nTPM — Flocculonodular lobe (9.3), Cerebellar cortex (8.1), Vermis (7.9), Blood vessel (2.4), Periaquaductal grey, lateral (2.0).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, ASCL1, BARHL2, INPP5K, NRF1, TFAM

miRNA regulators (miRDB)

Targeting AVPR2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

22 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-6877-3P	98.98	65.83	560
HSA-MIR-6819-3P	98.95	65.57	572
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-6760-5P	98.87	66.73	1515
HSA-MIR-6765-3P	97.83	64.59	1165
HSA-MIR-3162-5P	95.67	67.53	794
HSA-MIR-25-5P	87.02	64.95	84

Functional genomics

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000646375 — one region, missense o/e 0.80. ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• proteolytic cleavage of the V2 receptor requires a defined conformation and might play a role in signal termination at elevated hormone concentrations (PMID:10561596)
• A novel type of contiguous gene deletion of AVPR2 has been identified in unrelated Japanese kindreds with nephrogenic diabetes insipidus. (PMID:11754100)
• A new mutation associated with nephrogenic diabetes insipidus was isolated: a 6-AA deletion between G107 and C112. (PMID:11868598)
• Mutations causing NDI include R106C, F287L, and R337X. (PMID:11916004)
• a single amino acid difference in the first extracellular loop determines the efficiency of cell surface expression (PMID:11923476)
• HV2R has a serine/threonine motif that is required for retention in the cytoplasm (PMID:12482593)
• palmitoylation enhances the recruitment of beta-arrestin to the activated V2 vasopressin receptor thus facilitating processes requiring the scaffolding action of beta-arrestin (PMID:12900404)
• V2 vasopressin receptor degradation is regulated by agonist-promoted ubiquitination (PMID:12960162)
• examination of interaction with beta-arrestin and trafficking patterns by heterodimerization with V1 vasopressin receptor (PMID:14757828)
• analysis of pharmacochaperone cell surface delivery with a three-dimensional homology model of the antagonist-bound hV2R (PMID:15319430)
• a C-terminal region of the V2R important for calmodulin interaction is also important in modulation of V2R elevation of intracellular Ca2 (PMID:15319442)
• V2 vasopressin receptor has a role in inhibiting signaling through its interaction with receptor dimer and G protein (PMID:15452133)
• The data suggested that lysine 231 and glutamate 268 might interact with each other and might play a role in promoting GDP/GTP exchange in V2 vasopressin receptors. (PMID:16115624)
• Results show that the hydrophobic amino acid residues in the membrane-proximal C tail of the G protein-coupled vasopressin V2 receptor are necessary for transport-competent receptor folding. (PMID:16162341)
• Genetic analysis confirmed a mutation in AVPR2. (PMID:16240160)
• V2R-V206D and V2R-S167T were rescued and matured to a greater extent, suggesting that the rescuing activity of a pharmacological versus chemical chaperone is broader and stronger (PMID:16267275)
• molecular dynamics analysis of mechanism of desmopressin binding in vasopressin V2 receptor versus vasopressin V1a and oxytocin receptors (PMID:16333859)
• After VP stimulation of renal epithelial cells, AQP2 accumulates at the cell surface, while the V2R is actively internalized. This endocytotic block may involve a reduced capacity of phosphorylated AQP2 to interact with the endocytotic machinery. (PMID:16563128)
• Most missense AVPR2 mutations lead to receptors that are trapped intracellularly; a few mutant receptors reach the cell surface but are unable to bind AVP or to properly trigger an intracellular cyclic adenosine monophosphate signal. (PMID:16580609)
• The disorder nephrogenic diabetes insipidus (NDI) is inherited in an X-linked or autosomal fashion due to mutations in the genes encoding V2R or AQP2, respectively. (PMID:16825342)
• Two novel mutations were identified in each of AVPR2 and AQP2 underlying Congenital Nephrogenic Diabetes Insipidus in Arab families. (PMID:16845277)
• Findings of mutations scattered over the entire coding region of the AVPR2 gene are a valuable model to determine structure function relationship in G-protein-coupled receptor-related diseases. (PMID:17020465)
• These findings suggest that the two patients in a Chinese family suffering from congenital nephrogenic diabetes insipidus had a 5,995-bp deletion and 3-bp (GAG) insertion at Xq28. The deletion contained the entire AVPR2 gene and exon 22 of the C1 gene. (PMID:17101063)
• Y205F missense mutation would cause nephrogenic diabetes insipidus. (PMID:17216256)
• Mutations involved in nephrogenic syndrome of inappropriate antidiuresis in men and womwen. (PMID:17229917)
• Primary nocturanl enuresis and coexisting nephrogenic diabetes insipidus, as a result of a novel nonsense mutation in the V2R gene (C358X). (PMID:17389737)
• Urinary AQP2 excretion was absent in patients with severely debilitating mutations, a novel total deletion of the A VPR2 gene, and a novel nonsense mutation W296X. (PMID:17550212)
• V(2)R mRNA was expressed in medullary TAL (MTAL), macula densa, connecting tubule, and cortical and medullary collecting duct, and was weakly expressed in cortical TAL and distal convoluted tubule in rat, mouse, and human. (PMID:17626156)
• A novel missense mutation in exon 3 of the AVPR2 gene was identified in the nephrogenic diabetes insipidus patients. (PMID:17941907)
• Ubiquitin-like protein PLIC-2 is identified as a negative regulator of G protein-coupled receptor endocytosis. (PMID:18199683)
• The protective mechanism exerted by OPC-31260 stems from its influence on the renal vasopressin V(2) receptors. These observations might suggest an effective approach to the treatment of global hypoxia-induced cerebral oedema in humans. (PMID:18288441)
• Clinical nephrogenic diabetes insipidus phenotypes may correlate with the X-inactivation patterns in female carriers with heterozygote vasopressin type 2 receptor gene mutations. (PMID:18323675)
• Data demonstrated a direct and specific interaction between vasopressin V2 receptor and GC1q-Rthese two proteins via the arginine cluster of vasopressin V2 receptor. (PMID:18358546)
• identified a novel phosphorylation site (Ser(255))in the third intracellular loop that could be phosphorylated in vitro by protein kinase A, but not by Akt kinase (PMID:18578504)
• AVPR2 variants & mutations in nephrogenic diabetes insipidus(NDI); spectrum of mutations varies from rare gene variants or polymorphisms not causing NDI to rare mutations causing NDI, among which arginine and tyrosine are the most common missense (PMID:18726898)
• adults with intermittent, severe hyponatraemia may have a constitutively activating mutation in the AVPR2 with resultant nephrogenic syndrome of inappropriate antidiuresis (PMID:18753429)
• both pAVP (1.6-fold versus controls; P = 0.048) and inner ear V2R mRNA expression (41.5-fold versus controls; P = 0.022) were significantly higher in Meniere’s patients than controls (PMID:19094077)
• Wild-type V2R localized to the cell membrane while L57R V2R remained intracellular. (PMID:19170711)
• Data indicate that the vasopressin 2 receptor-R137C and V2R-R137L mutants traffic considerably more efficiently to the plasma membrane than V2R-R137H, identifying this as a potentially important mutation-dependent difference affecting V2R function. (PMID:19179480)
• Our study shows for the first time that renal cancer may effectively synthesize and express the V2-R. (PMID:19217806)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	avpr2aa	ENSDARG00000007436
danio_rerio	avpr2ab	ENSDARG00000029219
mus_musculus	Avpr2	ENSMUSG00000031390
rattus_norvegicus	Avpr2	ENSRNOG00000059862

Paralogs (16): NPFFR2 (ENSG00000056291), GNRHR (ENSG00000109163), CCKBR (ENSG00000110148), HCRTR1 (ENSG00000121764), GALR3 (ENSG00000128310), HCRTR2 (ENSG00000137252), NPFFR1 (ENSG00000148734), CCKAR (ENSG00000163394), AVPR1A (ENSG00000166148), GALR1 (ENSG00000166573), GPR22 (ENSG00000172209), GPR150 (ENSG00000178015), OXTR (ENSG00000180914), FFAR4 (ENSG00000186188), QRFPR (ENSG00000186867), AVPR1B (ENSG00000198049)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:88123) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 17 distinct phenotype terms.

Mouse phenotype (MP)	Records
hydronephrosis	2
decreased body weight	2
polydipsia	2
polyuria	2
decreased urine osmolality	2
hypoglycemia	1
abnormal kidney physiology	1
increased hematocrit	1
increased circulating chloride level	1
dry skin	1
decreased renal glomerular filtration rate	1
decreased urine potassium level	1
increased circulating sodium level	1
decreased urine sodium level	1
postnatal lethality, complete penetrance	1
decreased urine urea nitrogen level	1
decreased urine creatinine level	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Microtus montanus	Q9WTV8	99.0%	Diamond
Microtus ochrogaster	Q9WTV9	99.0%	Diamond
Macaca mulatta	P56494	97.4%	Diamond
Bos taurus	P56449	94.1%	Diamond
Ovis aries	Q28756	94.1%	Diamond
Sus scrofa	P32306	92.2%	Diamond
Canis lupus familiaris	O77808	88.6%	Diamond
Rhinella marina	Q90252	73.9%	Diamond
Catostomus commersonii	Q90334	69.4%	Diamond
Clarias gariepinus	O42329	62.3%	Diamond
Drosophila melanogaster	Q868T3	43.8%	Diamond
Octopus vulgaris	Q7YW31	43.4%	Diamond
Eisenia fetida	Q75W84	42.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
L1CAM	protein-coding	3897
ARHGAP4	protein-coding	393
PDZD4	protein-coding	57595
L1CAM-AS1	ncRNA	100996465
RENBP	protein-coding	5973
NAA10	protein-coding	8260
MIR3202-2	ncRNA	100422877
MIR3202-1	ncRNA	100422987
HCFC1-AS1	ncRNA	100873990
HCFC1	protein-coding	3054
TMEM187	protein-coding	8269
IDH3G	protein-coding	3421
SSR4	protein-coding	6748

Protein

Protein identifiers

Vasopressin V2 receptor — P30518 (reviewed: P30518)

Alternative names: AVPR V2, Antidiuretic hormone receptor, Renal-type arginine vasopressin receptor

All UniProt accessions (3): C9JV81, P30518, F8WET1

UniProt curated annotations — full annotation on UniProt →

Function. G protein-coupled receptor for arginine vasopressin, an antidiuretic that promotes renal water reabsorption. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (cAMP). AVPR2 is coupled to G(s) G alpha proteins and mediates activation of adenylate cyclase activity.

Subunit / interactions. Interacts with ARRDC4. Identified in a complex containing at least ARRDC4, V2R and HGS. Interacts with TMEM147. Interacts (when phosphorylated) with ARRB2; the interaction is associated with internalization of the receptor and short-term desensitization to the ligand.

Subcellular location. Cell membrane.

Tissue specificity. Kidney.

Post-translational modifications. Phosphorylation of the P-X-P-P motif promotes association with beta-arrestin ARRB2, leading to receptor desensitization and negative regulation of G protein-coupled receptor signaling.

Disease relevance. Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) [MIM:300539] Characterized by an inability to excrete a free water load, with inappropriately concentrated urine and resultant hyponatremia, hypoosmolarity, and natriuresis. The disease is caused by variants affecting the gene represented in this entry. Diabetes insipidus, nephrogenic, 1, X-linked (NDI1) [MIM:304800] A disorder caused by the inability of the renal collecting ducts to absorb water in response to arginine vasopressin. Characterized by excessive water drinking (polydipsia), excessive urine excretion (polyuria), persistent hypotonic urine, and hypokalemia. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The P-X-P-P motif is phosphorylated in response to ligand binding, promoting. association with beta-arrestin ARRB2.

Similarity. Belongs to the G protein-coupled receptor 1 family. Vasopressin/oxytocin receptor subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P30518-1	1	yes
P30518-2	2

RefSeq proteins (2): NP_000045, NP_001139623 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000161	Vprsn_rcpt_V2	Family
IPR000276	GPCR_Rhodpsn	Family
IPR001817	Vasoprsn_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (176 total): sequence variant 99, helix 17, mutagenesis site 13, modified residue 11, topological domain 8, transmembrane region 7, strand 5, turn 3, region of interest 3, compositionally biased region 2, lipid moiety-binding region 2, splice variant 2, chain 1, short sequence motif 1, glycosylation site 1, disulfide bond 1

Structure

Experimental structures (PDB)

showing 30 of 44 structures by resolution:

PDB	Title	Method	Resolution (Å)
7DFC	Crystal of Arrestin2-V2Rpp-3-Fab30 complex	X-RAY DIFFRACTION	2.49
9HAP	Cryo-EM structure of inactive human arginine-vasopressin (AVP) V2 receptor (V2R) with …	ELECTRON MICROSCOPY	2.5
9HB3	cryo-EM structure of inactive human arginine-vasopressin (AVP) V2 receptor (V2R) with …	ELECTRON MICROSCOPY	2.5
7DFA	Crystal of Arrestin2-V2Rpp-4-Fab30 complex	X-RAY DIFFRACTION	2.54
4JQI	Structure of active beta-arrestin1 bound to a G protein-coupled receptor phosphopeptide	X-RAY DIFFRACTION	2.6
7DW9	Cryo-EM structure of human V2 vasopressin receptor in complex with an Gs protein	ELECTRON MICROSCOPY	2.6
9ZZO	MP1104-bound Kappa Opioid Receptor in complex with beta-arrestin1	ELECTRON MICROSCOPY	2.6
22GM	C5a bound C5aR1 in complex with beta-arrestin1	ELECTRON MICROSCOPY	2.7
7KH0	Cryo-EM structure of the human arginine vasopressin AVP-vasopressin receptor V2R-Gs …	ELECTRON MICROSCOPY	2.8
9WSV	Cryo-EM structure of DAMGO-muOR-arrestin-1-Fab30 complex	ELECTRON MICROSCOPY	2.8
9WSW	Cryo-EM structure of endomorphin-1-muOR-Gz-scFv16 complex	ELECTRON MICROSCOPY	2.8
9WSX	Cryo-EM structure of endomorphin-1-muOR-arrestin2-Fab30 complex	ELECTRON MICROSCOPY	2.8
9UVW	Cryo-EM structure of Vasopressin receptor 2 (V2R)-BRIL/anti BRIL SRP2070 Fab antibody …	ELECTRON MICROSCOPY	2.89
9UYN	Cryo-EM structure of the G protein-coupled receptor 1 (GPR1) bound to beta-arrestin 1 in …	ELECTRON MICROSCOPY	2.9
9U80	Cryo-EM structure of conivaptan-bound human vasopressin V2 receptor complex with Fab	ELECTRON MICROSCOPY	2.94
9UVY	Cryo-EM structure of Vasopressin receptor 2 (V2R)-ARK1 with tolvaptan	ELECTRON MICROSCOPY	2.98
9LZ2	Cryo-EM structure of PTH1R(V2RC)-beta-arrestin1 complex	ELECTRON MICROSCOPY	3
9UVV	Cryo-EM structure of Vasopressin receptor 2 (V2R)-BRIL/anti BRIL SRP2070 Fab antibody …	ELECTRON MICROSCOPY	3.02
9U81	Cryo-EM structure of tolvaptan-bound human vasopressin V2 receptor complex with Fab	ELECTRON MICROSCOPY	3.08
9LY2	A Cryo-EM structure of LA-PTH-PTH1R-V2RT-Beta-arrestin1 complex (state 1 conformation)	ELECTRON MICROSCOPY	3.1
7DF9	Crystal of Arrestin2-V2Rpp-1-Fab30 complex	X-RAY DIFFRACTION	3.17
8WU1	Cryo-EM structure of CB1-beta-arrestin1 complex	ELECTRON MICROSCOPY	3.2
9UYI	Cryo-EM structure of the G protein-coupled receptor 1 (GPR1) bound to chemerin and …	ELECTRON MICROSCOPY	3.2
7DFB	Crystal of Arrestin2-V2Rpp-6-7-Fab30 complex	X-RAY DIFFRACTION	3.28
8JRV	Cryo-EM structure of the glucagon receptor bound to glucagon and beta-arrestin 1	ELECTRON MICROSCOPY	3.3
9UYH	Cryo-EM structure of the G protein-coupled receptor 1 (GPR1) bound to chemerin and …	ELECTRON MICROSCOPY	3.3
9UYJ	Cryo-EM structure of the G protein-coupled receptor 1 (GPR1) bound to chemerin and …	ELECTRON MICROSCOPY	3.3
9UYL	Cryo-EM structure of the G protein-coupled receptor 1 (GPR1) bound to chemerin and …	ELECTRON MICROSCOPY	3.3
9UVX	Cryo-EM structure of Vasopressin receptor 2 (V2R)-BRIL/anti BRIL SRP2070 Fab antibody …	ELECTRON MICROSCOPY	3.31
9BT8	Structure of Src in complex with beta-arrestin 1 revealing SH3 binding sites	ELECTRON MICROSCOPY	3.34

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30518-F1	76.84	0.32

Antibody-complex structures (SAbDab)

29 antibodies co-crystallized with this protein: 4JQI, 6NI2, 6U1N, 7BB6, 7BB7, 7DF9, 7DFA, 7DFB, 7DFC, 7DW9, 7KH0, 7R0C, 7R0J, 8GOC, 8I10, 8WRZ, 8WU1, 9BT8, 9CX3, 9CX9, 9HB3, 9UYH, 9UYI, 9UYJ, 9UYL (+4 more)

Human Protein Atlas

Protein class: Transporters, G-protein coupled receptors, GPCRs excl olfactory receptors, Predicted membrane proteins, GPCRHMM predicted membrane proteins, Disease related genes, FDA approved drug targets, Biotech drugs, Small molecule drugs, Human disease related genes

Protein evidence: Evidence at protein level

Functional residue map

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

Post-translational modifications (13)

Type	Positions
Phosphothreonine	347, 359, 360, 369
Phosphoserine	350, 357, 362, 363, 364, 370, 371
S-palmitoyl cysteine	341, 342

Disulfide bonds (1)

Type	Positions
Disulfide bond	112–192

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	22

Mutagenesis-validated functional residues (13)

Position	Phenotype
31	does not affect signaling and ability to activate adenylate cyclase.
96	strongly decreased signaling and ability to activate adenylate cyclase.
105	strongly decreased signaling and ability to activate adenylate cyclase.
123	does not affect arginine vasopressin-binding.
174	strongly decreased signaling and ability to activate adenylate cyclase.
202	does not affect signaling and ability to activate adenylate cyclase.
205	strongly decreased signaling and ability to activate adenylate cyclase.
287	strongly decreased signaling and ability to activate adenylate cyclase.
291	does not affect arginine vasopressin-binding.
302	does not affect signaling and ability to activate adenylate cyclase.
312	does not affect arginine vasopressin-binding.
341	reduced palmitoylation, reduced cell surface localization but coupling to g protein unaffected.
342	reduced palmitoylation, reduced cell surface localization but coupling to g protein unaffected.

Function

Pathways and Gene Ontology

Reactome pathways

6 curated (TAS) of 19; 4 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

19 pathways:

ID	Pathway	Evidence
R-HSA-9036092	Defective AVP does not bind AVPR2 and causes neurohypophyseal diabetes insipidus (NDI) ⚕	curated
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis	curated
R-HSA-8856828	Clathrin-mediated endocytosis	curated
R-HSA-418555	G alpha (s) signalling events	curated
R-HSA-432040	Vasopressin regulates renal water homeostasis via Aquaporins	curated
R-HSA-388479	Vasopressin-like receptors	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5619115	Disorders of transmembrane transporters ⚕	—
R-HSA-5619102	SLC transporter disorders ⚕	—
R-HSA-445717	Aquaporin-mediated transport	—
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)	—
R-HSA-388396	GPCR downstream signalling	—
R-HSA-500792	GPCR ligand binding	—
R-HSA-199991	Membrane Trafficking	—
R-HSA-375276	Peptide ligand-binding receptors	—
R-HSA-162582	Signal Transduction	—
R-HSA-372790	Signaling by GPCR	—
R-HSA-382551	Transport of small molecules	—
R-HSA-5653656	Vesicle-mediated transport	—

MSigDB gene sets: 223 (showing top): GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_RESPONSE_TO_PEPTIDE, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE, GOBP_POSITIVE_REGULATION_OF_LYASE_ACTIVITY, REACTOME_MEMBRANE_TRAFFICKING, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_WATER_TRANSPORT, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, GOBP_REGULATION_OF_ADENYLATE_CYCLASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_VASOCONSTRICTION, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION

GO Biological Process (19): regulation of systemic arterial blood pressure by vasopressin (GO:0001992), positive regulation of systemic arterial blood pressure (GO:0003084), renal water retention (GO:0003092), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), activation of adenylate cyclase activity (GO:0007190), hemostasis (GO:0007599), positive regulation of cell population proliferation (GO:0008284), negative regulation of cell population proliferation (GO:0008285), positive regulation of gene expression (GO:0010628), telencephalon development (GO:0021537), cellular response to hormone stimulus (GO:0032870), positive regulation of vasoconstriction (GO:0045907), renal water absorption (GO:0070295), positive regulation of intracellular signal transduction (GO:1902533), signal transduction (GO:0007165), negative regulation of urine volume (GO:0035811), positive regulation of blood pressure (GO:0045777)

GO Molecular Function (4): vasopressin receptor activity (GO:0005000), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515), signaling receptor activity (GO:0038023)

GO Cellular Component (8): endosome (GO:0005768), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), membrane (GO:0016020), endocytic vesicle (GO:0030139), clathrin-coated endocytic vesicle membrane (GO:0030669), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

14 top-level categories:

Category	Pathways
Signaling by GPCR	2
Peptide ligand-binding receptors	1
GPCR downstream signalling	1
Aquaporin-mediated transport	1
Clathrin-mediated endocytosis	1
Membrane Trafficking	1
SLC transporter disorders	1
Vesicle-mediated transport	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1
Transport of small molecules	1
Disorders of transmembrane transporters	1
Disease	1

GO top-level categories

53 GO namespaces:

Category	Terms
endomembrane system	3
cytoplasm	3
G protein-coupled receptor signaling pathway	2
cell population proliferation	2
regulation of cell population proliferation	2
cytoplasmic vesicle	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
regulation of systemic arterial blood pressure by hormone	1
regulation of systemic arterial blood pressure	1
positive regulation of blood pressure	1
negative regulation of urine volume	1
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase activity	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
positive regulation of adenylate cyclase activity	1
regulation of body fluid levels	1
positive regulation of cellular process	1
negative regulation of cellular process	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
forebrain development	1
animal gross anatomical part developmental process	1
response to hormone	1
cellular response to chemical stimulus	1
cellular response to endogenous stimulus	1
regulation of vasoconstriction	1
vasoconstriction	1
positive regulation of multicellular organismal process	1
renal water transport	1
renal absorption	1
positive regulation of signal transduction	1
intracellular signal transduction	1
regulation of intracellular signal transduction	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of urine volume	1
regulation of blood pressure	1
G protein-coupled peptide receptor activity	1
transmembrane signaling receptor activity	1
binding	1
molecular transducer activity	1
membrane	1
cell periphery	1
clathrin-coated vesicle membrane	1
endocytic vesicle membrane	1
clathrin-coated endocytic vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 31 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
adenylate cyclase-activating G protein-coupled receptor signaling pathway	BP	direct assay
negative regulation of cell population proliferation	BP	direct assay
renal water absorption	BP	direct assay
endocytic vesicle	CC	direct assay
endosome	CC	direct assay
perinuclear region of cytoplasm	CC	direct assay
plasma membrane	CC	direct assay
vasopressin receptor activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,288 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AVPR2	AQP2	P41181	966
AVPR2	AVP	P01185	924
AVPR2	ARHGAP4	P98171	857
AVPR2	RENBP	P51606	817
AVPR2	C1QTNF1	Q9BXJ1	761
AVPR2	GNAO1	P09471	743
AVPR2	NAA10	P41227	735
AVPR2	L1CAM	P32004	731
AVPR2	REN	P00797	715
AVPR2	VN1R1	Q9GZP7	688
AVPR2	ARRB1	P49407	675
AVPR2	GPRASP1	Q5JY77	660
AVPR2	AGTR1	P30556	659
AVPR2	OLIG3	Q7RTU3	652
AVPR2	ARRB2	P32121	651

IntAct

Human interaction partners of AVPR2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

8 partners by confidence:

Partner	Interaction type	MIscore	Records
COMT	physical association	0.560	3
SLC41A1	physical association	0.560	3
ARRDC4	physical association	0.400	2
RAMP1	physical association	0.400	1
RAMP2	physical association	0.400	1
RAMP3	physical association	0.400	1
ATP9B	association	0.350	1
GXYLT2	association	0.350	1

BioGRID (128 interactions; top human partners by supporting records): ARRDC4 (Affinity Capture-Western; 2 records), C1QTNF1 (Two-hybrid; 2 records), HGS (Affinity Capture-Western; 2 records), ABCB8 (Affinity Capture-MS), ABHD17B (Affinity Capture-MS), ALG10 (Affinity Capture-MS), ALG3 (Affinity Capture-MS), ARRB2 (Affinity Capture-Western), ARV1 (Affinity Capture-MS), ATL2 (Affinity Capture-MS), ATM (Affinity Capture-MS), ATP13A3 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), ATP2B3 (Affinity Capture-MS), ATP2B4 (Affinity Capture-MS)

SIGNOR signaling

showing 7 of 8 signaling interactions:

A	Effect	B	Mechanism
AVP	up-regulates	AVPR2	binding
AVPR2	“up-regulates activity”	GNAS	binding
AVPR2	“up-regulates activity”	GNAL	binding
vasopressin	“up-regulates activity”	AVPR2	“chemical activation”
AVPR2	“up-regulates activity”	GNAI1	binding
AVPR2	“up-regulates activity”	GNAQ	binding
conivaptan	“down-regulates activity”	AVPR2	“chemical inhibition”

Protein complexes (CORUM) (3)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

3 complexes by size:

Complex	Subunits	Members
★ AVPR2-OXTR complex	2	AVPR2, OXTR
★ AVPR2-CNIH4 complex	2	AVPR2, CNIH4
★ Vasopressin V2 receptor	1	AVPR2

Ligand–receptor pairs (CellPhoneDB) (2)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

2 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
OXT	receptor	Signaling by Oxytocin
AVP	receptor	Signaling by Vasopressin

Disease & clinical

Genetic variants

Variant evidence for AVPR2: 461 ClinVar records (119 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	66
Likely pathogenic	53
Uncertain significance	103
Likely benign	131
Benign	22

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 119 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
10844	NM_000054.7(AVPR2):c.1009C>T (p.Arg337Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	7
10849	NM_000054.7(AVPR2):c.410G>A (p.Arg137His)	Pathogenic	criteria provided, multiple submitters, no conflicts	7
10854	NM_000054.7(AVPR2):c.409C>T (p.Arg137Cys)	Pathogenic	criteria provided, multiple submitters, no conflicts	7
10840	NM_000054.7(AVPR2):c.337C>T (p.Arg113Trp)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
10850	NM_000054.7(AVPR2):c.541C>T (p.Arg181Cys)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
10835	NM_000054.7(AVPR2):c.738del (p.Arg247fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
10842	NM_000054.7(AVPR2):c.213G>A (p.Trp71Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
10845	NM_000054.7(AVPR2):c.253G>A (p.Asp85Asn)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
2577986	NM_000054.7(AVPR2):c.262G>A (p.Val88Met)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
235612	NM_000054.7(AVPR2):c.392T>C (p.Leu131Pro)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2504686	NM_000054.7(AVPR2):c.296G>A (p.Trp99Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2728308	NM_000054.7(AVPR2):c.212G>A (p.Trp71Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2812101	NM_000054.7(AVPR2):c.888G>A (p.Trp296Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
3382215	NM_000054.7(AVPR2):c.135_136del (p.Ile46fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
3775465	NM_000054.7(AVPR2):c.614_615del (p.Tyr205fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2

Per-variant reference — Sugi Variant

Explore AVPR2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 18 predictions of 197):

Position(s)	Effect	Δscore	Sites
X:153904773	donor_loss	1.0000
X:153905530–153905531	acceptor_loss	1.0000	2
X:153904772–153904773	donor_loss	0.9900	3
X:153904972–153904973	acceptor_loss	0.9900	4
X:153905530–153905531	acceptor_loss	0.9900	3
X:153905533	acceptor_gain	0.9900
X:153904772	donor_loss	0.9800
X:153904972	acceptor_loss	0.9800
X:153905518	acceptor_gain	0.9800
X:153905531	acceptor_loss	0.9800

AlphaMissense

748 missense substitutions predicted likely pathogenic (of 2,360 scored), across 201 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D85	8	0.973	0.987
F178	8	0.957	0.997
F105	8	0.953	0.996
F196	8	0.951	0.997
N321	8	0.907	0.984
F328	8	0.893	0.985
F214	8	0.885	0.970
F288	8	0.872	0.974
S318	8	0.853	0.989
D136	8	0.851	0.926
C112	7	0.980	0.993
C192	7	0.966	0.982
F287	7	0.951	0.992
F77	7	0.920	0.965
M272	7	0.920	0.963
N55	7	0.910	0.981
W284	7	0.901	0.978
N317	7	0.879	0.986
W164	7	0.876	0.985
W99	7	0.858	0.972

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000132

Disease associations

OMIM: gene MIM:300538 | disease phenotypes: MIM:304800, MIM:300539, MIM:300673

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
diabetes insipidus, nephrogenic, X-linked	Definitive	X-linked	3
nephrogenic diabetes insipidus	Definitive	X-linked recessive	2
nephrogenic syndrome of inappropriate antidiuresis	Strong	X-linked	5

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (4 panels, 4 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

4 panels:

Panel	Rating
Hereditary isolated diabetes insipidus	green
Monogenic nephrogenic diabetes insipidus	green
Renal tubulopathies	green
Unexplained young onset end-stage renal disease	green

Mondo (4): diabetes insipidus, nephrogenic, X-linked (MONDO:0010581), nephrogenic diabetes insipidus (MONDO:0016383), nephrogenic syndrome of inappropriate antidiuresis (MONDO:0010356), severe neonatal-onset encephalopathy with microcephaly (MONDO:0010397)

Orphanet (3): Arginine vasopressin resistance (Orphanet:223), Nephrogenic syndrome of inappropriate antidiuresis (Orphanet:93606), MECP2-related severe neonatal encephalopathy (Orphanet:209370)

HPO phenotypes

42 phenotypes (HPO-id order):

HPO	Term
HP:0000009	Functional abnormality of the bladder
HP:0000021	Megacystis
HP:0000072	Hydroureter
HP:0000083	Renal insufficiency
HP:0000103	Polyuria
HP:0000737	Irritability
HP:0000873	Diabetes insipidus
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001419	X-linked recessive inheritance
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001561	Polyhydramnios
HP:0001945	Fever
HP:0001955	Unexplained fevers
HP:0001959	Polydipsia
HP:0001986	Hypertonic dehydration
HP:0002013	Vomiting
HP:0002017	Nausea and vomiting
HP:0002019	Constipation
HP:0002039	Anorexia
HP:0002197	Generalized-onset seizure
HP:0002902	Hyponatremia
HP:0003158	Hyposthenuria
HP:0003228	Hypernatremia
HP:0003351	Decreased circulating renin concentration
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0004322	Short stature
HP:0004421	Elevated systolic blood pressure
HP:0004906	Hypernatremic dehydration
HP:0008872	Feeding difficulties in infancy
HP:0009806	Nephrogenic diabetes insipidus
HP:0010677	Enuresis nocturna
HP:0011106	Hypovolemia
HP:0011968	Feeding difficulties
HP:0012101	Decreased serum creatinine
HP:0012605	Hypernatriuria
HP:0031969	Reduced blood urea nitrogen
HP:0040085	Abnormal circulating aldosterone concentration

MeSH disease descriptors

3 disease descriptors:

Descriptor	Name	Tree numbers
D018500	Diabetes Insipidus, Nephrogenic	C12.050.351.968.419.135.500; C12.200.777.419.135.500; C12.950.419.135.500
C566878	Encephalopathy, Neonatal Severe, Due To Mecp2 Mutations *(supp.)*
C564491	Nephrogenic Syndrome of Inappropriate Antidiuresis *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL1790 (SINGLE PROTEIN), CHEMBL2363078 (PROTEIN FAMILY), CHEMBL4523980 (SELECTIVITY GROUP), CHEMBL5482972 (CHIMERIC PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the AVPR2 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

8 curated-mechanism drugs:

Drug	Modality	Max phase
CONIVAPTAN HYDROCHLORIDE	Small molecule	4
MOZAVAPTAN	Small molecule	4
TERLIPRESSIN	Protein	4
TOLVAPTAN	Small molecule	4
VASOPRESSIN TANNATE	Protein	4
LIXIVAPTAN	Small molecule	3
SATAVAPTAN	Small molecule	3
PECAVAPTAN	Small molecule	2

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes AVPR2 — the drug acts on the assembly or class, not necessarily on this subunit alone.

4 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
DESMOPRESSIN ACETATE	Vasopressin receptor	3	4
LYPRESSIN	Vasopressin receptor	3	4
VASOPRESSIN	Vasopressin receptor	3	4
ARGIPRESSIN TANNATE	Vasopressin receptor	3	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 322,838 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

51 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1755	CONIVAPTAN	4	3,171
CHEMBL420762	MOZAVAPTAN	4	254
CHEMBL344159	TOLVAPTAN	4	3,719
CHEMBL633	AMIODARONE	4	30,023
CHEMBL1113	AMOXAPINE	4	20,303
CHEMBL382301	ATOSIBAN	4	2,383
CHEMBL1201346	BALSALAZIDE	4	8,382
CHEMBL288441	BOSUTINIB	4	12,869
CHEMBL3301668	CARBETOCIN	4	1,744
CHEMBL790	CHLORHEXIDINE	4	85,849
CHEMBL1201284	CINACALCET	4	5,997
CHEMBL104	CLOTRIMAZOLE	4	56,839
CHEMBL1429	DESMOPRESSIN	4	125
CHEMBL46516	FLUSPIRILENE	4	41,280
CHEMBL252556	IDEBENONE	4	8,664
CHEMBL126224	IPRINDOLE	4	4,422
CHEMBL64391	ITRACONAZOLE	4	624
CHEMBL328190	LASOFOXIFENE	4	10,696
CHEMBL416956	MEFLOQUINE	4	15,730
CHEMBL434394	NEBIVOLOL	4	9,764
CHEMBL180022	NERATINIB	4
CHEMBL56367	NIMESULIDE	4
CHEMBL1401	NITAZOXANIDE	4
CHEMBL395429	OXYTOCIN	4
CHEMBL1423	PIMOZIDE	4
CHEMBL1201303	PYRVINIUM	4
CHEMBL374478	RIFAMPIN	4
CHEMBL1617	RIFAXIMIN	4
CHEMBL12713	SERTINDOLE	4
CHEMBL809	SERTRALINE	4
CHEMBL535	SUNITINIB	4
CHEMBL76370	TEGASEROD	4
CHEMBL17157	TERFENADINE	4
CHEMBL1201	THIOTHIXENE	4
CHEMBL422	TRIFLUOPERAZINE	4
CHEMBL373742	VASOPRESSIN	4
CHEMBL49429	LIXIVAPTAN	3
CHEMBL4297183	BALOVAPTAN	3
CHEMBL2103773	OTILONIUM BROMIDE	3
CHEMBL35228	PYRONARIDINE	3
CHEMBL50	QUERCETIN	3
CHEMBL429736	RETOSIBAN	3
CHEMBL4594444	PECAVAPTAN	2
CHEMBL1182210	BENZETHONIUM	2
CHEMBL1187011	DOMIPHEN	2
CHEMBL2037511	EPELSIBAN	2
CHEMBL518043	FEDOVAPAGON	2
CHEMBL582857	NELIVAPTAN	2
CHEMBL1819440	ORNIPRESSIN	2
CHEMBL419667	RELCOVAPTAN	2
CHEMBL1817709	SELEPRESSIN	2

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Vasopressin and oxytocin receptors

Most potent curated ligand interactions (63 total), top 25:

Ligand	Action	Affinity	Parameter
[125I]d(CH2)5[D-Ile2,Ile4,Tyr-NH29]AVP	Antagonist	9.5	pKd
conivaptan	Antagonist	9.44	pKi
[3H]AVP (human, mouse, rat)	Full agonist	9.4	pKd
tolvaptan	Antagonist	9.37	pKi
satavaptan	Antagonist	9.3	pKi
[3H]SR 121463A	Inverse agonist	9.3	pKd
[125I]d(CH2)5[D-Ile2,Val4,Tyr-NH29]AVP	Antagonist	9.2	pKd
lixivaptan	Inverse agonist	9.2	pKi
vasopressin	Full agonist	9.1	pKi
[3H]dDAVP	Full agonist	9.1	pKd
dVDAVP	Full agonist	9.1	pKi
d(CH2)5[D-Tyr(Et)2,Val4,Tyr-NH29]AVP	Antagonist	9.1	pKi
[125I]d(CH2)5[D-Tyr(Et)2,Ile4,Tyr-NH29]AVP	Antagonist	9.1	pKd
[125I]d(CH2)5[D-Tyr(Et)2,Val4,Tyr-NH29]AVP	Antagonist	9.1	pKd
RWJ-351647	Antagonist	9.0	pKi
YM 471	Antagonist	8.9	pKi
SKF-105494	Antagonist	8.9	pKi
[3H]desGly-NH2[D-Ile2,Ile4]VP		8.6	pKd
desmopressin	Full agonist	8.6	pKi
LVP	Full agonist	8.5	pKi
[Val4]AVP	Full agonist	8.4	pKi
d(CH2)5[D-Ile2,Ile4]AVP	Antagonist	8.4	pKi
dAVP	Full agonist	8.3	pKi
d(CH2)5[Tyr(Et)2,Val4,des-Gly9]AVP	Antagonist	8.3	pKi
arginine vasotocin	Full agonist	8.2	pKi

Binding affinities (BindingDB)

1030 measured of 1196 human assays (1205 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL3353956	EC50	0.007 nM
CHEMBL439044	EC50	0.009 nM
CHEBI:59204	EC50	0.01 nM
CHEMBL3354579	EC50	0.01 nM
CHEMBL3353948	EC50	0.01 nM
CHEMBL3353946	EC50	0.01 nM
CHEMBL3353940	EC50	0.01 nM
CHEMBL3353939	EC50	0.01 nM
CHEMBL3353932	EC50	0.01 nM
CHEMBL3353930	EC50	0.01 nM
[O-methyl-11C]2-{4-[4-(7-methoxynaphthalen-1-yl)piperazin-1-yl]butyl}-4-methyl-2H-[1,2,4]triazine-3,5-dione	EC50	0.01 nM
CHEMBL3354592	EC50	0.02 nM
CHEMBL3354571	EC50	0.02 nM
CHEMBL3353955	EC50	0.02 nM
CHEMBL3354594	EC50	0.025 nM
CHEMBL3353942	EC50	0.03 nM
CHEMBL3354597	EC50	0.04 nM
CHEMBL3354595	EC50	0.04 nM
CHEMBL3354588	EC50	0.04 nM
CHEMBL6087371	KI	0.04 nM
CHEMBL3354598	EC50	0.05 nM
CHEMBL3354589	EC50	0.05 nM
CHEMBL3353929	EC50	0.05 nM
(2’-methylbiphenyl-4-yl)((1S,5R)-1,3,3-trimethyl-6-azabicyclo[3.2.1]octan-6-yl)methanone	KI	0.05 nM
CHEMBL3353949	EC50	0.06 nM
CHEMBL3353931	EC50	0.06 nM
CHEMBL3353935	EC50	0.06 nM
(2,2’-dimethylbiphenyl-4-yl)((1S,5R)-1,3,3-trimethyl-6-azabicyclo[3.2.1]octan-6-yl)methanone	KI	0.06 nM
CHEMBL3354587	EC50	0.07 nM
CHEMBL3354572	EC50	0.07 nM
CHEMBL3354591	EC50	0.08 nM
CHEMBL3354600	EC50	0.09 nM
CHEMBL3354584	EC50	0.09 nM
(4-(1H-indol-3-yl)-3-methoxyphenyl)((1S,5R)-1,3,3-trimethyl-6-azabicyclo[3.2.1]octan-6-yl)methanone	KI	0.1 nM
CHEMBL6150478	KI	0.1 nM
CHEMBL3354585	EC50	0.11 nM
CHEMBL3354575	EC50	0.11 nM
CHEMBL3354570	EC50	0.11 nM
CHEMBL3353944	EC50	0.11 nM
CHEMBL3354581	EC50	0.12 nM
CHEMBL3353954	EC50	0.12 nM
CHEMBL3353953	EC50	0.12 nM
CHEMBL3353945	EC50	0.12 nM
CHEMBL3354580	EC50	0.13 nM
CHEMBL3353938	EC50	0.13 nM
CHEMBL3354601	EC50	0.14 nM
CHEMBL3354582	EC50	0.14 nM
CHEMBL6108956	KI	0.14 nM
CHEMBL3353947	EC50	0.15 nM
CHEMBL3354576	EC50	0.16 nM

ChEMBL bioactivities

1210 potent at pChembl≥5 of 1279 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.30	EC50	0.05	nM	VASOPRESSIN
10.30	EC50	0.05	nM	CHEMBL435323
10.30	EC50	0.05012	nM	VASOPRESSIN
10.28	EC50	0.052	nM	VASOPRESSIN
10.10	EC50	0.08	nM	CHEMBL4454891
10.00	EC50	0.1	nM	CHEMBL4528032
9.96	EC50	0.11	nM	CHEMBL4536454
9.85	EC50	0.14	nM	CHEMBL4532363
9.77	EC50	0.17	nM	CHEMBL4472007
9.72	EC50	0.19	nM	CHEMBL4459424
9.72	EC50	0.19	nM	CHEMBL4444891
9.70	EC50	0.2	nM	DESMOPRESSIN
9.70	EC50	0.2	nM	CHEMBL4571464
9.70	IC50	0.2	nM	CHEMBL102311
9.59	EC50	0.26	nM	CHEMBL4555263
9.57	EC50	0.27	nM	CHEMBL4451692
9.54	EC50	0.29	nM	CHEMBL4462616
9.52	EC50	0.3	nM	CHEMBL4439313
9.49	EC50	0.32	nM	CHEMBL4527761
9.46	EC50	0.35	nM	CHEMBL4521602
9.44	Ki	0.36	nM	CONIVAPTAN
9.37	Ki	0.43	nM	TOLVAPTAN
9.35	EC50	0.45	nM	CHEMBL4436571
9.35	EC50	0.4467	nM	ORNIPRESSIN
9.35	EC50	0.45	nM	ORNIPRESSIN
9.30	IC50	0.5	nM	CHEMBL311931
9.30	Ki	0.5	nM	CHEMBL2371605
9.28	Ki	0.53	nM	CHEMBL6101825
9.24	Ki	0.57	nM	CHEMBL603708
9.24	IC50	0.57	nM	CHEMBL603708
9.22	Ki	0.6	nM	PECAVAPTAN
9.22	Ki	0.6	nM	CONIVAPTAN
9.17	Ki	0.67	nM	CHEMBL445816
9.15	IC50	0.7	nM	CHEMBL49322
9.15	IC50	0.7	nM	CHEMBL420031
9.15	EC50	0.7	nM	CHEMBL363910
9.15	Ki	0.7	nM	CHEMBL6145092
9.15	Ki	0.7	nM	CHEMBL6103295
9.15	Ki	0.7	nM	CHEMBL2371604
9.13	EC50	0.74	nM	CHEMBL363910
9.10	Ki	0.8	nM	CHEMBL6103298
9.08	Ki	0.83	nM	CHEMBL2172291
9.05	Ki	0.9	nM	CHEMBL543854
9.05	Ki	0.9	nM	CHEMBL6102315
9.02	IC50	0.95	nM	CHEMBL434654
9.01	EC50	0.98	nM	CHEMBL594026
9.00	IC50	1	nM	CHEMBL310416
9.00	IC50	1	nM	LIXIVAPTAN
9.00	IC50	1	nM	CHEMBL3924331
9.00	Ki	1	nM	TOLVAPTAN

PubChem BioAssay actives

1084 with measured affinity, of 3220 total; 50 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
Tolvaptan	1720599: Antagonist activity at human AVPR2 by PathHunter beta-arrestin assay	ic50	<0.0001	uM
(4R)-3-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(ethylamino)-1-oxopentan-2-yl]-1,3-thiazolidine-4-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0001	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-hydroxyphenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2S)-5-(diaminomethylideneamino)-1-hydroxypentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0001	uM
(4R)-3-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[4-(diaminomethylideneamino)butyl]-1,3-thiazolidine-4-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0001	uM
(2S,4R)-1-[(4S,7S,10S,13S,16S)-7-(2-amino-2-oxoethyl)-16-[(4-chlorophenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-13-(thiophen-2-ylmethyl)-1-thia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(ethylamino)-1-oxopentan-2-yl]-4-hydroxypyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0001	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2S)-5-(diaminomethylideneamino)-1-hydroxypentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0001	uM
(4R)-3-[(4S,7S,10S,13S,16S)-7-(2-amino-2-oxoethyl)-16-[(4-chlorophenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-13-(thiophen-2-ylmethyl)-1-thia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(ethylamino)-1-oxopentan-2-yl]-1,3-thiazolidine-4-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0001	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-12-[(4-fluorophenyl)methyl]-15-[(4-hydroxyphenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[4-(diaminomethylideneamino)butyl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0001	uM
(2S)-1-[(4S,7S,10S,13S,16S)-7-(2-amino-2-oxoethyl)-16-[(4-hydroxyphenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-13-(thiophen-2-ylmethyl)-1-thia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-hydroxypentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0001	uM
(2S)-N-[(2R)-1-[(2-amino-2-oxoethyl)amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-1-[(4R,7S,10S,13S,16S)-7-(2-amino-2-oxoethyl)-13-benzyl-16-[(4-hydroxyphenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0001	uM
vasopressin	1178647: Agonist activity at human vasopressin V2 expressed in HEK293 cells after 5 hrs by firefly luciferase reporter gene assay	ec50	0.0001	uM
(2S)-1-[(4S,7S,10S,13S,16S)-7-(2-amino-2-oxoethyl)-16-[(4-chlorophenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-13-(thiophen-2-ylmethyl)-1-thia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-hydroxypentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0001	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[4-(diaminomethylideneamino)butyl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0001	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-hydroxypentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0001	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(2-methylpropylamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0002	uM
(2S,4R)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(2-methylpropylamino)-1-oxopentan-2-yl]-4-hydroxypyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0002	uM
(2S)-1-[(4S,7S,10S,13S,16S)-7-(2-amino-2-oxoethyl)-16-[(4-chlorophenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-13-(thiophen-2-ylmethyl)-1-thia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(2-methylpropylamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0002	uM
(2S)-1-[(4S,7S,10S,13S,16S)-7-(2-amino-2-oxoethyl)-16-[(4-chlorophenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-13-(thiophen-2-ylmethyl)-1-thia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(ethylamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0002	uM
(4R)-3-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-12-[(4-fluorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[4-(diaminomethylideneamino)butyl]-1,3-thiazolidine-4-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0002	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-1-(cyclopropylmethylamino)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0002	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-1-(cyclopropylamino)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0002	uM
(4R)-3-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-oxo-1-(propylamino)pentan-2-yl]-1,3-thiazolidine-4-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0002	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-1-(benzylamino)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0002	uM
(2S)-N-(4-aminobutyl)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-hydroxyphenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0002	uM
(2S,4R)-1-[(4S,7S,10S,13S,16S)-7-(2-amino-2-oxoethyl)-16-[(4-chlorophenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-13-(thiophen-2-ylmethyl)-1-thia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(2-methylpropylamino)-1-oxopentan-2-yl]-4-hydroxypyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0002	uM
(4R)-3-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-oxo-1-(2-thiophen-2-ylethylamino)pentan-2-yl]-1,3-thiazolidine-4-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0002	uM
2-methoxy-N-[4-(spiro[3,5-dihydro-2H-1-benzazepine-4,3’-cyclohexene]-1-carbonyl)phenyl]benzamide	217704: In vitro inhibitory concentration against [3H]AVP binding to cloned human vasopressin receptor	ic50	0.0002	uM
Desmopressin	1178647: Agonist activity at human vasopressin V2 expressed in HEK293 cells after 5 hrs by firefly luciferase reporter gene assay	ec50	0.0002	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-12-[(4-fluorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-hydroxypentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(methylamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2S)-5-(diaminomethylideneamino)-1-(2-methylpropylamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(2S)-1-[(4R,7S,10S,13S,16S)-7-(2-amino-2-oxoethyl)-16-[(4-chlorophenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-13-(thiophen-2-ylmethyl)-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(ethylamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-hydroxyphenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-1-(benzylamino)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(4R)-3-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-1-(benzylamino)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-1,3-thiazolidine-4-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(diethylamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(2S,4R)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-12-benzyl-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(ethylamino)-1-oxopentan-2-yl]-4-hydroxypyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-1-(butylamino)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-oxo-1-(propylamino)pentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-12-[(4-fluorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[4-(diaminomethylideneamino)butyl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(2S)-1-[(4S,7S,10S,13S,16S)-7-(2-amino-2-oxoethyl)-13-benzyl-16-[(4-chlorophenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-1-thia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(2-methylpropylamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(4R)-3-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-12-[(4-fluorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-oxo-1-(2-thiophen-2-ylethylamino)pentan-2-yl]-1,3-thiazolidine-4-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-ethylphenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-hydroxypentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(ethylamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-oxo-1-(propan-2-ylamino)pentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0004	uM
(2S)-1-[(4R,7S,10S,13S,16S)-7-(2-amino-2-oxoethyl)-13-benzyl-16-[(4-chlorophenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(ethylamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0004	uM
(2S)-N-[(2S)-5-amino-1-[(2-amino-2-oxoethyl)amino]-1-oxopentan-2-yl]-1-[(4R,7S,10S,13S,16S,19R)-19-amino-7-(2-amino-2-oxoethyl)-10-(3-amino-3-oxopropyl)-13-benzyl-16-[(4-hydroxyphenyl)methyl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]pyrrolidine-2-carboxamide	613481: Agonist activity at recombinant human vasopressin V2 receptor expressed in HEK293 cells by luciferase reporter gene assay	ec50	0.0004	uM
N-[4-(2-methyl-4,5-dihydro-3H-imidazo[4,5-d][1]benzazepine-6-carbonyl)phenyl]-2-phenylbenzamide	483982: Displacement [3H]Arg human recombinant Vasopressin V2 receptor	ki	0.0004	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-methylphenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-hydroxypentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0004	uM
N-[3-chloro-4-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepine-5-carbonyl)phenyl]-2,3-dimethylbenzamide	217845: Displacement of [3H]AVP from human V2 receptor expressed in murine fibroblast cell line (LV2) membranes	ic50	0.0005	uM
8’-chloro-1’-[4-(2,3-dihydro-1-benzofuran-7-yl)piperazin-1-yl]spiro[1,3-dioxolane-2,5’-4,6-dihydro-[1,2,4]triazolo[4,3-a][1]benzazepine]	2208013: Displacement of [3H]AVP from human vasopressin V2 receptor expressed in human 1321N1 cells assessed as inhibition constant	ki	0.0005	uM

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
antibiotic G 418	increases activity, increases expression	2
Cyclic AMP	affects binding, increases abundance, increases activity	2
aristolochic acid I	increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetamides	increases activity, affects binding	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cisplatin	decreases expression	1
Deamino Arginine Vasopressin	affects binding, increases activity	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	increases methylation	1
Endocannabinoids	increases activity, increases reaction, affects binding	1

ChEMBL screening assays

309 unique, capped per target: 208 binding, 100 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1009070	Binding	Displacement of [3H]vasopressin from human V2 receptor expressed in CHO cells	Synthesis and structure-activity relationships of amide derivatives of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene)acetic acid as selective arginine vasopressin V2 receptor agonists. — *Bioorg Med Chem*
CHEMBL1015239	Functional	Agonist activity at human vasopressin V2 receptor expressed in HEK293 cells assessed as increase in intracellular cAMP level by CRE-luciferase reporter gene assay	New benzylureas as a novel series of potent, nonpeptidic vasopressin V2 receptor agonists. — *J Med Chem*
CHEMBL4325235	ADMET	Agonist activity at recombinant human V2 receptor expressed in CHOK1 cells assessed as increase in cAMP level measured after 30 mins by HTRF assay	Engineering a Potent, Long-Acting, and Periphery-Restricted Oxytocin Receptor Agonist with Anorexigenic and Body Weight Reducing Effects. — *J Med Chem*

Cellosaurus cell lines

8 cell lines: 4 spontaneously immortalized cell line, 2 transformed cell line, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0S8	ACTOne AVPR2	Transformed cell line	Female
CVCL_H509	CHO-K1/V2/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KU81	cAMP Hunter CHO-K1 AVPR2 Gs	Spontaneously immortalized cell line	Female
CVCL_KW36	PathHunter CHO-K1 AVPR2 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_KZ33	PathHunter HEK 293 AVPR2 beta-arrestin	Transformed cell line	Female
CVCL_KZ78	PathHunter U2OS AVPR2 Activated GPCR Internalization	Cancer cell line	Female
CVCL_YK31	U2OS AVPR2 cAMP-Nomad	Cancer cell line	Female
CVCL_ZI81	GeneBLAzer AVPR2-CRE-bla CHO-K1	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

7 trials:

NCT	Phase	Status	Title
NCT05190744	Phase 2	COMPLETED	Probenecid (PB) to Treat Hereditary Nephrogenic Diabetes Insipidus (NDI), ADPKD Treated With Tolvaptan, and Severely Polyuric Patients With Previous Lithium Administration
NCT06065852	Not specified	RECRUITING	National Registry of Rare Kidney Diseases
NCT00478335	Not specified	COMPLETED	Pharmacologic Treatment of Congenital Nephrogenic Diabetes Insipidus
NCT04939753	Not specified	COMPLETED	Nephrogenic Diabetes Insipidus During Prolonged Sevoflurane Sedation in the ICU: a Retrospective Analysis
NCT05307042	Not specified	UNKNOWN	Decline in Renal Concentration Ability in Lithium Treated Patients
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT06604975	Not specified	NOT_YET_RECRUITING	Arginin-stimulated Copeptin in Polyuria-polydipsia Syndrome in Children

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for AVPR2 across ~30M SureChEMBL compounds — explore on Sugi Predict.