AVPR1A

Summary

AVPR1A (arginine vasopressin receptor 1A, HGNC:895) is a protein-coding gene on chromosome 12q14.2, encoding Vasopressin V1a receptor (P37288). Receptor for arginine vasopressin.

The protein encoded by this gene acts as receptor for arginine vasopressin. This receptor belongs to the subfamily of G-protein coupled receptors which includes AVPR1B, V2R and OXT receptors. Its activity is mediated by G proteins which stimulate a phosphatidylinositol-calcium second messenger system. The receptor mediates cell contraction and proliferation, platelet aggregation, release of coagulation factor and glycogenolysis.

Source: NCBI Gene 552 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autism spectrum disorder (Limited, GenCC)
• GWAS associations: 8
• Clinical variants (ClinVar): 66 total — 2 pathogenic
• GTEx eGene: eQTL in 23 tissues, sQTL in 1 (q < 0.05)
• Drug target: yes — 8 curated mechanism-of-action drugs, 5 via a complex or family; 46 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 2 — Conivaptan Hydrochloride, Vasopressin Tannate
• Approved drugs acting on a complex or family including it: 4 — Desmopressin Acetate, Lypressin, Terlipressin, +1 more (Vasopressin receptor; Vasopressin V1 receptor)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.26 (unconstrained)
• MANE Select transcript: NM_000706
• Notable: 66 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:895
Approved symbol	AVPR1A
Name	arginine vasopressin receptor 1A
Location	12q14.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000166148
Ensembl biotype	protein_coding
OMIM	600821
Entrez	552

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

MANE Select: ENST00000299178

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

ENST00000299178, ENST00000550940, ENST00001143283

RefSeq mRNA: 1 — MANE Select: NM_000706 NM_000706

CCDS: CCDS8965

Canonical transcript exons

ENST00000299178 — 2 exons

Exon	Start	End
ENSE00001100233	63142759	63147645
ENSE00001100236	63149867	63151201

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 89.92.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0002 / max 161.3604, expressed in 218 samples.

Highest expression (Bgee): adrenal gland, adrenal gland cortex, adrenal cortex, popliteal artery, tibial artery.

Genetic regulation across tissues (GTEx eQTL / sQTL)

AVPR1A is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 23 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 24 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	sqtl	1.0e-13	+0.42	12:63305312:G:A
Thyroid	eqtl	2.3e-08	+0.26	12:63390485:T:C
Skin Sun Exposed Lower leg	eqtl	2.9e-08	-0.22	12:63306351:C:T
Artery Tibial	eqtl	7.7e-08	+0.20	12:63110056:T:A
Vagina	eqtl	7.5e-07	-0.45	12:63300952:C:A
Adrenal Gland	eqtl	1.0e-05	+0.23	12:63168162:G:A
Testis	eqtl	4.9e-05	-0.35	12:63124757:TTTC:T
Skin Not Sun Exposed Suprapubic	eqtl	1.1e-04	-0.17	12:63300952:C:A
Nerve Tibial	eqtl	1.7e-04	-0.20	12:63298354:G:C
Prostate	eqtl	2.8e-04	-0.30	12:63312142:T:G
Brain Caudate basal ganglia	eqtl	9.7e-04	+0.32	12:63310667:G:T
Stomach	eqtl	3.4e-03	-0.28	12:62739440:C:G
Heart Left Ventricle	eqtl	5.1e-03	-0.19	12:63439095:A:G
Adipose Subcutaneous	eqtl	5.6e-03	+0.20	12:63392649:C:T
Brain Nucleus accumbens basal ganglia	eqtl	6.6e-03	+0.40	12:63459816:C:T
Esophagus Muscularis	eqtl	8.8e-03	+0.18	12:63305389:AT:A
Heart Atrial Appendage	eqtl	1.1e-02	+0.20	12:63110056:T:A
Adipose Visceral Omentum	eqtl	1.3e-02	-0.14	12:63122455:C:T
Colon Transverse	eqtl	1.8e-02	-0.16	12:63291517:T:C
Esophagus Mucosa	eqtl	2.9e-02	-0.15	12:63477135:ATT:A

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
131839	0.5453	153
131838	0.2855	107
131837	0.0937	46
131836	0.0758	29

Top tissues by expression

showing 100 of 282 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left adrenal gland	UBERON:0001234	89.92	gold quality
left adrenal gland cortex	UBERON:0035825	89.36	gold quality
adrenal cortex	UBERON:0001235	88.62	gold quality
popliteal artery	UBERON:0002250	88.16	gold quality
tibial artery	UBERON:0007610	88.13	gold quality
adrenal gland	UBERON:0002369	87.17	gold quality
parietal pleura	UBERON:0002400	86.59	gold quality
right adrenal gland	UBERON:0001233	86.01	gold quality
skin of hip	UBERON:0001554	85.45	gold quality
right adrenal gland cortex	UBERON:0035827	85.39	gold quality
adipose tissue	UBERON:0001013	84.34	gold quality
adipose tissue of abdominal region	UBERON:0007808	83.53	gold quality
connective tissue	UBERON:0002384	83.16	gold quality
omental fat pad	UBERON:0010414	83.14	gold quality
peritoneum	UBERON:0002358	83.07	gold quality
subcutaneous adipose tissue	UBERON:0002190	82.83	gold quality
superficial temporal artery	UBERON:0001614	82.22	gold quality
seminal vesicle	UBERON:0000998	81.45	gold quality
liver	UBERON:0002107	81.13	gold quality
calcaneal tendon	UBERON:0003701	80.80	gold quality
pericardium	UBERON:0002407	80.29	gold quality
pleura	UBERON:0000977	79.73	gold quality
endometrium	UBERON:0001295	79.68	gold quality
right lobe of liver	UBERON:0001114	79.65	gold quality
smooth muscle tissue	UBERON:0001135	77.68	gold quality
synovial joint	UBERON:0002217	77.54	gold quality
hindlimb stylopod muscle	UBERON:0004252	77.39	gold quality
gall bladder	UBERON:0002110	77.18	gold quality
myometrium	UBERON:0001296	76.77	gold quality
uterus	UBERON:0000995	76.51	gold quality
left uterine tube	UBERON:0001303	76.46	gold quality
aorta	UBERON:0000947	75.83	gold quality
body of uterus	UBERON:0009853	75.51	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.16	gold quality
tendon	UBERON:0000043	74.72	gold quality
left lobe of thyroid gland	UBERON:0001120	74.59	gold quality
thyroid gland	UBERON:0002046	74.54	gold quality
thoracic mammary gland	UBERON:0005200	74.45	gold quality
mammary gland	UBERON:0001911	74.39	gold quality
cauda epididymis	UBERON:0004360	73.68	gold quality
right lobe of thyroid gland	UBERON:0001119	73.08	gold quality
endocervix	UBERON:0000458	72.44	gold quality
cortical plate	UBERON:0005343	72.32	gold quality
upper leg skin	UBERON:0004262	71.75	gold quality
vena cava	UBERON:0004087	71.55	gold quality
colonic epithelium	UBERON:0000397	71.28	gold quality
mammary duct	UBERON:0001765	71.10	gold quality
urinary bladder	UBERON:0001255	70.58	gold quality
visceral pleura	UBERON:0002401	70.52	gold quality
left coronary artery	UBERON:0001626	69.35	gold quality
epithelium of mammary gland	UBERON:0003244	69.01	gold quality
ectocervix	UBERON:0012249	68.77	gold quality
coronary artery	UBERON:0001621	68.59	gold quality
bronchial epithelial cell	CL:0002328	68.18	gold quality
adult mammalian kidney	UBERON:0000082	68.07	gold quality
penis	UBERON:0000989	67.88	gold quality
layer of synovial tissue	UBERON:0007616	67.73	gold quality
urethra	UBERON:0000057	67.57	gold quality
monocyte	CL:0000576	67.54	gold quality
muscle of leg	UBERON:0001383	67.52	gold quality
mammalian vulva	UBERON:0000997	67.46	gold quality
mononuclear cell	CL:0000842	67.25	gold quality
right coronary artery	UBERON:0001625	67.23	gold quality
female reproductive system	UBERON:0000474	67.08	gold quality
mucosa of stomach	UBERON:0001199	66.98	gold quality
leukocyte	CL:0000738	66.55	gold quality
gastrocnemius	UBERON:0001388	66.49	gold quality
uterine cervix	UBERON:0000002	65.62	gold quality
buccal mucosa cell	CL:0002336	65.27	gold quality
skeletal muscle organ	UBERON:0014892	65.16	gold quality
muscle organ	UBERON:0001630	65.15	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	65.15	gold quality
kidney	UBERON:0002113	65.06	gold quality
epithelium of bronchus	UBERON:0002031	65.05	gold quality
fallopian tube	UBERON:0003889	65.05	gold quality
decidua	UBERON:0002450	64.91	silver quality
lower esophagus muscularis layer	UBERON:0035833	64.91	gold quality
heart left ventricle	UBERON:0002084	64.89	gold quality
lower esophagus	UBERON:0013473	64.86	gold quality
cardiac ventricle	UBERON:0002082	64.81	gold quality
bronchus	UBERON:0002185	64.76	gold quality
epithelial cell of pancreas	CL:0000083	64.42	silver quality
lymph node	UBERON:0000029	64.32	gold quality
tendon of biceps brachii	UBERON:0008188	64.24	gold quality
vagina	UBERON:0000996	64.12	gold quality
zone of skin	UBERON:0000014	63.62	gold quality
skin of leg	UBERON:0001511	63.60	gold quality
muscle layer of sigmoid colon	UBERON:0035805	63.44	gold quality
tibialis anterior	UBERON:0001385	63.11	silver quality
heart right ventricle	UBERON:0002080	62.77	silver quality
heart	UBERON:0000948	62.39	gold quality
deltoid	UBERON:0001476	62.30	silver quality
tibial nerve	UBERON:0001323	62.24	gold quality
lower lobe of lung	UBERON:0008949	61.84	silver quality
vermiform appendix	UBERON:0001154	61.80	gold quality
oviduct epithelium	UBERON:0004804	61.68	silver quality
prostate gland	UBERON:0002367	61.34	gold quality
fundus of stomach	UBERON:0001160	61.30	gold quality
biceps brachii	UBERON:0001507	61.06	silver quality
skin of abdomen	UBERON:0001416	60.99	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.13

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 75 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Adrenal gland	tissue	53.5
Liver	tissue	19.5
Adipose tissue	tissue	16.2
Olfactory bulb	tissue	11.6
Smooth muscle	tissue	11.4
Endometrium 1	tissue	10.2
Cerebral cortex	tissue	9.8
Thyroid gland	tissue	9.8
Insular cortex	tissue	9.8
Retrosplenial cortex	tissue	9.5
Amygdala	tissue	9.3
Retrosplenial and cingulate cortex	tissue	9.1
Temporal cortex	tissue	8.9
Cervix	tissue	8.5
Hippocampal formation	tissue	8.5
Entorhinal cortex	tissue	8.5
Prefrontal cortex	tissue	8.2
Cerebellum	tissue	8.0
Occipital cortex	tissue	7.8
Motor cortex	tissue	7.3
Basal ganglia	tissue	7.2
Ventral forebrain	tissue	6.8
Somatosensory cortex	tissue	6.7
Septum	tissue	6.4
Periaqueductal gray	tissue	6.3
Corpus callosum	tissue	6.1
Putamen	tissue	5.7
Gallbladder	tissue	5.7
Hypothalamus	tissue	5.5
Substantia nigra	tissue	4.8
Midbrain	tissue	4.7
Medulla oblongata	tissue	4.6
Spinal cord	tissue	4.5
Kidney	tissue	4.3
Thalamus	tissue	4.1
Seminal vesicle	tissue	4.0
Superior colliculi	tissue	3.7
Pons	tissue	3.6
Tongue	tissue	3.2
Choroid plexus	tissue	3.1
Fallopian tube	tissue	3.0
Esophagus	tissue	2.8
Vagina	tissue	2.2
Pancreas	tissue	2.2
Prostate	tissue	2.2
Parathyroid gland	tissue	2.0
Urinary bladder	tissue	2.0
Breast	tissue	1.8
Skeletal muscle	tissue	1.8
Heart muscle	tissue	1.6
Appendix	tissue	1.4
Retina	tissue	1.3
Thymus	tissue	1.3
Lymph node	tissue	1.1
Rectum	tissue	1.1
Epididymis	tissue	1.1
Ovary	tissue	1.0
Salivary gland	tissue	1.0
Colon	tissue	1.0
Skin 1	tissue	0.9

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Blood vessel (29.9), Subiculum (7.9), Ventral hippocampus (6.9), White matter (6.1), Dorsal hippocampus (6.0).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR

miRNA regulators (miRDB)

Targeting AVPR1A by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 148 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-551B-5P	99.96	71.28	3493

Functional genomics

gnomAD constraint: pLI 1.28e-10, LOEUF 1.26, missense Z 0.511 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000299178 — one region, missense o/e 0.99.

Literature-anchored findings (GeneRIF, showing 40)

• transmission disequilibrium testing of polymorphism in autism (PMID:12082568)
• residue Phe225, located in transmembrane domain V, directly participates in the binding of the V1a-selective nonpeptide antagonist SR49059 (PMID:12869559)
• In the wildtype V1aR, Arg46 constrains the inactive conformation of the receptor; on binding AVP this constraint is alleviated, promoting the transition to active V1aR (PMID:14622255)
• examination of interaction with beta-arrestin and trafficking patterns by heterodimerization with V2 vasopressin receptor (PMID:14757828)
• AVPR1a’s exons were screened in 125 independent autistic probands. 2 promoter polymorphisms were typed in 65 autism-affected sibling-pair families. Linkage & linkage disequilibrium were seen in a subset with relatively less severe language impairment. (PMID:15098001)
• Glu54 is critical for arginine vasopressin binding by V1aR. (PMID:15994199)
• Association between AVPR1a and SLC6A4 reflects the social communication, courtship, and spiritual facets of the dancing phenotype. (PMID:16205790)
• molecular dynamics analysis of mechanism of desmopressin binding in vasopressin V2 receptor versus vasopressin V1a and oxytocin receptors (PMID:16333859)
• This study confirms an association between the AVPR1a gene and autism spectrum disorders and identifies a third microsatellite associated with autism spectrum disorders as well as haplotypes consisting of all three markers. (PMID:16520824)
• analysis of a pharmacological chaperone ligand that acts on misfolded mutant V(1a) receptors (PMID:16565083)
• These results suggest that the four SNPs in the promoter region of the V1aR gene may not be useful as genetic markers for platelet aggregation heterogeneity. (PMID:16721832)
• There is an association of the V1aR SNP-6951 with essential hypertension in nonobese individuals. (PMID:17653244)
• This gene contributes to social bonding in lower animals and in human behavior, suggesting a common evolutionary mechanism. (PMID:17696996)
• study is the first to report associations between AVPR1A and OXTR genetic variation with life history traits in humans (PMID:17939166)
• human amygdala function is strongly associated with genetic variation in AVPR1A. (PMID:18490926)
• AVPR1a has been linked to eating behaviour in both clinical and non-clinical groups, reflecting the social and ritualistic side of eating behaviour.[REVIEW] (PMID:18655900)
• report an association between one of the human AVPR1A repeat polymorphisms (RS3) and traits reflecting pair-bonding behavior in men (PMID:18765804)
• Genetic variation of the human arginine vasopressin 1A (AVPR1A) gene is associated with uncoupling of the usual direct relation between glucose and triglycerides and an increased prevalence of diabetes in subjects with a high fat intake or who are obese (PMID:19056558)
• A role of the AVPR1a gene in contributing to the prepulse inhibition response to auditory stimuli. (PMID:19195791)
• The amplified region was polymorphic in length in all species investigated. This region could be a marker to further survey functional difference between and within species. (PMID:19350216)
• AVPR1A haplotype AVR+RS1 further suggested a positive association with creative functions in music using haplotype-based association test HBAT. (PMID:19461995)
• polymorphism rs1042615 of the V1a receptor altered body mass index and diastolic pressure in middle-aged and older men and the training-induced responses of DBP and low-density lipoprotein cholesterol, whereas women did not show any of these responses (PMID:20142561)
• Possible roles of oxytocin receptor and vasopressin-1alpha receptor in the pathomechanism of dysperistalsis and dysmenorrhea in patients with adenomyosis uteri. (PMID:20413116)
• The results of this study found a statistically significant association between microsatellites and Korean autism spectrum disorders. (PMID:20452058)
• Evidence provided for a possible association between these SNPs and the phenotype of autism spectrum disorders. (PMID:20546835)
• The importance of subtle, quantitative measures of endophenotype are emphasized in this review of the neural distribution of vasopressin 1a receptor (V1aR), a recent focus for studies of social behavior. (PMID:20889332)
• A positive association between the AVPR1A haplotype (RS1 and AVR) and active current listening to music (permuted P=0.0019) was observed. (PMID:21307861)
• report finds an association between AVPR1A and the risk for DUD. (PMID:21514569)
• Our results demonstrate a role for V1A-mediated signaling in the development of heart failure. (PMID:21747049)
• AVPR1A variant associated with preschoolers’ lower altruistic behavior. (PMID:21980412)
• data suggest a possible interrelation between AVR and RS3 gene variants of the AVPR1A gene and impulsive aggression in patients with borderline personality disorder (PMID:22008661)
• In a sample of European mothers, a microsatellite variant RS3 of the vasopressin 1a receptor gene is associated with maternal sensitivity; this association is strongest under conditions of high maternal early adversity. (PMID:22288734)
• analysis of AVPR1A and SLC6A4 polymorphisms in choral singers and non-musicians (PMID:22384070)
• greater perceived threat predicted lower commitment to civic duty for individuals with one or two short alleles for AVPR1a rs1, but not for individuals with only long alleles (PMID:22457427)
• Human maternal behaviour is associated with arginine vasopressin receptor 1A gene (PMID:22764113)
• There was moderate statistical evidence for interactions shoulder pain phenotypes between AVPR1A and depressive symptoms, pain catastrophizing, or kinesiophobia (PMID:24373571)
• Early caregiving combined with genetic liability along the axis of vasopressin-oxytocin gene pathways: G x E contributions to PTSD. (PMID:24618689)
• Men, but not women, with high levels of poststressor AVP and the 320 allele of the RS1 polymorphism reported more poststressor anger than noncarriers. (PMID:24660771)
• Gene-level tests showed that DRD2 was associated with vocabulary, ASPM with vocabulary and reading decoding, and AVPR1A with all three endophenotypes. (PMID:24849541)
• humanized AVPR1A mice displayed increased reciprocal social interactions compared with wild-type animals. (PMID:24924430)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	avpr1ab	ENSDARG00000045788
danio_rerio	avpr1aa	ENSDARG00000077083
mus_musculus	Avpr1a	ENSMUSG00000020123
rattus_norvegicus	Avpr1a	ENSRNOG00000004400

Paralogs (16): NPFFR2 (ENSG00000056291), GNRHR (ENSG00000109163), CCKBR (ENSG00000110148), HCRTR1 (ENSG00000121764), AVPR2 (ENSG00000126895), GALR3 (ENSG00000128310), HCRTR2 (ENSG00000137252), NPFFR1 (ENSG00000148734), CCKAR (ENSG00000163394), GALR1 (ENSG00000166573), GPR22 (ENSG00000172209), GPR150 (ENSG00000178015), OXTR (ENSG00000180914), FFAR4 (ENSG00000186188), QRFPR (ENSG00000186867), AVPR1B (ENSG00000198049)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1859216) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 18 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased anxiety-related response	2
abnormal vasoconstriction	1
abnormal adrenal gland morphology	1
abnormal social investigation	1
hypotension	1
abnormal heart rate	1
poor circulation	1
abnormal B cell differentiation	1
abnormal immunoglobulin level	1
abnormal baroreceptor physiology	1
abnormal circulating corticosterone level	1
decreased circulating atrial natriuretic factor	1
increased B-1a cell number	1
abnormal long-term spatial reference memory	1
decreased IgG2b level	1
increased IgG2a level	1
decreased prepulse inhibition	1
decreased grip strength	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
Caenorhabditis elegans	Q9U320	35.6%	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
LINC03238	ncRNA	105369797
LINC03056	ncRNA	124902951
DPY19L2	protein-coding	283417

Protein

Protein identifiers

Vasopressin V1a receptor — P37288 (reviewed: P37288)

Alternative names: AVPR V1a, Antidiuretic hormone receptor 1a, Vascular/hepatic-type arginine vasopressin receptor

All UniProt accessions (3): F8VW98, P37288, X5D2B0

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for arginine vasopressin. The activity of this receptor is mediated by G proteins which activate a phosphatidyl-inositol-calcium second messenger system. Has been involved in social behaviors, including affiliation and attachment.

Subcellular location. Cell membrane.

Miscellaneous. Differences in regional receptor expression in the brain as well as differences in social behavior may result from a highly variable repetitive sequence in the 5’ flanking region of AVPR1A. One such allelic variant has been linked to autism.

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

RefSeq proteins (1): NP_000697* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR001224	Vprs_V1A_rcpt	Family
IPR001817	Vasoprsn_rcpt	Family
IPR015076	V1R_C	Domain
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001, PF08983

UniProt features (26 total): topological domain 8, transmembrane region 7, region of interest 2, lipid moiety-binding region 2, glycosylation site 2, chain 1, compositionally biased region 1, modified residue 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

5 structures by resolution:

PDB	Title	Method	Resolution (Å)
1YTV	Maltose-binding protein fusion to a C-terminal fragment of the V1a vasopressin receptor	X-RAY DIFFRACTION	1.8
9UWL	Cryo-EM structure of human V1aR bound with SRX246 at a resolution of 2.6 angstrom	ELECTRON MICROSCOPY	2.6
9UWI	Cryo-EM structure of human V1aR bound with atosiban at a resolution of 2.8 angstrom	ELECTRON MICROSCOPY	2.8
9XB1	Cryo-EM structure of human V1aR in apo state at a resolution of 2.8 angstrom	ELECTRON MICROSCOPY	2.8
9UWJ	Cryo-EM structure of human V1aR bound with balovaptan at a resolution of 3.0 angstrom	ELECTRON MICROSCOPY	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P37288-F1	74.11	0.33

Human Protein Atlas

Protein class: G-protein coupled receptors, GPCRs excl olfactory receptors, Predicted membrane proteins, GPCRHMM predicted membrane proteins, Plasma proteins, FDA approved drug targets, Biotech drugs, Small molecule drugs

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 (3)

Type	Positions
Phosphoserine	404
S-palmitoyl cysteine	365, 366

Disulfide bonds (1)

Type	Positions
Disulfide bond	124–203

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	27, 196

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 12; 4 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

12 pathways:

ID	Pathway	Evidence
R-HSA-5619099	Defective AVP does not bind AVPR1A,B and causes neurohypophyseal diabetes insipidus (NDI) ⚕	—
R-HSA-1643685	Disease ⚕	—
R-HSA-5619115	Disorders of transmembrane transporters ⚕	—
R-HSA-5619102	SLC transporter disorders ⚕	—
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)	—
R-HSA-416476	G alpha (q) signalling events	—
R-HSA-388396	GPCR downstream signalling	—
R-HSA-500792	GPCR ligand binding	—
R-HSA-375276	Peptide ligand-binding receptors	—
R-HSA-162582	Signal Transduction	—
R-HSA-372790	Signaling by GPCR	—
R-HSA-388479	Vasopressin-like receptors	—

MSigDB gene sets: 304 (showing top): GOBP_GLUTAMATE_SECRETION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_REGULATION_OF_ORGANIC_ACID_TRANSPORT, GOBP_RESPONSE_TO_ACID_CHEMICAL, GOBP_RESPONSE_TO_CORTICOSTEROID, MODULE_64, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_GROWTH, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE, GOBP_NEGATIVE_REGULATION_OF_NERVOUS_SYSTEM_PROCESS, GOBP_CELLULAR_RESPONSE_TO_ACID_CHEMICAL, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS

GO Biological Process (29): regulation of systemic arterial blood pressure by vasopressin (GO:0001992), maternal aggressive behavior (GO:0002125), positive regulation of systemic arterial blood pressure (GO:0003084), generation of precursor metabolites and energy (GO:0006091), G protein-coupled receptor signaling pathway (GO:0007186), positive regulation of cytosolic calcium ion concentration (GO:0007204), negative regulation of female receptivity (GO:0007621), grooming behavior (GO:0007625), blood circulation (GO:0008015), positive regulation of cell population proliferation (GO:0008284), positive regulation of heart rate (GO:0010460), positive regulation of glutamate secretion (GO:0014049), myotube differentiation (GO:0014902), calcium-mediated signaling (GO:0019722), telencephalon development (GO:0021537), positive regulation of cell growth (GO:0030307), positive regulation of prostaglandin biosynthetic process (GO:0031394), cellular response to hormone stimulus (GO:0032870), social behavior (GO:0035176), cellular response to water deprivation (GO:0042631), maternal behavior (GO:0042711), sperm ejaculation (GO:0042713), positive regulation of vasoconstriction (GO:0045907), response to corticosterone (GO:0051412), negative regulation of transmission of nerve impulse (GO:0051970), transport across blood-brain barrier (GO:0150104), signal transduction (GO:0007165), regulation of blood pressure (GO:0008217), positive regulation of blood pressure (GO:0045777)

GO Molecular Function (7): vasopressin receptor activity (GO:0005000), protein kinase C binding (GO:0005080), peptide hormone binding (GO:0017046), V1A vasopressin receptor binding (GO:0031894), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515), G protein-coupled peptide receptor activity (GO:0008528)

GO Cellular Component (4): endosome (GO:0005768), plasma membrane (GO:0005886), endocytic vesicle (GO:0030139), membrane (GO:0016020)

Reactome top-level categories

9 top-level categories:

Category	Pathways
Signaling by GPCR	2
Peptide ligand-binding receptors	1
GPCR downstream signalling	1
SLC transporter disorders	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1
Disorders of transmembrane transporters	1
Disease	1

GO top-level categories

51 GO namespaces:

Category	Terms
G protein-coupled receptor activity	2
behavior	2
positive regulation of cellular process	2
cytoplasmic vesicle	2
regulation of systemic arterial blood pressure by hormone	1
aggressive behavior	1
regulation of systemic arterial blood pressure	1
positive regulation of blood pressure	1
metabolic process	1
signal transduction	1
regulation of biological quality	1
regulation of female receptivity	1
circulatory system process	1
cell population proliferation	1
regulation of cell population proliferation	1
regulation of heart rate	1
positive regulation of heart contraction	1
glutamate secretion	1
regulation of glutamate secretion	1
positive regulation of organic acid transport	1
positive regulation of amino acid transport	1
positive regulation of secretion by cell	1
striated muscle cell differentiation	1
intracellular signaling cassette	1
forebrain development	1
animal gross anatomical part developmental process	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
prostaglandin biosynthetic process	1
regulation of prostaglandin biosynthetic process	1
positive regulation of unsaturated fatty acid biosynthetic process	1
response to hormone	1
cellular response to chemical stimulus	1
cellular response to endogenous stimulus	1
biological process involved in intraspecies interaction between organisms	1
response to water deprivation	1
cellular response to stress	1
cellular response to water stimulus	1
G protein-coupled peptide receptor activity	1
protein kinase binding	1
hormone binding	1
vasopressin receptor binding	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
binding	1
peptide receptor activity	1
endomembrane system	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 41 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
G protein-coupled receptor signaling pathway	BP	direct assay
endocytic vesicle	CC	direct assay
endosome	CC	direct assay
plasma membrane	CC	direct assay
vasopressin receptor activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 758 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AVPR1A	OXT	P01178	871
AVPR1A	AVP	P01185	823
AVPR1A	POMC	P01189	683
AVPR1A	GIPR	P48546	673
AVPR1A	ESR1	P03372	527
AVPR1A	ADRA1D	P25100	527
AVPR1A	MAOA	P21397	518
AVPR1A	CRHR1	P34998	515
AVPR1A	CRH	P06850	514
AVPR1A	GIP	P09681	500
AVPR1A	CRHR2	Q13324	500
AVPR1A	REN	P00797	493
AVPR1A	CD38	P28907	486
AVPR1A	TPH2	Q8IWU9	479
AVPR1A	AQP2	P41181	475

IntAct

Human interaction partners of AVPR1A in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

7 partners by confidence:

Partner	Interaction type	MIscore	Records
ACKR3	proximity	0.570	5
CXCR4	proximity	0.420	1
AVP	physical association	0.400	1
RAMP1	physical association	0.400	1
RAMP2	physical association	0.400	1
RAMP3	physical association	0.400	1
VIP	physical association	0.400	1

BioGRID (4 interactions; top human partners by supporting records): GRK5 (Affinity Capture-Western), PARP16 (Proximity Label-MS), PRKCA (Affinity Capture-Western), PSMD14 (Affinity Capture-MS)

SIGNOR signaling

showing 11 of 12 signaling interactions:

A	Effect	B	Mechanism
AVPR1A	“up-regulates activity”	GNAS	binding
AVPR1A	“up-regulates activity”	GNAL	binding
AVPR1A	“up-regulates activity”	GNAQ	binding
vasopressin	“up-regulates activity”	AVPR1A	“chemical activation”
AVPR1A	“up-regulates activity”	GNAI1	binding
AVPR1A	“up-regulates activity”	GNAI2	binding
AVPR1A	“up-regulates activity”	GNAZ	binding
AVPR1A	“up-regulates activity”	GNA11	binding
AVPR1A	“up-regulates activity”	GNA14	binding
AVPR1A	“up-regulates activity”	GNAO1	binding
AVPR1A	“up-regulates activity”	GNA15	binding

Protein complexes (CORUM) (5)

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

5 complexes by size:

Complex	Subunits	Members
★ ACKR3-ADRA1A-AVPR1A-CXCR4 complex	4	ACKR3, ADRA1A, AVPR1A, CXCR4
★ ACKR3-AVPR1A-CXCR4 complex	3	ACKR3, AVPR1A, CXCR4
★ ACKR3-ADRA1A-AVPR1A complex	3	ACKR3, ADRA1A, AVPR1A
★ AVPR1A-OXTR complex	2	OXTR, AVPR1A
★ Vasopressin V1a receptor	1	AVPR1A

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
AVP	receptor	Signaling by Vasopressin
OXT	receptor	Signaling by Oxytocin

Disease & clinical

Genetic variants

Variant evidence for AVPR1A: 66 ClinVar records (2 pathogenic / likely pathogenic); 8 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	53
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (2)

Showing all 2 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
2685437	GRCh37/hg19 12q14.1-15(chr12:61755618-70035424)x1	Pathogenic	criteria provided, single submitter	1
150076	GRCh38/hg38 12q14.1-14.3(chr12:60907151-66568077)x1	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore AVPR1A’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; 19 predictions of 118):

Position(s)	Effect	Δscore	Sites
12:63149844	donor_gain	1.0000
12:63147650	acceptor_gain	0.9900
12:63149865–63149866	donor_loss	0.9900	4
12:63149866	donor_loss	0.9700
12:63147646–63147647	acceptor_loss	0.9600	6
12:63147657–63147659	acceptor_loss	0.9600	2
12:63149865	donor_loss	0.9200
12:63149896	donor_gain	0.9100
12:63147648	acceptor_loss	0.8300
12:63144693	acceptor_gain	0.6600

AlphaMissense

814 missense substitutions predicted likely pathogenic (of 2,761 scored), across 217 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
D97	8	0.981	0.989
F117	8	0.963	0.996
D148	8	0.958	0.979
F189	8	0.958	0.998
N69	8	0.954	0.991
F207	8	0.919	0.991
F89	8	0.904	0.969
F225	8	0.889	0.962
D202	8	0.801	0.938
C124	7	0.990	0.996
C203	7	0.989	0.995
M292	7	0.934	0.965
F136	7	0.933	0.985
F307	7	0.933	0.986
N344	7	0.903	0.982
W175	7	0.898	0.994
H92	7	0.895	0.981
W111	7	0.886	0.976
W316	7	0.883	0.966
F351	7	0.882	0.972

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Kidney Chromophobe)

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

3 prognostic cancer types:

Cancer	Prognostic	p-value
Skin Cutaneous Melanoma (TCGA)	unfavorable	4.02e-06
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	4.85e-05
Kidney Renal Clear Cell Carcinoma (validation)	favorable	8.06e-05

Disease associations

OMIM: gene MIM:600821 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
autism spectrum disorder	Limited	Autosomal dominant

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
autism spectrum disorder	Disputed	UD

Mondo (1): autism spectrum disorder (MONDO:0005258)

GWAS associations

8 associations:

Study	Trait	p-value
GCST007565_119	Morning person	4e-18
GCST007576_343	Chronotype	4e-18
GCST007576_140	Chronotype	1e-17
GCST007565_90	Morning person	2e-16
GCST006190_87	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	3e-8
GCST006190_91	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	5e-8
GCST006134_7	Hippocampal volume	7e-6
GCST008114_8	Type 2 diabetes	8e-6

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0005035	hippocampal volume
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0008328	chronotype measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL1889 (SINGLE PROTEIN), CHEMBL2111456 (PROTEIN FAMILY), CHEMBL2363078 (PROTEIN FAMILY), CHEMBL4523980 (SELECTIVITY GROUP)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the AVPR1A 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
VASOPRESSIN TANNATE	Protein	4
BALOVAPTAN	Small molecule	3
PECAVAPTAN	Small molecule	2
RELCOVAPTAN	Small molecule	2
SELEPRESSIN	Protein	2
SRX246	Small molecule	2
SRX251	Unknown	1

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 AVPR1A — the drug acts on the assembly or class, not necessarily on this subunit alone.

5 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
DESMOPRESSIN ACETATE	Vasopressin receptor	3	4
LYPRESSIN	Vasopressin receptor	3	4
TERLIPRESSIN	Vasopressin V1 receptor	2	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: 942,843 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

46 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1755	CONIVAPTAN	4	3,171
CHEMBL1112	ARIPIPRAZOLE	4	24,497
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
CHEMBL178	DAUNORUBICIN	4	205,873
CHEMBL1429	DESMOPRESSIN	4	125
CHEMBL411	DIETHYLSTILBESTROL	4	373,838
CHEMBL56337	EPALRESTAT	4	111
CHEMBL46516	FLUSPIRILENE	4	41,280
CHEMBL1201304	INDOCYANINE GREEN ACID FORM	4	7,331
CHEMBL420762	MOZAVAPTAN	4	254
CHEMBL1401	NITAZOXANIDE	4	9,637
CHEMBL395429	OXYTOCIN	4	42,099
CHEMBL1423	PIMOZIDE	4	17,468
CHEMBL1171837	PONATINIB	4	9,435
CHEMBL1201303	PYRVINIUM	4	1,837
CHEMBL374478	RIFAMPIN	4	94,660
CHEMBL1617	RIFAXIMIN	4
CHEMBL111	RIMONABANT	4
CHEMBL163	RITONAVIR	4
CHEMBL114	SAQUINAVIR	4
CHEMBL76370	TEGASEROD	4
CHEMBL2135460	TERLIPRESSIN	4
CHEMBL344159	TOLVAPTAN	4
CHEMBL373742	VASOPRESSIN	4
CHEMBL4297183	BALOVAPTAN	3
CHEMBL41286	DIACEREIN	3
CHEMBL49429	LIXIVAPTAN	3
CHEMBL1254025	NOLASIBAN	3
CHEMBL2103773	OTILONIUM BROMIDE	3
CHEMBL276711	SEMAXANIB	3
CHEMBL4594444	PECAVAPTAN	2
CHEMBL419667	RELCOVAPTAN	2
CHEMBL1817709	SELEPRESSIN	2
CHEMBL244243	SRX246	2
CHEMBL1182210	BENZETHONIUM	2
CHEMBL1187011	DOMIPHEN	2
CHEMBL151	LUTEOLIN	2
CHEMBL582857	NELIVAPTAN	2
CHEMBL1819440	ORNIPRESSIN	2
CHEMBL13828	OXATOMIDE	2
CHEMBL285802	ZOTEPINE	2
CHEMBL3416885	RO-5028442	1

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 (66 total), top 25:

Ligand	Action	Affinity	Parameter
[125I]OH-LVA	Antagonist	10.4	pKd
[3H]AVP (human, mouse, rat)	Full agonist	10.2	pKd
[125I]3-N3-Phpa-LVA	Antagonist	9.9	pKd
3-N3-Phpa-LVA	Antagonist	9.6	pKi
SRX246	Antagonist	9.52	pKi
YM 218	Antagonist	9.5	pKi
vasopressin	Full agonist	9.3	pKi
relcovaptan	Antagonist	9.3	pKi
OH-LVA	Antagonist	9.3	pKi
d(CH2)5[Tyr(Me)2,Thr4,Phe(3125I,4N3)-NH29]OVT	Antagonist	9.3	pKd
d[D-Phe2]AVP	Full agonist	9.2	pKi
YM 471	Antagonist	9.2	pKi
[Phaa1,D-Tyr2,Val4,Arg6,Arg-NH29]AVP	Antagonist	9.2	pKi
d(CH2)5[Tyr(Me)2]AVP	Antagonist	9.2	pKi
[Phaa1,D-Tyr(Et)2,Lys6,des-Gly9]AVP	Antagonist	9.1	pKi
[Phaa1,D-Tyr(Me)2,Arg6,Tyr-NH29]AVP	Antagonist	9.1	pKi
[tBaa1,D-Tyr(Et)2,Val4,Lys6,Arg-NH28,des-Gly9]AVP	Antagonist	9.1	pKi
d(CH2)5[D-Tyr(Et)2,Val4,Tyr-NH29]AVP	Antagonist	9.1	pKi
d(CH2)5[Tyr(Et)2,Val4,des-Gly9]AVP	Antagonist	9.1	pKi
d[Pen1,Tyr(Me)2]AVP	Antagonist	9.1	pKi
d(CH2)5[Tyr(Me)2,Thr4,Tyr(3125I)-NH29]OVT	Antagonist	9.0	pKd
[3H]d(CH2)5[Tyr(Me)2]AVP	Antagonist	9.0	pKd
d(CH2)5[Tyr(Me)2,Arg8]VP	Antagonist	9.0	pKi
Ro5028442	Antagonist	9.0	pKi
d(CH2)5[Tyr(Me)2,Thr4,Phe(3I,4N3)-NH29]OVT	Antagonist	8.9	pKi

Binding affinities (BindingDB)

1612 measured of 1916 human assays (1922 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL4074974	EC50	0.005 nM
CHEMBL4097965	EC50	0.005 nM
CHEMBL3353956	EC50	0.007 nM
CHEMBL4101658	EC50	0.007 nM
CHEMBL4070222	EC50	0.007 nM
CHEMBL4093631	EC50	0.007 nM
CHEMBL4066368	EC50	0.007 nM
CHEMBL3276119	EC50	0.007 nM
CHEMBL4104080	EC50	0.008 nM
CHEMBL439044	EC50	0.009 nM
CHEMBL4074335	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
CHEMBL4102192	EC50	0.01 nM
CHEMBL4093931	EC50	0.013 nM
CHEMBL3277916	EC50	0.013 nM
CHEMBL4095930	EC50	0.013 nM
CHEMBL4084223	EC50	0.014 nM
CHEMBL4078856	EC50	0.015 nM
CHEMBL3354592	EC50	0.02 nM
CHEMBL3354571	EC50	0.02 nM
CHEMBL3353955	EC50	0.02 nM
CHEMBL4096848	EC50	0.021 nM
CHEMBL3354594	EC50	0.025 nM
CHEMBL4065273	EC50	0.027 nM
CHEMBL4101771	EC50	0.027 nM
CHEMBL4474284	EC50	0.028 nM
CHEMBL3353942	EC50	0.03 nM
CHEMBL4094454	EC50	0.03 nM
CHEMBL4092971	EC50	0.031 nM
CHEMBL4583231	EC50	0.031 nM
HO-LVA	KI	0.032 nM
CHEMBL1807272	KI	0.0372 nM
CHEMBL1807267	KI	0.0398 nM
CHEMBL3354597	EC50	0.04 nM
CHEMBL3354595	EC50	0.04 nM
CHEMBL3354588	EC50	0.04 nM
CHEMBL6087371	KI	0.04 nM
CHEMBL4080341	EC50	0.042 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

ChEMBL bioactivities

2117 potent at pChembl≥5 of 2183 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.49	Ki	0.032	nM	CHEMBL394602
10.47	EC50	0.034	nM	CHEMBL4094454
10.44	Ki	0.036	nM	CHEMBL394602
10.43	Ki	0.03715	nM	CHEMBL1807272
10.40	Ki	0.04	nM	CHEMBL6087371
10.40	Ki	0.03981	nM	CHEMBL1807267
10.30	Ki	0.05	nM	CHEMBL1083094
10.22	Ki	0.06	nM	CHEMBL1084823
10.20	Ki	0.063	nM	CHEMBL6027125
10.15	Ki	0.07	nM	CHEMBL540192
10.10	Ki	0.08	nM	CHEMBL269012
10.05	Ki	0.09	nM	CHEMBL1161978
10.02	Ki	0.0955	nM	CHEMBL1807270
10.00	Ki	0.1	nM	CHEMBL5549819
10.00	Ki	0.1	nM	CHEMBL5573173
10.00	Ki	0.1	nM	CHEMBL5565555
10.00	Ki	0.1	nM	CHEMBL6150478
10.00	Ki	0.1	nM	CHEMBL1084008
9.92	EC50	0.12	nM	CHEMBL4094454
9.90	EC50	0.1259	nM	CHEMBL3342789
9.90	EC50	0.1259	nM	CHEMBL4165132
9.89	Ki	0.13	nM	CHEMBL6101825
9.85	Ki	0.14	nM	CHEMBL6108956
9.85	EC50	0.1413	nM	CHEMBL1819540
9.85	EC50	0.14	nM	CHEMBL1819540
9.82	Ki	0.15	nM	ATOSIBAN
9.82	EC50	0.15	nM	CHEMBL1819441
9.81	EC50	0.1549	nM	CHEMBL1819441
9.80	EC50	0.1585	nM	CHEMBL3342790
9.80	EC50	0.1585	nM	CHEMBL4173036
9.77	Ki	0.17	nM	CHEMBL412210
9.77	Ki	0.17	nM	CHEMBL430272
9.77	EC50	0.17	nM	CHEMBL4096848
9.77	Ki	0.17	nM	CHEMBL6108984
9.74	EC50	0.18	nM	OXYTOCIN
9.74	Ki	0.182	nM	CHEMBL1807266
9.72	EC50	0.19	nM	OXYTOCIN
9.72	Ki	0.19	nM	RELCOVAPTAN
9.70	Ki	0.2	nM	CHEMBL4281963
9.70	Ki	0.2	nM	CHEMBL397179
9.70	Ki	0.2	nM	CHEMBL5575561
9.70	Ki	0.2	nM	CHEMBL5575281
9.70	Ki	0.2	nM	CHEMBL5563095
9.70	Ki	0.2	nM	CHEMBL5569717
9.70	Ki	0.2	nM	CHEMBL5571184
9.70	Ki	0.2	nM	CHEMBL5542954
9.70	Ki	0.2	nM	CHEMBL5574628
9.70	Ki	0.2	nM	CHEMBL5575102
9.70	Ki	0.2	nM	CHEMBL5975276
9.70	Ki	0.2	nM	CHEMBL6102315

PubChem BioAssay actives

1651 with measured affinity, of 3891 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
(2S)-N-[(2S)-1-[(2-amino-2-oxoethyl)amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-1-[(4R,7S,10S,13S,16S)-7-(2-amino-2-oxoethyl)-10-(3-amino-3-oxopropyl)-13-[(2S)-butan-2-yl]-16-[(4-hydroxyphenyl)methyl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]pyrrolidine-2-carboxamide	1450441: Agonist activity at human V1b receptor expressed in CHO cells assessed as calcium mobilization measured after 30 mins by Fluo-4-AM dye based FLIPR assay	ec50	<0.0001	uM
8’-chloro-1’-spiro[1H-2-benzofuran-3,4’-piperidine]-1’-ylspiro[1,3-dioxolane-2,5’-4,6-dihydro-[1,2,4]triazolo[4,3-a][1]benzazepine]	2208012: Displacement of [3H]AVP from human vasopressin V1a receptor expressed in human 1321N1 cells assessed as inhibition constant	ki	<0.0001	uM
(2S)-N-[(2S)-4-amino-1-[[(2S)-1-[(3S)-3-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]-2-[[(2S)-2-[[(2R)-3-(4-hydroxyphenyl)-2-[[2-(4-hydroxyphenyl)acetyl]-methylamino]propanoyl]amino]-3-phenylpropanoyl]amino]pentanediamide	298221: Inhibition of human vasopressin V1a receptor expressed in CHO cells by polarisation binding assay using 96-well plate membranes	ki	<0.0001	uM
1-(4-chlorophenyl)-N-[(2R)-3-(4-chlorophenyl)-1-[[4-(dimethylamino)cyclohexyl]amino]-1-oxopropan-2-yl]cyclopropane-1-carboxamide	608204: Displacement of [3H]AVP from human V1A receptor expressed in CHO cells	ki	<0.0001	uM
N-[(2R)-3-(4-chlorophenyl)-1-[[4-(dimethylamino)cyclohexyl]amino]-1-oxopropan-2-yl]-1-(4-fluorophenyl)cyclopentane-1-carboxamide	608204: Displacement of [3H]AVP from human V1A receptor expressed in CHO cells	ki	<0.0001	uM
vasopressin	1593564: Agonist activity at recombinant human V1a receptor expressed in HEK293 cells assessed as increase in intracellular calcium level measured at 3 secs interval for 5 mins by fura-2/AM dye based micro spectrofluorometric method	ec50	<0.0001	uM
(5S)-8-chloro-5-(fluoromethyl)-1-(4-pyridin-2-yloxycyclohexyl)-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepine	2093664: Displacement of [3H]vasopressin from human V1A receptor assessed as inhibition constant by Cheng-Prusoff equation analysis	ki	0.0001	uM
(5R)-8-chloro-5-(fluoromethyl)-1-(4-pyridin-2-yloxycyclohexyl)-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepine	2093664: Displacement of [3H]vasopressin from human V1A receptor assessed as inhibition constant by Cheng-Prusoff equation analysis	ki	0.0001	uM
8’-chloro-1’-(4-pyridin-2-yloxycyclohexyl)spiro[1,3-dioxepane-2,5’-4,6-dihydro-[1,2,4]triazolo[4,3-a][1]benzazepine]	2093664: Displacement of [3H]vasopressin from human V1A receptor assessed as inhibition constant by Cheng-Prusoff equation analysis	ki	0.0001	uM
8’-chloro-1’-(4-pyridin-2-yloxypiperidin-1-yl)spiro[1,3-dioxolane-2,5’-4,6-dihydro-[1,2,4]triazolo[4,3-a][1]benzazepine]	2208012: Displacement of [3H]AVP from human vasopressin V1a receptor expressed in human 1321N1 cells assessed as inhibition constant	ki	0.0001	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]	2208012: Displacement of [3H]AVP from human vasopressin V1a receptor expressed in human 1321N1 cells assessed as inhibition constant	ki	0.0001	uM
8’-chloro-1’-(4-thieno[2,3-c]pyridin-7-ylpiperazin-1-yl)spiro[1,3-dioxolane-2,5’-4,6-dihydro-[1,2,4]triazolo[4,3-a][1]benzazepine]	2208012: Displacement of [3H]AVP from human vasopressin V1a receptor expressed in human 1321N1 cells assessed as inhibition constant	ki	0.0001	uM
4-chloro-N-(2-methylpyrazol-3-yl)benzenesulfonamide	1507372: Antagonist activity at human vasopressin 1a receptor expressed in HEK293 cell membranes assessed as inhibition of AVP-induced increase in Ca2+ flux preincubated for 5 mins followed by AVP addition measured after 5 mins for every 2 secs by Ca5 dye based FLIPR assay	ec50	0.0001	uM
(2S)-N-[(2S)-4-amino-1-[[(2S)-1-[(2S)-2-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]-2-[[(2S)-2-[[(2R)-3-(4-hydroxyphenyl)-2-[[2-(4-hydroxyphenyl)acetyl]-methylamino]propanoyl]amino]-3-phenylpropanoyl]amino]pentanediamide	217092: Displacement of [125I]- HO-LVA from human Vasopressin V1a receptor in membranes of CHO cells	ki	0.0001	uM
(2S)-N-[(2S)-4-amino-1-[[(2S)-1-[(2S)-2-[[3’,6’-bis(dimethylamino)-3-oxospiro[2-benzofuran-1,9’-xanthene]-5-carbonyl]-[(2S)-1,6-diamino-1-oxohexan-2-yl]carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]-2-[[(2S)-2-[[(2R)-3-(4-hydroxyphenyl)-2-[3-(4-hydroxyphenyl)propanoyl-methylamino]propanoyl]amino]-3-phenylpropanoyl]amino]pentanediamide	217092: Displacement of [125I]- HO-LVA from human Vasopressin V1a receptor in membranes of CHO cells	ki	0.0001	uM
4-[2-[[6-[[(3S)-1-[(2S)-2-[[(2S)-4-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2R)-3-(4-hydroxyphenyl)-2-[3-(4-hydroxyphenyl)propanoyl-methylamino]propanoyl]amino]-3-phenylpropanoyl]amino]-5-oxopentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]pyrrolidine-3-carbonyl]-[(2S)-1,6-diamino-1-oxohexan-2-yl]amino]-6-oxohexyl]amino]-2-oxoethyl]sulfanyl-2,3,5-trichloro-6-(7,7,9,17,19,19-hexamethyl-4,22-disulfo-2-oxa-6,20-diazapentacyclo[12.8.0.03,12.05,10.016,21]docosa-1(14),5,12,15,21-pentaen-13-yl)benzoic acid	298215: Displacement of [3H]AVP from human vasopressin V1a receptor expressed in CHO cells	ki	0.0001	uM
[4-(2-methylphenyl)phenyl]-[(1S,5R)-1,3,3-trimethyl-6-azabicyclo[3.2.1]octan-6-yl]methanone	483981: Displacement [3H]Arg human recombinant Vasopressin V1a receptor	ki	0.0001	uM
[3-methyl-4-(2-methylphenyl)phenyl]-[(1S,5R)-1,3,3-trimethyl-6-azabicyclo[3.2.1]octan-6-yl]methanone	483981: Displacement [3H]Arg human recombinant Vasopressin V1a receptor	ki	0.0001	uM
[4-(1H-indol-3-yl)-3-methoxyphenyl]-[(1S,5R)-1,3,3-trimethyl-6-azabicyclo[3.2.1]octan-6-yl]methanone	483981: Displacement [3H]Arg human recombinant Vasopressin V1a receptor	ki	0.0001	uM
(2S)-N-[(2S)-5-amino-1-[(2-amino-2-oxoethyl)amino]-1-oxopentan-2-yl]-1-[(4R,7S,10S,13S,16R)-7-(2-amino-2-oxoethyl)-13-[(2S)-butan-2-yl]-16-[(4-ethoxyphenyl)methyl]-10-[(1R)-1-hydroxyethyl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]pyrrolidine-2-carboxamide	317413: Binding affinity to human vasopressin V1a receptor	ki	0.0001	uM
(2S)-1-[(4R,7S,10S,13S,16S,19R)-19-amino-7-(2-amino-2-oxoethyl)-10-(3-amino-3-oxopropyl)-13,16-dibenzyl-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]-N-[(2S)-1-[(2-amino-2-oxoethyl)amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	613479: Agonist activity at recombinant human vasopressin V1a receptor expressed in HEK293 cells by luciferase reporter gene assay	ec50	0.0001	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)-13,16-dibenzyl-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]pyrrolidine-2-carboxamide	613479: Agonist activity at recombinant human vasopressin V1a receptor expressed in HEK293 cells by luciferase reporter gene assay	ec50	0.0001	uM
1-(4-chlorophenyl)-N-[(2R)-3-(4-chlorophenyl)-1-[[4-(dimethylamino)cyclohexyl]amino]-1-oxopropan-2-yl]cyclobutane-1-carboxamide	608204: Displacement of [3H]AVP from human V1A receptor expressed in CHO cells	ki	0.0001	uM
4-chloro-N-(2-pyridin-2-ylpyrazol-3-yl)benzenesulfonamide	1507372: Antagonist activity at human vasopressin 1a receptor expressed in HEK293 cell membranes assessed as inhibition of AVP-induced increase in Ca2+ flux preincubated for 5 mins followed by AVP addition measured after 5 mins for every 2 secs by Ca5 dye based FLIPR assay	ec50	0.0001	uM
(2S)-N-[(2S)-1-[(2-amino-2-oxoethyl)amino]-1-oxopropan-2-yl]-1-[(4R,7S,10S,13S,16S)-7-(2-amino-2-oxoethyl)-10-(3-amino-3-oxopropyl)-13-[(2S)-butan-2-yl]-16-[(4-hydroxyphenyl)methyl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]pyrrolidine-2-carboxamide	1450441: Agonist activity at human V1b receptor expressed in CHO cells assessed as calcium mobilization measured after 30 mins by Fluo-4-AM dye based FLIPR assay	ec50	0.0002	uM
(2S)-N-[(2S)-4-amino-1-[[(2S)-1-[(2S)-2-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]-2-[[(2S)-2-[[(2R)-2-[3-(4-hydroxyphenyl)propanoylamino]-3-(4-methoxyphenyl)propanoyl]amino]-3-phenylpropanoyl]amino]pentanediamide	1409547: Displacement of [Se-Se]-AVP from human V1A receptor expressed in CHO cells after 4 hrs by RP-LC-ICPMS analysis	ki	0.0002	uM
(5R)-8-chloro-5-methoxy-1-(4-pyridin-2-yloxycyclohexyl)-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepine	2093664: Displacement of [3H]vasopressin from human V1A receptor assessed as inhibition constant by Cheng-Prusoff equation analysis	ki	0.0002	uM
N-[(5R)-8-chloro-1-(4-pyridin-2-yloxycyclohexyl)-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepin-5-yl]-3-(dimethylamino)propanamide	2093664: Displacement of [3H]vasopressin from human V1A receptor assessed as inhibition constant by Cheng-Prusoff equation analysis	ki	0.0002	uM
8’-bromo-1’-(4-pyridin-2-yloxycyclohexyl)spiro[1,3-dioxolane-2,5’-4,6-dihydro-[1,2,4]triazolo[4,3-a][1]benzazepine]	2093664: Displacement of [3H]vasopressin from human V1A receptor assessed as inhibition constant by Cheng-Prusoff equation analysis	ki	0.0002	uM
8’-fluoro-1’-(4-pyridin-2-yloxycyclohexyl)spiro[1,3-dioxolane-2,5’-4,6-dihydro-[1,2,4]triazolo[4,3-a][1]benzazepine]	2093664: Displacement of [3H]vasopressin from human V1A receptor assessed as inhibition constant by Cheng-Prusoff equation analysis	ki	0.0002	uM
[4-(8’-chlorospiro[1,3-dioxolane-2,5’-4,6-dihydro-[1,2,4]triazolo[4,3-a][1]benzazepine]-1’-yl)cyclohexyl]-morpholin-4-ylmethanone	2093664: Displacement of [3H]vasopressin from human V1A receptor assessed as inhibition constant by Cheng-Prusoff equation analysis	ki	0.0002	uM
8’-chloro-1’-(4-methoxy-4-methylcyclohexyl)spiro[1,3-dioxolane-2,5’-4,6-dihydro-[1,2,4]triazolo[4,3-a][1]benzazepine]	2093664: Displacement of [3H]vasopressin from human V1A receptor assessed as inhibition constant by Cheng-Prusoff equation analysis	ki	0.0002	uM
8’-methyl-1’-(4-pyridin-2-yloxycyclohexyl)spiro[1,3-dioxolane-2,5’-4,6-dihydro-[1,2,4]triazolo[4,3-a][1]benzazepine]	2093664: Displacement of [3H]vasopressin from human V1A receptor assessed as inhibition constant by Cheng-Prusoff equation analysis	ki	0.0002	uM
8-chloro-1-(4-pyridin-2-yloxycyclohexyl)spiro[4,6-dihydro-[1,2,4]triazolo[4,3-a][1]benzazepine-5,4’-oxane]	2093664: Displacement of [3H]vasopressin from human V1A receptor assessed as inhibition constant by Cheng-Prusoff equation analysis	ki	0.0002	uM
8’-chloro-1’-[1-(2,3-dihydro-1-benzofuran-7-yl)piperidin-4-yl]spiro[1,3-dioxolane-2,5’-4,6-dihydro-[1,2,4]triazolo[4,3-a][1]benzazepine]	2208012: Displacement of [3H]AVP from human vasopressin V1a receptor expressed in human 1321N1 cells assessed as inhibition constant	ki	0.0002	uM
1’-[4-(1,3-benzodioxol-4-yl)piperidin-1-yl]-8’-chlorospiro[1,3-dioxolane-2,5’-4,6-dihydro-[1,2,4]triazolo[4,3-a][1]benzazepine]	2208012: Displacement of [3H]AVP from human vasopressin V1a receptor expressed in human 1321N1 cells assessed as inhibition constant	ki	0.0002	uM
8’-chloro-1’-[4-(2,3-dihydro-1-benzofuran-7-yl)piperidin-1-yl]spiro[1,3-dioxolane-2,5’-4,6-dihydro-[1,2,4]triazolo[4,3-a][1]benzazepine]	2208012: Displacement of [3H]AVP from human vasopressin V1a receptor expressed in human 1321N1 cells assessed as inhibition constant	ki	0.0002	uM
8’-chloro-1’-[1-(1,3-dihydro-2-benzofuran-4-yl)piperidin-4-yl]spiro[1,3-dioxolane-2,5’-4,6-dihydro-[1,2,4]triazolo[4,3-a][1]benzazepine]	2208012: Displacement of [3H]AVP from human vasopressin V1a receptor expressed in human 1321N1 cells assessed as inhibition constant	ki	0.0002	uM
8’-chloro-1’-(4-methoxy-4-phenylpiperidin-1-yl)spiro[1,3-dioxolane-2,5’-4,6-dihydro-[1,2,4]triazolo[4,3-a][1]benzazepine]	2208012: Displacement of [3H]AVP from human vasopressin V1a receptor expressed in human 1321N1 cells assessed as inhibition constant	ki	0.0002	uM
Oxytocin	1591640: Agonist activity at human V1A receptor expressed in HEK293 cells assessed as intracellular calcium level measured at 3 secs interval for 5 mins by fura-2/AM dye based micro spectrofluorometric method	ec50	0.0002	uM
(2S)-N-[(2S)-4-amino-1-[[(2S)-5-(diaminomethylideneamino)-1-[(2S)-2-[[(2S)-1,6-diamino-1-oxohexan-2-yl]-(3’,6’-dihydroxy-1-oxospiro[2-benzofuran-3,9’-xanthene]-5-carbonyl)carbamoyl]pyrrolidin-1-yl]-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]-2-[[(2S)-2-[[(2R)-3-(4-hydroxyphenyl)-2-[3-(4-hydroxyphenyl)propanoyl-methylamino]propanoyl]amino]-3-phenylpropanoyl]amino]pentanediamide	217092: Displacement of [125I]- HO-LVA from human Vasopressin V1a receptor in membranes of CHO cells	ki	0.0002	uM
(2S)-N-[(2S)-4-amino-1-[[(2S)-1-[(2S)-2-[[3’,6’-bis(dimethylamino)-1-oxospiro[2-benzofuran-3,9’-xanthene]-5-carbonyl]-[(2S)-1,6-diamino-1-oxohexan-2-yl]carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]-2-[[(2S)-2-[[(2R)-3-(4-hydroxyphenyl)-2-[3-(4-hydroxyphenyl)propanoyl-methylamino]propanoyl]amino]-3-phenylpropanoyl]amino]pentanediamide	217092: Displacement of [125I]- HO-LVA from human Vasopressin V1a receptor in membranes of CHO cells	ki	0.0002	uM
(2S)-N-[(2S)-4-amino-1-[[(2S)-5-(diaminomethylideneamino)-1-[(2S)-2-[[(2S)-1,6-diamino-1-oxohexan-2-yl]-(3’,6’-dihydroxy-3-oxospiro[2-benzofuran-1,9’-xanthene]-5-carbonyl)carbamoyl]pyrrolidin-1-yl]-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]-2-[[(2S)-2-[[(2R)-3-(4-hydroxyphenyl)-2-[3-(4-hydroxyphenyl)propanoyl-methylamino]propanoyl]amino]-3-phenylpropanoyl]amino]pentanediamide	217092: Displacement of [125I]- HO-LVA from human Vasopressin V1a receptor in membranes of CHO cells	ki	0.0002	uM
(2S)-5-(4-cyclohexylpiperazin-1-yl)-N-[[2-fluoro-3-(trifluoromethyl)phenyl]methyl]-5-oxo-2-[(3S,4R)-2-oxo-3-[(4S)-2-oxo-4-phenyl-1,3-oxazolidin-3-yl]-4-[(E)-2-phenylethenyl]azetidin-1-yl]pentanamide	293624: Binding affinity for human cloned vasopressin V1a receptor expressed in CHO cells	ki	0.0002	uM
N-(2-methylpyrazol-3-yl)-4-(trifluoromethyl)benzenesulfonamide	1507372: Antagonist activity at human vasopressin 1a receptor expressed in HEK293 cell membranes assessed as inhibition of AVP-induced increase in Ca2+ flux preincubated for 5 mins followed by AVP addition measured after 5 mins for every 2 secs by Ca5 dye based FLIPR assay	ec50	0.0002	uM
(2S)-1-[(4R,7S,10S,13S,16S,19R)-19-amino-7-(2-amino-2-oxoethyl)-10-(3-amino-3-oxopropyl)-16-benzyl-13-[(2S)-butan-2-yl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]-N-[(2S)-1-[(2-amino-2-oxoethyl)amino]-1-oxo-5-(propylamino)pentan-2-yl]pyrrolidine-2-carboxamide	613479: Agonist activity at recombinant human vasopressin V1a receptor expressed in HEK293 cells by luciferase reporter gene assay	ec50	0.0002	uM
N-[(2R)-3-(4-chlorophenyl)-1-[[4-(dimethylamino)cyclohexyl]amino]-1-oxopropan-2-yl]-1-(4-fluorophenyl)cyclopropane-1-carboxamide	608204: Displacement of [3H]AVP from human V1A receptor expressed in CHO cells	ki	0.0002	uM
(2R)-N-[(1S,5R)-8-azabicyclo[3.2.1]octan-3-yl]-3-(4-chlorophenyl)-2-[[2-(4-chlorophenyl)acetyl]amino]propanamide	596611: Displacement of [3H]AVP from human V1A receptor expressed in CHO cells	ki	0.0002	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-[(2S)-butan-2-yl]-16-[(4-hydroxyphenyl)methyl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]pyrrolidine-2-carboxamide	613479: Agonist activity at recombinant human vasopressin V1a receptor expressed in HEK293 cells by luciferase reporter gene assay	ec50	0.0002	uM
(2R)-3-(4-chlorophenyl)-2-[[2-(4-chlorophenyl)acetyl]amino]-N-(2-hydroxycyclohexyl)propanamide	608204: Displacement of [3H]AVP from human V1A receptor expressed in CHO cells	ki	0.0002	uM

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	2
arsenite	increases methylation	1
mono-(2-ethylhexyl)phthalate	increases expression	1
vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-	decreases reaction, increases activity	1
relcovaptan	decreases activity	1
CGP 52608	increases reaction, affects binding	1
2,7-dihydroxynaphthalene	decreases expression	1
F-180 vasoconstrictor peptide	affects activity	1
bardoxolone methyl	decreases activity	1
GW 7647	increases expression	1
gypenoside	decreases expression	1
vasopressin, Phe(2)-Ile(3)-Hgn(4)-Orn(iPr)(8)-	affects binding, increases activity	1
Arginine Vasopressin	increases activity, decreases reaction	1
Carmustine	increases expression	1
Cycloheximide	decreases expression, decreases reaction	1
Doxorubicin	increases expression	1
Chlorpyrifos	affects response to substance, affects expression	1
Etoposide	increases expression	1
Monobactams	affects binding	1
Progesterone	increases expression	1
Tetrachlorodibenzodioxin	decreases expression, decreases reaction	1
Valproic Acid	increases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	decreases expression	1

ChEMBL screening assays

437 unique, capped per target: 321 binding, 108 functional, 8 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1001061	Binding	Binding affinity to vasopressin 1A receptor	Synthesis and evaluation of dibenzothiazepines: a novel class of selective cannabinoid-1 receptor inverse agonists. — *J Med Chem*
CHEMBL1015245	Functional	Agonist activity at human vasopressin V1a receptor upto 10 uM by reporter gene assay	New benzylureas as a novel series of potent, nonpeptidic vasopressin V2 receptor agonists. — *J Med Chem*
CHEMBL4018362	ADMET	Agonist activity at human V1a receptor expressed in CHO cells assessed as calcium mobilization measured after 30 mins by Fluo-4-AM dye based FLIPR assay	Potent and selective oxytocin receptor agonists without disulfide bridges. — *Bioorg Med Chem Lett*

Cellosaurus cell lines

5 cell lines: 2 spontaneously immortalized cell line, 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_H507	CHO-K1/V1A	Spontaneously immortalized cell line	Female
CVCL_KZ75	PathHunter U2OS AVPR1A beta-arrestin	Cancer cell line	Female
CVCL_KZ76	PathHunter U2OS AVPR1A Total GPCR Internalization	Cancer cell line	Female
CVCL_LB56	GeneBLAzer AVPR1a-NFAT-bla CHO-K1	Spontaneously immortalized cell line	Female
CVCL_YK01	HEK293 AVPR1A HiTSeeker	Transformed cell line	Female

Clinical trials (associated diseases)

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

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00391261	Phase 4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	Phase 4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	Phase 4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	Phase 4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	Phase 4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	Phase 4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	Phase 4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	Phase 4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	Phase 4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	Phase 4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	Phase 4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	Phase 4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	Phase 4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	Phase 4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	Phase 4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	Phase 4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	Phase 4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	Phase 4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	Phase 4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	Phase 4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	Phase 4	RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT07770152	Phase 4	NOT_YET_RECRUITING	Semaglutide in Youth With Autism Spectrum Disorder
NCT01302964	Phase 3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	Phase 3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	Phase 3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	Phase 3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	Phase 3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	Phase 3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	Phase 3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	Phase 3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	Phase 3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	Phase 3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	Phase 3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	Phase 3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	Phase 3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	Phase 3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	Phase 3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	Phase 3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	Phase 3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	Phase 3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	Phase 3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder
NCT06333964	Phase 3	COMPLETED	A Study to Evaluate the Efficacy and Safety of AST-001 in ASD Children
NCT07257939	Phase 3	NOT_YET_RECRUITING	NTI164 in Autism Spectrum Disorder
NCT07655115	Phase 3	RECRUITING	Single Dose Double-blind, Placebo-controlled Cross-over (SDDBPCCO) Shiftability Study, Will be Followed by a 10-week Open-label Study With Arbaclofen (4 Weeks of Titration and Then 6 Weeks of Active/Stable Treatment). The Effects of Arbaclofen on Target EEG and ERG Metrics Will be Associated With th
NCT00251303	Phase 2	COMPLETED	Riluzole to Treat Child and Adolescent Obsessive-Compulsive Disorder With or Without Autism Spectrum Disorders
NCT00614198	Phase 2	COMPLETED	ScanBrit Dietary Intervention in Autism
NCT00619190	Phase 2	COMPLETED	Study of Aripiprazole to Treat Children and Adolescents With Autism
NCT00709202	Phase 2	COMPLETED	Efficacy and Tolerability Study of Betahistine to Ameliorate Antipsychotic Associated Weight Gain
NCT00846547	Phase 2	COMPLETED	Open-Label Study of the Safety and Tolerability of STX209 in Subjects With Autism Spectrum Disorders
NCT01064973	Phase 2	TERMINATED	An Open Label Extension Study of STX209 in Subjects With Autism Spectrum Disorders
NCT01170325	Phase 2	WITHDRAWN	A Study of Divalproex Sodium in Children With ASD and Epileptiform EEG
NCT01205282	Phase 2	COMPLETED	Dose Finding Study of Pioglitazone in Children With Autism Spectrum Disorders (ASD) (PIO)
NCT01248130	Phase 2	TERMINATED	Omega-3 Fatty Acids Monotherapy in Children and Adolescents With Autism Spectrum Disorders
NCT01248728	Phase 2	COMPLETED	Omega-3 Fatty Acids For Treatment Of Young Children With Autism (OMG)
NCT01256060	Phase 2	COMPLETED	Intranasal Oxytocin for the Treatment of Children and Adolescents With ASD (OXY)
NCT01288716	Phase 2	COMPLETED	Study of Arbaclofen for the Treatment of Social Withdrawal in Subjects With Autism Spectrum Disorders
NCT01300923	Phase 2	COMPLETED	Acamprosate in Youth With Fragile X Syndrome
NCT01366859	Phase 2	COMPLETED	Nutritional Intervention in Children With Autism Using Whey Protein (Immunocal): Impact on Core Areas of Behavior
NCT01372449	Phase 2	COMPLETED	A Multi-site Double-blind Placebo-controlled Trial of Memantine Versus Placebo in Children With Autism (MEM)
NCT01395953	Phase 2	WITHDRAWN	Double-blind Trial of Buspirone for the Treatment of Anxiety in Youth With Autism Spectrum Disorders

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for AVPR1A across ~30M SureChEMBL compounds — explore on Sugi Predict.