AVP

Summary

AVP (arginine vasopressin, HGNC:894) is a protein-coding gene on chromosome 20p13, encoding Vasopressin-neurophysin 2-copeptin (P01185). Has a direct antidiuretic action on the kidney, it also causes vasoconstriction of the peripheral vessels.

This gene encodes a member of the vasopressin/oxytocin family and preproprotein that is proteolytically processed to generate multiple protein products. These products include the neuropeptide hormone arginine vasopressin, and two other peptides, neurophysin 2 and copeptin. Arginine vasopressin is a posterior pituitary hormone that is synthesized in the supraoptic nucleus and paraventricular nucleus of the hypothalamus. Along with its carrier protein, neurophysin 2, it is packaged into neurosecretory vesicles and transported axonally to the nerve endings in the neurohypophysis where it is either stored or secreted into the bloodstream. The precursor is thought to be activated while it is being transported along the axon to the posterior pituitary. Arginine vasopressin acts as a growth factor by enhancing pH regulation through acid-base transport systems. It has a direct antidiuretic action on the kidney, and also causes vasoconstriction of the peripheral vessels. This hormone can contract smooth muscle during parturition and lactation. It is also involved in cognition, tolerance, adaptation and complex sexual and maternal behaviour, as well as in the regulation of water excretion and cardiovascular functions. Mutations in this gene cause autosomal dominant neurohypophyseal diabetes insipidus (ADNDI). This gene is present in a gene cluster with the related gene oxytocin on chromosome 20.

Source: NCBI Gene 551 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurohypophyseal diabetes insipidus (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 159 total — 24 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 18
• MANE Select transcript: NM_000490

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:894
Approved symbol	AVP
Name	arginine vasopressin
Location	20p13
Locus type	gene with protein product
Status	Approved
Aliases	ADH
Ensembl gene	ENSG00000101200
Ensembl biotype	protein_coding
OMIM	192340
Entrez	551

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000380293

RefSeq mRNA: 1 — MANE Select: NM_000490 NM_000490

CCDS: CCDS13045

Canonical transcript exons

ENST00000380293 — 3 exons

Exon	Start	End
ENSE00000656646	3082977	3083178
ENSE00000858717	3082556	3082802
ENSE00001484506	3084555	3084724

Expression profiles

Bgee: expression breadth ubiquitous, 125 present calls, max score 80.97.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.1819 / max 3365.7628, expressed in 35 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
186120	2.1819	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hypothalamus	UBERON:0001898	80.97	gold quality
ileal mucosa	UBERON:0000331	66.32	silver quality
buccal mucosa cell	CL:0002336	66.16	gold quality
medial globus pallidus	UBERON:0002477	60.97	silver quality
mucosa of stomach	UBERON:0001199	59.46	gold quality
gluteal muscle	UBERON:0002000	58.18	gold quality
globus pallidus	UBERON:0001875	58.14	silver quality
apex of heart	UBERON:0002098	57.08	gold quality
parotid gland	UBERON:0001831	54.84	gold quality
myocardium	UBERON:0002349	53.73	gold quality
adult mammalian kidney	UBERON:0000082	53.39	gold quality
biceps brachii	UBERON:0001507	53.36	gold quality
nasal cavity epithelium	UBERON:0005384	53.09	gold quality
monocyte	CL:0000576	52.53	gold quality
mononuclear cell	CL:0000842	52.50	gold quality
triceps brachii	UBERON:0001509	52.48	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	52.29	gold quality
leukocyte	CL:0000738	51.74	gold quality
deltoid	UBERON:0001476	51.59	gold quality
left testis	UBERON:0004533	51.32	gold quality
amygdala	UBERON:0001876	51.10	gold quality
adenohypophysis	UBERON:0002196	50.79	gold quality
right adrenal gland cortex	UBERON:0035827	50.79	gold quality
middle temporal gyrus	UBERON:0002771	50.61	gold quality
lateral globus pallidus	UBERON:0002476	50.43	gold quality
quadriceps femoris	UBERON:0001377	50.36	gold quality
subcutaneous adipose tissue	UBERON:0002190	50.09	gold quality
right testis	UBERON:0004534	49.85	gold quality
mammalian vulva	UBERON:0000997	49.63	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.52	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-10432	yes	659.75
E-HCAD-6	yes	518.88
E-HCAD-4	yes	352.69
E-GEOD-76312	yes	204.20
E-ANND-3	yes	10.07
E-MTAB-8884	no	1034.96

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 40)

• autosomal dominant neurohypophyseal diabetes insipidus associated with a novel and recurrent mutations in the vasopressin-neurophysin II gene. (PMID:11980620)
• identification of a missense mutation of the AVP-NPII gene and a novel mutation predicting a truncated protein in the gene in familial central diabetes insipidus (PMID:12012274)
• Autosomal dominant neurohypophyseal diabetes insipidus due to substitution of histidine for tyrosine(2) in the vasopressin moiety of the hormone precursor. (PMID:12107248)
• novel mutation substituting cysteine with phenylalanine in one AVP-NPII gene allele in autosomal dominant neurohypophyseal diabetes insipidus (PMID:12359138)
• AVP responses to hypotension in adipsic diabetes insipidus are heterogeneous and reflect the site of the lesion causing the diabetes insipidus (PMID:12364435)
• demonstrated a novel mechanism for upstream stimulatory factor activation, which contributes to differential vasopressin expression in lung cancer. (PMID:12403649)
• Non-suppressible release of AVP is crucially involved in the impaired water excretion and hyponatremia seen in elderly patients with secondary adrenal insufficiency. (PMID:12590641)
• As a result of this mutation cysteine residue is exchanged, which is involved in disulfide bond with cysteine 44 of NPII moiety. Resulting misfolded protein may lead to chronic neurotoxicity by accumulation of these products in endoplasmatic reticulum. (PMID:12931042)
• wild-type vasopressin precursor and pathogenic mutants are degraded by the proteasome (PMID:14996841)
• Plasma arginine vasopressin (AVP) was determined before the stressor, at the time of maximum ACTH secretion, and 75 min after stress onset. Activation of the HPA system by psychosocial stress is accompanied by an increase in peripheral plasma AVP levels. (PMID:15203290)
• In the present study we found decreased vasopressin in several hypothalamic nuclei in vascular dementia indicating diminished production of certain hormones and neurotransmitters. (PMID:15624761)
• molecular dynamics analysis of mechanism of desmopressin binding in vasopressin V2 receptor versus vasopressin V1a and oxytocin receptors (PMID:16333859)
• These results suggest that the elevation of plasma vasopressin in the acute phase of Meniere’s disease is related to the pathogenesis of Meniere’s attacks. (PMID:17927668)
• Data show AVP was significantly increased in multiple trauma patients and seems to be an integral part of the neuroendocrine response to severe injury. In ICU patients, AVP decreased to moderately elevated levels within 24 h after ED admission. (PMID:18092379)
• No significant differences are found in the amount of DNA methylation in the vasopressin promoter compared to that of atrial natriuretic peptide, in females with bulemia nervosa. (PMID:18172431)
• Study suggests that symptomatic intradialytic hypotension patients are unable to mount an appropriate increase in AVP secretion in the setting of hypotension. (PMID:18256370)
• there is a relationship between plasma osmolality, plasma apelin and plasma AVP in various states of hydration (PMID:18272843)
• Presence of this mutation suggests that the portion of the neurophysin peptide encoded by this sequence is important for the appropriate expression of vasopressin. (PMID:18316776)
• Data demonstrate need for autophagy-mediated degradation of toxic, mutated arginine vasopressin C98X peptides, and suggest that, in the presence of mis-folded proteins, the stimulation of Akt signalling counteracts autophagy and precipitates cell death. (PMID:18673414)
• This article reviews mutations of the arginine vasopressin neurophysin-II gene in familial neurohypophyseal diabetes insipidus patients. (PMID:18807739)
• Correlations between copeptin and left ventricular dysfunction appear stronger at follow-up compared with predischarge, suggesting that the AVP system may have progressive effects on left ventricular impairment over the subsequent period. (PMID:18995178)
• data support the hypothesis that impaired AVP response is at least partially responsible for the failure to restore vascular tone in septic shock. (PMID:19114902)
• Autosomal dominant neurohypophyseal diabetes insipidus in two families. Molecular analysis of the vasopressin-neurophysin II gene and functional studies of three missense mutations. (PMID:19129716)
• Low nocturnal AVP and urine osmolality may play a role in the pathophysiology of enuretics with nocturnal polyuria. (PMID:19260089)
• Report plasma levels of copeptin in patients with coronary heart disease. (PMID:19337789)
• A novel cross-sectional association between plasma copeptin and measures of insulin resistance and metabolic syndrome. (PMID:19366852)
• Results indicate that arginine vasopressin and oxytocin gene expression in the paraventricular and supraoptic nuclei is unchanged in depressed Alzheimer’s disease patients, in contrast with the enhanced AVP gene expression in major depressive disorder. (PMID:19500216)
• MR-proADM, CT-proET-1, CT-proAVP, and MR-proANP were all elevated in patients with future cardiovascular events and independently correlated to serum creatinine. (PMID:19564455)
• a negative feedback system between AVP and vasopressin 2 receptor in the endolymphatic sac may function for inner ear fluid homeostasis against stress-induced increases in AVP (PMID:19638944)
• Gene expression of vasopressin and oxytocin was significant increased in the hypothalamo-neurohypophysial system of patients with chronic heart failure. (PMID:19672816)
• The subsequent mutation screen of AVP failed to identify any putative functional polymorphisms in childhood-onset mood disorders. (PMID:19821843)
• Dominant pro-vasopressin mutants progressively accumulate as endoplasmic reticulum-associated aggregates. (PMID:19825939)
• plasma copeptin levels are associated with microalbuminuria, consistent with the hypothesis that vasopressin is involved in urinary albumin excretion (PMID:19847155)
• Factors beside allelism of AVP-related genes must influence the age of familial neurohypophyseal diabetes insipidus presentation given the founder effect demonstrated for the P26L mutation (PMID:19897608)
• In depression with above-normal plasma vasopressin (AVP) concentration, a negative correlation was found between plasma AVP and NE concentrations, and no such relation was found in melancholia according to DSM-IV (PMID:19942636)
• Vasopressin (VP) is a homeostatic neuroendocrine hormone whose chief role is to maintain plasma osmolality. Although important in health, in this review of disease states the breadth of VP’s functional repertoire has become widely apparent. (PMID:19945299)
• men and women with high plasma copeptin have a highly prevalent microalbuminuria in addition to the low level of hydration typical of persons with high vasopressin secretion (PMID:20010879)
• These data confirm and extend prior evidence implicating oxytocin and vasopressin in couples’ positive and negative communication behaviors, and also provide further evidence of their role in an important health outcome, wound healing. (PMID:20144509)
• Copeptin is an independent predictor of cardiovascular events and appears to at least partly explain the prognostic impact of IGFBP-1 in patients with type 2 diabetes and myocardial infarction (PMID:20413521)
• Elevated copeptin predicts increased risk for diabetes mellitus independently of established clinical risk factors, including fasting glucose and insulin (PMID:20439785)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	oxt	ENSDARG00000042845
danio_rerio	avp	ENSDARG00000058567
mus_musculus	Avp	ENSMUSG00000037727
rattus_norvegicus	Avp	ENSRNOG00000021229

Paralogs (1): OXT (ENSG00000101405)

Protein

Protein identifiers

Vasopressin-neurophysin 2-copeptin — P01185 (reviewed: P01185)

Alternative names: AVP-NPII

All UniProt accessions (2): P01185, X5DQP6

UniProt curated annotations — full annotation on UniProt →

Function. Has a direct antidiuretic action on the kidney, it also causes vasoconstriction of the peripheral vessels. Acts by binding to vasopressin receptors (V1bR/AVPR1B, V1aR/AVPR1A, and V2R/AVPR2). Specifically binds vasopressin.

Subunit / interactions. Interacts with vasopressin receptors V1bR/AVPR1B (Ki=85 pM), V1aR/AVPR1A (Ki=0.6 nM) and V2R/AVPR2 (Ki=4.9 nM). Interacts with oxytocin receptor (OXTR) (Ki=110 nM). (Microbial infection) May interact with SARS coronavirus-2/SARS-CoV-2; they may form a complex with secreted ACE2.

Subcellular location. Secreted.

Disease relevance. Diabetes insipidus, neurohypophyseal (NDI) [MIM:125700] A disease characterized by persistent thirst, polydipsia and polyuria. Affected individuals are apparently normal at birth, but characteristically develop symptoms of vasopressin deficiency during childhood. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the vasopressin/oxytocin family.

RefSeq proteins (1): NP_000481* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000981	Neurhyp_horm	Family
IPR022423	Neurohypophysial_hormone_CS	Conserved_site
IPR036387	Neurhyp_horm_dom_sf	Homologous_superfamily

Pfam: PF00184, PF00220

UniProt features (60 total): sequence variant 42, disulfide bond 8, peptide 2, sequence conflict 2, signal peptide 1, chain 1, site 1, modified residue 1, mutagenesis site 1, glycosylation site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
7DW9	ELECTRON MICROSCOPY	2.6
7KH0	ELECTRON MICROSCOPY	2.8
7BB6	ELECTRON MICROSCOPY	4.2
7BB7	ELECTRON MICROSCOPY	4.4
7R0C	ELECTRON MICROSCOPY	4.73

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P01185-F1	78.83	0.40

Antibody-complex structures (SAbDab): 5 — 7BB6, 7BB7, 7DW9, 7KH0, 7R0C

Functional residue map

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

Catalytic / active sites (1): 28 (important for agonist activity on v1ar/avpr1a)

Post-translational modifications (1): 28

Disulfide bonds (8): 52–75, 59–65, 92–104, 98–116, 105–110, 20–25, 41–85, 44–58

Glycosylation sites (1): 131

Mutagenesis-validated functional residues (1):

Position	Phenotype
28	gain of antagonist activity on v1ar/avpr1a (and loss of agonist activity on this receptor). 42-fold decrease in affinity

Function

Pathways and Gene Ontology

Reactome pathways

26 pathways

ID	Pathway
R-HSA-1368108	BMAL1:CLOCK,NPAS2 activates circadian expression
R-HSA-388479	Vasopressin-like receptors
R-HSA-416476	G alpha (q) signalling events
R-HSA-418555	G alpha (s) signalling events
R-HSA-432040	Vasopressin regulates renal water homeostasis via Aquaporins
R-HSA-5619099	Defective AVP does not bind AVPR1A,B and causes neurohypophyseal diabetes insipidus (NDI)
R-HSA-879518	Organic anion transport by SLCO transporters
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-9036092	Defective AVP does not bind AVPR2 and causes neurohypophyseal diabetes insipidus (NDI)
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-199991	Membrane Trafficking
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-382551	Transport of small molecules
R-HSA-388396	GPCR downstream signalling
R-HSA-400253
R-HSA-425397	Transport of vitamins, nucleosides, and related molecules
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-445717	Aquaporin-mediated transport
R-HSA-500792	GPCR ligand binding
R-HSA-5619102	SLC transporter disorders
R-HSA-5619115	Disorders of transmembrane transporters
R-HSA-5653656	Vesicle-mediated transport

MSigDB gene sets: 290 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_RESPONSE_TO_ETHANOL, GOBP_GLUTAMATE_SECRETION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_RESPONSE_TO_ELECTRICAL_STIMULUS, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_REGULATION_OF_ORGANIC_ACID_TRANSPORT, GOBP_RESPONSE_TO_PEPTIDE, GOCC_SECRETORY_GRANULE, GOBP_GROWTH, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE, GOBP_NEGATIVE_REGULATION_OF_NERVOUS_SYSTEM_PROCESS, REACTOME_MEMBRANE_TRAFFICKING, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS

GO Biological Process (38): maternal aggressive behavior (GO:0002125), positive regulation of systemic arterial blood pressure (GO:0003084), generation of precursor metabolites and energy (GO:0006091), water transport (GO:0006833), signal transduction (GO:0007165), positive regulation of cytosolic calcium ion concentration (GO:0007204), cell-cell signaling (GO:0007267), negative regulation of female receptivity (GO:0007621), grooming behavior (GO:0007625), locomotory behavior (GO:0007626), positive regulation of cell population proliferation (GO:0008284), response to xenobiotic stimulus (GO:0009410), response to salt stress (GO:0009651), positive regulation of gene expression (GO:0010628), positive regulation of glutamate secretion (GO:0014049), positive regulation of cell growth (GO:0030307), positive regulation of prostaglandin biosynthetic process (GO:0031394), obsolete positive regulation of cellular pH reduction (GO:0032849), multicellular organismal response to stress (GO:0033555), response to testosterone (GO:0033574), response to nicotine (GO:0035094), social behavior (GO:0035176), intracellular signal transduction (GO:0035556), vasoconstriction (GO:0042310), maternal behavior (GO:0042711), negative regulation of apoptotic process (GO:0043066), response to ethanol (GO:0045471), positive regulation of vasoconstriction (GO:0045907), symbiont entry into host cell (GO:0046718), response to electrical stimulus (GO:0051602), negative regulation of transmission of nerve impulse (GO:0051970), renal water absorption (GO:0070295), response to peptide (GO:1901652), response to 2,3,7,8-tetrachlorodibenzodioxine (GO:1904612), response to nerve growth factor (GO:1990089), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), multicellular organismal-level water homeostasis (GO:0050891), blood vessel diameter maintenance (GO:0097746)

GO Molecular Function (8): protein kinase activity (GO:0004672), signaling receptor binding (GO:0005102), hormone activity (GO:0005179), neuropeptide hormone activity (GO:0005184), neurohypophyseal hormone activity (GO:0005185), V1A vasopressin receptor binding (GO:0031894), V1B vasopressin receptor binding (GO:0031895), protein binding (GO:0005515)

GO Cellular Component (7): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytosol (GO:0005829), secretory granule (GO:0030141), dendrite (GO:0030425), clathrin-coated endocytic vesicle membrane (GO:0030669), neuronal dense core vesicle (GO:0098992)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
GPCR downstream signalling	2
SLC transporter disorders	2
Circadian clock	1
Peptide ligand-binding receptors	1
Aquaporin-mediated transport	1
SLC-mediated transport of organic anions	1
Clathrin-mediated endocytosis	1
Membrane Trafficking	1
Vesicle-mediated transport	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1
Signaling by GPCR	1
SLC-mediated transmembrane transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell communication	2
signaling	2
behavior	2
positive regulation of cellular process	2
vasopressin receptor binding	2
cellular anatomical structure	2
aggressive behavior	1
regulation of systemic arterial blood pressure	1
positive regulation of blood pressure	1
metabolic process	1
fluid transport	1
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of biological quality	1
regulation of female receptivity	1
cell population proliferation	1
regulation of cell population proliferation	1
response to chemical	1
response to osmotic stress	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	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
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 stress	1
multicellular organismal process	1
response to lipid	1
response to ketone	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1

Protein interactions and networks

STRING

2016 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AVP	AVPR2	P30518	988
AVP	ADH1B	P00325	969
AVP	ADH1A	P07327	963
AVP	AVPR1B	P47901	956
AVP	ADH1C	P00326	956
AVP	ADH7	P40394	955
AVP	ADH4	P08319	947
AVP	ADH6	P28332	946
AVP	AVPR1A	P37288	926
AVP	ALDH2	P05091	923
AVP	ADH5	P11766	917
AVP	AQP2	P41181	908
AVP	OXT	P01178	900
AVP	NPTX2	P47972	833
AVP	OXTR	P30559	830

IntAct

10 interactions, top by confidence:

A	B	Type	Score
PRKAB2	AVP	psi-mi:“MI:0915”(physical association)	0.560
AVP	ATE1	psi-mi:“MI:0914”(association)	0.530
AVP	DLX2	psi-mi:“MI:0915”(physical association)	0.370
AVP	B4GALT5	psi-mi:“MI:0914”(association)	0.350
ASB9	A2ML1	psi-mi:“MI:0914”(association)	0.350
SMPD2	A2ML1	psi-mi:“MI:0914”(association)	0.350
PRKAB2	AVP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (44): VHL (Affinity Capture-MS), NIF3L1 (Affinity Capture-MS), HTRA1 (Affinity Capture-MS), CDKN2C (Affinity Capture-MS), FNTB (Affinity Capture-MS), ATE1 (Affinity Capture-MS), ARSB (Affinity Capture-MS), BDH2 (Affinity Capture-MS), GALNT18 (Affinity Capture-MS), B4GALT6 (Affinity Capture-MS), B4GALT5 (Affinity Capture-MS), CUL2 (Affinity Capture-MS), NDUFAF5 (Affinity Capture-MS), CHST3 (Affinity Capture-MS), MICA (Affinity Capture-MS)

ESM2 similar proteins: A6NCL2, D3ZTT2, O19131, O46655, O70280, P01177, P01178, P01179, P01180, P01183, P01185, P01186, P03973, P13389, P19438, P22298, P22934, P25118, P35454, P35455, P50555, P58658, P58659, Q02509, Q14AE4, Q32LD3, Q3URS3, Q5T700, Q68US5, Q6UWE3, Q6UWL2, Q6V9X0, Q6WN34, Q76LW6, Q86Y78, Q8BPP5, Q8BVP6, Q8N6Q3, Q8VEA6, Q8WXA2

Diamond homologs: A0A291NVT7, A0A4Y5X186, A0A4Y5X1A7, O42493, O42499, P01175, P01176, P01177, P01178, P01179, P01180, P01181, P01182, P01183, P01184, P01185, P01186, P05486, P08162, P08163, P0DN42, P0DN43, P0DTJ2, P0DTJ3, P10769, P13389, P15210, P15211, P16041, P16042, P16229, P17668, P21916, P24787, P32005, P35454, P35455, P58990, P81768, Q00945

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
AVP	down-regulates	BAD
AVP	up-regulates	AVPR2	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	24
Likely pathogenic	11
Uncertain significance	82
Likely benign	21
Benign	9

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
12204	NM_000490.5(AVP):c.262G>A (p.Gly88Ser)	Pathogenic
12205	NM_000490.5(AVP):c.143G>T (p.Gly48Val)	Pathogenic
12206	NM_000490.5(AVP):c.55G>A (p.Ala19Thr)	Pathogenic
12208	NM_000490.5(AVP):c.294C>A (p.Cys98Ter)	Pathogenic
12209	NM_000490.5(AVP):c.277G>T (p.Gly93Trp)	Pathogenic
12210	NM_000490.5(AVP):c.3del (p.Met1fs)	Pathogenic
12212	NM_000490.5(AVP):c.56C>T (p.Ala19Val)	Pathogenic
12214	NM_000490.5(AVP):c.160G>C (p.Gly54Arg)	Pathogenic
12215	NM_000490.5(AVP):c.337G>T (p.Glu113Ter)	Pathogenic
12216	NM_000490.5(AVP):c.260C>T (p.Ser87Phe)	Pathogenic
12218	NM_000490.5(AVP):c.200T>C (p.Val67Ala)	Pathogenic
12219	NM_000490.5(AVP):c.20C>T (p.Pro7Leu)	Pathogenic
12220	NM_000490.5(AVP):c.346T>G (p.Cys116Gly)	Pathogenic
12221	NM_000490.5(AVP):c.61T>C (p.Tyr21His)	Pathogenic
1699275	NM_000490.5(AVP):c.347G>A (p.Cys116Tyr)	Pathogenic
2736933	NM_000490.5(AVP):c.164C>T (p.Pro55Leu)	Pathogenic
3587176	NM_000490.5(AVP):c.77C>T (p.Pro26Leu)	Pathogenic
3723686	NM_000490.5(AVP):c.322G>T (p.Glu108Ter)	Pathogenic
3723687	NM_000490.5(AVP):c.286G>T (p.Gly96Cys)	Pathogenic
3723689	NM_000490.5(AVP):c.262G>C (p.Gly88Arg)	Pathogenic
3723690	NM_000490.5(AVP):c.176G>A (p.Cys59Tyr)	Pathogenic
4072436	NM_000490.5(AVP):c.160G>A (p.Gly54Arg)	Pathogenic
4710565	NM_000490.5(AVP):c.292T>G (p.Cys98Gly)	Pathogenic
562238	NM_000490.5(AVP):c.322+2T>G	Pathogenic
12213	NM_000490.5(AVP):c.161G>T (p.Gly54Val)	Likely pathogenic
12217	NM_000490.5(AVP):c.275G>A (p.Cys92Tyr)	Likely pathogenic
3065457	NM_000490.5(AVP):c.290G>A (p.Arg97His)	Likely pathogenic
3236029	NM_000490.5(AVP):c.328T>A (p.Cys110Ser)	Likely pathogenic
3347467	NM_000490.5(AVP):c.346T>C (p.Cys116Arg)	Likely pathogenic
3358364	NM_000490.5(AVP):c.287G>A (p.Gly96Asp)	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1060 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:3083144:C:G	C52S	0.994
20:3083145:A:T	C52S	0.994
20:3083075:C:G	C75S	0.993
20:3083076:A:T	C75S	0.993
20:3084585:C:A	K30N	0.991
20:3084585:C:G	K30N	0.991
20:3083105:C:G	C65S	0.990
20:3083106:A:T	C65S	0.990
20:3083145:A:G	C52R	0.990
20:3083126:C:G	C58S	0.989
20:3083127:A:T	C58S	0.989
20:3083125:G:C	C58W	0.988
20:3083076:A:G	C75R	0.987
20:3083106:A:G	C65R	0.987
20:3083138:C:T	G54E	0.987
20:3083143:G:C	C52W	0.987
20:3083123:C:G	C59S	0.986
20:3083124:A:T	C59S	0.986
20:3083127:A:G	C58R	0.986
20:3083177:C:G	C41S	0.986
20:3083178:A:T	C41S	0.986
20:3082985:C:G	C105S	0.985
20:3082985:C:T	C105Y	0.985
20:3082986:A:T	C105S	0.985
20:3083126:C:T	C58Y	0.984
20:3083178:A:G	C41R	0.984
20:3083141:A:C	F53C	0.983
20:3083168:C:T	C44Y	0.983
20:3084582:C:A	R31S	0.983
20:3084582:C:G	R31S	0.983

dbSNP variants (sampled 300 via entrez): RS1000003333 (20:3082498 G>A,C,T), RS1000162789 (20:3085737 G>A), RS1000504167 (20:3082707 C>A,G,T), RS1000618144 (20:3085949 A>G), RS1002443759 (20:3084049 C>G,T), RS1003482739 (20:3086240 T>G), RS1003488459 (20:3086603 A>C,G), RS1003867221 (20:3085133 G>A), RS1004084536 (20:3084714 G>A), RS1005281728 (20:3082609 C>T), RS1006418624 (20:3085873 T>G), RS1006967676 (20:3083680 C>G,T), RS1007147648 (20:3085060 C>A), RS1007304951 (20:3084871 A>G), RS1008979856 (20:3084364 C>G)

Disease associations

OMIM: gene MIM:192340 | disease phenotypes: MIM:125700, MIM:613850

GenCC curated gene-disease

Disease	Classification	Inheritance
neurohypophyseal diabetes insipidus	Strong	Autosomal dominant

Mondo (3): neurohypophyseal diabetes insipidus (MONDO:0007450), inosine triphosphatase deficiency (MONDO:0013461), diabetes insipidus (MONDO:0004782)

Orphanet (3): Arginine vasopressin deficiency (Orphanet:178029), Hereditary arginine vasopressin deficiency (Orphanet:30925), NON RARE IN EUROPE: Inosine triphosphate pyrophosphatase deficiency (Orphanet:319684)

HPO phenotypes

18 total (18 of 18 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000316	Hypertelorism
HP:0000343	Long philtrum
HP:0000445	Wide nose
HP:0000737	Irritability
HP:0000863	Central diabetes insipidus
HP:0000873	Diabetes insipidus
HP:0000938	Osteopenia
HP:0001254	Lethargy
HP:0001510	Growth delay
HP:0001824	Weight loss
HP:0001945	Fever
HP:0001959	Polydipsia
HP:0002013	Vomiting
HP:0002014	Diarrhea
HP:0002171	Gliosis
HP:0003196	Short nose
HP:0031429	Decreased circulating osteocalcin level

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001011_5	Oral cavity and pharyngeal cancer	1.000000e-08

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D003919	Diabetes Insipidus	C12.050.351.968.419.135; C12.200.777.419.135; C12.950.419.135; C19.700.159
C564127	Inosine Triphosphatase Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
U 0126	decreases expression, decreases reaction	1
1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone	decreases expression, decreases reaction	1
sotrastaurin	decreases expression, decreases reaction	1
4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-3H-cyclopenta(c)quinoline	decreases expression, decreases reaction	1
Carvedilol	decreases expression	1
Desflurane	affects cotreatment, increases expression	1
Cyclic AMP	affects binding, increases abundance, increases activity	1
Air Pollutants	increases abundance, increases expression	1
Apomorphine	increases expression, decreases reaction	1
Benzo(a)pyrene	decreases methylation	1
Chloroquine	affects localization, decreases reaction	1
Chlorpromazine	increases expression	1
Chlorpropamide	decreases secretion	1
Chlorpyrifos	affects expression, affects response to substance	1
Hydrochlorothiazide	affects secretion	1
Ifosfamide	affects cotreatment, increases expression	1
Indomethacin	decreases secretion	1
Isoflurane	affects cotreatment, increases expression	1
Labetalol	affects cotreatment, increases expression	1
Levodopa	decreases secretion	1
Methotrexate	increases secretion	1
Metoclopramide	decreases reaction, increases expression	1
Naloxone	decreases secretion	1
Oxprenolol	decreases expression	1
Sodium Chloride	increases expression	1
Antipsychotic Agents	decreases expression	1
Valproic Acid	increases methylation	1
Vincristine	increases expression	1
Mesna	affects cotreatment, increases expression	1
Propofol	increases expression, affects cotreatment	1

Cellosaurus cell lines

5 cell lines: 5 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A9XT	FHUi003-A	Induced pluripotent stem cell	Male
CVCL_A9XU	FHUi003-B	Induced pluripotent stem cell	Male
CVCL_A9XV	FHUi004-A	Induced pluripotent stem cell	Female
CVCL_A9XW	FHUi004-B	Induced pluripotent stem cell	Female
CVCL_JJ78	AVP-Ser18del-iPSC	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06676774	PHASE2	RECRUITING	Effect of Intranasal Oxytocin on Emotion Recognition and Acute Psycho-Social Stress-induced Cortisol Increase in Patients With Central Diabetes Insipidus and Healthy Controls
NCT06808516	PHASE2	RECRUITING	Effects of Intranasal Oxytocin on Sexual Well-Being in Patients With Arginine Vasopressin Deficiency and Healthy Controls
NCT06368817	PHASE2	RECRUITING	A Study of Lower Radiotherapy Dose to Treat Children With CNS Germinoma
NCT04789148	PHASE1	RECRUITING	Effects of Intranasal Oxytocin in Patients With Arginine-vasopressin Deficiency
NCT02460354	PHASE1	TERMINATED	Metformin and Congenital Nephrogenic Diabetes Insipidus
NCT06460948	EARLY_PHASE1	COMPLETED	Identifying Oxytocin Deficiency in Adults With Pituitary Disease
NCT07568509	EARLY_PHASE1	RECRUITING	Identifying Oxytocin Deficiency in Pediatric Patients With Pituitary Disease
NCT05890690	Not specified	COMPLETED	Plasma Copeptin in Response to Oral Urea in Healthy Adults and Patients With Polyuria-polydipsia Syndrome
NCT06422975	Not specified	RECRUITING	Registry of Patients in Shock Treated With Vasopressin
NCT06542198	Not specified	COMPLETED	Mannitol-induced Release of Copeptin in Healthy Adults and Patients With Polyuria-Polydipsia Syndrome (MARS Study)
NCT07361263	Not specified	RECRUITING	Plasma Oxytocin Response to Oral Estrogens in Healthy Controls and AVP-Deficiency
NCT07569861	Not specified	NOT_YET_RECRUITING	Copeptin Measurement After Mannitol and Hypertonic Saline for the Diagnosis of Polyuria-polydipsia Syndrome
NCT00004363	Not specified	COMPLETED	Study of the Pathogenesis and Pathophysiology of Familial Neurohypophyseal Diabetes Insipidus
NCT00004364	Not specified	UNKNOWN	Study of Novel Types of Familial Diabetes Insipidus
NCT00757276	Not specified	COMPLETED	Copeptin in the Diagnosis and Differential Diagnosis of Diabetes Insipidus. The CoSIP-Study
NCT01940614	Not specified	COMPLETED	Use of Copeptin in Diabetes Insipidus
NCT02132676	Not specified	COMPLETED	Shared Health Appointments and Reciprocal Enhanced Support
NCT02455414	Not specified	COMPLETED	Tracking Neurodegeneration in Early Wolfram Syndrome
NCT02523001	Not specified	COMPLETED	Effect of Statin Treatment on Urinary AQP2 (uAQP2/01)
NCT02841553	Not specified	RECRUITING	Wolfram Syndrome and WFS1-related Disorders International Registry and Clinical Study
NCT03572166	Not specified	COMPLETED	Use of Copeptin Measurement After Arginine Infusion for the Differential Diagnosis of Diabetes Insipidus - the CARGOx Study
NCT04351945	Not specified	UNKNOWN	Endocrine Changes and Their Correction in Heart and Lung Transplant Recipients and Donors
NCT04550520	Not specified	COMPLETED	Copeptin After a Subcutaneous Stimulation With Glucagon in Adults
NCT04648137	Not specified	COMPLETED	Circulating Oxytocin Changes in Response to the Oxytocin System Stimulator MDMA in Patients With Diabetes Insipidus and Healthy Controls