AVP

protein-coding

arginine vasopressin, the group of Neuropeptides

Gene summary

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. [provided by RefSeq, Nov 2015]

Previous symbols:

ARVP

MANE transcript

NM_000490.5

Inheritance

AD, AR

ClinVar variants

P:45U:78B:30

Top phenotype

Diabetes insipidus, neurohypophyseal

gnomAD constraint

pLI —, LoF o/e 0.48

Max pathogenic AF

—

Genomic locus

chr20:3,082,556-3,084,724

External References & Databases

Ensembl (ENSG00000101200)

Transcript & Mutation Effects

hg38 • Region Span ~2.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurohypophyseal diabetes insipidusSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007450

Submitter: PanelApp Australia

neurohypophyseal diabetes insipidusSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007450

Submitter: Labcorp Genetics (formerly Invitae)

neurohypophyseal diabetes insipidusSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007450

Submitter: Orphanet

Clinical Genomic Database (CGD)

Diabetes insipidus, neurohypophysealAD/AR

Manifestation: Endocrine; Renal

Intervention: Endocrine; Renal

Rationale: Treatment/prevention of hypernatremia can be effective; Medications related to osteoporosis/osteopenia may be beneficial

Refs: 10404801; 10369876; 14673472; 15070970; 22524462

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AVP variants in ClinVar

7 Conditions Cataloged

not providedTotal: 76

Neurohypophyseal diabetes insipidusTotal: 66

Inborn genetic diseasesTotal: 29

AVP-related disorderTotal: 24

not specifiedTotal: 5

Diabetes insipidus, neurohypophyseal, autosomal recessiveTotal: 1

early-onset neurohypophyseal diabetes insipidusTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000490.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous		1 clinvar	1 clinvar	21 clinvar	1 clinvar	24
missense	19 clinvar	15 clinvar	74 clinvar	6 clinvar	2 clinvar	116
nonsense	3 clinvar	1 clinvar	2 clinvar			6
start loss	1 clinvar	1 clinvar				2
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)	1 clinvar	2 clinvar	1 clinvar			4
Total	25	20	78	27	3	153

Highest pathogenic variant AF is 0.00005081156

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000490.5	RefSeq	NP_000481.2	3	MANE Select
ENST00000380293.3	Ensembl	ENSP00000369647.3	3	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Vasopressin-regulated water reabsorption - Homo sapiens (human)
Phospholipase D signaling pathway - Homo sapiens (human)
BMAL1-CLOCK,NPAS2 activates circadian gene expression
Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways
Signaling by GPCR

Biological Process

maternal aggressive behavior
positive regulation of systemic arterial blood pressure
renal water homeostasis
generation of precursor metabolites and energy
water transport

Molecular Function

protein kinase activity
signaling receptor binding
neuropeptide hormone activity
neurohypophyseal hormone activity
V1A vasopressin receptor binding

Cellular Component

extracellular region
extracellular space
cytosol
secretory granule
dendrite

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000380293
Coding exons: 3
Length: 2169
Individuals with no LoFs: 125584
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125590
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.05	40	63.7	0.628	0.00000351	1025
Missense (PolyPhen)		10	27.371	0.36534		352
Synonymous	0.468	27	30.3	0.892	0.00000204	330
Loss of Function	0.981	2	4.16	0.481	1.78e-7	58

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Neurophysin 2 specifically binds vasopressin.;
Disease: DISEASE: 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. {ECO:0000269|PubMed:10369876, ECO:0000269|PubMed:10487710, ECO:0000269|PubMed:10677561, ECO:0000269|PubMed:11017955, ECO:0000269|PubMed:11150885, ECO:0000269|PubMed:11161827, ECO:0000269|PubMed:11443218, ECO:0000269|PubMed:11748489, ECO:0000269|PubMed:11980620, ECO:0000269|PubMed:12012274, ECO:0000269|PubMed:12107248, ECO:0000269|PubMed:12359138, ECO:0000269|PubMed:12519420, ECO:0000269|PubMed:12931042, ECO:0000269|PubMed:14510916, ECO:0000269|PubMed:14673472, ECO:0000269|PubMed:15538939, ECO:0000269|PubMed:1740104, ECO:0000269|PubMed:7714110, ECO:0000269|PubMed:8045958, ECO:0000269|PubMed:8103767, ECO:0000269|PubMed:8370682, ECO:0000269|PubMed:8514868, ECO:0000269|PubMed:8554046, ECO:0000269|PubMed:9360520, ECO:0000269|PubMed:9580132, ECO:0000269|PubMed:9814475}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.585

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium