AVPR2

arginine vasopressin receptor 2, the group of Arginine vasopressin and oxytocin receptors

Basic information

Region (hg38): X:153902531-153907166

Previous symbols: [ "DIR3", "DIR" ]

Links

ENSG00000126895NCBI:554OMIM:300538HGNC:897Uniprot:P30518AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • nephrogenic diabetes insipidus (Supportive), mode of inheritance: AD
  • nephrogenic syndrome of inappropriate antidiuresis (Supportive), mode of inheritance: XL
  • diabetes insipidus, nephrogenic, X-linked (Strong), mode of inheritance: XL
  • nephrogenic syndrome of inappropriate antidiuresis (Strong), mode of inheritance: XL
  • nephrogenic syndrome of inappropriate antidiuresis (Moderate), mode of inheritance: XL
  • diabetes insipidus, nephrogenic, X-linked (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Diabetes insipidus 1, nephrogenic, X-linked; Nephrogenic syndrome of inappropriate antidiuresisXLEndocrine; RenalIn Diabetes insipidus, nephrogenic, X-linked, sequelae may be prevented with early genetic knowledge to allow management of electrolyte and fluid balances (eg, with specific diuretics) has been reported as potentially beneficial); In Nephrogenic syndrome of inappropriate antidiuresis, patients can have electrolyte and fluid imbalances, and management of these issues through initial fluid restriction and osmotic agents) have been reported to be beneficialEndocrine; Renal13644230; 3970081; 3080575; 1356229; 1303271; 8104196; 9329382; 10477148; 15872203; 16845277; 22722264

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AVPR2 gene.

  • not provided (30 variants)
  • Diabetes insipidus, nephrogenic, X-linked (13 variants)
  • Nephrogenic diabetes insipidus (3 variants)
  • Nephrogenic syndrome of inappropriate antidiuresis (2 variants)
  • AVPR2-related disorder (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AVPR2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
1
clinvar
95
clinvar
8
clinvar
104
missense
13
clinvar
16
clinvar
41
clinvar
21
clinvar
10
clinvar
101
nonsense
14
clinvar
1
clinvar
1
clinvar
16
start loss
0
frameshift
10
clinvar
7
clinvar
17
inframe indel
3
clinvar
3
splice donor/acceptor (+/-2bp)
0
splice region
3
3
non coding
2
clinvar
7
clinvar
11
clinvar
6
clinvar
26
Total 39 27 50 127 24

Variants in AVPR2

This is a list of pathogenic ClinVar variants found in the AVPR2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
X-153904993-G-GC Benign (May 10, 2021)1289944
X-153905098-G-C Diabetes insipidus, nephrogenic, X-linked Uncertain significance (Jan 13, 2018)368070
X-153905157-G-A not specified • Diabetes insipidus, nephrogenic, X-linked • Diabetes insipidus, nephrogenic, X-linked;Nephrogenic syndrome of inappropriate antidiuresis Benign/Likely benign (Jan 30, 2024)254771
X-153905163-C-T Likely benign (May 22, 2023)2890168
X-153905164-A-T Diabetes insipidus, nephrogenic, X-linked • AVPR2-related disorder Benign (Jan 31, 2024)368071
X-153905167-TC-T Diabetes insipidus, nephrogenic, X-linked Pathogenic (Apr 20, 2017)438660
X-153905181-C-T Likely benign (Jan 24, 2023)2798685
X-153905188-A-G Likely benign (Feb 18, 2023)2838832
X-153905288-A-G Benign (May 11, 2021)1286248
X-153905512-T-C Likely benign (Nov 25, 2023)2696757
X-153905518-C-T Likely benign (Nov 30, 2023)2972617
X-153905519-G-A not specified Likely benign (May 23, 2024)2964993
X-153905519-G-C Likely benign (Nov 25, 2023)2698853
X-153905524-C-T Likely benign (Nov 05, 2023)2802324
X-153905526-T-G not specified • Diabetes insipidus, nephrogenic, X-linked • Diabetes insipidus, nephrogenic, X-linked;Nephrogenic syndrome of inappropriate antidiuresis • Nephrogenic syndrome of inappropriate antidiuresis Benign/Likely benign (Feb 01, 2024)254772
X-153905541-G-A not specified • Diabetes insipidus, nephrogenic, X-linked Benign (Jan 31, 2024)254773
X-153905542-G-A Likely benign (Feb 05, 2023)2832733
X-153905551-TCTGCCCAGCCTGCCCA-T AVPR2-related disorder Pathogenic (Sep 05, 2023)2630891
X-153905575-C-T Diabetes insipidus, nephrogenic, X-linked Conflicting classifications of pathogenicity (Dec 14, 2023)730476
X-153905582-G-C Inborn genetic diseases Uncertain significance (Oct 12, 2022)2387741
X-153905587-G-T Diabetes insipidus, nephrogenic, X-linked Uncertain significance (Jan 13, 2018)912621
X-153905590-A-C Likely benign (Jan 29, 2024)759980
X-153905594-G-A Inborn genetic diseases Uncertain significance (Sep 07, 2022)2257917
X-153905602-G-A Likely benign (Apr 16, 2023)2856870
X-153905607-C-T Inborn genetic diseases Uncertain significance (Feb 17, 2022)2219485

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
AVPR2protein_codingprotein_codingENST00000358927 34636
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.5560.432125386011253870.00000399
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.011481870.7920.00001782337
Missense in Polyphen4781.690.575341143
Synonymous-1.109178.61.160.00000710851
Loss of Function2.0316.630.1514.22e-799

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.00007220.0000544
Finnish0.000.00
European (Non-Finnish)0.000.00
Middle Eastern0.00007220.0000544
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Receptor for arginine vasopressin. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Involved in renal water reabsorption. {ECO:0000269|PubMed:19440390}.;
Disease
DISEASE: Diabetes insipidus, nephrogenic, X-linked (XNDI) [MIM:304800]: A disorder caused by the inability of the renal collecting ducts to absorb water in response to arginine vasopressin. Characterized by excessive water drinking (polydipsia), excessive urine excretion (polyuria), persistent hypotonic urine, and hypokalemia. {ECO:0000269|PubMed:10694923, ECO:0000269|PubMed:10770218, ECO:0000269|PubMed:11026555, ECO:0000269|PubMed:11232028, ECO:0000269|PubMed:11916004, ECO:0000269|PubMed:1303257, ECO:0000269|PubMed:1303271, ECO:0000269|PubMed:1356229, ECO:0000269|PubMed:16845277, ECO:0000269|PubMed:7560098, ECO:0000269|PubMed:7833930, ECO:0000269|PubMed:7984150, ECO:0000269|PubMed:7987330, ECO:0000269|PubMed:7999078, ECO:0000269|PubMed:8037205, ECO:0000269|PubMed:8045948, ECO:0000269|PubMed:8078903, ECO:0000269|PubMed:8267567, ECO:0000269|PubMed:8479490, ECO:0000269|PubMed:8514744, ECO:0000269|PubMed:9402087, ECO:0000269|PubMed:9452109, ECO:0000269|PubMed:9711877}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Vasopressin-regulated water reabsorption - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Vasopressin Regulation of Water Homeostasis;Peptide GPCRs;GPCRs, Class A Rhodopsin-like;Signaling by GPCR;Signal Transduction;Vesicle-mediated transport;Membrane Trafficking;G alpha (s) signalling events;Vasopressin-like receptors;Peptide ligand-binding receptors;Transport of small molecules;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;Clathrin-mediated endocytosis;Cargo recognition for clathrin-mediated endocytosis;Arf6 trafficking events;Vasopressin regulates renal water homeostasis via Aquaporins;Aquaporin-mediated transport;GPCR downstream signalling (Consensus)

Recessive Scores

pRec
0.589

Intolerance Scores

loftool
0.104
rvis_EVS
1.09
rvis_percentile_EVS
91.85

Haploinsufficiency Scores

pHI
0.179
hipred
N
hipred_score
0.445
ghis
0.514

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
S
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.731

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Avpr2
Phenotype
integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); renal/urinary system phenotype;

Gene ontology

Biological process
regulation of systemic arterial blood pressure by vasopressin;positive regulation of systemic arterial blood pressure;renal water homeostasis;G protein-coupled receptor signaling pathway;adenylate cyclase-modulating G protein-coupled receptor signaling pathway;activation of adenylate cyclase activity;I-kappaB kinase/NF-kappaB signaling;excretion;hemostasis;positive regulation of cell population proliferation;positive regulation of gene expression;telencephalon development;positive regulation of protein ubiquitination;interferon-gamma production;cellular response to hormone stimulus;response to cytokine;negative regulation of urine volume;negative regulation of renal sodium excretion;positive regulation of vasoconstriction;membrane organization
Cellular component
endosome;endoplasmic reticulum;Golgi apparatus;plasma membrane;integral component of plasma membrane;integral component of membrane;clathrin-coated vesicle membrane
Molecular function
vasopressin receptor activity;protein binding