AVPR2

Chr XXLR

arginine vasopressin receptor 2

Also known as: ADHR, DI1, DIR, DIR3, NDI, NDI1, V2R

NCBI Gene: 554ENSG00000126895UniProt: P30518OMIM: 300538

AVPR2 encodes the vasopressin V2 receptor, a G-protein-coupled receptor that responds to arginine vasopressin in the kidney to promote water reabsorption and concentrate urine. Mutations cause nephrogenic diabetes insipidus type 1 and nephrogenic syndrome of inappropriate antidiuresis, both affecting renal water homeostasis. The gene follows X-linked recessive inheritance, primarily affecting males.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismXLRLOEUF 0.712 OMIM phenotypes
Clinical Summary— AVPR2
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Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.56) — some intolerance to loss-of-function variants.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.71LOEUF
pLI 0.556
Z-score 2.03
OE 0.15 (0.05–0.71)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint
1.01Z-score
OE missense 0.79 (0.69–0.91)
148 obs / 186.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.15 (0.05–0.71)
0≤0.351.4
Missense OE0.79 (0.69–0.91)
0≤0.61.4
Synonymous OE1.16
0≤1.21.6
LoF obs/exp: 1 / 6.6Missense obs/exp: 148 / 186.9Syn Z: -1.10
DN
0.7131th %ile
GOF
0.86top 5%
LOF
0.3259th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

AVPR2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Identification of a novel large deletion mutation in the AVPR2 gene responsible for hereditary nephrogenic diabetes insipidus in an infant: a case report.
Huang Y et al.·Transl Pediatr
2026Open AccessCase report
De novo GNAS-Gsα variant (p.Thr55Ala) with constitutive gain-of-function effects on AVPR2 and PTH1R signalings.
Ikeda M et al.·J Hum Genet
2026
Functional characterization and cAMP-mediated rescue of a novel truncating AVPR2 mutation causing nephrogenic diabetes insipidus.
Manoel D et al.·Am J Physiol Endocrinol Metab
2025Functional
Novel AVPR2 mutations in congenital nephrogenic diabetes insipidus: clinical characteristics and genetic analysis.
Xue K et al.·Front Pediatr
2025Open Access
A Novel Pathogenic Variant of the AVPR2 Gene Leading to Arginine Vasopressin Resistance Since the Neonatal Period.
Szmigielska A et al.·Genes (Basel)
2025Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients