AVPR2

Chr XXLR

arginine vasopressin receptor 2

NCBI Gene: 554ENSG00000126895UniProt: P30518

G-protein-coupled receptor for arginine vasopressin, an antidiuretic that promotes renal water reabsorption (PubMed:1534149, PubMed:19440390, PubMed:33664408, PubMed:33742150). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (cAMP) (PubMed:33664408, PubMed:33742150). AVPR2 is coupled to G(s) G alpha proteins and mediates activation of adenylate cyclase activity (PubMed:33664408, PubMed:33742150)

Primary Disease Associations & Inheritance

Diabetes insipidus, nephrogenic, 1MIM #304800
XLR
Nephrogenic syndrome of inappropriate antidiuresisMIM #300539
XLR
0
ClinVar variants
0
Pathogenic / LP
0.56
pLI score
1
Active trials
Clinical Summary— AVPR2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.56) — some intolerance to loss-of-function variants.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.01Z-score
OE missense 0.79 (0.69–0.91)
148 obs / 186.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.15 (0.05–0.71)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.79 (0.69–0.91)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.16
0≤1.21.6
LoF obs/exp: 1 / 6.6Missense obs/exp: 148 / 186.9Syn Z: -1.10

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Diabetes insipidus, nephrogenic, 1

MIM #304800

Molecular basis of disorder known

X-linked recessive

Nephrogenic syndrome of inappropriate antidiuresis

MIM #300539

Molecular basis of disorder known

X-linked recessive
📖
GeneReview available — AVPR2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Pathophysiology, diagnosis and management of nephrogenic diabetes insipidus.
Bockenhauer D et al.·Nat Rev Nephrol
2015Review
Arginine vasopressin deficiency: diagnosis, management and the relevance of oxytocin deficiency.
Atila C et al.·Nat Rev Endocrinol
2024Review
Nephrogenic diabetes insipidus.
Bichet DG·Adv Chronic Kidney Dis
2006Review
Nephrogenic diabetes insipidus.
Bockenhauer D et al.·Curr Opin Pediatr
2017Review
AVPR2 variants and mutations in nephrogenic diabetes insipidus: review and missense mutation significance.
Spanakis E et al.·J Cell Physiol
2008Review
Nephrogenic diabetes insipidus.
Morello JP et al.·Annu Rev Physiol
2001Review
[Salt fever].
Tory K et al.·Orv Hetil
2024Case report
Nephrogenic diabetes insipidus.
Bichet DG·Am J Med
1998Review
[Nephrogenic diabetes insipidus].
Bichet DG·Nephrol Ther
2006Review
AVPR2 is a potential prognostic biomarker and correlated with immune infiltration in head and neck squamous cell carcinoma.
Mao L et al.·BMC Med Genomics
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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
2025🔓 Open Access
A Novel Pathogenic Variant of the AVPR2 Gene Leading to Arginine Vasopressin Resistance Since the Neonatal Period.
Szmigielska A et al.·Genes (Basel)
2025🔓 Open Access
Clinical and genetic analysis of X-linked nephrogenic diabetes insipidus caused by a novel AVPR2 mutation (NM_000054.6:exon3:c.245G>A (p.Cys82Tyr)) in a Chinese boy.
Yang J et al.·Intractable Rare Dis Res
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Adenine Phosphoribosyltransferase DeficiencyAH AmyloidosisAHL Amyloidosis

National Registry of Rare Kidney Diseases

RECRUITING
NCT06065852UK Kidney AssociationStarted 2009-11-06

External Resources

Links to major genomics databases and tools