Affinage

AVPR2

Vasopressin V2 receptor · UniProt P30518

Length
371 aa
Mass
40.3 kDa
Annotated
2026-06-09
100 papers in source corpus 18 papers cited in narrative 18 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AVPR2 (V2R) is a Gs-coupled vasopressin receptor of renal collecting duct epithelia whose activation by arginine vasopressin drives cAMP-dependent AQP2 phosphorylation and apical insertion for water reabsorption; loss-of-function point mutations cause X-linked nephrogenic diabetes insipidus (NDI) (PMID:1303271). High-affinity agonist binding and productive G protein coupling depend on specific residues in the extracellular and transmembrane regions, with mutations there separately impairing ligand binding, coupling, or folding (PMID:10820167). A large class of NDI mutants are not signaling-defective but trafficking-defective: they misfold and are retained in the ER, where calnexin engages both wild-type and mutant precursors and shows prolonged association with ER-retained mutants as part of receptor quality control (PMID:11389590, PMID:9171234). ER-retained misfolded V2R is cleared predominantly through the lysosomal rather than the proteasomal route (PMID:21629670), and small-molecule V2R ligands act as pharmacochaperones that restore glycosylation maturation, membrane trafficking, and agonist-stimulated cAMP signaling of trafficking-defective mutants (PMID:22144672, PMID:33009446, PMID:27601473). After agonist stimulation, surface V2R is internalized into endosomes as a process separable from AQP2 surface accumulation (PMID:16563128), with Alix binding the V2R C-terminus to accelerate ligand-induced lysosomal downregulation (PMID:17287200). The phosphorylated V2R C-tail encodes selective β-arrestin conformations, and the V2R–β-arrestin complex scaffolds Gβγ to drive sustained endosomal Gs signaling (PMID:33888704, PMID:38972875). Gain-of-function mutation causes constitutive β-arrestin-independent, dynamin-dependent internalization underlying nephrogenic syndrome of inappropriate antidiuresis (NSIAD) (PMID:26131744).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1992 High

    Established that AVPR2 itself is the disease gene, defining loss of V2R function as the molecular basis of X-linked NDI and grounding all subsequent mechanistic work in a clinical phenotype.

    Evidence Genomic sequencing and co-segregation analysis of missense mutations in NDI families

    PMID:1303271

    Open questions at the time
    • Did not resolve at which step (binding, coupling, trafficking) each mutation fails
    • No structural basis for the affected conserved residues
  2. 1997 High

    Identified ER retention and failure to reach the plasma membrane as a mechanism of NDI mutation pathogenicity, distinguishing trafficking defects from signaling defects and defining a minimum C-terminal length required for ER export.

    Evidence Surface ELISA, endoglycosidase H, adenylyl cyclase and binding assays with truncation mutants in COS.M6/HEK293 cells

    PMID:9171234

    Open questions at the time
    • Did not identify the chaperone machinery enforcing retention
    • Did not address how misfolded receptor is degraded
  3. 2000 Medium

    Mapped specific residues to discrete functional roles, separating folding/ER-retention defects from pure ligand-binding defects, refining the genotype-to-mechanism map for NDI.

    Evidence Radioligand binding, adenylyl cyclase coupling, and localization of A84D and W99R mutants in transfected cells

    PMID:10820167

    Open questions at the time
    • Only two mutations characterized
    • No structural model of binding pocket
  4. 2001 High

    Implicated calnexin in AVPR2 ER quality control, providing the chaperone mechanism that retains misfolded NDI mutants in the ER.

    Evidence Sequential co-IP, glycosylation maturation, and confocal localization of WT and mutant receptors in transfected cells

    PMID:11389590

    Open questions at the time
    • Did not define the degradative fate of calnexin-retained mutants
    • Other co-chaperones not characterized
  5. 2006 High

    Separated V2R endocytosis from AQP2 trafficking in space and time, showing the agonist-induced endocytic burst reflects receptor internalization rather than cAMP elevation.

    Evidence Live-cell confocal imaging of tagged V2R and AQP2 in polarized LLC-PK1 cells with forskolin controls

    PMID:16563128

    Open questions at the time
    • Endocytic adaptors driving V2R internalization not identified here
    • Fate of internalized receptor unresolved
  6. 2007 High

    Identified Alix as a direct V2R C-terminal partner that accelerates agonist-induced lysosomal degradation, defining a mechanism for vasopressin-induced receptor downregulation.

    Evidence Yeast two-hybrid, GST pull-down, co-localization, and chloroquine/MG132 inhibitor experiments in LLC-PK1 cells

    PMID:17287200

    Open questions at the time
    • Whether Alix acts via ESCRT for V2R sorting not resolved
    • In vivo contribution to renal V2R turnover untested
  7. 2008 Medium

    Extended V2R biology beyond the kidney by implicating it in vasopressin's anti-inflammatory action in the lung, and defined transcriptional regulation of V2R by hypertonicity and counteracting V1aR signaling.

    Evidence In vivo LPS sepsis model with V2R antagonist; V2R promoter luciferase reporter with JNK/PKA inhibitors and Ca2+ measurements

    PMID:18701631 PMID:18951114

    Open questions at the time
    • Cell type mediating lung anti-inflammatory effect not identified
    • Promoter regulation shown in cell line, not validated in vivo
  8. 2011 Medium

    Demonstrated that V2R antagonists can act as pharmacochaperones (protean agonists) rescuing trafficking-defective mutants, and clarified that misfolded V2R is degraded lysosomally with proteasome inhibition redirecting it to the surface.

    Evidence cAMP assays, localization imaging, and inverse-agonist rescue (OPC compounds); lysosome vs proteasome inhibitor dissection of L170P in MDCK cells

    PMID:21629670 PMID:22144672

    Open questions at the time
    • Generalizability across mutant classes incomplete
    • Mechanism by which ligand binding promotes folding not structurally defined
  9. 2015 Medium

    Defined the gain-of-function NSIAD mechanism, showing constitutive cAMP generation with β-arrestin-independent, dynamin-dependent internalization, contrasting with agonist-induced β-arrestin-dependent endocytosis.

    Evidence cAMP assays, dominant-negative dynamin, surface ELISA, and tolvaptan treatment of I130N in HEK293 cells

    PMID:26131744

    Open questions at the time
    • Structural basis of constitutive activity not resolved
    • How constitutive activity escapes β-arrestin engagement unexplained
  10. 2016 Medium

    Showed a single non-peptide ligand can both rescue ER-retained mutant maturation and act as a surface agonist driving β-arrestin-dependent desensitization, illustrating dual pharmacochaperone/agonist behavior.

    Evidence cAMP assays with peptide antagonist blocking and mutant characterization in COS-7/MDCK cells

    PMID:27601473

    Open questions at the time
    • Balance of intracellular rescue versus surface activation not quantified per mutant
    • Therapeutic window untested in vivo
  11. 2020 Medium

    Validated tolvaptan pharmacochaperone rescue across multiple ER-retained NDI mutants by restoring glycosylation maturation, sorting, and cAMP response.

    Evidence Glycosylation, localization, and cAMP assays with multiple rescue compounds for L86P/M272R/W323_I324insR in MDCK cells

    PMID:33009446

    Open questions at the time
    • Mutant-specific responsiveness not predictable a priori
    • In vivo efficacy not established
  12. 2021 High

    Provided the structural logic for biased signaling by showing V2R C-tail phosphorylation patterns encode distinct β-arrestin conformations through interdependent phospho-binding; separately identified a pure signaling-defect (type III) NDI mutant.

    Evidence X-ray crystallography of four arrestin-2/phosphopeptide complexes with FRET/NMR; localization and cAMP assay of L177Q in HEK-293T cells

    PMID:33888704 PMID:34956990

    Open questions at the time
    • Full-length phosphorylated V2R–arrestin structure not solved
    • L177Q coupling defect not mechanistically dissected (Low confidence)
  13. 2024 Medium

    Established that the V2R–β-arrestin complex scaffolds Gβγ to regenerate an endosomal Gs pool, explaining sustained non-canonical endosomal Gαs signaling.

    Evidence Protein-protein interaction studies and endosomal fractionation using V2R as a model GPCR

    PMID:38972875

    Open questions at the time
    • Physiological consequence of endosomal signaling for renal water handling not established
    • Structural basis of the β-arrestin–Gβγ interaction undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How distinct C-tail phosphorylation barcodes and endosomal Gs signaling translate into the divergent physiological and disease outcomes of V2R activation in vivo remains unresolved.
  • No in vivo link between endosomal signaling and AQP2-mediated water reabsorption
  • Predictive mutation-to-mechanism-to-therapy mapping incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005783 endoplasmic reticulum 3 GO:0005886 plasma membrane 3 GO:0005764 lysosome 2 GO:0005768 endosome 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-382551 Transport of small molecules 2
Partners
ARRB2CANXGNB1PDCD6IP

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 Point mutations in the AVPR2 gene (encoding the renal vasopressin V2 receptor) cause X-linked nephrogenic diabetes insipidus (NDI); missense mutations in conserved extracellular regions of AVPR2 co-segregate with NDI, establishing AVPR2 loss-of-function as the molecular basis of the disorder. Genomic sequencing, genetic mapping, co-segregation analysis in NDI families Nature genetics High 1303271
2001 Calnexin, an ER chaperone, associates with precursor forms of both wild-type and mutant AVPR2 receptors; ER-retained NDI mutants (e.g., W71X, R337X) show prolonged calnexin association compared to wild-type, indicating calnexin participates in quality control and ER retention of misfolded AVPR2. Sequential co-immunoprecipitation, immunofluorescence, confocal microscopy, Western blot, endoglycosidase H treatment in transfected cells Biochemistry High 11389590
1997 The NDI-causing truncation mutant V2R-R337ter is non-functional because it is retained in the ER and fails to reach the plasma membrane; a minimum C-terminal length (requiring at least residues up to position 341, with identity of residue 340 being important) is required for ER export and plasma membrane expression of AVPR2. ELISA on surface-tagged receptors, endoglycosidase H assay, adenylyl cyclase activity, binding assays, metabolic labeling in COS.M6 and HEK293 cells Molecular endocrinology High 9171234
2006 After vasopressin (VP) stimulation of renal epithelial cells, V2R is rapidly internalized into endosomes while AQP2 accumulates at the cell surface in endocytosis-resistant membrane domains; V2R endocytosis and AQP2 trafficking are spatially and temporally separable events, and the initial burst of endocytosis upon VP addition is due to V2R internalization rather than cAMP elevation. Confocal live-cell imaging, epitope-tagged V2R and AQP2 in LLC-PK1 cells, forskolin control, FITC-dextran fluid-phase marker, polarized filter-grown cells Biology of the cell High 16563128
2007 Alix (AIP1) directly interacts with the last 29 amino acids of the V2R C-terminus; upon vasopressin stimulation, Alix accelerates lysosomal (not proteasomal) degradation of V2R, providing a mechanism for VP-induced receptor downregulation in kidney principal cells. Yeast two-hybrid screening, GST pull-down assay, co-immunolocalization, V2R-GFP transfection in LLC-PK1 cells, Western blot, chloroquine and MG132 inhibitor experiments American journal of physiology. Renal physiology High 17287200
2008 Vasopressin reduces LPS-induced pulmonary inflammation (IL-6 levels and NF-κB/IκB phosphorylation) through the V2R; pre-treatment with a V2R antagonist completely abolished vasopressin's immunosuppressive effects, placing V2R as the mediator of vasopressin's anti-inflammatory action in the lung. In vivo mouse LPS sepsis model, receptor-selective antagonist pre-treatment, immunoblotting for phospho-IκB, IL-6 ELISA Resuscitation Medium 18951114
2008 V2R promoter activity is increased by hypertonicity via JNK and PKA pathways, and is suppressed by V1aR stimulation (Ca2+ pathway); hypertonicity enhances V1aR-mediated suppression of V2R expression, revealing a counteracting regulatory mechanism between V1aR and V2R signaling. Luciferase reporter assays with rV2R promoter in LLC-PK1/rV1aR cells, JNK inhibitor (SP600125), PKA inhibitor (H89), intracellular Ca2+ measurements American journal of physiology. Renal physiology Medium 18701631
2011 V2R antagonists (OPC41061, OPC31260) act as protean agonists: they function as pharmacological chaperones that rescue membrane trafficking of inactivating NDI mutants (Ser-333del, Y128S) whose defect is defective membrane trafficking rather than internalization, while acting as inverse agonists of wild-type V2R. COS-7 cell expression, cAMP accumulation assay, immunofluorescence for subcellular localization, internalization inhibition experiments The Journal of biological chemistry Medium 22144672
2015 The I130N gain-of-function mutation in AVPR2 causes constitutive cAMP generation (nephrogenic syndrome of inappropriate antidiuresis, NSIAD); this constitutive activity does not lead to β-arrestin interaction, causing constitutive dynamin-dependent, β-arrestin-independent internalization, whereas agonist-induced endocytosis remains β-arrestin dependent. cAMP assay in HEK293 cells, dominant-negative dynamin transfection, surface expression ELISA, tolvaptan (inverse agonist) treatment Kidney international Medium 26131744
2021 Crystal structures of arrestin-2 in complex with four different phosphopeptides derived from the V2R C-tail revealed that single phospho-interaction changes cause conformational changes at remote arrestin sites; interdependent phospho-binding between different sites was demonstrated, providing a mechanism by which V2R phosphorylation patterns encode selective arrestin functions. X-ray crystallography, FRET, 1H NMR with genetic code expansion, multiple phosphopeptide complexes Nature communications High 33888704
2000 A84D mutation near conserved D85 in AVPR2 causes receptor misfolding and ER retention, affecting both ligand binding and G protein coupling; W99R mutation at the start of the first extracellular loop greatly impairs ligand binding with minor effect on intracellular routing, indicating W99 is critical for high-affinity agonist binding. Functional expression in transfected cells, radioligand binding assays, adenylyl cyclase coupling assays, subcellular localization analysis Journal of the American Society of Nephrology Medium 10820167
2024 The V2R-βarrestin complex scaffolds Gβγ at the plasma membrane through a direct βarrestin-Gβγ interaction, enabling Gβγ transport to endosomes; endosomal Gβγ then potentiates Gαs translocation to endosomes, regenerating an endosomal pool of heterotrimeric Gs for sustained non-canonical endosomal G protein signaling. GPCR signaling assays, protein-protein interaction studies, endosomal fractionation, V2R as model GPCR Communications biology Medium 38972875
2020 NDI-causing AVPR2 mutants L86P, M272R, and W323_I324insR are retained in the ER with immature glycosylation and reduced stability; tolvaptan rescued M272R by restoring glycosylation maturation, membrane sorting, and dDAVP-stimulated cAMP response, demonstrating tolvaptan's pharmacochaperone activity for this specific mutant. MDCK cell expression, immunofluorescence, glycosylation maturation assay, cAMP assay, pharmacological rescue with tolvaptan, VX-809, sildenafil, ibuprofen Scientific reports Medium 33009446
2016 Non-peptide V2R agonist OPC51803 acts both as a pharmacochaperone that promotes ER-retained mutant V2R maturation and trafficking to plasma membrane, and as a conventional agonist causing β-arrestin-dependent desensitization at the cell surface; a peptide antagonist blocked OPC51803-stimulated cAMP, indicating the agonist primarily activates cell-surface receptors. COS-7 and MDCK cell expression, cAMP accumulation assay, peptide antagonist blocking experiments, T273M and other mutant characterization The Journal of biological chemistry Medium 27601473
2011 A novel NDI-causing AVPR2 mutation L170P is retained in the ER; inhibition of the lysosome (but not proteasome) increased intracellular accumulation of L170P, whereas proteasome inhibition resulted in plasma membrane localization, revealing that misfolded AVPR2 is degraded via the lysosomal pathway and that proteasome inhibition can redirect it to the plasma membrane. MDCK cell culture, immunofluorescence, lysosomal inhibitor (chloroquine/bafilomycin) and proteasome inhibitor (MG132) treatment, expression level comparison NDT plus Medium 21629670
2021 A novel AVPR2 missense mutation (c.530T>A, L177Q) results in normal cell-surface expression of the receptor but significantly impaired cAMP accumulation in response to AVP stimulation, classifying it as a type III receptor mutant with a signaling defect rather than a trafficking defect. Immunofluorescence for subcellular localization in HEK-293T cells, cAMP assay after AVP stimulation, wild-type vs mutant comparison Frontiers in pediatrics Low 34956990
2009 Renal carcinoma cells (CAKI-2 and A498) express functional V2R; DDAVP (V2R agonist) induced cell proliferation, and this effect was completely blocked by selective V2R antagonist SR121463B, demonstrating that V2R activation drives proliferation in renal cancer cells via a cAMP-dependent mechanism. Immunofluorescence, RT-PCR for V2R expression, cell proliferation assay with DDAVP and SR121463B in cancer cell lines Urologic oncology Low 19217806
2012 V2R-mediated siRNA delivery is feasible: dDAVP conjugated to nine D-arginines (dDAVP-9r) bound V2R on IMCD cells, induced AQP2 phosphorylation at Ser256, and delivered siRNA specifically into V2R-expressing cells (MDCK, LLC-PK1) but not V2R-negative COS-7 cells, demonstrating ligand-induced V2R internalization can be exploited for receptor-mediated cargo delivery. Peptide synthesis, polyplex formation assay, fluorescein-labeled siRNA delivery, AQP2 phosphorylation immunoblot, V2R-negative cell control PloS one Low 22761946

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Sequence of the human immunoglobulin diversity (D) segment locus: a systematic analysis provides no evidence for the use of DIR segments, inverted D segments, "minor" D segments or D-D recombination. Journal of molecular biology 221 9245589
2003 Functional expression of murine V2R pheromone receptors involves selective association with the M10 and M1 families of MHC class Ib molecules. Cell 212 12628182
1992 Mutations in the vasopressin type 2 receptor gene (AVPR2) associated with nephrogenic diabetes insipidus. Nature genetics 162 1303271
2010 A comparative study of human health risks via consumption of food crops grown on wastewater irrigated soil (Peshawar) and relatively clean water irrigated soil (lower Dir). Journal of hazardous materials 128 20399016
2007 V2R gene families degenerated in primates, dog and cow, but expanded in opossum. Trends in genetics : TIG 128 17382427
1994 Nature and recurrence of AVPR2 mutations in X-linked nephrogenic diabetes insipidus. American journal of human genetics 125 8037205
2006 Dirigent proteins in conifer defense: gene discovery, phylogeny, and differential wound- and insect-induced expression of a family of DIR and DIR-like genes in spruce (Picea spp.). Plant molecular biology 123 16463097
2000 Report of 33 novel AVPR2 mutations and analysis of 117 families with X-linked nephrogenic diabetes insipidus. Journal of the American Society of Nephrology : JASN 114 10820168
2005 Composition and evolution of the V2r vomeronasal receptor gene repertoire in mice and rats. Genomics 112 16024217
2008 AVPR2 variants and mutations in nephrogenic diabetes insipidus: review and missense mutation significance. Journal of cellular physiology 92 18726898
2001 Association of calnexin with wild type and mutant AVPR2 that causes nephrogenic diabetes insipidus. Biochemistry 85 11389590
2005 The gene repertoire and the common evolutionary history of glutamate, pheromone (V2R), taste(1) and other related G protein-coupled receptors. Gene 72 16229975
2012 DiR-labeled Embryonic Stem Cells for Targeted Imaging of in vivo Gastric Cancer Cells. Theranostics 69 22768029
2021 Structural studies of phosphorylation-dependent interactions between the V2R receptor and arrestin-2. Nature communications 67 33888704
2016 Rapamycin/DiR loaded lipid-polyaniline nanoparticles for dual-modal imaging guided enhanced photothermal and antiangiogenic combination therapy. Journal of controlled release : official journal of the Controlled Release Society 63 27388755
1994 Heterogeneous AVPR2 gene mutations in congenital nephrogenic diabetes insipidus. American journal of human genetics 53 7913579
2012 Hereditary nephrogenic diabetes insipidus in Japanese patients: analysis of 78 families and report of 22 new mutations in AVPR2 and AQP2. Clinical and experimental nephrology 47 23150186
1999 MCF-7 breast cancer cells express normal forms of all vasopressin receptors plus an abnormal V2R. Peptides 46 10477084
2010 Coordinated coexpression of two vomeronasal receptor V2R genes per neuron in the mouse. Molecular and cellular neurosciences 43 21112400
1997 An X-linked NDI mutation reveals a requirement for cell surface V2R expression. Molecular endocrinology (Baltimore, Md.) 43 9171234
2006 Aquaporin 2 (AQP2) and vasopressin type 2 receptor (V2R) endocytosis in kidney epithelial cells: AQP2 is located in 'endocytosis-resistant' membrane domains after vasopressin treatment. Biology of the cell 42 16563128
2015 Mutation in the V2 vasopressin receptor gene, AVPR2, causes nephrogenic syndrome of inappropriate diuresis. Kidney international 40 26131744
2006 No evidence for the use of DIR, D-D fusions, chromosome 15 open reading frames or VH replacement in the peripheral repertoire was found on application of an improved algorithm, JointML, to 6329 human immunoglobulin H rearrangements. Immunology 40 17005006
2008 Vasopressin decreases sepsis-induced pulmonary inflammation through the V2R. Resuscitation 38 18951114
2007 Patch-clamp analysis of gene-targeted vomeronasal neurons expressing a defined V1r or V2r receptor: ionic mechanisms underlying persistent firing. Journal of neurophysiology 35 17715188
2018 Molecular Characterization, Evolution, and Expression Profiling of the Dirigent (DIR) Family Genes in Chinese White Pear (Pyrus bretschneideri). Frontiers in genetics 34 29713336
2011 V2 vasopressin receptor (V2R) mutations in partial nephrogenic diabetes insipidus highlight protean agonism of V2R antagonists. The Journal of biological chemistry 34 22144672
2010 Diuretic activity and kidney medulla AQP1, AQP2, AQP3, V2R expression of the aqueous extract of sclerotia of Polyporus umbellatus FRIES in normal rats. Journal of ethnopharmacology 34 20083182
2002 Two novel types of contiguous gene deletion of the AVPR2 and ARHGAP4 genes in unrelated Japanese kindreds with nephrogenic diabetes insipidus. Human mutation 34 11754100
1998 AVPR2 variants and V2 vasopressin receptor function in nephrogenic diabetes insipidus. Kidney international 32 9853256
1992 Tandem duplication of the terminal band of the long arm of chromosome 7 (dir dup (7)(q36----qter)). Journal of medical genetics 31 1583663
2009 V2R mutations and nephrogenic diabetes insipidus. Progress in molecular biology and translational science 30 20374732
1994 Molecular characterization of human Ig heavy chain DIR genes. Journal of immunology (Baltimore, Md. : 1950) 30 8144963
2019 Genome-Wide Identification and Characterization of DIR Genes in Medicago truncatula. Biochemical genetics 29 30649641
1993 Dir dup(X) (q13-->qter) in a girl with growth retardation, microcephaly, developmental delay, seizures, and minor anomalies. American journal of medical genetics 29 7683452
2000 Nephrogenic diabetes insipidus: functional analysis of new AVPR2 mutations identified in Italian families. Journal of the American Society of Nephrology : JASN 28 10820167
2007 Partial nephrogenic diabetes insipidus caused by a novel mutation in the AVPR2 gene. Clinical endocrinology 27 17941907
1993 A Null mutation in the vasopressin V2 receptor gene (AVPR2) associated with nephrogenic diabetes insipidus in the Hopewell kindred. Human molecular genetics 25 8401502
2012 Identification and characterization of a novel X-linked AVPR2 mutation causing partial nephrogenic diabetes insipidus: a case report and review of the literature. Metabolism: clinical and experimental 24 22386940
1992 Colocalization of the gene for nephrogenic diabetes insipidus (DIR) and the vasopressin type 2 receptor gene (AVPR2) in the Xq28 region. Genomics 23 1324225
2018 Ménière's Disease Pathophysiology: Endolymphatic Sac Immunohistochemical Study of Aquaporin-2, V2R Vasopressin Receptor, NKCC2, and TRPV4. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery 22 29436285
2006 Urinary pheromones promote ERK/Akt phosphorylation, regeneration and survival of vomeronasal (V2R) neurons. The European journal of neuroscience 22 17229082
2016 Coordinated shift of olfactory amino acid responses and V2R expression to an amphibian water nose during metamorphosis. Cellular and molecular life sciences : CMLS 21 27990576
1994 Partial trisomy for 2q in a patient with dir dup(2) (q33.1q35). Journal of medical genetics 21 7815427
2021 Evolution, expression and functional analysis of cultivated allotetraploid cotton DIR genes. BMC plant biology 20 33568051
1996 De novo 46,XX, dir dup (11)(q133.3-->q14.2) in a patient with mental retardation, congenital cardiopathy and thrombopenia. Clinical genetics 20 8828987
2017 Detection of intramyocardially injected DiR-labeled mesenchymal stem cells by optical and optoacoustic tomography. Photoacoustics 19 28540184
2012 A novel contiguous gene deletion of AVPR2 and ARHGAP4 genes in male dizygotic twins with nephrogenic diabetes insipidus and intellectual disability. American journal of medical genetics. Part A 19 22965914
2007 Alix (AIP1) is a vasopressin receptor (V2R)-interacting protein that increases lysosomal degradation of the V2R. American journal of physiology. Renal physiology 19 17287200
2007 Contiguous gene deletion involving L1CAM and AVPR2 causes X-linked hydrocephalus with nephrogenic diabetes insipidus. American journal of medical genetics. Part A 19 17318848
2012 Mutations in the AVPR2, AVP-NPII, and AQP2 genes in Turkish patients with diabetes insipidus. Endocrine 18 22644838
2009 Aquaretic inhibits renal cancer proliferation: Role of vasopressin receptor-2 (V2-R). Urologic oncology 18 19217806
2008 Nephrogenic diabetes insipidus in a patient with L1 syndrome: a new report of a contiguous gene deletion syndrome including L1CAM and AVPR2. American journal of medical genetics. Part A 18 18553546
2008 V1R and V2R segregated vomeronasal pathways to the hypothalamus. Neuroreport 18 18845942
1996 Three novel AVPR2 mutations in three Japanese families with X-linked nephrogenic diabetes insipidus. Pediatric research 18 8929875
1994 Patient with de novo 12p+ syndrome identified as dir dup (12) (p13) using subchromosomal painting libraries from somatic cell hybrids. Clinical genetics 18 7889648
1989 Direct duplication of chromosome 1, dir dup(1)(p21.2----p32) in a Bedouin boy with multiple congenital anomalies. American journal of medical genetics 18 2729356
2016 Nephrogenic syndrome of inappropriate antidiuresis secondary to an activating mutation in the arginine vasopressin receptor AVPR2. Clinical endocrinology 17 26715131
1996 Identification and molecular confirmation of a small chromosome 10q duplication [dir dup(10)(q24.2-->q24.3)] inherited from a mother mosaic for the abnormality. American journal of medical genetics 17 8741911
2021 Pre-clinical evaluation of dual targeting of the GPCRs CaSR and V2R as therapeutic strategy for autosomal dominant polycystic kidney disease. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 16 34486176
2020 Characterization of five novel vasopressin V2 receptor mutants causing nephrogenic diabetes insipidus reveals a role of tolvaptan for M272R-V2R mutation. Scientific reports 16 33009446
2008 Immunological profile in a family with nephrogenic diabetes insipidus with a novel 11 kb deletion in AVPR2 and ARHGAP4 genes. BMC medical genetics 16 18489790
2006 Congenital nephrogenic diabetes insipidus presented with bilateral hydronephrosis: genetic analysis of V2R gene mutations. Yonsei medical journal 16 16502494
2015 Effects of Qili Qiangxin Capsule on AQP2, V2R, and AT1R in Rats with Chronic Heart Failure. Evidence-based complementary and alternative medicine : eCAM 15 26074997
2011 Novel mutation in the AVPR2 gene in a Danish male with nephrogenic diabetes insipidus caused by ER retention and subsequent lysosomal degradation of the mutant receptor. NDT plus 15 21629670
1984 De novo direct tandem duplication of the proximal long arm of chromosome 2: 46,XX,dir dup(2)(q11 X 2q14 X 2). Journal of medical genetics 15 6694186
1978 [Trisomy 13qter by tandem duplication 46, XX, dir dup 13 (q21 qter), 9qh+]. Annales de genetique 15 314266
2002 Characterization of Dir: a putative potassium inward rectifying channel in Drosophila. Mechanisms of development 14 12128223
1996 Analysis of vasopressin receptor type II (V2R) gene in three Japanese pedigrees with congenital nephrogenic diabetes insipidus: identification of a family with complete deletion of the V2R gene. European journal of endocrinology 14 8766937
2018 Novel and recurrent variants in AVPR2 in 19 families with X-linked congenital nephrogenic diabetes insipidus. European journal of pediatrics 13 29594432
2012 Two new large deletions of the AVPR2 gene causing nephrogenic diabetes insipidus and a review of previously published deletions. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 13 22879391
2008 Regulation of V2R transcription by hypertonicity and V1aR-V2R signal interaction. American journal of physiology. Renal physiology 13 18701631
2022 The barley DIR gene family: An expanded gene family that is involved in stress responses. Frontiers in genetics 12 36406120
2016 Analysis of the V2 Vasopressin Receptor (V2R) Mutations Causing Partial Nephrogenic Diabetes Insipidus Highlights a Sustainable Signaling by a Non-peptide V2R Agonist. The Journal of biological chemistry 12 27601473
2012 Vasopressin V2R-targeting peptide carrier mediates siRNA delivery into collecting duct cells. PloS one 12 22761946
2006 Novel vasopressin type 2 (AVPR2) gene mutations in Brazilian nephrogenic diabetes insipidus patients. Genetic testing 12 17020465
2024 Role of the V2R-βarrestin-Gβγ complex in promoting G protein translocation to endosomes. Communications biology 11 38972875
2018 Overlapping but distinct topology for zebrafish V2R-like olfactory receptors reminiscent of odorant receptor spatial expression zones. BMC genomics 11 29792162
2016 Fluorescence molecular tomography of DiR-labeled mesenchymal stem cell implants for osteochondral defect repair in rabbit knees. European radiology 11 27329519
1997 DIR: a novel DNA rearrangement associated with inverted repeats. Nucleic acids research 11 9016591
2023 Genome-wide identification and expression profiling analysis of DIR gene family in Setaria italica. Frontiers in plant science 10 37799547
2022 Lamprey possess both V1R and V2R olfactory receptors, but only V1Rs are expressed in olfactory sensory neurons. Chemical senses 10 35522082
2021 Anticancer activity of repurposed hemostatic agent desmopressin on AVPR2-expressing human osteosarcoma. Experimental and therapeutic medicine 10 33850538
2016 A novel AVPR2 splice site mutation leads to partial X-linked nephrogenic diabetes insipidus in two brothers. European journal of pediatrics 10 26795631
2023 Genome-wide identification, characterization, evolution and expression analysis of the DIR gene family in potato (Solanum tuberosum). Frontiers in genetics 9 37680198
2020 DiR-labeled tolerogenic dendritic cells for targeted imaging in collagen- induced arthritis rats. International immunopharmacology 9 33360828
2019 Obestatin ameliorates water retention in chronic heart failure by downregulating renal aquaporin 2 through GPR39, V2R and PPARG signaling. Life sciences 9 31153818
2018 Four Japanese Patients with Congenital Nephrogenic Diabetes Insipidus due to the AVPR2 Mutations. Case reports in pediatrics 9 30073107
2007 A case of nephrogenic diabetes insipidus with a novel missense mutation in the AVPR2 gene. Pediatric nephrology (Berlin, Germany) 9 17216256
2007 Correlation between AVPR2 mutations and urinary AQP2 excretion in patients with nephrogenic diabetes insipidus. Journal of pediatric endocrinology & metabolism : JPEM 9 17550212
2021 Clinical and Functional Characterization of a Novel Mutation in AVPR2 Causing Nephrogenic Diabetes Insipidus in a Four-Generation Chinese Family. Frontiers in pediatrics 8 34956990
2019 Longitudinal monitoring of cancer cell subpopulations in monolayers, 3D spheroids, and xenografts using the photoconvertible dye DiR. Scientific reports 8 30952965
2017 Therapeutic effects of Euphorbia Pekinensis and Glycyrrhiza glabra on Hepatocellular Carcinoma Ascites Partially Via Regulating the Frk-Arhgdib-Inpp5d-Avpr2-Aqp4 Signal Axis. Scientific reports 8 28165501
2016 A novel mutation affecting the arginine-137 residue of AVPR2 in dizygous twins leads to nephrogenic diabetes insipidus and attenuated urine exosome aquaporin-2. Physiological reports 8 27117808
1995 Recombination potential of the human DIR elements. Journal of immunology (Baltimore, Md. : 1950) 8 7868891
1988 Giemsa-11 technique elucidating three structurally altered nonfluorescent Y chromosomes: r (Y), idic (Yp), dir tan dup (Yp). Annales de genetique 8 3265307
2021 β-Arrestin inhibition induces autophagy, apoptosis, G0/G1 cell cycle arrest in agonist-activated V2R receptor in breast cancer cells. Medical oncology (Northwood, London, England) 7 33721131
2021 Novel AVPR2 mutations and clinical characteristics in 28 Chinese families with congenital nephrogenic diabetes insipidus. Journal of endocrinological investigation 7 34101133
2019 Periconceptional ethanol exposure induces a sex specific diuresis and increase in AQP2 and AVPR2 in the kidneys of aged rat offspring. Physiological reports 7 31691500
2018 Adult female with symptomatic AVPR2-related nephrogenic syndrome of inappropriate antidiuresis (NSIAD). Endocrinology, diabetes & metabolism case reports 7 29472987

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