Affinage

AVPR2

Vasopressin V2 receptor · UniProt P30518

Length
371 aa
Mass
40.3 kDa
Annotated
2026-04-28
100 papers in source corpus 14 papers cited in narrative 14 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AVPR2 encodes the vasopressin V2 receptor, a Gαs-coupled GPCR that mediates the antidiuretic response in renal collecting duct epithelium by activating adenylyl cyclase/cAMP signaling upon arginine vasopressin binding, thereby promoting AQP2 water channel trafficking to the apical membrane (PMID:16563128, PMID:9171234). Loss-of-function mutations in AVPR2 cause X-linked nephrogenic diabetes insipidus through mechanisms including ER retention of misfolded receptor (quality-controlled by calnexin) and impaired ligand binding or G protein coupling, while gain-of-function mutations produce constitutive, β-arrestin-independent cAMP signaling and receptor internalization leading to inappropriate antidiuresis (PMID:1303271, PMID:11389590, PMID:26131744, PMID:10820167). After agonist stimulation, V2R undergoes β-arrestin-dependent internalization into endosomes where the V2R–β-arrestin complex scaffolds Gβγ to regenerate heterotrimeric Gs and sustain endosomal cAMP signaling, while Alix directs V2R to lysosomal degradation (PMID:38972875, PMID:17287200). The phosphorylation pattern of the V2R C-terminal tail allosterically determines arrestin-2 conformation and biases selective downstream arrestin functions, as revealed by crystal structures of arrestin-2 bound to distinct V2R phosphopeptides (PMID:33888704).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1992 High

    Identification of AVPR2 as the causative gene for X-linked nephrogenic diabetes insipidus established the molecular basis of renal vasopressin resistance, linking a specific GPCR to water homeostasis.

    Evidence DNA sequencing and co-segregation analysis in NDI families

    PMID:1303271

    Open questions at the time
    • Mechanism by which individual mutations impair receptor function was unknown
    • No structure–function dissection of critical residues
  2. 1997 High

    Demonstrating that the NDI truncation mutant R337ter is retained in the ER as an immature glycoform incapable of ligand binding or adenylyl cyclase coupling established that the C-terminal tail is essential for V2R maturation and surface trafficking.

    Evidence Endoglycosidase H sensitivity, surface ELISA, adenylyl cyclase assay, and truncation series in COS.M6/HEK293 cells

    PMID:9171234

    Open questions at the time
    • Identity of chaperones involved in ER retention unknown
    • Structural basis of C-tail requirement unresolved
  3. 2000 Medium

    Functional dissection of A84D and W99R mutations revealed that specific residues contribute to distinct steps — protein folding/routing versus ligand recognition — showing that NDI mutations do not act through a single mechanism.

    Evidence Radioligand binding, adenylyl cyclase coupling, and immunofluorescence in transfected cells

    PMID:10820167

    Open questions at the time
    • Only two mutants examined
    • No structural context for folding versus binding defects
  4. 2001 High

    Identifying calnexin as an ER chaperone that associates with both wild-type and misfolded V2R — with prolonged association for ER-retained mutants — established the molecular basis for ER quality control of V2R.

    Evidence Sequential co-immunoprecipitation, confocal microscopy, and metabolic labeling in transfected cells

    PMID:11389590

    Open questions at the time
    • Whether calnexin is sufficient or necessary for retention unknown
    • Role of other ER quality control components not addressed
  5. 2006 High

    Live-cell imaging revealed that after vasopressin stimulation V2R is rapidly internalized while AQP2 remains at the surface in endocytosis-resistant domains, demonstrating that V2R signaling and V2R endocytosis are temporally uncoupled from the effector (AQP2) response.

    Evidence Confocal live-cell imaging with epitope-tagged V2R and AQP2 in polarized LLC-PK1 cells

    PMID:16563128

    Open questions at the time
    • Molecular identity of 'endocytosis-resistant' AQP2 domains unclear
    • Mechanism coupling basolateral V2R internalization to apical AQP2 not defined
  6. 2007 High

    Discovery that Alix binds the V2R C-terminus and promotes lysosomal rather than proteasomal degradation after vasopressin stimulation defined the post-endocytic sorting route that terminates V2R signaling.

    Evidence Yeast two-hybrid, GST pull-down, and lysosomal/proteasomal inhibitor experiments in LLC-PK1 cells

    PMID:17287200

    Open questions at the time
    • ESCRT-pathway components downstream of Alix not mapped
    • Stoichiometry and regulation of Alix–V2R interaction unknown
  7. 2008 Medium

    Reciprocal transcriptional regulation of AVPR2 by hypertonicity (via JNK/PKA) and V1aR signaling (via Ca²⁺) through a 10-bp Sp1 element revealed how extracellular tonicity and receptor cross-talk control V2R expression levels.

    Evidence Promoter-reporter deletion analysis and kinase inhibitors in LLC-PK1 cells

    PMID:18701631

    Open questions at the time
    • In vivo relevance of V1aR-V2R transcriptional cross-talk unverified
    • Whether Sp1 itself is the transcription factor binding this element not confirmed by direct binding assay
  8. 2011 Medium

    Showing that non-peptide V2R antagonists rescue surface trafficking of ER-retained NDI mutants while acting as inverse agonists on wild-type receptor established the pharmacological chaperone concept for V2R and its therapeutic potential in NDI.

    Evidence cAMP accumulation assay and immunofluorescence rescue in COS-7 cells with OPC41061/OPC31260

    PMID:22144672

    Open questions at the time
    • No in vivo pharmacochaperone rescue demonstrated in this study
    • Structural basis for chaperone versus inverse agonist activity unclear
  9. 2015 Medium

    The gain-of-function I130N mutation revealed that constitutive V2R internalization occurs through a dynamin-dependent but β-arrestin-independent pathway, mechanistically distinct from agonist-stimulated β-arrestin-dependent endocytosis.

    Evidence cAMP assay, dominant-negative dynamin, β-arrestin interaction assays in HEK293 cells

    PMID:26131744

    Open questions at the time
    • Adaptor mediating constitutive β-arrestin-independent internalization not identified
    • Only one gain-of-function mutation studied
  10. 2020 Medium

    Systematic functional characterization of five NDI mutations in polarized cells, including pharmacochaperone rescue of M272R by tolvaptan, confirmed that ER-retained V2R mutants can be functionally rescued to restore both surface expression and cAMP signaling.

    Evidence Endo H glycosylation assay, immunofluorescence in polarized MDCK cells, cAMP assay with tolvaptan rescue

    PMID:33009446

    Open questions at the time
    • Clinical efficacy of pharmacochaperone therapy not demonstrated
    • Rescue of R113Q and C192S (surface-expressed but non-functional) not achieved
  11. 2021 High

    Crystal structures of arrestin-2 with four distinct V2R C-tail phosphopeptides revealed that specific phosphorylation patterns allosterically determine arrestin conformation at remote sites, providing the structural basis for phosphorylation-barcode-dependent biased signaling.

    Evidence X-ray crystallography of four arrestin-2/V2Rpp complexes validated by FRET and ¹H NMR

    PMID:33888704

    Open questions at the time
    • Full-length V2R–arrestin complex structure not determined
    • Cellular phosphorylation dynamics at individual sites in native tissue not mapped
  12. 2024 Medium

    Demonstration that the V2R–β-arrestin complex scaffolds Gβγ and transports it to endosomes to regenerate heterotrimeric Gs established a mechanism for sustained endosomal G protein signaling, resolving how V2R continues cAMP production after internalization.

    Evidence Co-IP/pulldown of β-arrestin–Gβγ, live-cell imaging of G protein translocation, endosomal cAMP assays

    PMID:38972875

    Open questions at the time
    • Relative contribution of endosomal versus plasma membrane signaling to physiological water reabsorption not quantified
    • Whether this mechanism operates in collecting duct cells in vivo not shown

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full-length V2R–Gs–β-arrestin megacomplex structure and in vivo quantification of endosomal versus plasma membrane cAMP contributions to the antidiuretic response remain unresolved.
  • No full-length receptor–arrestin–G protein ternary complex structure exists
  • In vivo pharmacochaperone efficacy for NDI mutants unestablished in clinical trials driven by structural insights
  • Native phosphorylation barcode kinetics on V2R in renal tissue not characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005783 endoplasmic reticulum 3 GO:0005886 plasma membrane 3 GO:0005768 endosome 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 3 R-HSA-382551 Transport of small molecules 1
Partners
AQP2ARRB1ARRB2CANXGNASGNB1PDCD6IP

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 Mutations in AVPR2 (the vasopressin V2 receptor gene at Xq28) cause X-linked nephrogenic diabetes insipidus (NDI), establishing AVPR2 as the gene responsible for renal insensitivity to vasopressin; point mutations resulting in non-conservative amino acid substitutions co-segregated with NDI in affected families. DNA sequencing of AVPR2 in NDI probands; co-segregation analysis in families Nature genetics High 1303271
2001 Calnexin, an ER chaperone, associates with both wild-type AVPR2 and NDI-causing mutant receptors (W71X, R337X) during folding; ER-retained mutant R337X showed 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, RT-PCR, metabolic labeling in transfected cells Biochemistry High 11389590
1997 The NDI-associated truncation mutant V2R-R337ter fails to reach the plasma membrane because it is retained as an ER precursor form (endoglycosidase H-sensitive); minimum protein length including residues up to position 341 (and the identity of residue 340) is required for V2R to undergo maturation, acquire cell-surface expression, bind ligand, and couple to adenylyl cyclase. ELISA on epitope-tagged surface receptors, endoglycosidase H treatment, metabolic labeling, adenylyl cyclase activity assay, binding assay in COS.M6/HEK293 cells Molecular endocrinology High 9171234
2006 After vasopressin stimulation of renal epithelial cells, V2R is rapidly internalized into endosomes while AQP2 remains at the cell surface in 'endocytosis-resistant' membrane domains; V2R endocytosis is independent of cAMP elevation (forskolin does not induce it), and apical vasopressin can induce basolateral V2R down-regulation and vice versa. Confocal live-cell imaging of epitope-tagged V2R and AQP2 in LLC-PK1 cells, fluid-phase endocytosis marker (FITC-dextran) co-localization, polarized cell filter assays Biology of the cell High 16563128
2007 Alix (AIP1) interacts with the last 29 amino acids of the V2R C-terminus and increases lysosomal (not proteasomal) degradation of V2R after vasopressin stimulation; overexpression of Alix virtually eliminates V2R-GFP fluorescence within 2 h of vasopressin exposure, an effect blocked by chloroquine but not MG132. Yeast two-hybrid screening, GST pull-down assay, immunolocalization, transfection of Alix into LLC-PK1/V2R-GFP cells, Western blotting with chloroquine/MG132 inhibitors American journal of physiology. Renal physiology High 17287200
2008 Vasopressin reduces LPS-induced pulmonary inflammation (IL-6 levels and NF-κB/phospho-IκB) through the V2R; pretreatment with a V2R-specific antagonist completely abolished vasopressin's immunosuppressive pulmonary effects, placing V2R in an anti-inflammatory signaling pathway in the lung. In vivo mouse sepsis model (LPS), vasopressin infusion with receptor-subtype-selective antagonist pretreatment, immunoblotting for phospho-IκB, ELISA for IL-6 Resuscitation Medium 18951114
2008 V2R promoter activity is upregulated by hypertonicity via JNK and PKA pathways (10-bp Sp1 motif is the responsive element), and suppressed by V1aR stimulation through a Ca2+ pathway that is further enhanced under hypertonic conditions, demonstrating reciprocal transcriptional regulation between V1aR and V2R signaling. Promoter-reporter assays in LLC-PK1/rV1aR cells, JNK inhibitor (SP600125) and PKA inhibitor (H89) pharmacology, intracellular Ca2+ measurements, deletion analysis of promoter American journal of physiology. Renal physiology Medium 18701631
2011 Non-peptide V2R antagonists (OPC41061, OPC31260) act as protean agonists: they serve as pharmacological chaperones that rescue membrane trafficking of inactivating V2R mutants (Ser-333del, Y128S) while acting as inverse agonists of wild-type receptor; the trafficking defect of these mutants is not corrected by inhibiting internalization alone. cAMP accumulation assay, immunofluorescence localization in COS-7 cells, pharmacological chaperone rescue experiments The Journal of biological chemistry Medium 22144672
2015 A novel I130N gain-of-function AVPR2 mutation causes constitutive (ligand-independent) cAMP production and constitutive dynamin-dependent, β-arrestin-independent internalization of V2R; agonist-induced endocytosis remained β-arrestin-dependent, revealing mechanistically distinct modes of constitutive vs. agonist-stimulated V2R internalization. cAMP assay in HEK293 cells, dominant-negative dynamin rescue of surface expression, β-arrestin interaction assays, tolvaptan (inverse agonist) inhibition of basal cAMP Kidney international Medium 26131744
2021 Crystal structures of arrestin-2 in complex with four different phosphopeptides derived from the V2R C-tail reveal that individual phosphorylation sites allosterically influence arrestin conformation at remote sites; an interdependent phospho-binding mechanism exists between different arrestin phospho-interaction sites, and specific phosphorylation patterns bias arrestin structural states that correlate with selective arrestin functions. X-ray crystallography (four structures), FRET, 1H NMR with genetic code expansion in arrestin-2/V2R phosphopeptide complexes Nature communications High 33888704
2024 The V2R–β-arrestin complex scaffolds Gβγ at the plasma membrane through a direct β-arrestin–Gβγ interaction and transports Gβγ to endosomes, where Gβγ potentiates Gαs endosomal translocation, thereby regenerating an endosomal pool of heterotrimeric Gs and enabling sustained endosomal G protein signaling. Co-IP/pulldown demonstrating β-arrestin–Gβγ interaction, live-cell imaging of V2R, β-arrestin, and G protein subunit translocation, functional endosomal cAMP signaling assays Communications biology Medium 38972875
2012 dDAVP conjugated to nine D-arginines (dDAVP-9r) binds V2R on inner medullary collecting duct (IMCD) cells and mediates receptor-dependent internalization to deliver siRNA intracellularly; siRNA delivery was specific to V2R-expressing cells and not observed in V2R-negative COS-7 cells, and induced AQP2 phosphorylation at Ser256. siRNA polyplex formation assay, fluorescence microscopy in MDCK/LLC-PK1/COS-7 cells, AQP2 knockdown by Western blot, AQP2 phosphorylation assay in primary IMCD cells PloS one Medium 22761946
2000 The NDI-causing AVPR2 mutation A84D (near conserved D85) causes intracellular retention of the receptor and severely impairs both ligand binding and G protein coupling, while W99R (first extracellular loop) mainly impairs ligand binding with minor effect on intracellular routing, revealing residue-specific contributions to V2R folding vs. ligand recognition. Radioligand binding assay, adenylyl cyclase coupling assay, immunofluorescence localization in transfected cells Journal of the American Society of Nephrology : JASN Medium 10820167
2020 Five NDI-causing AVPR2 mutations were functionally characterized: R113Q and C192S localize normally to the basolateral membrane with mature glycosylation; L86P, M272R, and W323_I324insR are retained in the ER with immature glycosylation and reduced stability. Tolvaptan (V2R antagonist/pharmacochaperone) rescued M272R by restoring glycosylation maturation, membrane sorting, and cAMP response to dDAVP. Immunofluorescence localization in polarized MDCK cells, glycosylation maturation (Endo H assay), cAMP release assay, tolvaptan pharmacochaperone rescue Scientific reports Medium 33009446

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 220 9245589
2003 Functional expression of murine V2R pheromone receptors involves selective association with the M10 and M1 families of MHC class Ib molecules. Cell 211 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 126 20399016
2007 V2R gene families degenerated in primates, dog and cow, but expanded in opossum. Trends in genetics : TIG 126 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 111 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 66 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
1997 An X-linked NDI mutation reveals a requirement for cell surface V2R expression. Molecular endocrinology (Baltimore, Md.) 43 9171234
2010 Coordinated coexpression of two vomeronasal receptor V2R genes per neuron in the mouse. Molecular and cellular neurosciences 42 21112400
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 37 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
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
2011 V2 vasopressin receptor (V2R) mutations in partial nephrogenic diabetes insipidus highlight protean agonism of V2R antagonists. The Journal of biological chemistry 33 22144672
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
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
2006 Urinary pheromones promote ERK/Akt phosphorylation, regeneration and survival of vomeronasal (V2R) neurons. The European journal of neuroscience 21 17229082
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
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 20 29436285
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
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
2017 Detection of intramyocardially injected DiR-labeled mesenchymal stem cells by optical and optoacoustic tomography. Photoacoustics 18 28540184
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
2020 In silico identification and validation of miRNA and their DIR specific targets in Oryza sativa Indica under abiotic stress. Non-coding RNA research 17 33024905
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
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
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 15 34486176
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
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
2024 Role of the V2R-βarrestin-Gβγ complex in promoting G protein translocation to endosomes. Communications biology 9 38972875
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
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 Obestatin ameliorates water retention in chronic heart failure by downregulating renal aquaporin 2 through GPR39, V2R and PPARG signaling. Life sciences 8 31153818
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