Property Summary

NCBI Gene PubMed Count 99
PubMed Score 553.01
PubTator Score 333.32

Knowledge Summary

Patent (82,433)


  Disease (7)

Disease Target Count Z-score Confidence
Carcinoma 2147 0.0 1.0
Disease Target Count Z-score Confidence
Neurodegenerative disease 383 0.0 4.0
Neuropathy 210 0.0 4.0
Disease Target Count Z-score Confidence
Kidney disease 397 4.309 2.2
Metabolic acidosis 49 4.05 2.0


  Differential Expression (21)

Disease log2 FC p
interstitial lung disease 1.100 2.5e-02
esophageal adenocarcinoma -1.200 2.6e-02
psoriasis 1.400 3.8e-04
osteosarcoma 1.480 2.0e-02
posterior fossa group B ependymoma -1.800 4.2e-06
glioblastoma -2.000 2.0e-04
astrocytoma 1.400 2.1e-02
atypical teratoid / rhabdoid tumor 1.600 1.2e-05
medulloblastoma -1.200 2.4e-02
medulloblastoma, large-cell -2.200 1.9e-03
adult high grade glioma -1.400 3.0e-02
pilocytic astrocytoma -1.100 2.6e-02
non primary Sjogren syndrome sicca -1.100 1.9e-02
lung adenocarcinoma 1.253 1.9e-03
non-inflammatory breast cancer 1.100 8.4e-04
Alzheimer's disease 1.500 1.9e-02
Pick disease 2.000 1.2e-04
progressive supranuclear palsy 1.600 4.0e-02
gastric carcinoma 1.400 6.2e-03
ovarian cancer 2.400 3.0e-06
sarcoidosis 1.300 4.4e-02

Gene RIF (77)

27082544 Single nucleotide polymorphisms STK39 and WNK were associated with hypertension and BP in our multicenter Belgian case-control study
26241057 findings indicate that the proline-rich exons are modular cassettes that convert WNK1 into a NEDD4-2 substrate, thereby linking aldosterone and other NEDD4-2-suppressing antinatriuretic hormones to NCC phosphorylation status.
26126716 these data provide insight into the mechanism regulating Cl(-) homeostasis in immature neurons, and suggest that WNK1-regulated changes in KCC2 phosphorylation contribute to the developmental excitatory-to-inhibitory GABA sequence.
25803323 Identify a new chimeric transcript generated by the fusion of WNK1 and B4GALNT3 genes, correlated with B4GALNT3 overexpression in papillary thyroid carcinoma.
25739019 a novel gene, WNK1, for susceptibility to pelvic organ prolapse
25477473 Report generation of WNK1 knockout cell lines and effects on WNK signaling.
25362046 study identifies a separation of functions for the WNK1-activated protein kinases OSR1 and SPAK in mediating proliferation, invasion, and gene expression in endothelial cells
25321950 conclude that although multiple candidate genes are involved in development of hypertension, the genetic polymorphism in WNK1 is not a major contributor to the observed variability in blood pressure and familial clustering risk of hypertension
25145935 enhances BK channel function by reducing ERK1/2 signaling-mediated lysosomal degradation of the channel
24803536 data suggest that WNK1 functions as a chloride sensor through direct binding of a regulatory chloride ion to the active site, which inhibits autophosphorylation
24555568 our data show a novel role for the WNK1/OSR1/NKCC1 pathway in glioma migration
23797875 Wnk kinases are positive regulators of canonical Wnt/beta-catenin signaling.
23059770 The WNK1 gene might be mechanistically involved in the variation in BP response to dietary sodium and potassium intake among individuals, and might contribute to the variation of this complex phenotype.
22989884 Data show that intracellular association between WNK1 and oxidative stress-responsive 1 (OSR1) is required for stimulation of OSR1 and Na(+), K(+), Cl(-)-Cotransporter NKCC1 and NKCC2 activities by osmotic stress.
22934535 Findings suggest that inactivating mutations in WNK1 may cause hypokalemic salt-losing tubulopathies (SLT).
22701532 The results evidenced a striking tissue-specific distribution of the different isoforms and the unexpected presence of exon HSN2 in many tissues other than the nervous system.
22119528 WNK1 stimulates PLC-beta signaling in cells by promoting the synthesis of PIP2 via stimulation of phosphatidylinositol 4-kinase IIIalpha.
22080857 review focuses on the mechanisms by which deletions of the first intron of WNK1 found in pseudohypoaldosteronism type 2 patients trigger the disease
21704025 hypertension associated polymorphisms in WNK1 and WNK4 may not be predictors for antihypertensive response to diuretics.
21625937 we report a novel mutation in the WNK1/HSN2 gene in HSAN2 disease
21530900 These results suggested that WNK1 polymorphisms were involved in the predisposition of essential hypertension in Hani and Yi populations and its effects showed a clear population specificity.
21520334 WNK1 AluYb8 insertion might affect human blood pressure via altering the profile of alternatively spliced transcripts
21355052 PI3K-activating hormones inhibit ROMK by enhancing its endocytosis via a mechanism that involves phosphorylation of WNK1 by Akt1 and SGK1.
21317537 IRBIT opposes the effects of WNKs and SPAK by recruiting PP1 to the complex to dephosphorylate CFTR and NBCe1-B, restoring their cell surface expression, in addition to stimulating their activities
21242704 Both IRBIT (inositol 1,4,5-trisphosphate receptor-binding protein) and WNK [with no lysine (K)] kinase have been implicated as additional HCO(3)(-) secretory controllers.
21220314 Data show that a large percentage of WNK1 knockdown cells fail to complete cell division, displaying defects in mitotic spindles and also in abscission and cell survival.
20937822 WNK1 promotes cell surface expression of glucose transporter GLUT1 by regulating a Tre-2/USP6-BUB2-Cdc16 domain family member 4 (TBC1D4)-Rab8A complex
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20410525 Meta-analysis of gene-disease association. (HuGE Navigator)
20379614 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
19913121 Observational study of gene-disease association. (HuGE Navigator)
19739668 Double-reciprocal plots of the initial rates versus the concentration of the substrate revealed that the random sequential activity of WNK catalyzed OXSR1 (oxidative stress response kinase-1) phosphorylation.
19651702 Observational study of gene-disease association. (HuGE Navigator)
19609280 Variations in the WNK1 gene modulates the effect of dietary intake of sodium and potassium on blood pressure determination.
19609280 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
19363035 WNK1 is a novel signaling molecule involved in regulation of LINGO-1 mediated inhibition of neurite extension.
19361385 Single nucleotide polymorphism in the HSN2 exon of this protein cause hereditary sensory neuropathy type II.
19347040 data indicates that multiple rare and common WNK1 variants contribute to BP variation and hypertension, and provide compelling evidence to initiate further genetic and functional studies to explore the role of WNK1 in BP regulation and EH
19347040 Observational study of gene-disease association. (HuGE Navigator)
19244242 KS-WNK1 is an important physiological regulator of renal K(+) excretion, likely through its effects on the ROMK1 channel.
19228968 This study demonstrates that the carriers of a recessive mutation for HSAN2 display greater sensitivity to innocuous thermal stimuli, as well as for cold pain, suggesting a possible environmental adaptive advantage of the heterozygous state.
19068477 Coexpression with active Akt1 increased the phosphorylation of Ser397 and thereby SGK1 kinase activity. SGK1 activation was further augmented by coexpression with the protein kinase WNK1 (with no lysine kinase 1).
18976975 Knockdown of WNK lysine deficient protein kinase 1 (WNK1) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells
18955660 intron 1 deletion resulted in the overexpression of long- and kidney specific-WNK1 in the distal convoluted tubule and ubiquitous ectopic KS-WNK1 expression
18809789 WNK1 variants on blood pressure are mediated via effects on the gradient of blood pressure change with age.
18809789 Observational study of gene-disease association. (HuGE Navigator)
18591455 Physiological interaction between the ADD1 and WNK1-NEDD4L pathways influences the effects of variants in these genes on sodium-related BP regulation.
18591455 Observational study of gene-disease association, gene-gene interaction, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
18550644 Multiple intra- and/or intermolecular interactions of WNK1 domains are at play for regulation of ROMK1 by WNK1 in the kidney.
18521183 HSN2 is a nervous system-specific exon of the WNK1 gene (WNK1/HSN2 isoform).
18187620 Knockdown of WNK lysine deficient protein kinase 1 (WNK1) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells
17957199 WNK1 might mediate renal Na(+) retention and hypertension in K(+) deficiency
17392271 WNK1 is a dual modulator of TGFbeta-Smad signaling pathways
17380208 molecular mechanism for stimulation of endocytosis of ROMK1 by WNK kinases
17190791 These observations shed light on the mechanism by which WNK1 is regulated by hyperosmotic stress.
16949040 WNK1 increases paracellular chloride permeability and phosphorylation of claudin-4
16832045 odd-skipped related 1 and sterile20-related, proline-, alanine-rich kinase are likely links between WNK1 and solute carrier family 12 in a pathway that contributes to volume regulation and blood pressure homeostasis in mammals
16820787 WNK1 and WNK4 gene products and their regulatory effects suggest an essential role for WNKs in coordinating renal Na-Cl reabsorption and K(+) secretion.
16669787 data establish that the CCT domain functions as a multipurpose docking site, enabling SPAK/OSR1 to interact with substrates (NKCC1) and activators (WNK1/WNK4)
16534117 HSN2 mutations are associated with an early childhood onset of a predominantly sensory neuropathy.
16428287 ROMK is antagonistically regulated by long and kidney-specific WNK1 isoforms
16403833 data indicate that transient receptor potential channel 4(TRPV4) is functionally regulated by WNK family kinases 1 and 4 at the level of cell surface expression
16301342 role of WNK1 in blood pressure regulation; interactions of functional variants of WNK1 with dietary intake or with response to antihypertensive drugs, and their impact on cardiovascular morbidity and mortality
16263722 WNK1 and SPAK/OSR1 mediate the hypotonic stress signaling pathway to cation-chloride-coupled cotransporters
16204408 The kidney-specific WNK1 isoform suppresses thiazide-sensitive Na-Cl cotransport through the inhibition of full length WNK1 activity.
16172412 Observational study of gene-disease association. (HuGE Navigator)
16172412 Polymorphisms in genes regulating renal sodium transport, in particular WNK1, predict interindividual differences in antihypertensive responses to hydrochlorothiazide.
15911806 Two founder mutations are responsible for the apparently higher prevalence of HSAN2 in French Canadians. Genotype-phenotype correlation does not suggest any significant clinical variability.
15883153 WNK1 is activated by hypertonic stress. WNK1 phosphorylated both WNK4 and WNK2. In addition, the WNK1 autoinhibitory domain inhibited the catalytic activity of these WNKs.
15686619 WNK kinase may be able to influence ion homeostasis through its effects on synaptotagmin function (review)
15583131 stimulation of KS-WNK1 expression might be an important element of aldosterone-induced Na(+) retention and hypertension
15455397 Screening of hsn2 gene in an HSAN type II Lebanese family showed a 1bp deletion mutation found in a homozygous state in all affected individuals.
15350218 WNK1 selectively binds to and phosphorylates synaptotagmin 2 (Syt2) within its calcium binding C2 domains. Endogenous WNK1 and Syt2 coimmunoprecipitate and colocalize on a subset of secretory granules in INS-1 cells.
15060842 Three different truncating mutations of HSN2 is associated with hereditary sensory and autonomic neuropathy
14645531 control of kidney WNK1 gene expression of kinase-active or -deficient isoforms is mediated predominantly through the use of multiple transcription initiation sites
14611643 Protein kinase B mediates the phosphorylation of WNK1 at Thr-60.
12374799 identification of autoinhibitory domain

AA Sequence

TT                                                                       2381 - 2382

Text Mined References (111)

PMID Year Title
27082544 2016 STK39 and WNK1 Are Potential Hypertension Susceptibility Genes in the BELHYPGEN Cohort.
26241057 2015 Alternatively spliced proline-rich cassettes link WNK1 to aldosterone action.
26126716 2015 WNK1-regulated inhibitory phosphorylation of the KCC2 cotransporter maintains the depolarizing action of GABA in immature neurons.
25803323 2015 New somatic mutations and WNK1-B4GALNT3 gene fusion in papillary thyroid carcinoma.
25739019 2015 Exome sequencing identifies a novel gene, WNK1, for susceptibility to pelvic organ prolapse (POP).
25477473 2015 Generation of WNK1 knockout cell lines by CRISPR/Cas-mediated genome editing.
25362046 2014 Actions of the protein kinase WNK1 on endothelial cells are differentially mediated by its substrate kinases OSR1 and SPAK.
25321950 2014 Lack of family-based association between common variations in WNK1 and blood pressure level.
25145935 2015 WNK1 activates large-conductance Ca2+-activated K+ channels through modulation of ERK1/2 signaling.
24836286 2014 Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk.
24803536 2014 Chloride sensing by WNK1 involves inhibition of autophosphorylation.
24555568 2014 WNK1-OSR1 kinase-mediated phospho-activation of Na+-K+-2Cl- cotransporter facilitates glioma migration.
24393035 2014 The WNK-regulated SPAK/OSR1 kinases directly phosphorylate and inhibit the K+-Cl- co-transporters.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
23838290 2013 KLHL2 interacts with and ubiquitinates WNK kinases.
23797875 2013 Wnk kinases are positive regulators of canonical Wnt/?-catenin signalling.
23576762 2013 Kelch-like 3 and Cullin 3 regulate electrolyte homeostasis via ubiquitination and degradation of WNK4.
23387299 2013 The CUL3-KLHL3 E3 ligase complex mutated in Gordon's hypertension syndrome interacts with and ubiquitylates WNK isoforms: disease-causing mutations in KLHL3 and WNK4 disrupt interaction.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23059770 2013 Common variation in with no-lysine kinase 1 (WNK1) and blood pressure responses to dietary sodium or potassium interventions- family-based association study.
22989884 2012 Interactions with WNK (with no lysine) family members regulate oxidative stress response 1 and ion co-transporter activity.
22934535 2013 Novel missense mutations of WNK1 in patients with hypokalemic salt-losing tubulopathies.
22701532 2012 A new methodology for quantification of alternatively spliced exons reveals a highly tissue-specific expression pattern of WNK1 isoforms.
22119528 2011 WNK1 promotes PIP? synthesis to coordinate growth factor and GPCR-Gq signaling.
22080857 2012 Pathogenesis of pseudohypoaldosteronism type 2 by WNK1 mutations.
21704025 2011 Hypertension associated polymorphisms in WNK1/WNK4 are not associated with hydrochlorothiazide response.
21625937 2011 Hereditary sensory and autonomic neuropathy II due to novel mutation in the HSN2 gene in Mexican families.
21530900 2011 Association of WNK1 exon 1 polymorphisms with essential hypertension in Hani and Yi minorities of China.
21520334 2011 Novel polymorphic AluYb8 insertion in the WNK1 gene is associated with blood pressure variation in Europeans.
21406692 2011 System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
21355052 2011 Activation of PI3-kinase stimulates endocytosis of ROMK via Akt1/SGK1-dependent phosphorylation of WNK1.
21317537 2011 IRBIT governs epithelial secretion in mice by antagonizing the WNK/SPAK kinase pathway.
21269460 2011 Initial characterization of the human central proteome.
21242704 2010 Primers on molecular pathways: bicarbonate transport by the pancreas.
21220314 2011 WNK1 is required for mitosis and abscission.
20937822 2010 Protein kinase WNK1 promotes cell surface expression of glucose transporter GLUT1 by regulating a Tre-2/USP6-BUB2-Cdc16 domain family member 4 (TBC1D4)-Rab8A complex.
20628086 2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
20410525 2010 Failure to validate association between 12p13 variants and ischemic stroke.
20379614 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
20068231 2010 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19739668 2009 Kinetic mechanism and inhibitor characterization of WNK1 kinase.
19690332 2009 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
19651702 2009 Genes for hereditary sensory and autonomic neuropathies: a genotype-phenotype correlation.
19609280 2009 Variations in the WNK1 gene modulates the effect of dietary intake of sodium and potassium on blood pressure determination.
19413330 2009 Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.
19389623 2009 Docking motif-guided mapping of the interactome of protein phosphatase-1.
19363035 2009 LINGO-1 interacts with WNK1 to regulate nogo-induced inhibition of neurite extension.
19361385 2009 [Mutations in the HSN2 exon of WNK1 cause hereditary sensory neuropathy type II].
19347040 2009 Polymorphisms in the WNK1 gene are associated with blood pressure variation and urinary potassium excretion.
19244242 2009 Regulation of ROMK channel and K+ homeostasis by kidney-specific WNK1 kinase.
19228968 2009 Carriers of recessive WNK1/HSN2 mutations for hereditary sensory and autonomic neuropathy type 2 (HSAN2) are more sensitive to thermal stimuli.
19068477 2009 Regulation of a third conserved phosphorylation site in SGK1.
18955660 2008 Deletion of WNK1 first intron results in misregulation of both isoforms in renal and extrarenal tissues.
18809789 2008 Common variation in the WNK1 gene and blood pressure in childhood: the Avon Longitudinal Study of Parents and Children.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18591455 2008 Physiological interaction between alpha-adducin and WNK1-NEDD4L pathways on sodium-related blood pressure regulation.
18550644 2008 Domains of WNK1 kinase in the regulation of ROMK1.
18521183 2008 Mutations in the nervous system--specific HSN2 exon of WNK1 cause hereditary sensory neuropathy type II.
18220336 2008 Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis.
17957199 2007 Mechanisms of disease: WNK-ing at the mechanism of salt-sensitive hypertension.
17721439 2007 Structural insights into the recognition of substrates and activators by the OSR1 kinase.
17673510 2007 SLC26A9 is a Cl(-) channel regulated by the WNK kinases.
17456239 2007 Discovery of tissue-specific exons using comprehensive human exon microarrays.
17456004 2007 Selective translational repression of truncated proteins from frameshift mutation-derived mRNAs in tumors.
17392271 2007 Biological cross-talk between WNK1 and the transforming growth factor beta-Smad signaling pathway.
17380208 2007 Intersectin links WNK kinases to endocytosis of ROMK1.
17344846 2007 Patterns of somatic mutation in human cancer genomes.
17190791 2007 Regulation of activity and localization of the WNK1 protein kinase by hyperosmotic stress.
17081983 2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.
16964243 2006 A probability-based approach for high-throughput protein phosphorylation analysis and site localization.
16959974 2006 The consensus coding sequences of human breast and colorectal cancers.
16949040 2006 Overexpression of human WNK1 increases paracellular chloride permeability and phosphorylation of claudin-4 in MDCKII cells.
16832045 2006 WNK1 and OSR1 regulate the Na+, K+, 2Cl- cotransporter in HeLa cells.
16820787 2006 WNK kinases regulate sodium chloride and potassium transport by the aldosterone-sensitive distal nephron.
16713569 2006 A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration.
16669787 2006 Functional interactions of the SPAK/OSR1 kinases with their upstream activator WNK1 and downstream substrate NKCC1.
16541075 2006 The finished DNA sequence of human chromosome 12.
16534117 2006 Novel mutations in the HSN2 gene causing hereditary sensory and autonomic neuropathy type II.
16428287 2006 Antagonistic regulation of ROMK by long and kidney-specific WNK1 isoforms.
16403833 2006 WNK kinases influence TRPV4 channel function and localization.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16301342 2005 Association of WNK1 gene polymorphisms and haplotypes with ambulatory blood pressure in the general population.
16263722 2005 WNK1 regulates phosphorylation of cation-chloride-coupled cotransporters via the STE20-related kinases, SPAK and OSR1.
16204408 2006 Dominant-negative regulation of WNK1 by its kidney-specific kinase-defective isoform.
16172412 2005 WNK1 kinase polymorphism and blood pressure response to a thiazide diuretic.
15911806 2005 Two mutations in the HSN2 gene explain the high prevalence of HSAN2 in French Canadians.
15883153 2005 Properties of WNK1 and implications for other family members.
15686619 2005 WNK1: analysis of protein kinase structure, downstream targets, and potential roles in hypertension.
15583131 2004 The kidney-specific WNK1 isoform is induced by aldosterone and stimulates epithelial sodium channel-mediated Na+ transport.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15455397 2004 A mutation in the HSN2 gene causes sensory neuropathy type II in a Lebanese family.
15350218 2004 WNK1 phosphorylates synaptotagmin 2 and modulates its membrane binding.
15324660 2004 Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization.
15203218 2004 Circular rapid amplification of cDNA ends for high-throughput extension cloning of partial genes.
15060842 2004 Identification of a novel gene (HSN2) causing hereditary sensory and autonomic neuropathy type II through the Study of Canadian Genetic Isolates.
14681216 2004 WNK1 activates ERK5 by an MEKK2/3-dependent mechanism.
14645531 2003 Multiple promoters in the WNK1 gene: one controls expression of a kidney-specific kinase-defective isoform.
14611643 2004 WNK1, the kinase mutated in an inherited high-blood-pressure syndrome, is a novel PKB (protein kinase B)/Akt substrate.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12374799 2002 Regulation of WNK1 by an autoinhibitory domain and autophosphorylation.
12168954 2002 Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones.
11571656 2001 WNK kinases, a novel protein kinase subfamily in multi-cellular organisms.
11498583 2001 Human hypertension caused by mutations in WNK kinases.
10869238 2000 A new locus on chromosome 12p13.3 for pseudohypoaldosteronism type II, an autosomal dominant form of hypertension.
10660600 2000 PSK, a novel STE20-like kinase derived from prostatic carcinoma that activates the c-Jun N-terminal kinase mitogen-activated protein kinase pathway and regulates actin cytoskeletal organization.
9205841 1997 Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.
8889549 1996 Generation and analysis of 280,000 human expressed sequence tags.
8889548 1996 Normalization and subtraction: two approaches to facilitate gene discovery.
4351257 1973 Hereditary sensory neuropathy, type II. Clinical, electrophysiologic, histologic, and biochemical studies of a Quebec kinship.
2507249 1989 Nucleoplasmic and cytoplasmic glycoproteins.