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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

WNK1 Gene

protein-coding GIFtS: 67
GCID: GC12P000862

WNK Lysine Deficient Protein Kinase 1

(Previous names: protein kinase, lysine deficient 1, hereditary sensory neuropathy,...)
(Previous symbols: PRKWNK1, HSN2)

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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
About This Section

Aliases
WNK Lysine Deficient Protein Kinase 1¹ ²		PSK²
HSN2¹ ² ³ ⁵		Prostate-Derived Sterile 20-Like Kinase²
PRKWNK1¹ ² ³ ⁵		Serine/Threonine-Protein Kinase WNK1²
KDP² ³ ⁵		WNK Lysine Deficient Protein Kinase 1 Isoform²
Erythrocyte 65 KDa Protein² ³		KIAA0344³
Protein Kinase With No Lysine 1² ³		hWNK1³
p65² ³		Kinase Deficient Protein³
EC 2.7.11.1³ ⁸		Protein Kinase Lysine-Deficient 1³
HSAN2² ⁵		PHA2C⁵
Hereditary Sensory Neuropathy, Type II¹		EC 2.7.11⁸
Protein Kinase, Lysine Deficient 1¹

External Ids:	HGNC: 14540¹	Entrez Gene: 65125²	Ensembl: ENSG00000060237⁷	OMIM: 605232⁵	UniProtKB: Q9H4A3³

Export aliases for WNK1 gene to outside databases

Previous GC identifer: GC12P000733

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for WNK1 Gene:

This gene encodes a member of the WNK subfamily of serine/threonine protein kinases. The encoded protein may be a

key regulator of blood pressure by controlling the transport of sodium and chloride ions. Mutations in this gene

have been associated with pseudohypoaldosteronism type II and hereditary sensory neuropathy type II.

Alternatively spliced transcript variants encoding different isoforms have been described but the full-length

nature of all of them has yet to be determined.(provided by RefSeq, May 2010)

GeneCards Summary for WNK1 Gene:

WNK1 (WNK lysine deficient protein kinase 1) is a protein-coding gene. Diseases associated with WNK1 include hereditary sensory and autonomic neuropathy type ii, and pseudohypoaldosteronism type ii. GO annotations related to this gene include protein kinase inhibitor activity and protein serine/threonine kinase activity. An important paralog of this gene is WNK4.

UniProtKB/Swiss-Prot: WNK1_HUMAN, Q9H4A3

Function: Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell

signaling, survival, and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride

cotransporters and potassium-coupled chloride cotransporters respectively. Activates SCNN1A, SCNN1B, SCNN1D and

SGK1. Controls sodium and chloride ion transport by inhibiting the activity of WNK4, by either phosphorylating

the kinase or via an interaction between WNK4 and the autoinhibitory domain of WNK1. WNK4 regulates the activity

of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation. WNK1 may also play a role in actin

cytoskeletal reorganization. Phosphorylates NEDD4L (By similarity)

Gene Wiki entry for WNK1 Gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000012.11 NT_009759.16 NC_018923.2

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the WNK1 gene promoter:
Pax-5 AP-1 AP-2alpha isoform 3 ATF-2 AP-2alpha isoform 2 LCR-F1 AP-2alpha isoform 4 c-Jun AP-2alpha AP-2alphaA
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: WNK1 promoter sequence

Search SABiosciences Chromatin IP Primers for WNK1

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat WNK1

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 12p13.3 Ensembl cytogenetic band: 12p13.33 HGNC cytogenetic band: 12p13.3

WNK1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
WNK1 gene location

GeneLoc information about chromosome 12 GeneLoc Exon Structure

GeneLoc location for GC12P000862: view genomic region (about GC identifiers)

Start:	861,759 bp from pter	End:	1,020,618 bp from pter
Size:	158,860 bases	Orientation:	plus strand

(According to UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MAXQB RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
About This Section

UniProtKB/Swiss-Prot: WNK1_HUMAN, Q9H4A3 (See protein sequence)

Recommended Name: Serine/threonine-protein kinase WNK1

Size: 2382 amino acids; 250794 Da

Cofactor: Magnesium

Subunit: Interacts with SYT2 (By similarity). Interacts with WNK3 and WNK4 (By similarity)

Subcellular location: Cytoplasm

Caution: PubMed:2507249 describes a peptide sequence containing a GlcNAc glycosylated Ser in position 164 while it

is an Arg residue according to others

Caution: Cys-250 is present instead of the conserved Lys which is expected to be an active site residue. Lys-233

appears to fulfill the required catalytic function

Caution: HSN2 was originally thought to be an intronless gene lying within a WNK1 gene intron. It has been shown

to be a nervous system-specific exon of WNK1 included in isoform 4 and isoform 5 (PubMed:18521183)

Caution: It is uncertain whether Met-1 or Met-214 is the initiator in isoform 4 and isoform 5

Sequence caution: Sequence=AAF31483.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of

unknown origin in the C-terminal part; Sequence=AAI30468.1; Type=Miscellaneous discrepancy; Note=Probable cloning

artifact; Sequence=AAI30470.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact;

Sequence=DAA04494.1; Type=Erroneous gene model prediction; Note=Includes 3' and 3' intronic sequences;

Secondary accessions: A1L4B0 C5HTZ5 C5HTZ6 C5HTZ7 O15052 P54963 Q4VBX9 Q6IFS5 Q86WL5 Q8N673

Q9P1S9

Alternative promoter usage, Alternative splicing: 5 isoforms: Q9H4A3-1 Q9H4A3-2 Q9H4A3-4 Q9H4A3-5 Q9H4A3-6 (Contains the nervous system-specific exon HSN2. Produced by alternative splicing)

Explore the universe of human proteins at neXtProt for WNK1: NX_Q9H4A3

Explore proteomics data for WNK1 at MOPED

Post-translational modifications:

UniProtKB: O-glycosylated

View modification sites using PhosphoSitePlus

View neXtProt modification sites for NX_Q9H4A3

4/19 DME Specific Peptides for WNK1 (Q9H4A3) (see all 19)

PLLPQVP

EIGRGSF

YDESVDV

EYPYSEC

WNK1 Protein expression data from MOPED¹, PaxDb² and MAXQB³ : About this image

REFSEQ proteins (4 alternative transcripts):

NP_001171914.1 NP_055638.2 NP_061852.3 NP_998820.3

ENSEMBL proteins:

ENSP00000441972 ENSP00000313059 ENSP00000392542 ENSP00000438313 ENSP00000446462

ENSP00000439552 ENSP00000460651 ENSP00000459380 ENSP00000446253 ENSP00000437503

ENSP00000438985 ENSP00000444465 ENSP00000433548 ENSP00000341292

Human Recombinant Protein Products for WNK1:

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	Browse OriGene full length recombinant human proteins expressed in human HEK293 cells OriGene Protein Over-expression Lysate for WNK1 OriGene Custom MassSpec OriGene Custom Protein Services for WNK1
	GenScript Custom Purified and Recombinant Proteins Services for WNK1
	Novus Biologicals WNK1 Proteins Novus Biologicals WNK1 Lysate
	Browse Sino Biological Recombinant Proteins Browse Sino Biological Cell Lysates
	Browse ProSpec Recombinant Proteins
	Cloud-Clone Corp. Proteins for WNK1

Gene Ontology (GO): 1 cellular component term (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005737	cytoplasm	IDA	10660600

WNK1 for ontologies About GeneDecksing

WNK1 Antibody Products:

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	GenScript Custom Superior Antibodies Services for WNK1
	Novus Biologicals WNK1 Antibodies
	Abcam antibodies for WNK1
	Cloud-Clone Corp. Antibodies for WNK1
	ThermoFisher Antibody for WNK1
	LSBio Antibodies in human, mouse, rat for WNK1

Assay Products for WNK1:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Assay Services for WNK1
	R&D Systems ELISAs for WNK1 (see all)
	GenScript Custom Assay Services for WNK1
	Browse Enzo Life Sciences for kits & assays
	Cloud-Clone Corp. ELISAs for WNK1 Cloud-Clone Corp. CLIAs for WNK1

(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

IUPHAR Guide to PHARMACOLOGY protein family classification: WNK lysine deficient protein kinase 1

Wnk family

4 InterPro protein domains:

IPR011009 Kinase-like_dom

IPR024678 Kinase_OSR1/WNK_CCT

IPR008271 Ser/Thr_kinase_AS

IPR000719 Prot_kinase_cat_dom

Graphical View of Domain Structure for InterPro Entry Q9H4A3

ProtoNet protein and cluster: Q9H4A3

UniProtKB/Swiss-Prot: WNK1_HUMAN, Q9H4A3

Similarity: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily

Similarity: Contains 1 protein kinase domain

WNK1 for domains About GeneDecksing

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
About This Section

Molecular Function:

UniProtKB/Swiss-Prot Summary: WNK1_HUMAN, Q9H4A3

Function: Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell

signaling, survival, and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride

cotransporters and potassium-coupled chloride cotransporters respectively. Activates SCNN1A, SCNN1B, SCNN1D and

SGK1. Controls sodium and chloride ion transport by inhibiting the activity of WNK4, by either phosphorylating

the kinase or via an interaction between WNK4 and the autoinhibitory domain of WNK1. WNK4 regulates the activity

of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation. WNK1 may also play a role in actin

cytoskeletal reorganization. Phosphorylates NEDD4L (By similarity)

Catalytic activity: ATP + a protein = ADP + a phosphoprotein

Enzyme regulation: By hypertonicity. Activation requires autophosphorylation of Ser-382. Phosphorylation of

Ser-378 also promotes increased activity (By similarity)

Enzyme Numbers (IUBMB): EC 2.7.11.1¹ ² EC 2.7.11²

Gene Ontology (GO): 5/8 molecular function terms (GO ID links to tree view) (see all 8): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0004672	protein kinase activity	--	--
GO:0004674	protein serine/threonine kinase activity	IDA	10660600
GO:0004713	protein tyrosine kinase activity	--	--
GO:0004860	protein kinase inhibitor activity	IEA	--
GO:0005515	protein binding	IPI	15350218

WNK1 for ontologies About GeneDecksing

Phenotypes:
6 GenomeRNAi human phenotypes for WNK1:

Decreased Tat-dependent transc	Decreased p24 protein expressi	Decreased substrate adherent c	Decreased viability with pacli
Increased cell death HMECs cel	Upregulation of Wnt/beta-caten

8 MGI mutant phenotypes (inferred from 4 alleles) (MGI details for Wnk1):

cardiovascular system	embryogenesis	growth/size	homeostasis/metabolism	mortality/aging
muscle	nervous system	renal/urinary system

WNK1 for phenotypes About GeneDecksing

Animal Models:

inGenious Targeting Laboratory - Custom generated mouse model solutions for WNK1

inGenious Targeting Laboratory - Custom generated inducible mouse model solutions for WNK1

genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for WNK1

genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for WNK1

miRNA Products:		miRTarBase miRNAs that target WNK1: hsa-mir-215 (MIRT005583), hsa-mir-192 (MIRT005582)

		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat WNK1
		8/115 QIAGEN miScript miRNA Assays for microRNAs that regulate WNK1 (see all 115):
		hsa-miR-300 hsa-miR-199a-3p hsa-miR-4272 hsa-miR-106a hsa-miR-4305 hsa-miR-128 hsa-miR-3074-3p hsa-miR-1244

		SwitchGear 3'UTR luciferase reporter plasmid: WNK1 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene RNAi products in human, mouse, rat for WNK1
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat WNK1

Gene Editing Products:			DNA2.0 Custom Protein Engineering Service for WNK1

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
		OriGene clones in human, mouse for WNK1 (see all 18) OriGene ORF clones in mouse, rat for WNK1 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector (see all 4): WNK1 (NM_001184985)
		Browse Sino Biological Human cDNA Clones
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for WNK1
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat WNK1

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for WNK1
		Search LifeMap BioReagents cell lines for WNK1

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for WNK1

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene).
About This Section

SuperPaths for WNK1 About

See pathways by source

SuperPath

Contained pathways About

EGFR1 Signaling Pathway

EGFR1 Signaling Pathway

Diuretics Pathway, Pharmacodynamics

Diuretics Pathway, Pharmacodynamics

PI3K / Akt Signaling

PI3K / Akt Signaling

Pathways by source See SuperPaths
Show all pathways

1 Cell Signaling Technology (CST) Pathway for WNK1

PI3K / Akt Signaling

1 BioSystems Pathway for WNK1

EGFR1 Signaling Pathway

1 PharmGKB Pathway for WNK1

Diuretics Pathway, Pharmacodynamics

WNK1 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for WNK1

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/210 Interacting proteins for WNK1 (Q9H4A3^{1, 2, 3} ENSP00000313059⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 210)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
OXSR1	O95747²^,³, ENSP00000311713⁴	MINT-5207758 MINT-5207733 I2D: score=3 STRING: ENSP00000311713
GLIS2	Q9BZE0²^,³, ENSP00000262366⁴	MINT-4651487 I2D: score=2 STRING: ENSP00000262366
ABCF1	Q8NE71³	I2D: score=2
ENSG00000206427	P48634³	I2D: score=2
ENSG00000206490	Q8NE71³	I2D: score=2

About this table

Gene Ontology (GO): 5/8 biological process terms (GO ID links to tree view) (see all 8): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0003084	positive regulation of systemic arterial blood pressure	IEA	--
GO:0006468	protein phosphorylation	IDA	10660600
GO:0006811	ion transport	ISS	--
GO:0007243	intracellular protein kinase cascade	IDA	10660600
GO:0010923	negative regulation of phosphatase activity	IDA	19389623

WNK1 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

WNK1 for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for WNK1

5 HMDB Compounds for WNK1 About this table

Compound	Synonyms	CAS #	PubMed Ids
ADP	adenosindiphosphorsaeure (see all 8)	58-64-0	--
Adenosine triphosphate	5'-(tetrahydrogen triphosphate) Adenosine (see all 24)	56-65-5	--
Chlorine	Cl2 (see all 13)	16887-00-6	--
Magnesium	Magnesium (see all 2)	7439-95-4	--
Sodium	Sodium (see all 2)	7440-23-5	--

10/15 Novoseek inferred chemical compound relationships for WNK1 gene (see all 15) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
lysine	73.6	23	11571656 (1), 16083423 (1), 16081417 (1), 19609280 (1) (see all 13)
thiazide	72	2	16172412 (1), 18270262 (1)
threonine	65	8	16081417 (1), 19347040 (1), 19609280 (1), 18433299 (1) (see all 6)
potassium	61.1	20	19609280 (3), 16709664 (3), 18695394 (1), 16820787 (1) (see all 11)
chloride	55	6	16949040 (5), 17194447 (1)
serine	52.5	10	16263722 (2), 16083423 (1), 19347040 (1), 19609280 (1) (see all 6)
sodium	51.3	13	19609280 (3), 16006511 (2), 18591455 (2), 18695394 (1) (see all 8)
nacl	45.8	4	15841204 (2), 16820787 (1), 20375989 (1)
proline	43.6	4	16083423 (1), 16173916 (1), 17190791 (1)
wortmannin	18.6	2	15799971 (1), 14611643 (1)

Search CenterWatch for drugs/clinical trials and news about WNK1

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Sirion Biotech, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for WNK1 gene (4 alternative transcripts):

NM_001184985.1 NM_014823.2 NM_018979.3 NM_213655.4

Unigene Cluster for WNK1:

WNK lysine deficient protein kinase 1

Hs.744906 [show with all ESTs]

Unigene Representative Sequence: NM_001184985

18/21 Ensembl transcripts including schematic representations, and UCSC links where relevant (see all 21):

ENST00000535572 ENST00000315939(uc001qio.4 uc001qip.4) ENST00000447667(uc001qin.3)

ENST00000540360 ENST00000538787 ENST00000544965 ENST00000545285 ENST00000535698

ENST00000574564(uc001qiq.3) ENST00000574679 ENST00000542543 ENST00000545055

ENST00000534872 ENST00000542424 ENST00000537603(uc009zdn.1) ENST00000544559

ENST00000543065(uc009zdm.1) ENST00000540885

miRNA Products:		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat WNK1
		8/115 QIAGEN miScript miRNA Assays for microRNAs that regulate WNK1 (see all 115):
		hsa-miR-300 hsa-miR-199a-3p hsa-miR-4272 hsa-miR-106a hsa-miR-4305 hsa-miR-128 hsa-miR-3074-3p hsa-miR-1244

		SwitchGear 3'UTR luciferase reporter plasmid: WNK1 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
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		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat WNK1

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		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat WNK1

Additional mRNA sequence:

AB002342.2 AF061944.1 AJ296290.1 AY231477.1 BC013629.2 BC035146.1 BC044600.1 BC130467.1

BC130469.1 BC141881.1 DQ925669.1 DQ925670.1 DQ925671.1 DQ925672.1 JQ358908.1 U00946.1

24/33 DOTS entries (see all 33):

DT.92459680 DT.87018079 DT.100044219 DT.92459664 DT.100759856 DT.95070608 DT.92459669 DT.404388

DT.101956099 DT.91975018 DT.92459672 DT.95253682 DT.121107942 DT.87017039 DT.99929276 DT.101970808

DT.121107943 DT.121107982 DT.121108090 DT.100721871 DT.100824998 DT.121108059 DT.121108083 DT.121108099

24/695 AceView cDNA sequences (see all 695):

AA991835 AI168016 AI369805 AI090556 N22269 AI313426 BM128265 BF222318

AW295073 AA856825 AI697129 AI261755 BU787457 CN479604 AI149474 BP350214

AA651930 AA393667 BM662453 CA952889 N69240 AI346862 AA383319 CA449105

GeneLoc Exon Structure

5/8 Alternative Splicing Database (ASD) splice patterns (SP) for WNK1 (see all 8) About this scheme

ExUns:	1a	·	1b	·	1c	^	2	^	3a	·	3b	^	4	^	5	^	6	^	7a	·	7b	^	8	^	9	^	10	^	11a	·	11b	^	12	^	13	^	14a	·	14b	^	15a	·	15b	^	16	^	17	^	18	^	19	^
SP1:											-				-														-								-
SP2:											-				-														-				-		-		-
SP3:
SP4:																																	-		-		-
SP5:

ExUns:	20	^	21	^	22	^	23	^	24	^	25a	·	25b	^	26	^	27a	·	27b	^	28a	·	28b	^	29a	·	29b
SP1:																			-		-
SP2:																			-		-
SP3:
SP4:
SP5:

ECgene alternative splicing isoforms for WNK1

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

WNK1 expression in normal human tissues (normalized intensities) WNK1 embryonic expression: see
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: CAGCACATTA

About this image

WNK1 expression in embryonic tissues and stem cells About this table

Data from LifeMap, the Embryonic Development and Stem Cells Database

5/25 selected tissues (see all 25) fully expand


Brain (Nervous System) fully expand to see all 7 entries
Cerebral Cortex
ganglion/cranial

Blood (Hematopoietic System) fully expand to see all 3 entries
Proerythroblasts Hematopoietic Bone Marrow
umbilical cord reticulocytes

Heart (Cardiovascular System) fully expand to see all 3 entries
heart/ventricle

Neural Tube (Nervous System) fully expand to see all 3 entries
Metencephalon

Nose (Sensory Organs) fully expand to see all 2 entries
sensory organ/nose/nasal cavity

See WNK1 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for WNK1

SOURCE GeneReport for Unigene cluster: Hs.744906

UniProtKB/Swiss-Prot: WNK1_HUMAN, Q9H4A3

Tissue specificity: Widely expressed, with highest levels observed in the testis, heart, kidney and skeletal

muscle. Isoform 3 is kidney-specific

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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of eukaryotes.

Orthologs for WNK1 gene from 6/12 species (see all 12) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Wnk1^{1 , 5}	WNK lysine deficient protein kinase 1^{1, 5}	86.66(n)¹ 86.57(a)¹		6 (56.86 cM)⁵ 232341¹ NM_198703.3¹ NP_941992.2¹ 119923969⁵
chicken (Gallus gallus)	Aves	WNK1⁶	WNK lysine deficient protein kinase 1	68(a)	1 ↔ 1	1(60573792-60671286)
lizard (Anolis carolinensis)	Reptilia	WNK1⁶	WNK lysine deficient protein kinase 1	55(a)	1 ↔ 1	5(12207683-12335637)
African clawed frog (Xenopus laevis)	Amphibia	BJ089983.1²	--	75.66(n)		BJ089983.1
zebrafish (Danio rerio)	Actinopterygii	57090254²	--	79.71(n)		57090254
Alicante grape (Vitis vinifera)	eudicotyledons	CB006804.1²	--	71.81(n)		CB006804.1

ENSEMBL Gene Tree for WNK1 (if available)
TreeFam Gene Tree for WNK1 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for WNK1 gene

WNK4² WNK2² NRBP1² NRBP2² WNK3²

18/25 SIMAP similar genes for WNK1 using alignment to 21 protein entries: WNK1_HUMAN (see all proteins) (see all similar genes):

CAMK2A BRAF ULK1 BRSK2 STK11 TAOK3

MST094 NEK9 NRBP2 STK25 CDK4 NEK6

DKFZp564L2416 STK36 PAK2 STK17A WNK2 EGFR

WNK1 for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, ⁴UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 12 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
VAR_041321⁴		A lung adenocarcinoma sample⁴	--	see VAR_041321	2	F L	mis⁴		0	--	--	--	--
VAR_035640⁴		A colorectal cancer sample⁴	--	see VAR_035640	2	E G	mis⁴		0	--	--	--	--
VAR_035641⁴		Breast cancer samples⁴	--	see VAR_035641	2	Q E	mis⁴		0	--	--	--	--
VAR_041311⁴		A breast pleomorphic lobular carcinoma sample⁴	--	see VAR_041311	2	E Q	mis⁴		0	--	--	--	--
VAR_041320⁴		A breast pleomorphic lobular carcinoma sample⁴	--	see VAR_041320	2	S C	mis⁴		0	--	--	--	--
rs111033592^1,2	C	pathogenic¹	914610(+)	`ACTTCC/TAACCC`	6	Q *	stg¹ int¹		0	--	--	--	--
rs111033591^1,2	C	pathogenic¹	915261(+)	`TTTACC/TGAAAT`	6	R *	stg¹ int¹		0	--	--	--	--
rs111033590^1,2	C	pathogenic¹	915336(+)	`ACTTGC/TAGCCT`	6	Q *	stg¹ int¹		0	--	--	--	--
rs12322352^1,2	F	--	797309(+)	`ATGTTC/TGTAAC`	4	--	us2k¹		1		WA	118
rs182448065^1,2		--	797379(+)	`TGTAGC/TTTGTG`	4	--	us2k¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for WNK1 (861759 - 1020618 bp)

Structural Variations
Database of Genomic Variants (DGV) 10/28 variations for WNK1 (see all 28): About this table

Variant ID	Type	Subtype	PubMed ID
esv2745368	CNV	Deletion	23290073
nsv821212	CNV	Deletion	20802225
dgv27e180	CNV	Deletion	20482838
dgv254e199	CNV	Deletion	23128226
esv2745369	CNV	Deletion	23290073
esv2422082	CNV	Deletion	20811451
esv269252	CNV	Insertion	20981092
nsv898576	CNV	Loss	21882294
nsv518946	CNV	Loss	19592680
nsv898577	CNV	Loss	21882294

Human Gene Mutation Database (HGMD): WNK1

Locus Specific Mutation Databases (LSDB): WNK1

SABiosciences Cancer Mutation PCR Assays

SeqTarget long-range PCR primers for resequencing WNK1

DNA2.0 Custom Variant and Variant Library Synthesis for WNK1

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

OMIM gene information: 605232
OMIM disorders: 145260 201300
UniProtKB/Swiss-Prot: WNK1_HUMAN, Q9H4A3

Pseudohypoaldosteronism 2C (PHA2C) [MIM:614492]: An autosomal dominant disorder characterized by severe

hypertension, hyperkalemia, hyperchloremia, mild hyperchloremic metabolic acidosis in some cases, and correction

of physiologic abnormalities by thiazide diuretics. Note=The disease is caused by mutations affecting the gene

represented in this entry

Hereditary sensory and autonomic neuropathy 2A (HSAN2A) [MIM:201300]: A form of hereditary sensory and

autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration

of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN2A is an

autosomal recessive disorder characterized by impairment of pain, temperature and touch sensation, onset of

symptoms in infancy or early childhood, occurrence of distal extremity pathologies (paronychia, whitlows, ulcers,

and Charcot joints), frequent amputations, sensory loss that affects all modalities of sensation (lower and upper

limbs and perhaps the trunk as well), absence or diminution of tendon reflexes (usually in all limbs), minimal

autonomic dysfunction, absence of sensory nerve action potentials, and virtual absence of myelinated fibers with

decreased numbers of unmyelinated fibers in sural nerves. Note=The disease is caused by mutations affecting the

gene represented in this entry

20/27 diseases for WNK1 (see all 27): About MalaCards

hereditary sensory and autonomic neuropathy type ii pseudohypoaldosteronism type ii pseudohypoaldosteronism type iic hereditary sensory and autonomic neuropathy type iia

hereditary sensory neuropathy paronychia pseudohypoaldosteronism neuropathy

autonomic neuropathy gitelman syndrome autonomic dysfunction loeys-dietz syndrome

autosomal dominant disease metabolic acidosis essential hypertension hypertension

myotonic dystrophy adult t-cell leukemia peripheral neuropathy prostatitis

4 diseases from the University of Copenhagen DISEASES database for WNK1:

Pseudohypoaldosteronism Hypertension Peripheral neuropathy Gitelman syndrome

WNK1 for disorders About GeneDecksing

Congresses - knowledge worth sharing:
Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

8 Novoseek inferred disease relationships for WNK1 gene About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
pseudohypoaldosteronism	96.7	25	16006511 (2), 16081417 (1), 16709664 (1), 15686619 (1) (see all 22)
gordon syndrome	94.3	11	17957199 (2), 15888480 (2), 16709664 (1), 18277144 (1) (see all 8)
hyperkalemia	83.6	19	17957199 (2), 18550644 (2), 12522152 (2), 18695394 (1) (see all 15)
genetic hypertension	57.5	3	15309683 (1), 16501604 (1)
essential hypertension	55.6	5	19347040 (1), 18547946 (1), 18277144 (1), 15888480 (1)
hypertension arterial	32.3	2	18701621 (1), 14645531 (1)
hypotension	8.14	2	15309683 (1)
cancer	0	2	17667937 (1), 20094755 (1)

Genetic Association Database (GAD): WNK1
Human Genome Epidemiology (HuGE) Navigator: WNK1 (16 documents)

Export disorders for WNK1 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for WNK1 gene, integrated from 9 sources (see all 170):
(articles sorted by number of sources associating them with WNK1)

Utopia: connect your pdf to the dynamic
world of online information

Polymorphisms in the WNK1 gene are associated with blood pressure variation and urinary potassium excretion. (PubMed id 19347040)^{1, 4, 9} Newhouse S....Munroe P.B. (2009)
Variations in the WNK1 gene modulates the effect of d ietary intake of sodium and potassium on blood pressure determination. (PubMed id 19609280)^{1, 4, 9} Osada Y....Yamakawa-Kobayashi K. (2009)
Common variation in the WNK1 gene and blood pressure in childhood: the Avon Longitudinal Study of Parents and Children. (PubMed id 18809789)^{1, 4, 9} Tobin M.D....Burton P.R. (2008)
Multiple promoters in the WNK1 gene: one controls expression of a kidney-specific kinase-defective isoform. (PubMed id 14645531)^{1, 2, 9} Delaloy C.... Jeunemaitre X. (2003)
WNK kinases, a novel protein kinase subfamily in multi-cellular organisms. (PubMed id 11571656)^{1, 2, 9} Verissimo F. and Jordan P. (2001)
Physiological interaction between alpha-adducin and WNK1-NEDD4L pathways on sodium-related blood pressure regulation. (PubMed id 18591455)^{1, 4, 9} Manunta P....Samani N.J. (2008)
Human hypertension caused by mutations in WNK kinases. (PubMed id 11498583)^{1, 2, 9} Wilson F.H.... Lifton R.P. (2001)
WNK1 kinase polymorphism and blood pressure response to a thiazide diuretic. (PubMed id 16172412)^{1, 4, 9} Turner S.T....Boerwinkle E. (2005)
Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PubMed id 20379614)^{1, 4} Rose J.E....Uhl G.R. (2010)
Variation at the NFATC2 locus increases the risk of t hiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipr il and rosiglitazone Medication (DREAM) study. (PubMed id 20628086)^{1, 4} Bailey S.D....Anand S. (2010)

(in PubMed, OMIM, and NCBI Bookshelf)
About This Section

		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 65125	HGNC: 14540	AceView: PRKWNK1	Ensembl:ENSG00000060237	euGenes: HUgn65125
ECgene: WNK1	H-InvDB: WNK1

(According to HUGE)
About This Section

HUGE: KIAA0344

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for WNK1	Pharmacogenomics, SNPs, Pathways
GeneReviews	http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/WNK1

Intellectual Property for WNK1 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

About This Section

Patent Information for WNK1 gene:
Search GeneIP for patents involving WNK1

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, SABiosciences, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0 and Sirion Biotech, Clones from EMD Millipore, OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Sirion Biotech, Cell lines from GenScript, and LifeMap BioReagents, PCR Arrays from SABiosciences, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, and/or Enzo Life Sciences, In Situ Hybridization Assays from
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About This Section


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GeneCards Homepage - Last full update: 23 Oct 2013 - Incrementals: 3 Nov 2013 , 7 Nov 2013 , 23 Jan 2014

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WNK1 Gene

WNK Lysine Deficient Protein Kinase 1

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WNK1 (Gene Symbol)
WNK Lysine Deficient Protein Kinase 1
HSN2
PRKWNK1
KDP
Erythrocyte 65 KDa Protein
Protein Kinase With No Lysine 1
p65
EC 2.7.11.1
HSAN2
Hereditary Sensory Neuropathy, Type II
Protein Kinase, Lysine Deficient 1
PSK
Prostate-Derived Sterile 20-Like Kinase
Serine/Threonine-Protein Kinase WNK1
WNK Lysine Deficient Protein Kinase 1 Isoform
KIAA0344
hWNK1
Kinase Deficient Protein
Protein Kinase Lysine-Deficient 1
PHA2C
EC 2.7.11

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WNK1 Gene

WNK Lysine Deficient Protein Kinase 1

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