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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...)
(Previous symbols: PRKWNK1, HSN2)

Explore 31 diseases affiliated with
WNK1 via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
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
HSAN2¹ ² ⁵		WNK Lysine Deficient Protein Kinase 1 Isoform²
KDP² ³ ⁵		KIAA0344³
Erythrocyte 65 KDa Protein² ³		HWNK1¹
Protein Kinase With No Lysine 1² ³		Kinase Deficient Protein³
P65¹		Protein Kinase Lysine-Deficient 1³
EC 2.7.11.1³ ⁸		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:

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)

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

(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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000012.11 NC_018923.1 NT_009759.16

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 ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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 Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
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

Post-translational modifications:

O-glycosylated¹

View modification sites using PhosphoSitePlus²

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 MOPED and PaxDb: 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:

	Browse Purified and Recombinant Proteins at EMD Millipore
	Browse R&D Systems for human recombinant proteins
	Browse recombinant and purified proteins available from Enzo Life Sciences
	Browse OriGene full length recombinant human proteins expressed in human HEK293 cells OriGene Protein Over-expression Lysate: WNK1 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 ProSpec Recombinant Proteins
	Uscn Proteins for WNK1

Gene Ontology (GO): 3 cellular component terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005625	soluble fraction	--	--
GO:0005737	cytoplasm	IDA	10660600
GO:0042598	vesicular fraction	--	--

WNK1 for ontologies About GeneDecksing

WNK1 Antibody Products:

	Browse EMD Millipore's Extensive Line of Mono- and Polyclonal Antibodies
	R&D Systems Antibodies for WNK1
	Cell Signaling Technology (CST) Antibodies for WNK1
	OriGene Antibodies (see all 2): WNK1 OriGene Custom Antibody Services for WNK1
	GenScript Custom Superior Antibodies Services for WNK1
	Novus Biologicals WNK1 Antibodies
	Abcam antibodies for WNK1
	Uscn Antibodies for WNK1
	ThermoFisher Antibodies for WNK1

Assay Products for WNK1:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	R&D Systems ELISAs for WNK1 (see all)
	GenScript Custom Assay Services for WNK1
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for WNK1

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

WNK1 for domains About GeneDecksing

4 InterPro domains/families:

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

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
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, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

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)

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

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

		OriGene 3'-UTR Clone (see all 2): WNK1 Browse MicroRNA Expression Plasmids
		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 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for WNK1 (see all 6) OriGene siRNA: 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 Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for WNK1 (see all 9) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for WNK1 (see all 3) 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

Gene Ontology (GO): 5/6 molecular function terms (GO ID links to tree view) (see all 6): 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:0004860	protein kinase inhibitor activity	IEA	--
GO:0005515	protein binding	IPI	19389623
GO:0005524	ATP binding	IDA	10660600

WNK1 for ontologies About GeneDecksing

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

Animal Models:
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

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, 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 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Diuretics Pathway, Pharmacodynamics

Diuretics Pathway, Pharmacodynamics

1.00

EGFR1 Signaling Pathway

EGFR1 Signaling Pathway

1.00

PI3K / Akt Signaling

PI3K / Akt Signaling

1.00

Pathway sources
See GeneCards unified pathways
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)

5/198 Interacting proteins for WNK1 (Q9H4A3^{1, 2, 3} ENSP00000313059⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 198)

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
RPL9	P32969³	I2D: score=1
RPL9P7	P32969³	I2D: score=1
RPL9P8	P32969³	I2D: score=1

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, 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 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 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
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, 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.356604 [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:		OriGene 3'-UTR Clone (see all 2): WNK1 Browse OriGene MicroRNA Expression Plasmids
		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 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for WNK1 (see all 6) OriGene siRNA: WNK1
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat WNK1

Clone Products:		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for WNK1 (see all 9) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for WNK1 (see all 3) 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)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for WNK1
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat WNK1

Primer Products:		OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for WNK1 Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay in human, mouse, rat WNK1
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat WNK1
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat WNK1

Additional cDNA 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.92459669 DT.95070608 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):

AA856825 AA677083 AA618523 BM128265 N22269 AA383319 AI261755 BM715888

CK724903 AW967056 CA449105 AI567815 CN479604 BP350214 AI149474 W74493

AI313426 BQ956866 BE242673 AA400127 BM128440 AA235846 AW500925 BP361979

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)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: CAGCACATTA

About this image

WNK1 expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

1 LifeMap In Vivo Development Anatomical Compartment/Cell

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Kidney

Distal Tubule

Distal Tubule Cells

Kidney

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

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

SOURCE GeneReport for Unigene cluster: Hs.356604

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 8/24 species (see all 24) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	WNK1⁶	Uncharacterized protein	67(a)	1 ↔ 1	1(62561745-62658792)
lizard (Anolis carolinensis)	Reptilia	WNK1⁶ --	--	65(a) 15(a)	1 ↔ 1 possible ortholog	5(12207662-12335637) 1(205439218-205490633)
African clawed frog (Xenopus laevis)	Amphibia	BJ089983.1²	--	75.66(n)		BJ089983.1
zebrafish (Danio rerio)	Actinopterygii	57090254²	--	79.71(n)		57090254
fruit fly (Drosophila melanogaster)	Insecta	Wnk⁶	--	16(a)	1 → many	3L(21536950-21548028)
worm (Caenorhabditis elegans)	Secernentea	wnk-1⁶	mammalian WNK-type protein kinase homolog family m...	22(a)	1 → many	IV(9200100-9212216)
thale cress (Arabidopsis thaliana)	eudicotyledons	AT5G55560⁶ WNK3⁶ (see all 11)	putative serine/threonine-protein kinase WNK3 (see all 11)	39(a) 32(a) (see all 11)	many ↔ many many ↔ many (see all 11)	5(22506302-22507879) 3(17873012-17875220)
rice (Oryza sativa)	Liliopsida	-- -- (see all 10)	STE_PAK_Ste20_Slob_Wnk.5 - STE kinases include hom... STE_PAK_Ste20_Slob_Wnk.6 - STE kinases include hom... (see all 10)	39(a) 35(a) (see all 10)	many ↔ many many ↔ many (see all 10)	7(23676870-23678955) 12(3127501-3130910)

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 NRBP1² WNK2² NRBP2² WNK3²

18/24 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, UniProtKB, 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
				--	--	--		--	--
rs111033592^1,2	C	pathogenic	977212(+)	`ACTTCC/TAACCC`	6	Q *	stg¹ int¹		0	--	--	--	--
rs111033591^1,2	C	pathogenic	977863(+)	`TTTACC/TGAAAT`	6	R *	stg¹ int¹		0	--	--	--	--
rs111033590^1,2	C	pathogenic	977938(+)	`ACTTGC/TAGCCT`	6	Q *	stg¹ int¹		0	--	--	--	--
rs12322352^1,2	F,	--	860172(+)	`ATGTTC/TGTAAC`	4	--	us2k¹		1		WA	118
rs182448065^1,2		--	860242(+)	`TGTAGC/TTTGTG`	4	--	us2k¹		0	--	--	--	--
rs78209992^1,2	C,F,	--	860449(+)	`GTTCCG/TCAGCG`	4	--	us2k¹		1		WA	118
rs113378640^1,2		--	860462(+)	`CGCTGG/AAGAGA`	4	--	us2k¹		2		CSA	2
rs189057667^1,2		--	860534(+)	`CCGGTA/TGGACT`	4	--	us2k¹		0	--	--	--	--
rs192337339^1,2		--	860560(+)	`CAGTCC/TGCTCC`	4	--	us2k¹		0	--	--	--	--
rs7957649^1,2	C,H,	--	860595(+)	`GGTGCC/ACCCTG`	4	--	us2k¹		10		NA WA CSA	18

HapMap Linkage Disequilibrium report for WNK1 (861759 - 1020618 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 11 variations for WNK1
11 CNVs: 1493 86136 30574 58597 39095 38817 2966 86135 66118 3871 75894
Human Gene Mutation Database (HGMD): WNK1

Locus Specific Mutation Databases (LSDB): WNK1

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

WNK1 for disorders           About GeneDecksing

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

Defects in WNK1 are a cause of pseudohypoaldosteronism type 2C (PHA2C) [MIM:614492]. An autosomal dominant

disease characterized by severe hypertension, hyperkalemia, hyperchloremia, mild hyperchloremic metabolic acidosis in

some cases, and correction of physiologic abnormalities by thiazide diuretics

Defects in WNK1 are a cause of hereditary sensory and autonomic neuropathy type 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

20/31 diseases for WNK1 (see all 31): About MalaCards

hereditary sensory neuropathy neuropathy pseudohypoaldosteronism type ii pseudohypoaldosteronism

pseudohypoaldosteronism type iic hereditary sensory and autonomic neuropathy type ii high blood pressure autonomic neuropathy

autonomic dysfunction prostatitis paronychia autosomal dominant disease

essential hypertension myotonic dystrophy adult t-cell leukemia peripheral neuropathy

fanconi's anemia hypercalciuria hypertension t-cell leukemia

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

Pseudohypoaldosteronism Hypertension Gitelman syndrome Peripheral neuropathy

8 Novoseek 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 159):
(articles sorted by number of sources associating them with WNK1)

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

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)
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)
Mutations in the nervous system--specific HSN2 exon of WNK1 cause hereditary sensory neuropathy type II. (PubMed id 18521183)^{1, 2} Shekarabi M....Rouleau G.A. (2008)
A probability-based approach for high-throughput protein phosphorylation analysis and site localization. (PubMed id 16964243)^{1, 2} Beausoleil S.A.... Gygi S.P. (2006)
The finished DNA sequence of human chromosome 12. (PubMed id 16541075)^{1, 2} Scherer S.E.... Gibbs R.A. (2006)
Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. (PubMed id 17081983)^{1, 2} Olsen J.V....Mann M. (2006)
Two mutations in the HSN2 gene explain the high prevalence of HSAN2 in French Canadians. (PubMed id 15911806)^{1, 2} Roddier K.... Brais B. (2005)
Identification of a novel gene (HSN2) causing hereditary sensory and autonomic neuropathy type II through the study of Canadian genetic isolates. (PubMed id 15060842)^{1, 2} Lafreniere R.G.... Samuels M.E. (2004)

(in PubMed, OMIM, and NCBI Bookshelf)
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		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
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Patent Information for WNK1 gene:
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GeneCards and IP:
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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
HSAN2
KDP
Erythrocyte 65 KDa Protein
Protein Kinase With No Lysine 1
P65
EC 2.7.11.1
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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