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WNK1 Gene

protein-coding GIFtS: 65
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)
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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, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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 pseudohypoaldosteronism type iic, and hereditary sensory and autonomic neuropathy type iia. 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

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 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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Regulatory elements:

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 Chromatin IP Primers for WNK1

Epigenetics:

DNA Methylation CpG Assay Predesigned for Pyrosequencing 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, ²neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, 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., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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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). Interacts with KLHL3

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 H6WZW3 O15052 P54963 Q4VBX9 Q6IFS5 Q86WL5

Q8N673 Q96CZ6 Q9P1S9

Alternative promoter usage, Alternative splicing: 6 isoforms: Q9H4A3-1 Q9H4A3-2 Q9H4A3-4 Q9H4A3-5 Q9H4A3-6 Q9H4A3-7 (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:

O-glycosylated¹

Ubiquitinated in vitro by the BCR(KLHL3) complex; additional evidences are required in vivo¹

Ubiquitination² at Lys375

Modification sites at PhosphoSitePlus

Selected DME Specific Peptides for WNK1 (Q9H4A3) (see all 19)

PLLPQVP

EIGRGSF

YDESVDV

EYPYSEC

See WNK1 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

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

Reactome Protein details: Q9H4A3

WNK1 Human Recombinant Protein Products:

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	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

WNK1 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of WNK1
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	OriGene Antibodies for WNK1 OriGene Custom Antibody 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

WNK1 Assay Products:

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

Wnk family

4 InterPro protein domains:

IPR011009 Kinase-like_dom

IPR008271 Ser/Thr_kinase_AS

IPR000719 Prot_kinase_dom

IPR024678 Kinase_OSR1/WNK_CCT

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,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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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

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): Selected molecular function terms (see all 9): 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

9 MGI mutant phenotypes (inferred from 5 alleles) (MGI details for Wnk1):

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

WNK1 for phenotypes About GeneDecksing

Animal Models:

inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for WNK1

inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models 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-877-3p (MIRT037011), hsa-mir-378a-3p (MIRT043954), hsa-mir-149-5p (MIRT045660), hsa-mir-93-3p (MIRT038785), hsa-mir-615-3p (MIRT040135), hsa-mir-192-5p (MIRT005582), hsa-mir-550a-5p (MIRT037785), hsa-let-7b-5p (MIRT052359), hsa-mir-18a-3p (MIRT040788), hsa-mir-320a (MIRT044712), hsa-mir-331-3p (MIRT043274), hsa-mir-125b-5p (MIRT046056), hsa-mir-197-3p (MIRT048089), hsa-mir-183-5p (MIRT047108), hsa-mir-186-5p (MIRT045005), hsa-mir-21-5p (MIRT030974), hsa-mir-215-5p (MIRT005583), hsa-mir-106b-3p (MIRT038570), hsa-mir-193b-3p (MIRT041474), hsa-mir-423-3p (MIRT042524)

		Block miRNA regulation of human, mouse, rat WNK1 using miScript Target Protectors
		Selected qRT-PCR 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:		OriGene RNAi products in human, mouse, rat for WNK1
		Predesigned siRNA for gene silencing in human, mouse, rat WNK1

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for WNK1

Clone Products:		OriGene clones in human, mouse for WNK1 (see all 17) 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
		Browse ESI BIO Cell Lines and PureStem Progenitors for WNK1

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for WNK1

(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from UniProtKB/Swiss-Prot

WNK1_HUMAN, Q9H4A3: Cytoplasm

Subcellular locations from COMPARTMENTS:

Compartment	Confidence
cytosol	2
nucleus	2
plasma membrane	2
peroxisome	1

About this image

Gene Ontology (GO): 1 cellular component term: About this table

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

WNK1 for ontologies About GeneDecksing

(SuperPaths according to PathCards, Pathways according to 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 QIAGEN, 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 Apr 2014 via Entrez Gene).
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SuperPaths for WNK1 About

See pathways by source

SuperPath

Contained pathways About

Ion channel transport

Ion channel transport

0.58

Stimuli-sensing channels

0.58

Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds

Transmembrane transport of small molecules

0.47

PI3K / Akt Signaling

PI3K / Akt Signaling

EGFR1 Signaling Pathway

EGFR1 Signaling Pathway

Diuretics Pathway, Pharmacodynamics

Diuretics Pathway, Pharmacodynamics

Pathways by source See SuperPaths
Show all pathways

3 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for WNK1

	MAPK Signaling
	Akt Signaling
	ERK5 Signaling

1 Cell Signaling Technology (CST) Pathway for WNK1

PI3K / Akt Signaling

1 BioSystems Pathway for WNK1

EGFR1 Signaling Pathway

1 Reactome Pathway for WNK1

Stimuli-sensing channels

1 PharmGKB Pathway for WNK1

Diuretics Pathway, Pharmacodynamics

WNK1 for pathways About GeneDecksing

Custom Pathway & Disease-focused RT² Profiler PCR Arrays for WNK1
Interactions:

GeneGlobe Interaction Network for WNK1

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

Selected Interacting proteins for WNK1 (Q9H4A3^{1, 2, 3} ENSP00000313059⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 211)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
OXSR1	O95747¹^,²^,³, ENSP00000311713⁴	EBI-457907,EBI-620853 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): Selected biological process terms (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:0010923	negative regulation of phosphatase activity	IDA	19389623
GO:0035556	intracellular signal transduction	IDA	10660600

WNK1 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse compounds at ApexBio

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	--

Selected 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)

WNK1 for compounds About GeneDecksing

(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,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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REFSEQ mRNAs for WNK1 gene (4 alternative transcripts):

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

Selected 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:		Block miRNA regulation of human, mouse, rat WNK1 using miScript Target Protectors
		Selected qRT-PCR 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

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		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 qSTAR qPCR primer pairs in human, mouse for WNK1
		Pre-validated RT² qPCR Primer Assay in human, mouse, rat WNK1
		QuantiTect SYBR Green Assays in human, mouse, rat WNK1
		QuantiFast Probe-based Assays in human, mouse, rat WNK1

Selected AceView cDNA sequences (see all 695):

AI149474 AW967056 AW295073 CA952889 BM715888 AI697129 AI313426 CK724903

AA393667 W74493 AI492425 BC013629 AI492452 AI804294 AI374806 AA705259

AA603085 AA234119 BU739794 BC044600 AA587555 BQ717639 BF115281 AA700748

GeneLoc Exon Structure

Selected 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™, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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WNK1 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: CAGCACATTA

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WNK1 expression in embryonic tissues and stem cells About this table

Data from LifeMap, the Embryonic Development and Stem Cells Database
selected tissues (see all 16) fully expand


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

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

Eye (Sensory Organs) fully expand to see all 2 entries
Retina

Testis (Reproductive System)
Leydig Cells Testis Interstitium

Kidney (Urinary System)
Distal Tubule Cells Distal Tubule

WNK1 Protein expression data from MOPED¹, PaxDb² and MaxQB³:

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WNK1 Protein Expression

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 and specifically expressed in the distal convoluted tubule (DCT) and

connecting tubule (CNT) of the nephron

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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)
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This gene was present in the common ancestor of eukaryotes.

Orthologs for WNK1 gene from Selected species (see all 16) 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}	86.87(n)¹ 86.11(a)¹		6 (56.86 cM)⁵ 232341¹ NM_001199084.1¹ NP_001186013.1¹ 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
fruit fly (Drosophila melanogaster)	Insecta	Wnk⁶	--	23(a)	1 → many	3L(21536950-21548028)
worm (Caenorhabditis elegans)	Secernentea	wnk-1⁶	Protein WNK-1, isoform l (wnk-1) mRNA, complete cd...	26(a)	1 → many	IV(9200116-9212232) WBGene00006941
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)
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Paralogs for WNK1 gene

WNK4² WNK2² NRBP1² NRBP2² WNK3²

17 SIMAP similar genes for WNK1 using alignment to 19 protein entries: WNK1_HUMAN (see all proteins):

CAMK2A BRAF STK11 MST094 NEK9 STK25

CDK4 NEK6 DKFZp564L2416 STK36 PAK2 STK17A

WNK2 WNK4 DAPK1 MAP4K5 ZAK

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), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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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) Selected 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

Site Specific Mutation Identification with PCR Assays

SeqTarget long-range PCR primers for resequencing WNK1

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(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.)
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OMIM gene information: 605232
OMIM disorders: 614492 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

Neuropathy, hereditary sensory and autonomic, 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

Selected diseases for WNK1 (see all 36):
About MalaCards

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

paronychia neuropathy hereditary sensory neuropathy pseudohypoaldosteronism

autonomic neuropathy gitelman syndrome loeys-dietz syndrome autonomic dysfunction

autosomal dominant disease metabolic acidosis essential hypertension hypertension

myotonic dystrophy adult t-cell leukemia prostatitis peripheral neuropathy

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:
The International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD) 9 - 13 March 2014
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)
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PubMed articles for WNK1 gene, integrated from 10 sources (see all 178):
(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. (PLoS ONE 2009)
Variations in the WNK1 gene modulates the effect of dietary intake of sodium and potassium on blood pressure determination. (PubMed id 19609280)^{1, 4, 9} Osada Y....Yamakawa-Kobayashi K. (J. Hum. Genet. 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. (Hypertension 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. (Mol. Cell. Biol. 2003)
WNK kinases, a novel protein kinase subfamily in multi-cellular organisms. (PubMed id 11571656)^{1, 2, 9} Verissimo F. and Jordan P. (Oncogene 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. (Hypertension 2008)
Human hypertension caused by mutations in WNK kinases. (PubMed id 11498583)^{1, 2, 9} Wilson F.H.... Lifton R.P. (Science 2001)
WNK1 kinase polymorphism and blood pressure response to a thiazide diuretic. (PubMed id 16172412)^{1, 4, 9} Turner S.T....Boerwinkle E. (Hypertension 2005)
Kelch-like 3 and Cullin 3 regulate electrolyte homeostasis via ubiquitination and degradation of WNK4. (PubMed id 23576762)^{1, 2} Shibata S....Lifton R.P. (Proc. Natl. Acad. Sci. U.S.A. 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. (PubMed id 23387299)^{1, 2} Ohta A....Kurz T. (Biochem. J. 2013)

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

(According to HUGE)
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HUGE: KIAA0344

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for WNK1	Pharmacogenomics, SNPs, Pathways
GeneReviews	http://www.ncbi.nlm.nih.gov/books/NBK1116/?term=WNK1[genesymbol]

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

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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

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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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