Human Gene WNK1 (ENST00000340908.9_6) from GENCODE V47lift37
  Description: WNK lysine deficient protein kinase 1, transcript variant 3 (from RefSeq NM_213655.5)
Gencode Transcript: ENST00000340908.9_6
Gencode Gene: ENSG00000060237.19_17
Transcript (Including UTRs)
   Position: hg19 chr12:861,745-1,020,618 Size: 158,874 Total Exon Count: 28 Strand: +
Coding Region
   Position: hg19 chr12:862,732-1,017,958 Size: 155,227 Coding Exon Count: 28 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsOther NamesGeneReviewsModel InformationMethods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr12:861,745-1,020,618)mRNA (may differ from genome)Protein (2634 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
HGNCHuman Cortex Gene ExpressionMalacardsMGIOMIMPubMed
ReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: WNK1_HUMAN
DESCRIPTION: RecName: Full=Serine/threonine-protein kinase WNK1; EC=2.7.11.1; AltName: Full=Erythrocyte 65 kDa protein; Short=p65; AltName: Full=Kinase deficient protein; AltName: Full=Protein kinase lysine-deficient 1; AltName: Full=Protein kinase with no lysine 1; Short=hWNK1;
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.
COFACTOR: Magnesium.
ENZYME REGULATION: By hypertonicity. Activation requires autophosphorylation of Ser-382. Phosphorylation of Ser-378 also promotes increased activity (By similarity).
SUBUNIT: Interacts with SYT2 (By similarity). Interacts with WNK3 and WNK4 (By similarity).
INTERACTION: P62136:PPP1CA; NbExp=2; IntAct=EBI-457907, EBI-357253; P29101:Syt2 (xeno); NbExp=2; IntAct=EBI-457907, EBI-458017;
SUBCELLULAR LOCATION: Cytoplasm.
TISSUE SPECIFICITY: Widely expressed, with highest levels observed in the testis, heart, kidney and skeletal muscle. Isoform 3 is kidney-specific.
PTM: O-glycosylated.
PTM: Phosphorylated upon DNA damage, probably by ATM or ATR.
DISEASE: 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.
DISEASE: 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.
SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily.
SIMILARITY: Contains 1 protein kinase domain.
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;
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/WNK1";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: WNK1
Diseases sorted by gene-association score: neuropathy, hereditary sensory and autonomic, type ii* (1450), pseudohypoaldosteronism, type iic* (1350), pseudohypoaldosteronism (26), paronychia (13), neuropathy (13), arthrogryposis, distal, type 3 (12), autonomic neuropathy (12), familial hypertension (12), pseudohyperkalemia, familial, 2, due to red cell leak (9), autonomic dysfunction (7), renal tubular transport disease (7), insensitivity to pain, congenital (5), hypertension, essential (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 60.27 RPKM in Brain - Spinal cord (cervical c-1)
Total median expression: 1015.61 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -525.80987-0.533 Picture PostScript Text
3' UTR -675.002660-0.254 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR011009 - Kinase-like_dom
IPR024678 - Kinase_OSR1/WNK_CCT
IPR000719 - Prot_kinase_cat_dom
IPR008271 - Ser/Thr_kinase_AS

Pfam Domains:
PF00069 - Protein kinase domain
PF07714 - Protein tyrosine and serine/threonine kinase
PF12202 - Oxidative-stress-responsive kinase 1 C-terminal domain

SCOP Domains:
56112 - Protein kinase-like (PK-like)
57501 - Cystine-knot cytokines

ModBase Predicted Comparative 3D Structure on Q9H4A3
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGD    
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0000287 magnesium ion binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004860 protein kinase inhibitor activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0019869 chloride channel inhibitor activity
GO:0019870 potassium channel inhibitor activity
GO:0019901 protein kinase binding
GO:0019902 phosphatase binding
GO:0030291 protein serine/threonine kinase inhibitor activity
GO:0030295 protein kinase activator activity

Biological Process:
GO:0002028 regulation of sodium ion transport
GO:0003084 positive regulation of systemic arterial blood pressure
GO:0006468 protein phosphorylation
GO:0006469 negative regulation of protein kinase activity
GO:0006811 ion transport
GO:0010766 negative regulation of sodium ion transport
GO:0010923 negative regulation of phosphatase activity
GO:0016310 phosphorylation
GO:0018107 peptidyl-threonine phosphorylation
GO:0023016 signal transduction by trans-phosphorylation
GO:0032147 activation of protein kinase activity
GO:0033673 negative regulation of kinase activity
GO:0035556 intracellular signal transduction
GO:0046777 protein autophosphorylation
GO:0048666 neuron development
GO:0050794 regulation of cellular process
GO:0071277 cellular response to calcium ion
GO:0071901 negative regulation of protein serine/threonine kinase activity
GO:0090188 negative regulation of pancreatic juice secretion
GO:0090263 positive regulation of canonical Wnt signaling pathway

Cellular Component:
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0016020 membrane


-  Descriptions from all associated GenBank mRNAs
  AF061944 - Homo sapiens kinase deficient protein KDP mRNA, partial cds.
LF384181 - JP 2014500723-A/191684: Polycomb-Associated Non-Coding RNAs.
BC021121 - Homo sapiens WNK lysine deficient protein kinase 1, mRNA (cDNA clone IMAGE:4653173), with apparent retained intron.
BC071959 - Homo sapiens WNK lysine deficient protein kinase 1, mRNA (cDNA clone IMAGE:4651132), with apparent retained intron.
BC094862 - Homo sapiens WNK lysine deficient protein kinase 1, mRNA (cDNA clone IMAGE:4650586), with apparent retained intron.
BC172444 - Synthetic construct Homo sapiens clone IMAGE:100069138, MGC:199149 WNK lysine deficient protein kinase 1 (WNK1) mRNA, encodes complete protein.
KJ903118 - Synthetic construct Homo sapiens clone ccsbBroadEn_12512 WNK1 gene, encodes complete protein.
KJ905529 - Synthetic construct Homo sapiens clone ccsbBroadEn_15140 WNK1 gene, encodes complete protein.
AJ296290 - Homo sapiens mRNA for putative protein kinase (WNK1 gene).
JQ358908 - Homo sapiens WNK lysine deficient protein kinase 1 isoform (WNK1) mRNA, complete cds, alternatively spliced.
BC141881 - Homo sapiens WNK lysine deficient protein kinase 1, mRNA (cDNA clone IMAGE:40126884), partial cds.
AB002342 - Homo sapiens mRNA for KIAA0344 gene, partial cds.
MA619758 - JP 2018138019-A/191684: Polycomb-Associated Non-Coding RNAs.
LF365544 - JP 2014500723-A/173047: Polycomb-Associated Non-Coding RNAs.
LF365542 - JP 2014500723-A/173045: Polycomb-Associated Non-Coding RNAs.
LF365541 - JP 2014500723-A/173044: Polycomb-Associated Non-Coding RNAs.
JD020646 - Sequence 1670 from Patent EP1572962.
JD036178 - Sequence 17202 from Patent EP1572962.
JD020671 - Sequence 1695 from Patent EP1572962.
JD029655 - Sequence 10679 from Patent EP1572962.
LF365540 - JP 2014500723-A/173043: Polycomb-Associated Non-Coding RNAs.
JD019614 - Sequence 638 from Patent EP1572962.
JD021269 - Sequence 2293 from Patent EP1572962.
JD030606 - Sequence 11630 from Patent EP1572962.
JD035859 - Sequence 16883 from Patent EP1572962.
JD035526 - Sequence 16550 from Patent EP1572962.
LF365538 - JP 2014500723-A/173041: Polycomb-Associated Non-Coding RNAs.
MA601121 - JP 2018138019-A/173047: Polycomb-Associated Non-Coding RNAs.
MA601119 - JP 2018138019-A/173045: Polycomb-Associated Non-Coding RNAs.
MA601118 - JP 2018138019-A/173044: Polycomb-Associated Non-Coding RNAs.
MA601117 - JP 2018138019-A/173043: Polycomb-Associated Non-Coding RNAs.
MA601115 - JP 2018138019-A/173041: Polycomb-Associated Non-Coding RNAs.
LF365530 - JP 2014500723-A/173033: Polycomb-Associated Non-Coding RNAs.
LF365526 - JP 2014500723-A/173029: Polycomb-Associated Non-Coding RNAs.
LF365525 - JP 2014500723-A/173028: Polycomb-Associated Non-Coding RNAs.
LF365523 - JP 2014500723-A/173026: Polycomb-Associated Non-Coding RNAs.
LF365522 - JP 2014500723-A/173025: Polycomb-Associated Non-Coding RNAs.
LF365521 - JP 2014500723-A/173024: Polycomb-Associated Non-Coding RNAs.
LF365520 - JP 2014500723-A/173023: Polycomb-Associated Non-Coding RNAs.
BC130467 - Homo sapiens hereditary sensory neuropathy, type II, mRNA (cDNA clone MGC:163339 IMAGE:40146498), complete cds.
BC130469 - Homo sapiens hereditary sensory neuropathy, type II, mRNA (cDNA clone MGC:163341 IMAGE:40146500), complete cds.
HQ258417 - Synthetic construct Homo sapiens clone IMAGE:100072846 Unknown protein gene, encodes complete protein.
KJ905093 - Synthetic construct Homo sapiens clone ccsbBroadEn_14487 WNK1 gene, encodes complete protein.
LF365510 - JP 2014500723-A/173013: Polycomb-Associated Non-Coding RNAs.
LF365509 - JP 2014500723-A/173012: Polycomb-Associated Non-Coding RNAs.
LF365508 - JP 2014500723-A/173011: Polycomb-Associated Non-Coding RNAs.
LF365507 - JP 2014500723-A/173010: Polycomb-Associated Non-Coding RNAs.
LF365495 - JP 2014500723-A/172998: Polycomb-Associated Non-Coding RNAs.
LF365494 - JP 2014500723-A/172997: Polycomb-Associated Non-Coding RNAs.
LF365493 - JP 2014500723-A/172996: Polycomb-Associated Non-Coding RNAs.
LF365492 - JP 2014500723-A/172995: Polycomb-Associated Non-Coding RNAs.
LF365490 - JP 2014500723-A/172993: Polycomb-Associated Non-Coding RNAs.
LF365489 - JP 2014500723-A/172992: Polycomb-Associated Non-Coding RNAs.
LF365488 - JP 2014500723-A/172991: Polycomb-Associated Non-Coding RNAs.
LF365486 - JP 2014500723-A/172989: Polycomb-Associated Non-Coding RNAs.
LF365482 - JP 2014500723-A/172985: Polycomb-Associated Non-Coding RNAs.
LF365481 - JP 2014500723-A/172984: Polycomb-Associated Non-Coding RNAs.
LF365479 - JP 2014500723-A/172982: Polycomb-Associated Non-Coding RNAs.
LF365478 - JP 2014500723-A/172981: Polycomb-Associated Non-Coding RNAs.
DQ925671 - Homo sapiens clone 2-1 WNK lysine deficient protein kinase 1 (WNK1) mRNA, partial cds, alternatively spliced.
DQ925672 - Homo sapiens clone 3B-4 WNK lysine deficient protein kinase 1 (WNK1) mRNA, partial cds, alternatively spliced.
DQ925669 - Homo sapiens clone 2A-3 WNK lysine deficient protein kinase 1 (WNK1) mRNA, partial cds, alternatively spliced.
DQ925670 - Homo sapiens clone 1B-2 WNK lysine deficient protein kinase 1 (WNK1) mRNA, partial cds, alternatively spliced.
BC013629 - Homo sapiens WNK lysine deficient protein kinase 1, mRNA (cDNA clone IMAGE:3445410), partial cds.
LF365468 - JP 2014500723-A/172971: Polycomb-Associated Non-Coding RNAs.
LF365466 - JP 2014500723-A/172969: Polycomb-Associated Non-Coding RNAs.
LF365465 - JP 2014500723-A/172968: Polycomb-Associated Non-Coding RNAs.
BC035146 - Homo sapiens cDNA clone IMAGE:5264735.
BC044600 - Homo sapiens cDNA clone IMAGE:4814776.
LF365463 - JP 2014500723-A/172966: Polycomb-Associated Non-Coding RNAs.
LF365462 - JP 2014500723-A/172965: Polycomb-Associated Non-Coding RNAs.
LF365461 - JP 2014500723-A/172964: Polycomb-Associated Non-Coding RNAs.
DQ580784 - Homo sapiens piRNA piR-48896, complete sequence.
LF365460 - JP 2014500723-A/172963: Polycomb-Associated Non-Coding RNAs.
LF365458 - JP 2014500723-A/172961: Polycomb-Associated Non-Coding RNAs.
LF365457 - JP 2014500723-A/172960: Polycomb-Associated Non-Coding RNAs.
MA601107 - JP 2018138019-A/173033: Polycomb-Associated Non-Coding RNAs.
MA601103 - JP 2018138019-A/173029: Polycomb-Associated Non-Coding RNAs.
MA601102 - JP 2018138019-A/173028: Polycomb-Associated Non-Coding RNAs.
MA601100 - JP 2018138019-A/173026: Polycomb-Associated Non-Coding RNAs.
MA601099 - JP 2018138019-A/173025: Polycomb-Associated Non-Coding RNAs.
MA601098 - JP 2018138019-A/173024: Polycomb-Associated Non-Coding RNAs.
MA601097 - JP 2018138019-A/173023: Polycomb-Associated Non-Coding RNAs.
MA601087 - JP 2018138019-A/173013: Polycomb-Associated Non-Coding RNAs.
MA601086 - JP 2018138019-A/173012: Polycomb-Associated Non-Coding RNAs.
MA601085 - JP 2018138019-A/173011: Polycomb-Associated Non-Coding RNAs.
MA601084 - JP 2018138019-A/173010: Polycomb-Associated Non-Coding RNAs.
MA601072 - JP 2018138019-A/172998: Polycomb-Associated Non-Coding RNAs.
MA601071 - JP 2018138019-A/172997: Polycomb-Associated Non-Coding RNAs.
MA601070 - JP 2018138019-A/172996: Polycomb-Associated Non-Coding RNAs.
MA601069 - JP 2018138019-A/172995: Polycomb-Associated Non-Coding RNAs.
MA601067 - JP 2018138019-A/172993: Polycomb-Associated Non-Coding RNAs.
MA601066 - JP 2018138019-A/172992: Polycomb-Associated Non-Coding RNAs.
MA601065 - JP 2018138019-A/172991: Polycomb-Associated Non-Coding RNAs.
MA601063 - JP 2018138019-A/172989: Polycomb-Associated Non-Coding RNAs.
MA601059 - JP 2018138019-A/172985: Polycomb-Associated Non-Coding RNAs.
MA601058 - JP 2018138019-A/172984: Polycomb-Associated Non-Coding RNAs.
MA601056 - JP 2018138019-A/172982: Polycomb-Associated Non-Coding RNAs.
MA601055 - JP 2018138019-A/172981: Polycomb-Associated Non-Coding RNAs.
MA601045 - JP 2018138019-A/172971: Polycomb-Associated Non-Coding RNAs.
MA601043 - JP 2018138019-A/172969: Polycomb-Associated Non-Coding RNAs.
MA601042 - JP 2018138019-A/172968: Polycomb-Associated Non-Coding RNAs.
MA601040 - JP 2018138019-A/172966: Polycomb-Associated Non-Coding RNAs.
MA601039 - JP 2018138019-A/172965: Polycomb-Associated Non-Coding RNAs.
MA601038 - JP 2018138019-A/172964: Polycomb-Associated Non-Coding RNAs.
MA601037 - JP 2018138019-A/172963: Polycomb-Associated Non-Coding RNAs.
MA601035 - JP 2018138019-A/172961: Polycomb-Associated Non-Coding RNAs.
MA601034 - JP 2018138019-A/172960: Polycomb-Associated Non-Coding RNAs.

-  Other Names for This Gene
  Alternate Gene Symbols: A1L4B0, C5HTZ5, C5HTZ6, C5HTZ7, ENST00000340908.1, ENST00000340908.2, ENST00000340908.3, ENST00000340908.4, ENST00000340908.5, ENST00000340908.6, ENST00000340908.7, ENST00000340908.8, H6WZW3, HSN2 , KDP, KIAA0344 , NM_213655, O15052, P54963, PRKWNK1 , Q4VBX9, Q6IFS5, Q86WL5, Q8N673, Q96CZ6, Q9H4A3, Q9P1S9, uc317vvn.1, uc317vvn.2, WNK1 , WNK1_HUMAN
UCSC ID: ENST00000340908.9_6
RefSeq Accession: NM_213655.5
Protein: Q9H4A3 (aka WNK1_HUMAN)

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene WNK1:
hsan2 (Hereditary Sensory and Autonomic Neuropathy Type II)
pha2 (Pseudohypoaldosteronism Type II)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.