WNK4

Protein identityUniProt · HPA

UniProt accession

Q96J92

Gene

WNK4

Ensembl

ENSG00000126562

Chromosome

17

Canonical length

1243 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Transporters

OverviewNCBI Gene

This gene encodes a member of the WNK family of serine-threonine protein kinases. The kinase is part of the tight junction complex in kidney cells, and regulates the balance between NaCl reabsorption and K(+) secretion. The kinase regulates the activities of several types of ion channels, cotransporters, and exchangers involved in electrolyte flux in epithelial cells. Mutations in this gene result in pseudohypoaldosteronism type IIB.[provided by RefSeq, Sep 2009]

Canonical amino-acid sequenceUniProt

1243 residues, UniProt reviewed canonical sequence.

>Q96J92|WNK4
     1  MLASPATETT VLMSQTEADL ALRPPPPLGT AGQPRLGPPP RRARRFSGKA EPRPRSSRLS
    61  RRSSVDLGLL SSWSLPASPA PDPPDPPDSA GPGPARSPPP SSKEPPEGTW TEGAPVKAAE
   121  DSARPELPDS AVGPGSREPL RVPEAVALER RREQEEKEDM ETQAVATSPD GRYLKFDIEI
   181  GRGSFKTVYR GLDTDTTVEV AWCELQTRKL SRAERQRFSE EVEMLKGLQH PNIVRFYDSW
   241  KSVLRGQVCI VLVTELMTSG TLKTYLRRFR EMKPRVLQRW SRQILRGLHF LHSRVPPILH
   301  RDLKCDNVFI TGPTGSVKIG DLGLATLKRA SFAKSVIGTP EFMAPEMYEE KYDEAVDVYA
   361  FGMCMLEMAT SEYPYSECQN AAQIYRKVTS GRKPNSFHKV KIPEVKEIIE GCIRTDKNER
   421  FTIQDLLAHA FFREERGVHV ELAEEDDGEK PGLKLWLRME DARRGGRPRD NQAIEFLFQL
   481  GRDAAEEVAQ EMVALGLVCE ADYQPVARAV RERVAAIQRK REKLRKAREL EALPPEPGPP
   541  PATVPMAPGP PSVFPPEPEE PEADQHQPFL FRHASYSSTT SDCETDGYLS SSGFLDASDP
   601  ALQPPGGVPS SLAESHLCLP SAFALSIPRS GPGSDFSPGD SYASDAASGL SDVGEGMGQM
   661  RRPPGRNLRR RPRSRLRVTS VSDQNDRVVE CQLQTHNSKM VTFRFDLDGD SPEEIAAAMV
   721  YNEFILPSER DGFLRRIREI IQRVETLLKR DTGPMEAAED TLSPQEEPAP LPALPVPLPD
   781  PSNEELQSST SLEHRSWTAF STSSSSPGTP LSPGNPFSPG TPISPGPIFP ITSPPCHPSP
   841  SPFSPISSQV SSNPSPHPTS SPLPFSSSTP EFPVPLSQCP WSSLPTTSPP TFSPTCSQVT
   901  LSSPFFPPCP STSSFPSTTA APLLSLASAF SLAVMTVAQS LLSPSPGLLS QSPPAPPSPL
   961  PSLPLPPPVA PGGQESPSPH TAEVESEASP PPARPLPGEA RLAPISEEGK PQLVGRFQVT
  1021  SSKEPAEPLP LQPTSPTLSG SPKPSTPQLT SESSDTEDSA GGGPETREAL AESDRAAEGL
  1081  GAGVEEEGDD GKEPQVGGSP QPLSHPSPVW MNYSYSSLCL SSEESESSGE DEEFWAELQS
  1141  LRQKHLSEVE TLQTLQKKEI EDLYSRLGKQ PPPGIVAPAA MLSSRQRRLS KGSFPTSRRN
  1201  SLQRSEPPGP GIMRRNSLSG SSTGSQEQRA SKGVTFAGDV GRM

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against WNK4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.55

Highest tissue expression

42 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about WNK4.

Disease | AllUniProt

Conditions WNK4 is implicated in, by any mechanism.

• Pseudohypoaldosteronism 2B (PHA2B) MIM:614491

Disease | GeneticClinVar

6 pathogenic / likely-pathogenic of 662 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Pseudohypoaldosteronism type 2B
• Renal tubulopathies
• WNK4-related disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.05

gnomAD pLI

0

gnomAD missense Z

0.81

DepMap mean gene effect

-0.23

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• calcium ion homeostasis
• cellular response to xenobiotic stimulus
• chloride transport
• distal tubule morphogenesis
• ERK1 and ERK2 cascade
• gene expression
• inflammatory response
• intracellular chloride ion homeostasis
• intracellular protein localization
• intracellular signal transduction
• macrophage activation
• monoatomic ion homeostasis
• negative regulation of pancreatic juice secretion
• negative regulation of protein localization to plasma membrane
• negative regulation of sodium ion transport
• potassium ion transmembrane transport
• protein phosphorylation
• regulation of blood pressure
• regulation of potassium ion export across plasma membrane
• renal sodium ion absorption
• renal sodium ion transport
• response to dietary excess
• signal transduction
• sodium ion transmembrane transport
• aldosterone secretion

Molecular functions

• ATP binding
• chloride ion binding
• ion channel inhibitor activity
• protein kinase activity
• protein serine kinase activity
• protein serine/threonine kinase activity

Cellular components

• bicellular tight junction
• cell body
• cytoplasm
• cytosol
• membrane
• protein-containing complex

Protein domainsUniProt · Pfam · InterPro

• Protein kinase domain
• Serine/threonine-protein kinase, active site
• Protein kinase-like domain superfamily
• Serine/threonine-protein kinase OSR1/WNK, CCT domain
• With No Lysine (K) Ser/Thr Protein Kinase
• Serine/threonine-protein kinase WNK, CCTL2 domain
• Protein kinase domain
• Oxidative-stress-responsive kinase 1 C-terminal domain
• WNK CCTL2 domain

KeywordsUniProt

• ATP-binding
• Cell junction
• Isopeptide bond
• Kinase
• Nucleotide-binding
• Phosphoprotein
• Serine/threonine-protein kinase
• Tight junction
• Transferase
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of WNK4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• WNK3
• WNK1