Gene Details | GeDiPNet - Complete Gene Info, Disease Associations & Pathways

Gene Gene information from NCBI Gene database. Gene SNPs miRNA Gene ontology Other IDs Protein Pathways Associated diseases
Entrez ID	65266
Gene name	WNK lysine deficient protein kinase 4
Gene symbol	WNK4
Synonyms (NCBI Gene)	PHA2BPRKWNK4
Chromosome	17
Chromosome location	17q21.2
Summary	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

Show/Hide all (8)

SNP ID	Visualize variation	Clinical significance	Consequence
rs137853092	C>G	Pathogenic	Coding sequence variant, missense variant
rs137853093	G>A	Pathogenic	Coding sequence variant, missense variant
rs137853094	A>C	Pathogenic	Coding sequence variant, missense variant
rs137853095	C>T	Pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs193922734	A>G	Pathogenic	Missense variant, coding sequence variant
rs193922735	C>T	Pathogenic	Missense variant, coding sequence variant
rs193922736	G>C	Pathogenic	Missense variant, coding sequence variant
rs193922737	A>G	Pathogenic	Missense variant, coding sequence variant

Show/Hide all (6)

miRTarBase ID	miRNA	Experiments	Reference
MIRT004559	hsa-miR-296-5p	Luciferase reporter assayqRT-PCRWestern blot	20561597
MIRT004559	hsa-miR-296-5p	Luciferase reporter assayqRT-PCRWestern blot	20561597
MIRT2369163	hsa-miR-383	CLIP-seq
MIRT2369164	hsa-miR-4422	CLIP-seq
MIRT2369165	hsa-miR-4711-5p	CLIP-seq
MIRT2369166	hsa-miR-4772-5p	CLIP-seq

Show/Hide all (62)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0002021	Process	Response to dietary excess	IEA
GO:0003096	Process	Renal sodium ion transport	IEA
GO:0003096	Process	Renal sodium ion transport	ISS
GO:0004672	Function	Protein kinase activity	IBA
GO:0004672	Function	Protein kinase activity	IEA
GO:0004674	Function	Protein serine/threonine kinase activity	IDA	16832045
GO:0004674	Function	Protein serine/threonine kinase activity	IEA
GO:0004674	Function	Protein serine/threonine kinase activity	ISS
GO:0005515	Function	Protein binding	IPI	17721439, 23453970, 23576762, 35044719, 36931259
GO:0005524	Function	ATP binding	IEA
GO:0005524	Function	ATP binding	ISS
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	ISS
GO:0005923	Component	Bicellular tight junction	IEA
GO:0005923	Component	Bicellular tight junction	ISS	11498583
GO:0005923	Component	Bicellular tight junction	ISS
GO:0006468	Process	Protein phosphorylation	ISS
GO:0006821	Process	Chloride transport	IEA
GO:0006954	Process	Inflammatory response	IEA
GO:0007165	Process	Signal transduction	IBA
GO:0007165	Process	Signal transduction	IEA
GO:0008104	Process	Intracellular protein localization	IEA
GO:0008200	Function	Ion channel inhibitor activity	IEA
GO:0008200	Function	Ion channel inhibitor activity	ISS
GO:0008217	Process	Regulation of blood pressure	IEA
GO:0009410	Process	Response to xenobiotic stimulus	IEA
GO:0010467	Process	Gene expression	IEA
GO:0010766	Process	Negative regulation of sodium ion transport	IEA
GO:0010766	Process	Negative regulation of sodium ion transport	ISS
GO:0016020	Component	Membrane	IEA
GO:0016020	Component	Membrane	ISS
GO:0016301	Function	Kinase activity	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0030644	Process	Intracellular chloride ion homeostasis	IEA
GO:0031404	Function	Chloride ion binding	IEA
GO:0032991	Component	Protein-containing complex	IEA
GO:0035556	Process	Intracellular signal transduction	ISS
GO:0035725	Process	Sodium ion transmembrane transport	IEA
GO:0035932	Process	Aldosterone secretion	IEA
GO:0042116	Process	Macrophage activation	IEA
GO:0042592	Process	Homeostatic process	IEA
GO:0044297	Component	Cell body	IEA
GO:0050801	Process	Monoatomic ion homeostasis	IEA
GO:0050801	Process	Monoatomic ion homeostasis	IMP	23453970, 23576762
GO:0055074	Process	Calcium ion homeostasis	IEA
GO:0070161	Component	Anchoring junction	IEA
GO:0070294	Process	Renal sodium ion absorption	IDA	18270262
GO:0070294	Process	Renal sodium ion absorption	IEA
GO:0070294	Process	Renal sodium ion absorption	IMP	23453970, 23576762
GO:0070294	Process	Renal sodium ion absorption	ISS	14608358, 17975670
GO:0070371	Process	ERK1 and ERK2 cascade	IEA
GO:0071466	Process	Cellular response to xenobiotic stimulus	IEA
GO:0071805	Process	Potassium ion transmembrane transport	IEA
GO:0072156	Process	Distal tubule morphogenesis	IMP	23453970, 23576762
GO:0090188	Process	Negative regulation of pancreatic juice secretion	IEA
GO:0106310	Function	Protein serine kinase activity	IEA
GO:1903077	Process	Negative regulation of protein localization to plasma membrane	IEA
GO:1903077	Process	Negative regulation of protein localization to plasma membrane	ISS
GO:1903764	Process	Regulation of potassium ion export across plasma membrane	IEA

MIM	HGNC	e!Ensembl
601844	14544	ENSG00000126562

Q96J92

Protein name

Serine/threonine-protein kinase WNK4 (EC 2.7.11.1) (Protein kinase lysine-deficient 4) (Protein kinase with no lysine 4)

Protein function

Serine/threonine-protein kinase component of the WNK4-SPAK/OSR1 kinase cascade, which acts as a key regulator of ion transport in the distal nephron and blood pressure (By similarity). The WNK4-SPAK/OSR1 kinase cascade is composed of WNK4, which

PDB

2V3S , 4CH9 , 4CHB

Family and domains

Pfam

Accession	ID	Position in sequence	Description	Type
PF00069	Pkinase	174 → 432	Protein kinase domain	Domain
PF12202	OSR1_C	453 → 515	Oxidative-stress-responsive kinase 1 C-terminal domain	Domain

Tissue specificity

TISSUE SPECIFICITY: Expressed in kidney, colon and skin. {ECO:0000269|PubMed:11571656}.

Sequence

MLASPATETTVLMSQTEADLALRPPPPLGTAGQPRLGPPPRRARRFSGKAEPRPRSSRLS
RRSSVDLGLLSSWSLPASPAPDPPDPPDSAGPGPARSPPPSSKEPPEGTWTEGAPVKAAE
DSARPELPDSAVGPGSREPLRVPEAVALERRREQEEKEDMETQAVATSPDGRYLKFDIEI
GRGSFKTVYRGLDTDTTVEVAWCELQTRKLSRAERQRFSEEVEMLKGLQHPNIVRFYDSW
KSVLRGQVCIVLVTELMTSGTLKTYLRRFREMKPRVLQRWSRQILRGLHFLHSRVPPILH
RDLKCDNVFITGPTGSVKIGDLGLATLKRASFAKSVIGTPEFMAPEMYEEKYDEAVDVYA
FGMCMLEMATSEYPYSECQNAAQIYRKVTSGRKPNSFHKVKIPEVKEIIEGCIRTDKNER
FTIQDLLAHAFFREERGVHVELAEEDDGEKPGLKLWLRMEDARRGGRPRDNQAIEFLFQL
GRDAAEEVAQEMVALGLVCEADYQPVARAVRERVAAIQRKREKLRKARELEALPPEPGPP
PATVPMAPGPPSVFPPEPEEPEADQHQPFLFRHASYSSTTSDCETDGYLSSSGFLDASDP
ALQPPGGVPSSLAESHLCLPSAFALSIPRSGPGSDFSPGDSYASDAASGLSDVGEGMGQM
RRPPGRNLRRRPRSRLRVTSVSDQNDRVVECQLQTHNSKMVTFRFDLDGDSPEEIAAAMV
YNEFILPSERDGFLRRIREIIQRVETLLKRDTGPMEAAEDTLSPQEEPAPLPALPVPLPD
PSNEELQSSTSLEHRSWTAFSTSSSSPGTPLSPGNPFSPGTPISPGPIFPITSPPCHPSP
SPFSPISSQVSSNPSPHPTSSPLPFSSSTPEFPVPLSQCPWSSLPTTSPPTFSPTCSQVT
LSSPFFPPCPSTSSFPSTTAAPLLSLASAFSLAVMTVAQSLLSPSPGLLSQSPPAPPSPL
PSLPLPPPVAPGGQESPSPHTAEVESEASPPPARPLPGEARLAPISEEGKPQLVGRFQVT
SSKEPAEPLPLQPTSPTLSGSPKPSTPQLTSESSDTEDSAGGGPETREALAESDRAAEGL
GAGVEEEGDDGKEPQVGGSPQPLSHPSPVWMNYSYSSLCLSSEESESSGEDEEFWAELQS
LRQKHLSEVETLQTLQKKEIEDLYSRLGKQPPPGIVAPAAMLSSRQRRLSKGSFPTSRRN
SLQRSEPPGPGIMRRNSLSGSSTGSQEQRASKGVTFAGDVGRM

Sequence length

1243

Interactions

View interactions

	KEGG		Reactome
	Parathyroid hormone synthesis, secretion and action		Stimuli-sensing channels

Evidence Score: ★☆☆☆☆ Gene-disease association found in Text Mining only ★★☆☆☆ Found in Text Mining and Unknown/Other Associations ★★★☆☆ Reported in Unknown/Other Associations across ≥2 Sources ★★★★☆ ClinVar: Pathogenic/Likely Pathogenic (<5 Variants) ★★★★★ ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Show/Hide Causal Diseases (3)

Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Causal Diseases associated with Pathogenic or Likely Pathogenic variants in ClinVar
Pseudohypoaldosteronism type 2B	Likely pathogenic; Pathogenic	rs2144087861, rs2143987485, rs137853092, rs137853093, rs137853094	RCV001533200 RCV001849665 RCV000008099 RCV000008100 RCV000008101	★★★★★ ★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Renal tubulopathies	Likely pathogenic	rs137853093	RCV006276049	★★★★★ ★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
WNK4-related disorder	Likely pathogenic	rs2544005779	RCV003393132	★★★★★ ★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Show/Hide Unknown Diseases (15)

Phenotype Name	Clinical Significance	Source	Evidence Score
Unknown / Other Associations ClinVar entries with uncertain/conflicting evidence, and associations from other databases (OMIM, Orphanet, GWAS, etc.) where the gene is not established as causal.
Cervical cancer	Benign	ClinVar	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Benign	ClinVar	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Benign	ClinVar	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTENSION	—	CTD	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTENSIVE DISEASE	—	Disgenet	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign	ClinVar	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Benign	ClinVar	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign	ClinVar	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PSEUDOHYPOALDOSTERONISM	—	CTD, Disgenet CTD, Disgenet	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pseudohypoaldosteronism type 2A	Conflicting classifications of pathogenicity	ClinVar	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PSEUDOHYPOALDOSTERONISM, TYPE IIB	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Show/Hide Text Mining Associations (45)

Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Associations from Text Mining Disease associations identified through text mining
Adult Medulloblastoma	Medulloblastoma	BEFREE	21652733		★★★★★ ★☆☆☆☆ Found in Text Mining only
Apparent mineralocorticoid excess	Apparent Mineralocorticoid Excess	BEFREE	17647025		★★★★★ ★☆☆☆☆ Found in Text Mining only
ARTHROGRYPOSIS MULTIPLEX CONGENITA, DISTAL, TYPE IIA	Gordon syndrome	BEFREE	14764624, 15866321, 21236712, 23387299, 23683032, 25503323		★★★★★ ★☆☆☆☆ Found in Text Mining only
Childhood Medulloblastoma	Medulloblastoma	BEFREE	21652733		★★★★★ ★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	36793496	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Cystic Fibrosis	Cystic Fibrosis	BEFREE	17194447		★★★★★ ★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 2	Diabetes mellitus, type 2	Pubtator	27314050	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	27314050		★★★★★ ★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	BEFREE	20956807		★★★★★ ★☆☆☆☆ Found in Text Mining only
Essential Hypertension	Hypertension	BEFREE	12642508, 12719438, 14616768, 14967840, 15309683, 15866321, 18547946, 19330605, 19340547, 27314050		★★★★★ ★☆☆☆☆ Found in Text Mining only
Essential Hypertension	Hypertension	Pubtator	19330605, 27314050	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Gordon syndrome	Gorlin syndrome	Pubtator	23387299	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Hyperchloremia	Hyperchloremia	HPO_DG			★★★★★ ★☆☆☆☆ Found in Text Mining only
Hyperkalemia	Hyperkalemia	Pubtator	17380208	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Hyperlipidemia	Hyperlipidemia	BEFREE	15309683		★★★★★ ★☆☆☆☆ Found in Text Mining only
Hyperpotassemia and Hypertension, Familial	Hyperpotassemia And Hypertension	CTD_human_DG	22949526		★★★★★ ★☆☆☆☆ Found in Text Mining only
Hypertension	Hypertension	Pubtator	14681216, 16669787, 17380208, 18312414, 19330605, 21520334, 23387299, 24266877, 24641320, 25266424, 27314050	Associate	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypertensive disease	Hypertension	BEFREE	12642508, 12719438, 14967840, 15110905, 15292344, 15300163, 15309683, 15637347, 15696009, 15866321, 16083423, 16403833, 16669787, 16761023, 16820787 View all (27 more)		★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypertensive disease	Hypertension	LHGDN	12719438, 15110905, 15292344, 17018846		★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypertensive disease	Hypertension	CTD_human_DG	22949526		★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypertensive disease	Hypertension	HPO_DG			★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypocalciuric hypercalcemia, familial, type 1	Hypocalciuric Hypercalcemia	BEFREE	17018846, 17634397		★★★★★ ★☆☆☆☆ Found in Text Mining only
Kidney Failure	Kidney Failure	BEFREE	15110905		★★★★★ ★☆☆☆☆ Found in Text Mining only
Medulloblastoma	Medulloblastoma	BEFREE	21652733		★★★★★ ★☆☆☆☆ Found in Text Mining only
Medulloblastoma	Medulloblastoma	Pubtator	21652733	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Metastatic melanoma	Metastatic Melanoma	UNIPROT_DG			★★★★★ ★☆☆☆☆ Found in Text Mining only
Osteoporosis	Osteoporosis	BEFREE	21236712		★★★★★ ★☆☆☆☆ Found in Text Mining only
Ovarian Mucinous Adenocarcinoma	Ovarian adenocarcinoma	UNIPROT_DG			★★★★★ ★☆☆☆☆ Found in Text Mining only
Pseudohypoaldosteronism	Pseudohypoparathyroidism	Pubtator	10869238, 17380208, 18312414, 26732173, 30931564, 31044551, 35093948	Associate	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pseudohypoaldosteronism	Pseudohypoaldosteronism	CTD_human_DG	22949526		★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pseudohypoaldosteronism	Pseudohypoaldosteronism	BEFREE	23665031		★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pseudohypoaldosteronism	Pseudohypoaldosteronism	HPO_DG			★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pseudohypoaldosteronism type 2B	Pseudohypoaldosteronism	Orphanet			★★★★★ ★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Pseudohypoaldosteronism, Type I	Pseudohypoaldosteronism	CTD_human_DG	22949526		★★★★★ ★☆☆☆☆ Found in Text Mining only
Pseudohypoaldosteronism, Type I, Autosomal Dominant	Pseudohypoaldosteronism	CTD_human_DG	22949526		★★★★★ ★☆☆☆☆ Found in Text Mining only
Pseudohypoaldosteronism, Type I, Autosomal Recessive	Pseudohypoaldosteronism	CTD_human_DG	22949526		★★★★★ ★☆☆☆☆ Found in Text Mining only
Pseudohypoaldosteronism, Type II	Pseudohypoaldosteronism	BEFREE	12642508, 12719438, 14764624, 15110905, 15300163, 15309683, 15637347, 15866321, 15998707, 16964266, 18280177, 18547946, 18701621, 19016006, 19587141 View all (26 more)		★★★★★ ★☆☆☆☆ Found in Text Mining only
Pseudohypoaldosteronism, Type II	Pseudohypoaldosteronism	CTD_human_DG	22949526		★★★★★ ★☆☆☆☆ Found in Text Mining only
Pseudohypoaldosteronism, Type IIb	Pseudohypoaldosteronism	GENOMICS_ENGLAND_DG	11498583		★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pseudohypoaldosteronism, Type IIb	Pseudohypoaldosteronism	UNIPROT_DG	11498583, 23387299, 23453970, 23576762		★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pseudohypoaldosteronism, Type IIb	Pseudohypoaldosteronism	CLINVAR_DG			★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pseudohypoaldosteronism, Type IIb	Pseudohypoaldosteronism	CTD_human_DG			★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PSEUDOHYPOALDOSTERONISM, TYPE IID	Pseudohypoaldosteronism	BEFREE	17018846, 17194447, 17634397, 22406640, 23885063, 25113964, 29412704, 29459793, 29846116		★★★★★ ★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	20819979		★★★★★ ★☆☆☆☆ Found in Text Mining only
Sex Reversal, Female, With Dysgenesis Of Kidneys, Adrenals, And Lungs	Sex Reversal, Female, With Dysgenesis Of Kidneys, Adrenals, And Lungs	GENOMICS_ENGLAND_DG	18179883		★★★★★ ★☆☆☆☆ Found in Text Mining only

WNK4 (WNK lysine deficient protein kinase 4)