WNK2 (WNK lysine deficient protein kinase 2)

Gene

• Entrez ID: 65268
• Gene name: WNK lysine deficient protein kinase 2
• Gene symbol: WNK2
• Synonyms (NCBI Gene): NY-CO-43, P/OKcl.13, PRKWNK2, SDCCAG43
• Chromosome: 9
• Chromosome location: 9q22.31
• Summary: The protein encoded by this gene is a cytoplasmic serine-threonine kinase that belongs to the protein kinase superfamily. The protein plays an important role in the regulation of electrolyte homeostasis, cell signaling survival, and proliferation. Alterna

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs757473977	->G	Likely-pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant, intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT713201	hsa-miR-4267	HITS-CLIP	19536157
MIRT713200	hsa-miR-766-3p	HITS-CLIP	19536157
MIRT713199	hsa-miR-3925-3p	HITS-CLIP	19536157
MIRT713198	hsa-miR-3194-3p	HITS-CLIP	19536157
MIRT713197	hsa-miR-3160-5p	HITS-CLIP	19536157
MIRT713196	hsa-miR-760	HITS-CLIP	19536157
MIRT713195	hsa-miR-515-5p	HITS-CLIP	19536157
MIRT713194	hsa-miR-519e-5p	HITS-CLIP	19536157
MIRT713193	hsa-miR-629-3p	HITS-CLIP	19536157
MIRT491929	hsa-miR-936	PAR-CLIP	23592263
MIRT491927	hsa-miR-199a-3p	PAR-CLIP	23592263
MIRT491926	hsa-miR-199b-3p	PAR-CLIP	23592263
MIRT491925	hsa-miR-3129-5p	PAR-CLIP	23592263
MIRT491924	hsa-miR-7114-5p	PAR-CLIP	23592263
MIRT491923	hsa-miR-134-3p	PAR-CLIP	23592263
MIRT491921	hsa-miR-4493	PAR-CLIP	23592263
MIRT491922	hsa-miR-4747-5p	PAR-CLIP	23592263
MIRT491920	hsa-miR-5196-5p	PAR-CLIP	23592263
MIRT491919	hsa-miR-4648	PAR-CLIP	23592263
MIRT491918	hsa-miR-1233-5p	PAR-CLIP	23592263
MIRT491917	hsa-miR-6778-5p	PAR-CLIP	23592263
MIRT491915	hsa-miR-4654	PAR-CLIP	23592263
MIRT491916	hsa-miR-4769-5p	PAR-CLIP	23592263
MIRT491914	hsa-miR-222-5p	PAR-CLIP	23592263
MIRT713201	hsa-miR-4267	HITS-CLIP	19536157
MIRT713200	hsa-miR-766-3p	HITS-CLIP	19536157
MIRT713199	hsa-miR-3925-3p	HITS-CLIP	19536157
MIRT713198	hsa-miR-3194-3p	HITS-CLIP	19536157
MIRT713197	hsa-miR-3160-5p	HITS-CLIP	19536157
MIRT713196	hsa-miR-760	HITS-CLIP	19536157
MIRT713195	hsa-miR-515-5p	HITS-CLIP	19536157
MIRT713194	hsa-miR-519e-5p	HITS-CLIP	19536157
MIRT713193	hsa-miR-629-3p	HITS-CLIP	19536157
MIRT491929	hsa-miR-936	PAR-CLIP	23592263
MIRT491927	hsa-miR-199a-3p	PAR-CLIP	23592263
MIRT491926	hsa-miR-199b-3p	PAR-CLIP	23592263
MIRT491925	hsa-miR-3129-5p	PAR-CLIP	23592263
MIRT491924	hsa-miR-7114-5p	PAR-CLIP	23592263
MIRT491923	hsa-miR-134-3p	PAR-CLIP	23592263
MIRT491921	hsa-miR-4493	PAR-CLIP	23592263
MIRT491922	hsa-miR-4747-5p	PAR-CLIP	23592263
MIRT491920	hsa-miR-5196-5p	PAR-CLIP	23592263
MIRT491919	hsa-miR-4648	PAR-CLIP	23592263
MIRT491918	hsa-miR-1233-5p	PAR-CLIP	23592263
MIRT491917	hsa-miR-6778-5p	PAR-CLIP	23592263
MIRT491915	hsa-miR-4654	PAR-CLIP	23592263
MIRT491916	hsa-miR-4769-5p	PAR-CLIP	23592263
MIRT491914	hsa-miR-222-5p	PAR-CLIP	23592263
MIRT1493442	hsa-miR-3616-5p	CLIP-seq
MIRT1493443	hsa-miR-3647-5p	CLIP-seq
MIRT1493444	hsa-miR-4436b-5p	CLIP-seq
MIRT1493445	hsa-miR-4795-5p	CLIP-seq
MIRT1493446	hsa-miR-483-5p	CLIP-seq
MIRT1493447	hsa-miR-573	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0004672	Function	Protein kinase activity	IEA
GO:0004674	Function	Protein serine/threonine kinase activity	IBA
GO:0004674	Function	Protein serine/threonine kinase activity	IEA
GO:0004674	Function	Protein serine/threonine kinase activity	ISS
GO:0005515	Function	Protein binding	IPI	35044719, 35271311
GO:0005524	Function	ATP binding	IEA
GO:0005524	Function	ATP binding	ISS
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IDA	17667937
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IDA
GO:0005886	Component	Plasma membrane	IEA
GO:0006468	Process	Protein phosphorylation	IDA	21733846
GO:0006974	Process	DNA damage response	IBA
GO:0008285	Process	Negative regulation of cell population proliferation	IMP	17667937
GO:0016020	Component	Membrane	IEA
GO:0016301	Function	Kinase activity	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0035556	Process	Intracellular signal transduction	ISS
GO:0042592	Process	Homeostatic process	IEA
GO:0046777	Process	Protein autophosphorylation	IDA	17667937
GO:0050801	Process	Monoatomic ion homeostasis	IMP	21733846
GO:0070373	Process	Negative regulation of ERK1 and ERK2 cascade	IMP	17667937
GO:0090263	Process	Positive regulation of canonical Wnt signaling pathway	IEA
GO:0090263	Process	Positive regulation of canonical Wnt signaling pathway	IMP	23797875
GO:0106310	Function	Protein serine kinase activity	IEA
GO:1904062	Process	Regulation of monoatomic cation transmembrane transport	IEA
GO:2000651	Process	Positive regulation of sodium ion transmembrane transporter activity	IMP	21733846

Other IDs

• MIM: 606249
• HGNC: 14542
• e!Ensembl: ENSG00000165238

Protein

• UniProt ID: Q9Y3S1
• Protein name: Serine/threonine-protein kinase WNK2 (EC 2.7.11.1) (Antigen NY-CO-43) (Protein kinase lysine-deficient 2) (Protein kinase with no lysine 2) (Serologically defined colon cancer antigen 43)
• Protein function: Serine/threonine-protein kinase component of the WNK2-SPAK/OSR1 kinase cascade, which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival, and proliferation (PubMed:17667937, PubMed:18593598, PubMed:217
• PDB: 6ELM, 6FBK
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00069	Pkinase	195 → 453	Protein kinase domain	Domain
  PF12202	OSR1_C	474 → 537	Oxidative-stress-responsive kinase 1 C-terminal domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in various cancer cell lines (at protein level). Predominantly expressed in heart, brain, skeletal muscle and colon. {ECO:0000269|PubMed:11571656, ECO:0000269|PubMed:17667937, ECO:0000269|PubMed:21733846}.
• Sequence:

  MDGDGGRRDVPGTLMEPGRGAGPAGMAEPRAKAARPGPQRFLRRSVVESDQEEPPGLEAA
  EAPGPQPPQPLQRRVLLLCKTRRLIAERARGRPAAPAPAALVAQPGAPGAPADAGPEPVG
  TQEPGPDPIAAAVETAPAPDGGPREEAAATVRKEDEGAAEAKPEPGRTRRDEPEEEEDDE
  DDLKAVATSLDGRFLKFDIELGRGSFKTVYKGLDTETWVEVAWCELQDRKLTKLERQRFK
  EEAEMLKGLQHPNIVRFYDFWESSAKGKRCIVLVTELMTSGTLKTYLKRFKVMKPKVLRS
  WCRQILKGLLFLHTRTPPIIHRDLKCDNIFITGPTGSVKIGDLGLATLKRASFAKSVIGT
  PEFMAPEMYEEHYDESVDVYAFGMCMLEMATSEYPYSECQNAAQIYRKVTCGIKPASFEK
  VHDPEIKEIIGECICKNKEERYEIKDLLSHAFFAEDTGVRVELAEEDHGRKSTIALRLWV
  EDPKKLKGKPKDNGAIEFTFDLEKETPDEVAQEMIESGFFHESDVKIVAKSIRDRVALIQ
  WRRERIWPALQPKEQQDVGSPDKARGPPVPLQVQVTYHAQAGQPGPPEPEEPEADQHLLP
  PTLPTSATSLASDSTFDSGQGSTVYSDSQSSQQSVMLGSLADAAPSPAQCVCSPPVSEGP
  VLPQSLPSLGAYQQPTAAPGLPVGSVPAPACPPSLQQHFPDPAMSFAPVLPPPSTPMPTG
  PGQPAPPGQQPPPLAQPTPLPQVLAPQPVVPLQPVPPHLPPYLAPASQVGAPAQLKPLQM
  PQAPLQPLAQVPPQMPPIPVVPPITPLAGIDGLPPALPDLPTATVPPVPPPQYFSPAVIL
  PSLAAPLPPASPALPLQAVKLPHPPGAPLAMPCRTIVPNAPATIPLLAVAPPGVAALSIH
  SAVAQLPGQPVYPAAFPQMAPTDVPPSPHHTVQNMRATPPQPALPPQPTLPPQPVLPPQP
  TLPPQPVLPPQPTRPPQPVLPPQPMLPPQPVLPPQPALPVRPEPLQPHLPEQAAPAATPG
  SQILLGHPAPYAVDVAAQVPTVPVPPAAVLSPPLPEVLLPAAPELLPQFPSSLATVSASV
  QSVPTQTATLLPPANPPLPGGPGIASPCPTVQLTVEPVQEEQASQDKPPGLPQSCESYGG
  SDVTSGKELSDSCEGAFGGGRLEGRAARKHHRRSTRARSRQERASRPRLTILNVCNTGDK
  MVECQLETHNHKMVTFKFDLDGDAPDEIATYMVEHDFILQAERETFIEQMKDVMDKAEDM
  LSEDTDADRGSDPGTSPPHLSTCGLGTGEESRQSQANAPVYQQNVLHTGKRWFIICPVAE
  HPAPEAPESSPPLPLSSLPPEASQGPCRGLTLPCLPWRRAACGAVFLSLFSAESAQSKQP
  PDSAPYKDQLSSKEQPSFLASQQLLSQAGPSNPPGAPPAPLAPSSPPVTALPQDGAAPAT
  STMPEPASGTASQAGGPGTPQGLTSELETSQPLAETHEAPLAVQPLVVGLAPCTPAPEAA
  STRDASAPREPLPPPAPEPSPHSGTPQPALGQPAPLLPAAVGAVSLATSQLPSPPLGPTV
  PPQPPSALESDGEGPPPRVGFVDSTIKSLDEKLRTLLYQEHVPTSSASAGTPVEVGDRDF
  TLEPLRGDQPRSEVCGGDLALPPVPKEAVSGRVQLPQPLVEKSELAPTRGAVMEQGTSSS
  MTAESSPRSMLGYDRDGRQVASDSHVVPSVPQDVPAFVRPARVEPTDRDGGEAGESSAEP
  PPSDMGTVGGQASHPQTLGARALGSPRKRPEQQDVSSPAKTVGRFSVVSTQDEWTLASPH
  SLRYSAPPDVYLDEAPSSPDVKLAVRRAQTASSIEVGVGEPVSSDSGDEGPRARPPVQKQ
  ASLPVSGSVAGDFVKKATAFLQRPSRAGSLGPETPSRVGMKVPTISVTSFHSQSSYISSD
  NDSELEDADIKKELQSLREKHLKEISELQSQQKQEIEALYRRLGKPLPPNVGFFHTAPPT
  GRRRKTSKSKLKAGKLLNPLVRQLKVVASSTGHLADSSRGPPAKDPAQASVGLTADSTGL
  SGKAVQTQQPCSVRASLSSDICSGLASDGGGARGQGWTVYHPTSERVTYKSSSKPRARFL
  SGPVSVSIWSALKRLCLGKEHSSRSSTSSLAPGPEPGPQPALHVQAQVNNSNNKKGTFTD
  DLHKLVDEWTSKTVGAAQLKPTLNQLKQTQKLQDMEAQAGWAAPGEARAMTAPRAGVGMP
  RLPPAPGPLSTTVIPGAAPTLSVPTPDGALGTARRNQVWFGLRVPPTACCGHSTQPRGGQ
  RVGSKTASFAASDPVRS

• Sequence length: 2297

Pathways

KEGG:

Parathyroid hormone synthesis, secretion and action

Reactome:

Stimuli-sensing channels

Associated diseases

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)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BIPOLAR DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY ARTERY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ESSENTIAL TREMOR	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GOUT	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alzheimer Disease	Alzheimer disease	Pubtator	36035305	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ANOPHTHALMIA AND PULMONARY HYPOPLASIA	Syndromic microphthalmia	BEFREE	23912455, 31046874		★☆☆☆☆ Found in Text Mining only
Brain Neoplasms	Brain Neoplasms	BEFREE	23035050		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	31009242		★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	31349001	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Pancreatic Ductal	Pancreatic ductal carcinoma	Pubtator	31046874	Associate	★☆☆☆☆ Found in Text Mining only
Cerebral Hemorrhage	Cerebral hemorrhage	Pubtator	39433142	Associate	★☆☆☆☆ Found in Text Mining only
Esophageal Squamous Cell Carcinoma	Esophageal squamous cell carcinoma	Pubtator	26857264	Associate	★☆☆☆☆ Found in Text Mining only
Glaucoma	Glaucoma	BEFREE	27615513		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	BEFREE	23035050		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	32093151	Associate	★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	23035050		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	17578925, 25596741, 32093151	Associate	★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	BEFREE	25596741		★☆☆☆☆ Found in Text Mining only
Hyperlipidemias	Hyperlipidemia	Pubtator	39433142	Associate	★☆☆☆☆ Found in Text Mining only
Hypertension	Hypertension	Pubtator	39433142	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	BEFREE	31522654		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	31349001		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	31009242		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	17578925, 28765906		★☆☆☆☆ Found in Text Mining only
Melanoma	Melanoma	Pubtator	22589389	Associate	★☆☆☆☆ Found in Text Mining only
Meningioma	Meningioma	BEFREE	19001526, 23035050		★☆☆☆☆ Found in Text Mining only
Meningioma	Meningioma	Pubtator	19001526	Associate	★☆☆☆☆ Found in Text Mining only
Myocardial Infarction	Myocardial Infarction	GWASDB_DG	21211798		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	17578925, 19001526, 23035050, 23912455, 25596741, 27131446, 31009242, 31349001		★☆☆☆☆ Found in Text Mining only
Non-Small Cell Lung Carcinoma	Lung carcinoma	BEFREE	30221690		★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	35549643	Associate	★☆☆☆☆ Found in Text Mining only
Pancreatic Ductal Adenocarcinoma	Pancreatic adenocarcinoma	BEFREE	23912455		★☆☆☆☆ Found in Text Mining only
Pancreatitis	Pancreatitis	BEFREE	23912455		★☆☆☆☆ Found in Text Mining only
Pancreatitis, Chronic	Pancreatitis	BEFREE	23912455		★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	26857264	Associate	★☆☆☆☆ Found in Text Mining only
Subarachnoid Hemorrhage	Subarachnoid hemorrhage	BEFREE	20198315		★☆☆☆☆ Found in Text Mining only
Triple Negative Breast Neoplasms	Triple Negative Breast Neoplasms	BEFREE	28604765		★☆☆☆☆ Found in Text Mining only
Van der Woude syndrome	Van Der Woude Syndrome	BEFREE	31226473		★☆☆☆☆ Found in Text Mining only