WNK2

WNK lysine deficient protein kinase 2, the group of WNK lysine deficient protein kinases

Basic information

Region (hg38): 9:93184122-93320572

Previous symbols: [ "SDCCAG43", "PRKWNK2" ]

Links

ENSG00000165238 ∙ NCBI:65268 ∙ OMIM:606249 ∙ HGNC:14542 ∙ Uniprot:Q9Y3S1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the WNK2 gene.

• not_specified (2612 variants)
• not_provided (12 variants)
• WNK2-related_condition (1 variants)
• Inborn_genetic_diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the WNK2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006648.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				964		964
missense			1571	80	1	1652
nonsense						0
start loss						0
frameshift		1				1
splice donor/acceptor (+/-2bp)						0
Total	0	1	1571	1044	1

Highest pathogenic variant AF is 0.000004466724

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
WNK2	protein_coding	protein_coding	ENST00000297954	30	135657

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000187	125594	0	12	125606	0.0000478

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.58	1024	1.28e+3	0.797	0.0000858	14370
Missense in Polyphen		32	39.979	0.80043		402
Synonymous	-1.24	657	618	1.06	0.0000479	5047
Loss of Function	7.31	10	80.9	0.124	0.00000413	931

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000276	0.000272
Ashkenazi Jewish	0.000100	0.0000993
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000390	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000169	0.000163

dbNSFP

Source: dbNSFP

• Function: 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 SLC12A2, SCNN1A, SCNN1B, SCNN1D and SGK1 and inhibits SLC12A5. Negatively regulates the EGF-induced activation of the ERK/MAPK-pathway and the downstream cell cycle progression. Affects MAPK3/MAPK1 activity by modulating the activity of MAP2K1 and this modulation depends on phosphorylation of MAP2K1 by PAK1. WNK2 acts by interfering with the activity of PAK1 by controlling the balance of the activity of upstream regulators of PAK1 activity, RHOA and RAC1, which display reciprocal activity. {ECO:0000269|PubMed:17667937, ECO:0000269|PubMed:18593598, ECO:0000269|PubMed:21733846}.
• Pathway: Stimuli-sensing channels;Ion channel transport;Transport of small molecules (Consensus)

Recessive Scores

• pRec: 0.122

Haploinsufficiency Scores

• pHI: 0.141
• hipred: Y
• hipred_score: 0.630
• ghis: 0.550

Essentials

• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.583

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	High	Medium	High

Mouse Genome Informatics

• Gene name: Wnk2

Gene ontology

• Biological process: protein phosphorylation;negative regulation of cell population proliferation;negative regulation of sodium ion transport;positive regulation of ion transmembrane transporter activity;intracellular signal transduction;protein autophosphorylation;ion homeostasis;negative regulation of ERK1 and ERK2 cascade;positive regulation of canonical Wnt signaling pathway;positive regulation of potassium ion import across plasma membrane;positive regulation of sodium ion transmembrane transporter activity
• Cellular component: cytoplasm;cytosol;plasma membrane
• Molecular function: protein serine/threonine kinase activity;ATP binding;chloride channel inhibitor activity;potassium channel inhibitor activity