WNK3

WNK lysine deficient protein kinase 3, the group of WNK lysine deficient protein kinases

Basic information

Region (hg38): X:54192823-54358642

Previous symbols: [ "PRKWNK3" ]

Links

ENSG00000196632 ∙ NCBI:65267 ∙ OMIM:300358 ∙ HGNC:14543 ∙ Uniprot:Q9BYP7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Prieto syndrome (Moderate), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Prieto syndrome	XL	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic	35678782

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the WNK3 gene.

• not_specified (126 variants)
• not_provided (106 variants)
• Prieto_syndrome (12 variants)
• Neurodevelopmental_disorder (6 variants)
• WNK3-related_condition (2 variants)
• Retrognathia (1 variants)
• Congenital_laryngomalacia (1 variants)
• Moderate_intellectual_disability (1 variants)
• Sleep_apnea (1 variants)
• Motor_stereotypies (1 variants)
• Delayed_speech_and_language_development (1 variants)
• See_cases (1 variants)
• Autism (1 variants)
• Abnormal_facial_shape (1 variants)
• Subglottic_stenosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the WNK3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000020922.5. 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			21	6	6	33
missense	3		250	27	2	282
nonsense	3	1	7			11
start loss			1			1
frameshift		1	1			2
splice donor/acceptor (+/-2bp)	2		10			12
Total	8	2	290	33	8

Highest pathogenic variant AF is 9.114923e-7

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
WNK3	protein_coding	protein_coding	ENST00000354646	23	165820

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000755	125551	3	4	125558	0.0000279

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.55	453	634	0.715	0.0000466	11756
Missense in Polyphen		74	197.53	0.37462		3703
Synonymous	1.68	195	227	0.858	0.0000167	3519
Loss of Function	6.26	5	55.1	0.0907	0.00000421	1040

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000433	0.0000433
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000636	0.0000463
European (Non-Finnish)	0.0000130	0.00000880
Middle Eastern	0.00	0.00
South Asian	0.000258	0.000131
Other	0.00	0.00

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 (PubMed:16275913, PubMed:16275911, PubMed:16357011). Phosphorylates WNK4. Regulates the phosphorylation of SLC12A1 and SLC12A2. Increases Ca(2+) influx mediated by TRPV5 and TRPV6 by enhancing their membrane expression level via a kinase-dependent pathway (PubMed:18768590). Inhibits the activity of KCNJ1 by decreasing its expression at the cell membrane in a non-catalytic manner. {ECO:0000269|PubMed:16275911, ECO:0000269|PubMed:16275913, ECO:0000269|PubMed:16357011, ECO:0000269|PubMed:16501604, ECO:0000269|PubMed:17975670, ECO:0000269|PubMed:18768590, ECO:0000269|PubMed:20525693}.
• Pathway: Diuretics Pathway, Pharmacodynamics;Stimuli-sensing channels;Ion channel transport;Transport of small molecules (Consensus)

Recessive Scores

• pRec: 0.123

Intolerance Scores

• rvis_EVS: -1.33
• rvis_percentile_EVS: 4.71

Haploinsufficiency Scores

• pHI: 0.313
• hipred: Y
• hipred_score: 0.575
• ghis: 0.483

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0876

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Wnk3
• Phenotype: normal phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Gene ontology

• Biological process: protein phosphorylation;positive regulation of sodium ion transport;negative regulation of sodium ion transport;positive regulation of peptidyl-threonine phosphorylation;positive regulation of ion transmembrane transporter activity;intracellular signal transduction;negative regulation of apoptotic process;protein autophosphorylation;ion homeostasis;positive regulation of calcium ion transport;protein localization to plasma membrane;negative regulation of pancreatic juice secretion;regulation of calcium ion import;positive regulation of protein localization to plasma membrane;positive regulation of potassium ion import across plasma membrane;positive regulation of sodium ion transmembrane transporter activity
• Cellular component: cytoplasm;cytosol;adherens junction;bicellular tight junction
• Molecular function: protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding;chloride channel inhibitor activity;potassium channel inhibitor activity