Human Gene Module / Chromosome X / WNK3

WNK3WNK lysine deficient protein kinase 3

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 9
Rare Variants / Common Variants
5 / 0
Aliases
WNK3, PRKWNK3,  FLJ30437,  FLJ42662,  KIAA1566,  WNK3
Associated Syndromes
-
Chromosome Band
Xp11.22
Associated Disorders
SCZ, ID
Relevance to Autism

Studies have found rare mutations in the WNK3 gene that are associated with autism (Piton et al., 2011; Qiao et al., 2008).

Molecular Function

The encoed protein belongs to the family of serine-threonine kinases that functions as modulator of diverse ion transport pathways.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to WNK3 (9 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited WNK3 modulates transport of Cl- in and out of cells: implications for control of cell volume and neuronal excitability Kahle KT , et al. (2005) No -
2 Support Autism-associated familial microdeletion of Xp11.22 Qiao Y , et al. (2008) Yes ID
3 Recent Recommendation Regulation of NKCC2 by a chloride-sensing mechanism involving the WNK3 and SPAK kinases Ponce-Coria J , et al. (2008) No -
4 Recent Recommendation Cell-type specific distribution of chloride transporters in the rat suprachiasmatic nucleus Belenky MA , et al. (2009) No -
5 Primary Systematic resequencing of X-chromosome synaptic genes in autism spectrum disorder and schizophrenia Piton A , et al. (2010) Yes SCZ
6 Recent Recommendation Benign hyperphosphatasemia Kricka LJ , et al. (1990) No -
7 Support - Mona Abdi et al. (2023) Yes ADHD
8 Support - Yasser Al-Sarraj et al. (2024) Yes Epilepsy/seizures
9 Support - Ashlesha Gogate et al. (2024) Yes -
Rare Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss Familial Maternal Multiplex 18498374 Qiao Y , et al. (2008)
c.614A>G p.Asn205Ser missense_variant Familial Maternal Simplex 37805537 Mona Abdi et al. (2023)
c.2413G>C p.Glu805Gln missense_variant Familial Maternal Simplex 37805537 Mona Abdi et al. (2023)
c.2608C>T p.Arg870Trp missense_variant Familial Maternal Simplex 39632905 Ashlesha Gogate et al. (2024)
c.236A>G p.Glu79Gly missense_variant Familial Maternal Multiplex 38572415 Yasser Al-Sarraj et al. (2024)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Studies have found rare mutations in the WNK3 gene that are associated with autism. In particular, Qiao et al. (2008) found two brothers with a microdeletion of Xp11.22 that included WNK3 and two other genes, of which PHF8 had previously been associated with mental retardation. Additional screening in that study revealed nothing further. Also, Piton et al. (2011) found two nonsynonymous variants in ASD cases.

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

Studies have found rare mutations in the WNK3 gene that are associated with autism. In particular, Qiao et al. (2008) found two brothers with a microdeletion of Xp11.22 that included WNK3 and two other genes, of which PHF8 had previously been associated with mental retardation. Additional screening in that study revealed nothing further. Also, Piton et al. (2011) found two nonsynonymous variants in ASD cases.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Studies have found rare mutations in the WNK3 gene that are associated with autism. In particular, Qiao et al. (2008) found two brothers with a microdeletion of Xp11.22 that included WNK3 and two other genes, of which PHF8 had previously been associated with mental retardation. Additional screening in that study revealed nothing further. Also, Piton et al. (2011) found two nonsynonymous variants in ASD cases.

Reports Added
[New Scoring Scheme]
7/1/2014
No data
icon
4

Increased from No data to 4

Description

Studies have found rare mutations in the WNK3 gene that are associated with autism. In particular, Qiao et al. (2008) found two brothers with a microdeletion of Xp11.22 that included WNK3 and two other genes, of which PHF8 had previously been associated with mental retardation. Additional screening in that study revealed nothing further. Also, Piton et al. (2011) found two nonsynonymous variants in ASD cases.

4/1/2014
No data
icon
4

Increased from No data to 4

Description

Studies have found rare mutations in the WNK3 gene that are associated with autism. In particular, Qiao et al. (2008) found two brothers with a microdeletion of Xp11.22 that included WNK3 and two other genes, of which PHF8 had previously been associated with mental retardation. Additional screening in that study revealed nothing further. Also, Piton et al. (2011) found two nonsynonymous variants in ASD cases.

Krishnan Probability Score

Score 0.49540356715009

Ranking 2993/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.99999836654063

Ranking 337/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.94637315654715

Ranking 16844/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
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