Human Gene Module / Chromosome 11 / KCNK7

KCNK7potassium two pore domain channel subfamily K member 7

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
5 / 0
Aliases
KCNK7, K2p7.1,  TWIK3
Associated Syndromes
-
Chromosome Band
11q13.1
Associated Disorders
-
Relevance to Autism

Targeted sequencing of a cohort of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 identified three inherited loss-of-function variants and one damaging missense variant in the KCNK7 gene in ASD probands. Transmission and De Novo Association (TADA) analysis of this cohort of Chinese ASD cases and controls in Guo et al., 2017 identified the KCNK7 gene as an ASD candidate gene with a PTADA between 0.001 and 0.005 (0.008245); however, PTADA for this gene failed to reach significance (P < 0.01) following TADA analysis using a combined cohort of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium.

Molecular Function

This gene encodes a member of the superfamily of potassium channel proteins containing two pore-forming P domains. The product of this gene has not been shown to be a functional channel; however, it may require other non-pore-forming proteins for activity.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to KCNK7 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders Li J , et al. (2017) Yes -
2 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
3 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.748G>T p.Gly250Ter stop_gained Familial - - 28831199 Li J , et al. (2017)
c.313A>G p.Thr105Ala missense_variant Familial - - 28831199 Li J , et al. (2017)
c.176del p.Pro59HisfsTer76 frameshift_variant Familial - - 28831199 Li J , et al. (2017)
c.632del p.Ser211ThrfsTer19 frameshift_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.508C>T p.Gln170Ter stop_gained Familial Paternal Multiplex (monozygotic twins) 31398340 Ruzzo EK , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Targeted sequencing of a cohort of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 identified three inherited loss-of-function variants and one damaging missense variant in the KCNK7 gene in ASD probands. Transmission and De Novo Association (TADA) analysis of this cohort of Chinese ASD cases and controls in Guo et al., 2017 identified the KCNK7 gene as an ASD candidate gene with a PTADA between 0.001 and 0.005 (0.008245); however, PTADA for this gene failed to reach significance (P < 0.01) following TADA analysis using a combined cohort of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium.

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

Targeted sequencing of a cohort of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 identified three inherited loss-of-function variants and one damaging missense variant in the KCNK7 gene in ASD probands. Transmission and De Novo Association (TADA) analysis of this cohort of Chinese ASD cases and controls in Guo et al., 2017 identified the KCNK7 gene as an ASD candidate gene with a PTADA between 0.001 and 0.005 (0.008245); however, PTADA for this gene failed to reach significance (P < 0.01) following TADA analysis using a combined cohort of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Targeted sequencing of a cohort of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 identified three inherited loss-of-function variants and one damaging missense variant in the KCNK7 gene in ASD probands. Transmission and De Novo Association (TADA) analysis of this cohort of Chinese ASD cases and controls in Guo et al., 2017 identified the KCNK7 gene as an ASD candidate gene with a PTADA between 0.001 and 0.005 (0.008245); however, PTADA for this gene failed to reach significance (P < 0.01) following TADA analysis using a combined cohort of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium.

Reports Added
[New Scoring Scheme]
7/1/2019
4
icon
4

Decreased from 4 to 4

Description

Targeted sequencing of a cohort of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 identified three inherited loss-of-function variants and one damaging missense variant in the KCNK7 gene in ASD probands. Transmission and De Novo Association (TADA) analysis of this cohort of Chinese ASD cases and controls in Guo et al., 2017 identified the KCNK7 gene as an ASD candidate gene with a PTADA between 0.001 and 0.005 (0.008245); however, PTADA for this gene failed to reach significance (P < 0.01) following TADA analysis using a combined cohort of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium.

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
7/1/2017
icon
4

Increased from to 4

Description

Targeted sequencing of a cohort of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 identified three inherited loss-of-function variants and one damaging missense variant in the KCNK7 gene in ASD probands. Transmission and De Novo Association (TADA) analysis of this cohort of Chinese ASD cases and controls in Guo et al., 2017 identified the KCNK7 gene as an ASD candidate gene with a PTADA between 0.001 and 0.005 (0.008245); however, PTADA for this gene failed to reach significance (P < 0.01) following TADA analysis using a combined cohort of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium.

Krishnan Probability Score

Score 0.44717979644159

Ranking 13866/25841 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 6.4272612000749E-6

Ranking 14404/18225 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 0.81421687632564

Ranking 2480/18665 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
Zhang D Score

Score -0.52398289018291

Ranking 19431/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
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