Human Gene Module / Chromosome 21 / KCNJ15

KCNJ15potassium voltage-gated channel subfamily J member 15

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
3 / 0
Aliases
KCNJ15, IRKK,  KIR1.3,  KIR4.2
Associated Syndromes
-
Chromosome Band
21q22.13-q22.2
Associated Disorders
-
Relevance to Autism

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module. Sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism; this finding was further validated by exome sequencing of an independent cohort of 505 ASD cases and 491 controls (Li et al., 2014).

Molecular Function

The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein has a greater tendency to allow potassium to flow into a cell rather than out of a cell.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to KCNJ15 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Primary Integrated systems analysis reveals a molecular network underlying autism spectrum disorders Li J , et al. (2015) Yes -
3 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
Rare Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - nonsynonymous_variant Unknown - Unknown 25549968 Li J , et al. (2015)
c.397C>T p.Arg133Cys missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.584T>A p.Leu195Ter stop_gained Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module. Sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism; this finding was further validated by exome sequencing of an independent cohort of 505 ASD cases and 491 controls (Li et al., 2014). The KCNJ15 non-synonymous variant identified in this study was not reported in 1000 Genomes (as of Jan/ Feb. 2013) or dbSNP and had a high GERP++ conservation score (4.81). A rare de novo missense variant that was predicted to be damaging was identified in the KCNJ15 gene in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014.

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

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module. Sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism; this finding was further validated by exome sequencing of an independent cohort of 505 ASD cases and 491 controls (Li et al., 2014). The KCNJ15 non-synonymous variant identified in this study was not reported in 1000 Genomes (as of Jan/ Feb. 2013) or dbSNP and had a high GERP++ conservation score (4.81). A rare de novo missense variant that was predicted to be damaging was identified in the KCNJ15 gene in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module. Sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism; this finding was further validated by exome sequencing of an independent cohort of 505 ASD cases and 491 controls (Li et al., 2014). The KCNJ15 non-synonymous variant identified in this study was not reported in 1000 Genomes (as of Jan/ Feb. 2013) or dbSNP and had a high GERP++ conservation score (4.81). A rare de novo missense variant that was predicted to be damaging was identified in the KCNJ15 gene in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014.

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

Decreased from 4 to 4

Description

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module. Sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism; this finding was further validated by exome sequencing of an independent cohort of 505 ASD cases and 491 controls (Li et al., 2014). The KCNJ15 non-synonymous variant identified in this study was not reported in 1000 Genomes (as of Jan/ Feb. 2013) or dbSNP and had a high GERP++ conservation score (4.81). A rare de novo missense variant that was predicted to be damaging was identified in the KCNJ15 gene in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014.

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
7/1/2018
icon
4

Increased from to 4

Description

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module. Sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism; this finding was further validated by exome sequencing of an independent cohort of 505 ASD cases and 491 controls (Li et al., 2014). The KCNJ15 non-synonymous variant identified in this study was not reported in 1000 Genomes (as of Jan/ Feb. 2013) or dbSNP and had a high GERP++ conservation score (4.81). A rare de novo missense variant that was predicted to be damaging was identified in the KCNJ15 gene in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014.

Krishnan Probability Score

Score 0.44079985044887

Ranking 19278/25841 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 0.15046203852881

Ranking 7386/18225 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 0.65435593493251

Ranking 915/18665 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 -0.096201798939156

Ranking 12223/20870 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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