Human Gene Module / Chromosome 17 / KCNJ2

KCNJ2Potassium inwardly-rectifying channel, subfamily J, member 2

Hypothesized Criteria 5.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
2 / 0
Associated Syndromes
Genetic Category
Rare Single Gene Mutation, Genetic Association
Chromosome Band
Associated Disorders
Relevance to Autism

A gain-of-function missense variant in the KCNJ2 gene was identified in monozygotic twins displaying a short QT interval and an autism/epilepsy phenotype and their mother, whose motor clumsiness, obsessive-compulsive symptoms, mood swings with impulsivity, and motor and vocal tics fit a diagnosis of Tourette Syndrome (Ambrosini et al., 2014); these twins had previously been reported to also carry a gain-of-function missense variant in the KCNJ10 gene (Sicca et al., 2011).

Molecular Function

The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, probably participates in establishing action potential waveform and excitability of neuronal and muscle tissues. Involved in long QT syndrome 7 (LQT7) [MIM:170390], short QT syndrome 3 (SQT3) [MIM:609622], and atrial fibrillation, familial, 9 (ATFB9) [MIM:613980].

Reports related to KCNJ2 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Genetically induced dysfunctions of Kir2.1 channels: implications for short QT3 syndrome and autism-epilepsy phenotype. Ambrosini E , et al. (2014) Yes TS
2 Support A Novel KCNJ2 Mutation Identified in an Autistic Proband Affects the Single Channel Properties of Kir2.1. Binda A , et al. (2018) Yes -
3 Negative Association Association study between inwardly rectifying potassium channels 2.1 and 4.1 and autism spectrum disorders. Sun C , et al. (2018) Yes -
Rare Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.173T>C p.Phe58Ser missense_variant Familial Paternal Multi-generational 29615871 Binda A , et al. (2018)
c.1037A>C p.Lys346Thr missense_variant Familial Maternal Multi-generational (multiplex ASD, mother with TS) 24794859 Ambrosini E , et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score





See all Category 5 Genes

Category 5.1 includes genes for which the only evidence comes from studies of model organisms, without statistical or genetic support in human studies.

Krishnan Probability Score

Score 0.49536507277841

Ranking 3017/25841 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: A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at
ExAC Score

Score 0.82022902764473

Ranking 3814/18225 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 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: aned_exac_nonTCGA_z_pli_rec_null_data.txt
Sanders TADA Score

Score 0.92711041212851

Ranking 10593/18665 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
Larsen Cumulative Evidence Score

Score 8

Ranking 228/461 scored genes

[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Zhang D Score

Score 0.16569607788738

Ranking 4877/20870 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.
CNVs associated with KCNJ2(1 CNVs)
17q24.3 7 Deletion-Duplication 12  /  58
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