Human Gene Module / Chromosome 9 / KDM4C

KDM4Clysine demethylase 4C

Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
2 / 2
Rare Variants / Common Variants
3 / 0
Aliases
KDM4C, GASC1,  JHDM3C,  JMJD2C,  TDRD14C
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
9p24.1
Associated Disorders
-
Relevance to Autism

CNV analysis of 1,108 ASD cases, 2,458 schizophrenia (SCZ) cases, and 2,095 controls from a Japanese population in Kushima et al., 2018 demonstrated that significant enrichment of exonic CNVs affecting the KDM4C gene was observed in a combined cohort of ASD and SCZ cases compared to controls [3 CNVs from ASD cases and 6 CNVs from SCZ cases (9 total) vs. 0 CNVs in controls (Odds ratio 10.46, P = 8.6E-03)].

Molecular Function

This gene is a member of the Jumonji domain 2 (JMJD2) family. The encoded protein is a trimethylation-specific demethylase, and converts specific trimethylated histone residues to the dimethylated form. This enzymatic action regulates gene expression and chromosome segregation.

External Links
Gene CardOpen Targets PlatformPubMed
Human
Entrez GeneOMIMUniProtHumanBase
Reports related to KDM4C (2 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Comparative Analyses of Copy-Number Variation in Autism Spectrum Disorder and Schizophrenia Reveal Etiological Overlap and Biological Insights. Kushima I , et al. (2018) Yes -
2 Support Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes. Feliciano P , et al. (2019) Yes -
Rare Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_gain Unknown - - 30208311 Kushima I , et al. (2018)
- - copy_number_loss Unknown - - 30208311 Kushima I , et al. (2018)
c.2557T>G p.Trp853Gly missense_variant De novo NA - 31452935 Feliciano P , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

CNV analysis of 1,108 ASD cases, 2,458 schizophrenia (SCZ) cases, and 2,095 controls from a Japanese population in Kushima et al., 2018 demonstrated that significant enrichment of exonic CNVs affecting the KDM4C gene was observed in a combined cohort of ASD and SCZ cases compared to controls [3 CNVs from ASD cases and 6 CNVs from SCZ cases (9 total) vs. 0 CNVs in controls (Odds ratio 10.46, P = 8.6E-03)].

Score Delta: Score remained at 3

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.

10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

CNV analysis of 1,108 ASD cases, 2,458 schizophrenia (SCZ) cases, and 2,095 controls from a Japanese population in Kushima et al., 2018 demonstrated that significant enrichment of exonic CNVs affecting the KDM4C gene was observed in a combined cohort of ASD and SCZ cases compared to controls [3 CNVs from ASD cases and 6 CNVs from SCZ cases (9 total) vs. 0 CNVs in controls (Odds ratio 10.46, P = 8.6E-03)].

Reports Added
[Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes.2019] [New Scoring Scheme]
10/1/2018
icon
3

Increased from to 3

Description

CNV analysis of 1,108 ASD cases, 2,458 schizophrenia (SCZ) cases, and 2,095 controls from a Japanese population in Kushima et al., 2018 demonstrated that significant enrichment of exonic CNVs affecting the KDM4C gene was observed in a combined cohort of ASD and SCZ cases compared to controls [3 CNVs from ASD cases and 6 CNVs from SCZ cases (9 total) vs. 0 CNVs in controls (Odds ratio 10.46, P = 8.6E-03)].

Krishnan Probability Score

Score 0.49192458415654

Ranking 4920/25841 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 0.00075873460262275

Ranking 11960/18225 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 0.94566687863515

Ranking 16561/18665 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 0.48587120147617

Ranking 613/20870 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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SFARI Gene Update

We are pleased to announce some changes to the ongoing curation of the data in SFARI Gene. In the context of a continued effort to develop the human gene module and its manually curated list of autism risk genes, we are modifying other aspects of the site to focus on the information that is of greatest interest to the research community. The version of SFARI Gene that has been developed until now will be frozen and will remain available as “SFARI Gene Archive”. Please see the announcement for more details.
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