Human Gene Module / Chromosome 1 / KDM5B

KDM5BLysine (K)-specific demethylase 5B

Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 8
Rare Variants / Common Variants
31 / 0
Aliases
KDM5B, CT31,  JARID1B,  PLU-1,  PLU1,  PPP1R98,  PUT1,  RBBP2H1A
Associated Syndromes
Tourette syndrome
Genetic Category
Rare Single Gene Mutation
Chromosome Band
1q32.1
Associated Disorders
DD/NDD
Relevance to Autism

Two de novo loss-of-function variants in the KDM5B gene have been identified in ASD probands from the Simons Simplex Collection (refs).

Molecular Function

This gene encodes a histone demethylase that demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code.

External Links
Gene CardEntrez GeneOMIMUniProt
Reports related to KDM5B (8 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Recent Recommendation Synaptic, transcriptional and chromatin genes disrupted in autism. De Rubeis S , et al. (2014) Yes -
2 Primary The contribution of de novo coding mutations to autism spectrum disorder. Iossifov I , et al. (2014) Yes -
3 Support Excess of rare, inherited truncating mutations in autism. Krumm N , et al. (2015) Yes -
4 Recent recommendation De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies. Homsy J , et al. (2016) No NDD (DD with or without learning disabilities) in
5 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder. C Yuen RK , et al. (2017) Yes -
6 Support Leveraging blood serotonin as an endophenotype to identify de novo and rare variants involved in autism. Chen R , et al. (2017) Yes -
7 Positive association De Novo Coding Variants Are Strongly Associated with Tourette Disorder. Willsey AJ , et al. (2017) No -
8 Support Genomic diagnosis for children with intellectual disability and/or developmental delay. Bowling KM , et al. (2017) No -
Rare Variants   (31)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1534_1535insG p.His512fs frameshift_variant De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.515G>C p.Arg172Thr missense_variant De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.3802C>T p.Arg1268Ter stop_gained Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.2818C>T p.Arg940Cys splice_site_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.520C>T p.Gln174Ter stop_gained Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.3004A>T p.Arg1002Ser missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.772A>T p.Thr258Ser missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.1157C>G p.Ser386Cys missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.249A>G p.Ile87Val missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.593G>C p.Gly198Ala missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.2386G>A p.Val796Met missense_variant Familial Maternal (n=1), paternal (n=1) Simplex 25363760 De Rubeis S , et al. (2014)
c.622G>A p.Val208Met missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.4000C>T p.Arg1334Ter stop_gained Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.3391G>C p.Ala1131Pro missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.532A>G p.Lys178Glu missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.304C>T p.Arg102Trp missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1100A>G p.Tyr367Cys missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.299G>A p.Arg100His missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.541C>G p.Pro181Ala missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.3650T>C p.Leu1217Pro missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.2444A>G p.Gln815Arg missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.3139C>T p.Arg1047Ter stop_gained De novo - Simplex 25363768 Iossifov I , et al. (2014)
c.4627C>T p.Arg1543Ter stop_gained De novo - Simplex 25363768 Iossifov I , et al. (2014)
c.2243T>C p.Leu748Ser missense_variant De novo - Simplex 25961944 Krumm N , et al. (2015)
c.208T>A p.Trp70Arg missense_variant De novo - Simplex 25961944 Krumm N , et al. (2015)
G>A - stop_gained De novo - - 26785492 Homsy J , et al. (2016)
G>A - stop_gained De novo - - 26785492 Homsy J , et al. (2016)
TG>TGG - frameshift_variant De novo - Simplex 28263302 C Yuen RK , et al. (2017)
G>A - stop_gained De novo - Simplex 28344757 Chen R , et al. (2017)
- - frameshift_variant De novo - Simplex 28472652 Willsey AJ , et al. (2017)
c.3835C>T p.Arg1279Ter stop_gained Unknown - - 28554332 Bowling KM , et al. (2017)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Two de novo LoF variants in the KDM5B gene (two nonsense, one frameshift) were identified in ASD probands from the Simons Simplex Collection (PMID 25363768), while a third de novo LoF variant in this gene was identified in one ASD proband from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760). A fourth de novo LoF variant in this gene was identified in an ASD proband from a simplex family by whole genome sequencing in Yuen et al., 2017.

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.

04-01-2017
2

Initial score established: 2

Description

Two de novo LoF variants in the KDM5B gene (two nonsense, one frameshift) were identified in ASD probands from the Simons Simplex Collection (PMID 25363768), while a third de novo LoF variant in this gene was identified in one ASD proband from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760). A fourth de novo LoF variant in this gene was identified in an ASD proband from a simplex family by whole genome sequencing in Yuen et al., 2017.

Reports Added
[Excess of rare, inherited truncating mutations in autism.2015] [De Novo Coding Variants Are Strongly Associated with Tourette Disorder.2017] [The contribution of de novo coding mutations to autism spectrum disorder.2014] [De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies.2016] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Leveraging blood serotonin as an endophenotype to identify de novo and rare variants involved in autism.2017] [Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.2017] [Genomic diagnosis for children with intellectual disability and/or developmental delay.2017]
CNVs associated with KDM5B(1 CNVs)
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1q32.1 15 Deletion-Duplication 26  /  105
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
AKR1C1 aldo-keto reductase family 1, member C1 Human Direct Regulation 1645 Q04828
ETS1 Protein C-ets-1 Human Protein Binding 2113 P14921
FAM90A1 Protein FAM90A1 Human Protein Binding 55138 Q86YD7
Hoxa7 homeobox A7 Mouse DNA Binding 15404 P02830
LMO2 Rhombotin-2 Human Protein Binding 4005 P25791
PLIN2 perilipin 2 Human Direct Regulation 123 Q99541
SLITRK3 SLIT and NTRK-like protein 3 Human Protein Binding 22865 O94933
TFAP2C Transcription factor AP-2 gamma Human Protein Binding 7022 Q92754
TSPYL6 Testis-specific Y-encoded-like protein 6 Human Protein Binding 388951 Q8N831
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