KDM5BLysine (K)-specific demethylase 5B
Autism Reports / Total Reports
12 / 18Rare Variants / Common Variants
51 / 0Aliases
KDM5B, CT31, JARID1B, PLU-1, PLU1, PPP1R98, PUT1, RBBP2H1AAssociated Syndromes
Tourette syndromeChromosome Band
1q32.1Associated Disorders
DD/NDDGenetic Category
Rare Single Gene Mutation, Syndromic, FunctionalRelevance 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.
Reports related to KDM5B (18 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 | DD, learning disabilities |
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 | - |
9 | Support | Whole exome sequencing reveals inherited and de novo variants in autism spectrum disorder: a trio study from Saudi families | Al-Mubarak B , et al. (2017) | Yes | - |
10 | Support | Histone Lysine Methylases and Demethylases in the Landscape of Human Developmental Disorders | Faundes V , et al. (2017) | No | - |
11 | Support | Novel KDM5B splice variants identified in patients with developmental disorders: Functional consequences | Lebrun N , et al. (2018) | Yes | - |
12 | Support | Drosophila Histone Demethylase KDM5 Regulates Social Behavior through Immune Control and Gut Microbiota Maintenance | Chen K , et al. (2019) | No | - |
13 | Support | Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes | Feliciano P et al. (2019) | Yes | - |
14 | Support | Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism | Satterstrom FK et al. (2020) | Yes | - |
15 | Support | Rare genetic susceptibility variants assessment in autism spectrum disorder: detection rate and practical use | Husson T , et al. (2020) | Yes | - |
16 | Support | - | Alonso-Gonzalez A et al. (2021) | Yes | - |
17 | Support | - | Lebon S et al. (2021) | No | - |
18 | Support | - | Mahjani B et al. (2021) | Yes | - |
Rare Variants (51)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
- | - | frameshift_variant | De novo | NA | Simplex | 28472652 | Willsey AJ , et al. (2017) | |
c.529C>T | p.Arg177Ter | stop_gained | De novo | NA | - | 26785492 | Homsy J , et al. (2016) | |
c.3058C>T | p.Arg1020Ter | stop_gained | De novo | NA | - | 26785492 | Homsy J , et al. (2016) | |
TG>TGG | - | frameshift_variant | De novo | NA | Simplex | 28263302 | C Yuen RK et al. (2017) | |
c.3835C>T | p.Arg1279Ter | stop_gained | Unknown | - | - | 28554332 | Bowling KM , et al. (2017) | |
c.1816C>T | p.Arg606Ter | stop_gained | De novo | NA | Simplex | 28344757 | Chen R , et al. (2017) | |
c.4189C>T | p.Arg1397Ter | stop_gained | Unknown | - | Simplex | 32094338 | Husson T , et al. (2020) | |
c.577-28A>T | - | intron_variant | De novo | NA | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
c.*18C>A | - | 3_prime_UTR_variant | De novo | NA | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
c.208T>A | p.Trp70Arg | missense_variant | De novo | NA | Simplex | 25961944 | Krumm N , et al. (2015) | |
c.3139C>T | p.Arg1047Ter | stop_gained | De novo | NA | Simplex | 25363768 | Iossifov I et al. (2014) | |
c.4627C>T | p.Arg1543Ter | stop_gained | De novo | NA | Simplex | 25363768 | Iossifov I et al. (2014) | |
c.4000C>T | p.Arg1334Ter | stop_gained | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
c.1903G>A | p.Ala635Thr | missense_variant | Unknown | - | Multiplex | 34573379 | Lebon S et al. (2021) | |
c.4548dup | p.Glu1517Ter | frameshift_variant | De novo | NA | - | 31452935 | Feliciano P et al. (2019) | |
c.2243T>C | p.Leu748Pro | missense_variant | De novo | NA | Simplex | 25961944 | Krumm N , et al. (2015) | |
c.2265C>A | p.Tyr755Ter | stop_gained | De novo | NA | Simplex | 28720891 | Al-Mubarak B , et al. (2017) | |
c.299G>A | p.Arg100His | 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.532A>G | p.Ile178Val | 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.3634dup | p.Ile1212AsnfsTer18 | frameshift_variant | Unknown | - | - | 34615535 | Mahjani B et al. (2021) | |
c.1100A>G | p.Asp367Gly | 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.515G>C | p.Arg172Thr | missense_variant | De novo | NA | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
c.3391G>C | p.Asp1131His | 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.292C>T | p.Arg98Cys | missense_variant | De novo | NA | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
c.1816C>T | p.Arg606Ter | stop_gained | De novo | NA | Simplex | 33431980 | Alonso-Gonzalez A et al. (2021) | |
c.520C>T | p.His174Tyr | stop_gained | Familial | Paternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
c.1052G>A | p.Cys351Tyr | splice_site_variant | De novo | NA | Multiplex | 30217758 | Lebrun N , et al. (2018) | |
c.3802C>T | p.Gln1268Ter | stop_gained | Familial | Paternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
c.4661T>G | p.Val1554Gly | missense_variant | De novo | NA | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
c.895C>T | p.Pro299Ser | stop_gained | Familial | Maternal and paternal | - | 29276005 | Faundes V , et al. (2017) | |
c.4109T>G | p.Leu1370Ter | stop_gained | Familial | Both parents | Simplex | 29276005 | Faundes V , et al. (2017) | |
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.622G>A | p.Val208Met | missense_variant | Familial | Maternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
c.772A>T | p.Asn258Tyr | missense_variant | Familial | Maternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
c.1157C>G | p.Ala386Gly | missense_variant | Familial | Maternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
c.2386G>A | p.Val796Met | missense_variant | Familial | Maternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
c.2386G>A | p.Val796Met | missense_variant | Familial | Paternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
c.3004A>T | p.Thr1002Ser | missense_variant | Familial | Paternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
c.2818C>T | p.Leu940Phe | splice_site_variant | Familial | Maternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
c.1182dup | p.Asn395GlnfsTer13 | frameshift_variant | De novo | NA | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
c.576+2T>C | - | splice_site_variant | De novo | NA | Multiplex (monozygotic twins) | 30217758 | Lebrun N , et al. (2018) | |
c.3463del | p.Ala1155ProfsTer22 | frameshift_variant | Familial | Maternal | Multiplex | 34573379 | Lebon S et al. (2021) | |
c.2473A>G | p.Lys825Glu | splice_site_variant | Familial | Maternal and paternal | - | 29276005 | Faundes V , et al. (2017) | |
c.1534_1535insG | p.Thr512SerfsTer3 | frameshift_variant | De novo | NA | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
c.622dup | p.Tyr208LeufsTer5 | frameshift_variant | Familial | Maternal and paternal | - | 29276005 | Faundes V , et al. (2017) | |
c.3907del | p.Gln1303SerfsTer80 | frameshift_variant | Familial | Maternal and paternal | - | 29276005 | Faundes V , et al. (2017) |
Common Variants
No common variants reported.
SFARI Gene score
High Confidence


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.
Score Delta: Score remained at 2
criteria met
See SFARI Gene'scoring criteriaWe 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.
1/1/2021

Score remained at 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.
1/1/2020

Score remained at 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.
10/1/2019

Score remained at 2
New Scoring Scheme
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.
4/1/2019

Score remained at 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.
10/1/2018

Score remained at 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.
4/1/2018

Score remained at 2.1
Description
2
7/1/2017

Score remained at 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.
4/1/2017

Score remained at 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
[Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [The contribution of de novo coding mutations to autism spectrum disorder2014] [Excess of rare, inherited truncating mutations in autism.2015] [De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies.2016] [Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder2017] [Leveraging blood serotonin as an endophenotype to identify de novo and rare variants involved in autism.2017] [De Novo Coding Variants Are Strongly Associated with Tourette Disorder.2017] [Genomic diagnosis for children with intellectual disability and/or developmental delay.2017]1/1/2016

Score remained at 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).
Reports Added
[Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [The contribution of de novo coding mutations to autism spectrum disorder2014] [Excess of rare, inherited truncating mutations in autism.2015] [De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies.2016]4/1/2015

Score remained at 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).
10/1/2014

Increased from to 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).
Krishnan Probability Score
Score 0.49587907608577
Ranking 2764/25841 scored genes
[Show Scoring Methodology]
ExAC Score
Score 5.0942014234463E-5
Ranking 13445/18225 scored genes
[Show Scoring Methodology]
Sanders TADA Score
Score 2.2857808817364E-5
Ranking 9/18665 scored genes
[Show Scoring Methodology]
Larsen Cumulative Evidence Score
Score 52
Ranking 30/461 scored genes
[Show Scoring Methodology]
Zhang D Score
Score 0.50791540770519
Ranking 468/20870 scored genes
[Show Scoring Methodology]
Interactome
- Protein Binding
- DNA Binding
- RNA Binding
- Protein Modification
- Direct Regulation
- ASD-Linked Genes
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 |