KDM5BLysine (K)-specific demethylase 5B
Autism Reports / Total Reports
16 / 25Rare Variants / Common Variants
79 / 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 LoF variants in the KDM5B gene (two nonsense, one frameshift) were identified in ASD probands from the Simons Simplex Collection (Iossifov et al., 2014), 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 (De Rubeis et al., 2014). 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. Additional de novo likely gene-disruptive/protein-truncating variants in KDM5B were identified in ASD probands from the SPARK cohort and the Autism Sequencing Consortium in Feliciano et al., 2019 and Satterstrom et al., 2020, respectively; furthermore, transmission and de novo association (TADA) analysis in both reports identified KDM5B as a candidate gene with a false discovery rate (FDR) 0.01. A two-stage analysis of rare de novo and inherited coding variants in 42,607 ASD cases, including 35,130 new cases from the SPARK cohort, in Zhou et al., 2022 identified KDM5B as a gene reaching exome-wide significance (P < 2.5E-06).
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
SFARI Genomic Platforms
Reports related to KDM5B (25 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 | - |
19 | Support | - | Zhou X et al. (2022) | Yes | - |
20 | Recent Recommendation | - | Weinschutz Mendes H et al. (2023) | Yes | - |
21 | Recent Recommendation | - | Chen CY et al. (2023) | No | - |
22 | Support | - | Wang J et al. (2023) | Yes | - |
23 | Support | - | Thomas V Fernandez et al. (2023) | No | - |
24 | Support | - | Mona Abdi et al. (2023) | Yes | ADHD, ID |
25 | Support | - | Leticia Pérez-Sisqués et al. (2024) | No | - |
Rare Variants (79)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
c.529C>T | p.Arg177Ter | stop_gained | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.1646+2T>C | - | splice_site_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
- | - | frameshift_variant | De novo | - | Simplex | 28472652 | Willsey AJ , et al. (2017) | |
c.1866C>A | p.Tyr622Ter | stop_gained | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.1975C>T | p.Arg659Ter | stop_gained | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.2803G>T | p.Glu935Ter | stop_gained | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.406-4A>G | - | splice_region_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.3865C>T | p.Arg1289Ter | stop_gained | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.4108C>T | p.Arg1370Ter | stop_gained | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.4297C>T | p.Arg1433Ter | stop_gained | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.4306C>T | p.Arg1436Ter | stop_gained | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.529C>T | p.Arg177Ter | stop_gained | De novo | - | - | 26785492 | Homsy J , et al. (2016) | |
c.292C>T | p.Arg98Cys | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.3058C>T | p.Arg1020Ter | stop_gained | De novo | - | - | 26785492 | Homsy J , et al. (2016) | |
TG>TGG | - | frameshift_variant | De novo | - | Simplex | 28263302 | C Yuen RK et al. (2017) | |
c.1211T>C | p.Phe404Ser | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.1637A>G | p.Tyr546Cys | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.1685C>T | p.Ala562Val | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.1730T>C | p.Leu577Pro | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.1915T>C | p.Cys639Arg | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.1989T>G | p.Phe663Leu | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.2335C>G | p.Pro779Ala | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.4031C>T | p.Pro1344Leu | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.688C>T | p.Arg230Ter | stop_gained | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
c.3835C>T | p.Arg1279Ter | stop_gained | Unknown | - | - | 28554332 | Bowling KM , et al. (2017) | |
c.1816C>T | p.Arg606Ter | stop_gained | De novo | - | Simplex | 28344757 | Chen R , et al. (2017) | |
c.577-28A>T | - | intron_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
c.292C>T | p.Arg98Cys | missense_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
c.4189C>T | p.Arg1397Ter | stop_gained | Unknown | - | Simplex | 32094338 | Husson T , et al. (2020) | |
c.*18C>A | - | 3_prime_UTR_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
c.1943G>A | p.Arg648Gln | missense_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
c.208T>A | p.Trp70Arg | missense_variant | De novo | - | Simplex | 25961944 | Krumm N , et al. (2015) | |
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.3084G>C | p.Thr1028%3D | missense_variant | De novo | - | Simplex | 37393044 | Wang J et al. (2023) | |
c.259A>T | p.Ile87Phe | missense_variant | De novo | - | Simplex | 37805537 | Mona Abdi et al. (2023) | |
c.4548dup | p.Glu1517Ter | frameshift_variant | De novo | - | - | 31452935 | Feliciano P et al. (2019) | |
c.2243T>C | p.Leu748Ser | missense_variant | De novo | - | Simplex | 25961944 | Krumm N , et al. (2015) | |
c.4000C>T | p.Arg1334Ter | stop_gained | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
c.2265C>A | p.Tyr755Ter | stop_gained | De novo | - | Simplex | 28720891 | Al-Mubarak B , et al. (2017) | |
c.1903G>A | p.Ala635Thr | missense_variant | Unknown | - | Multiplex | 34573379 | Lebon S et al. (2021) | |
c.365_366del | p.His122ArgfsTer12 | frameshift_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.515G>C | p.Arg172Thr | missense_variant | De novo | - | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
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.292C>T | p.Arg98Cys | missense_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
c.1816C>T | p.Arg606Ter | stop_gained | De novo | - | Simplex | 33431980 | Alonso-Gonzalez A et al. (2021) | |
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.1867C>T | p.His623Tyr | stop_gained | De novo | - | Simplex | 37788244 | Thomas V Fernandez et al. (2023) | |
c.2071C>T | p.Gln691Ter | stop_gained | De novo | - | Simplex | 37788244 | Thomas V Fernandez et al. (2023) | |
c.1052G>A | p.Cys351Tyr | splice_site_variant | De novo | - | Multiplex | 30217758 | Lebrun N , et al. (2018) | |
c.3671dup | p.Met1225TyrfsTer5 | frameshift_variant | De novo | - | Simplex | 37393044 | Wang J et al. (2023) | |
c.520C>T | p.His174Tyr | stop_gained | Familial | Paternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
c.4661T>G | p.Val1554Gly | missense_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
c.3802C>T | p.Gln1268Ter | stop_gained | Familial | Paternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
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.1182dup | p.Asn395GlnfsTer13 | frameshift_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
c.576+2T>C | - | splice_site_variant | De novo | - | Multiplex (monozygotic twins) | 30217758 | Lebrun N , et al. (2018) | |
c.2818C>T | p.Leu940Phe | splice_site_variant | Familial | Maternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
c.1534_1535insG | p.Thr512SerfsTer3 | frameshift_variant | De novo | - | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
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.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
Score Delta: Score remained at 1
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.
4/1/2022
Decreased from 2 to 1
1/1/2021
Decreased from 2 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). 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
Decreased from 2 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). 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
Decreased from 2 to 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
Decreased from 2 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). 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
Decreased from 2 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). 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.
7/1/2017
Decreased from 2 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). 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
Decreased from 2 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). 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
Decreased from 2 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).
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
Decreased from 2 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).
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 |