Human Gene Module / Chromosome 17 / KDM6B

KDM6BLysine (K)-specific demethylase 6B

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
5 / 7
Rare Variants / Common Variants
26 / 0
Aliases
KDM6B, JMJD3
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
17p13.1
Associated Disorders
-
Relevance to Autism

Two de novo loss-of-function variants in the KDM6B gene have been identified in ASD probands from the Simons Simplex Collection (refs).

Molecular Function

This gene encodes a histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code. Plays a central role in regulation of posterior development, by regulating HOX gene expression.

Reports related to KDM6B (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary De novo gene disruptions in children on the autistic spectrum. Iossifov I , et al. (2012) Yes -
2 Recent Recommendation Synaptic, transcriptional and chromatin genes disrupted in autism. De Rubeis S , et al. (2014) Yes -
3 Recent recommendation The contribution of de novo coding mutations to autism spectrum disorder. Iossifov I , et al. (2014) Yes -
4 Recent recommendation Low load for disruptive mutations in autism genes and their biased transmission. Iossifov I , et al. (2015) Yes -
5 Support Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability. Lelieveld SH , et al. (2016) No -
6 Support Diagnostic Yield and Novel Candidate Genes by Exome Sequencing in 152 Consanguineous Families With Neurodevelopmental Disorders. Reuter MS , et al. (2017) No Sleep disturbances, aggressive behavior
7 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder. C Yuen RK , et al. (2017) Yes -
Rare Variants   (26)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.575delG p.Arg192fs frameshift_variant De novo - Simplex 22542183 Iossifov I , et al. (2012)
c.4174G>A p.Glu1392Lys missense_variant De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.28G>A p.Ala10Thr missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.596G>A p.Arg199Gln missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.1120G>A p.Val374Ile missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.3626G>A p.Arg1209Gln missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.259C>T p.His87Tyr missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.982C>T p.Arg328Trp missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.1039C>T p.His347Tyr missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.2171C>T p.Pro724Leu missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.3532C>T p.Arg1178Trp missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.4571A>T p.Thr1524Met missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.325C>T p.Leu109Phe missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1105C>T p.Arg369Trp missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.3478C>T p.Leu1160Phe missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.3626G>A p.Arg1209Gln missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.4369C>G p.Arg1457Gly missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.4420G>A p.Ala1474Thr missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1069G>A p.Gly357Arg missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.2626G>A p.Gly876Arg missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.4571C>T p.Thr1524Met missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.138-2A>G - splice_site_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
delCTT - inframe_deletion De novo - Simplex 25363768 Iossifov I , et al. (2014)
c.4696C>A p.Arg1566Ser missense_variant De novo - - 27479843 Lelieveld SH , et al. (2016)
c.[1668_1673del];[1668_1673del] p.[Asn557_Ser558del];[Asn557_Ser558del] inframe_deletion;inframe_deletion Familial Both parents Multiplex 28097321 Reuter MS , et al. (2017)
c.343C>T p.Gln115Ter stop_gained Unknown - Simplex 28263302 C Yuen RK , et al. (2017)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

Two de novo LoF variants in the KDM6B gene (one frameshift, one splice-site) were identified in ASD probands from the Simons Simplex Collection (PMIDs 22542183, 25363768).

3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

CNVs associated with KDM6B(1 CNVs)
17p13.1 23 Deletion-Duplication 37  /  150
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
KMT2B Mouse Protein Binding Q6PDK2
WAS Wiskott-Aldrich syndrome protein Human Protein Binding 7454 P42768
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