Human Gene Module / Chromosome 11 / KMT5B

KMT5Blysine methyltransferase 5B

Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
6 / 9
Rare Variants / Common Variants
18 / 0
Aliases
KMT5B, CGI-85,  CGI85,  SUV420H1
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Syndromic
Chromosome Band
11q13.2
Associated Disorders
EPS, ASD
Relevance to Autism

A de novo loss-of-function (LoF) variant in the KMT5B gene (previously known as SUV420H1) was identified in an autistic proband from a simplex family in Iossifov et al., 2012 (PMID 22542183). In addition, two missense variants in the KMT5B gene that were predicted to be deleterious was also identified in ASD probands from the Simons Simplex Collection in Sanders et al., 2012 (PMID 22495306). Although population rate is not provided, many missense variants are listed in the NHLBI Exome Sequencing Project's Exome Variant Viewer for this gene. Two additional de novo LoF variants in this gene were identified in ASD probands from the Autism Sequencing Consortium in De Rubeis et al., 2014 (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in this report identified KMT5B as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Additional de novo variants in KMT5B have been identified in individuals with ASD and/or developmental delay/intellectual disability (Stessman et al., 2017; Yuen et al., 2017).

Molecular Function

Histone methyltransferase that specifically trimethylates 'Lys-20' of histone H4. H4 'Lys-20' trimethylation represents a specific tag for epigenetic transcriptional repression. Mainly functions in pericentric heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin in these regions. KMT5B is targeted to histone H3 via its interaction with RB1 family proteins (RB1, RBL1 and RBL2). Plays a role in myogenesis by regulating the expression of target genes, such as EID3.

Reports related to KMT5B (9 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Sanders SJ , et al. (2012) Yes -
2 Support De novo gene disruptions in children on the autistic spectrum. Iossifov I , et al. (2012) Yes -
3 Recent recommendation Synaptic, transcriptional and chromatin genes disrupted in autism. De Rubeis S , et al. (2014) Yes -
4 Recent recommendation Incorporating Functional Information in Tests of Excess De Novo Mutational Load. Jiang Y , et al. (2015) No -
5 Recent recommendation Low load for disruptive mutations in autism genes and their biased transmission. Iossifov I , et al. (2015) Yes -
6 Recent recommendation Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases. Stessman HA , et al. (2017) Yes -
7 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder. C Yuen RK , et al. (2017) Yes -
8 Support Genomic diagnosis for children with intellectual disability and/or developmental delay. Bowling KM , et al. (2017) No -
9 Support Histone Lysine Methylases and Demethylases in the Landscape of Human Developmental Disorders. Faundes V , et al. (2017) No ASD (2/4 cases), epilepsy/seizures (2/4 cases)
Rare Variants   (18)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.791G>C p.Trp264Ser missense_variant De novo - Simplex 22495306 Sanders SJ , et al. (2012)
c.1538C>T p.Ala513Val missense_variant De novo - Simplex 22495306 Sanders SJ , et al. (2012)
c.977+1G>A - splice_site_variant De novo - Simplex 22542183 Iossifov I , et al. (2012)
c.2347C>T p.Arg783Ter stop_gained De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.555_558del p.Tyr185fs frameshift_variant De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.2548A>G p.Ile850Val missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1619G>A p.Arg540Gln missense_variant Familial Maternal - 28191889 Stessman HA , et al. (2017)
c.725del p.Leu242HisfsTer30 frameshift_variant De novo - - 28191889 Stessman HA , et al. (2017)
c.1557_1558del p.Asn520SerfsTer33 frameshift_variant De novo - - 28191889 Stessman HA , et al. (2017)
c.1166dup p.Asn389LysfsTer6 frameshift_variant Unknown - - 28191889 Stessman HA , et al. (2017)
c.676G>A p.Asp226Asn missense_variant De novo - - 28191889 Stessman HA , et al. (2017)
:c.953_1028del;c.1157_1232del;c.1673_1748del p.Pro318fs;p.Pro386fs;p.Pro558fs frameshift_variant De novo - Multiplex 28263302 C Yuen RK , et al. (2017)
c.1876T>C;c.2080T>C;c.2596T>C p.Ser626Pro;p.Ser694Pro;p.Ser866Pro missense_variant De novo - Simplex 28263302 C Yuen RK , et al. (2017)
c.1981G>T p.Glu661Ter stop_gained De novo - - 28554332 Bowling KM , et al. (2017)
c.219delC p.Ala74ProfsTer10 frameshift_variant De novo - - 29276005 Faundes V , et al. (2017)
c.559C>T p.Arg187Ter stop_gained De novo - - 29276005 Faundes V , et al. (2017)
- - copy_number_loss De novo - - 29276005 Faundes V , et al. (2017)
- - copy_number_loss De novo - - 29276005 Faundes V , et al. (2017)
Common Variants  

No common variants reported.

SFARI Gene score
1

High Confidence

1

Score Delta: Score remained at 1.1

1

High Confidence

See all Category 1 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.

4/1/2017
1
icon
1

Score remained at 1

Description

An apparent LoF splice variant (de novo) in KMT5B (originally known as SUV420H1) was identified in an autistic proband (PMID 22542183). In addition, rare mutation in the KMT5B/SUV420H1 gene was also identified in PMID 22495306. Although population rate is not provided, many missense variants are listed in the NHLBI Exome Sequencing Project's Exome Variant Viewer. Two additional de novo LoF variants in this gene were identified in ASD probands from the Autism Sequencing Consortium (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified KMT5B/SUV420H1 as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

1/1/2017
1
icon
1

Score remained at 1

Description

An apparent LoF splice variant (de novo) in KMT5B (originally known as SUV420H1) was identified in an autistic proband (PMID 22542183). In addition, rare mutation in the KMT5B/SUV420H1 gene was also identified in PMID 22495306. Although population rate is not provided, many missense variants are listed in the NHLBI Exome Sequencing Project's Exome Variant Viewer. Two additional de novo LoF variants in this gene were identified in ASD probands from the Autism Sequencing Consortium (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified KMT5B/SUV420H1 as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

10/1/2016
icon
1

Increased from to 1

Description

An apparent LoF splice variant (de novo) in KMT5B (originally known as SUV420H1) was identified in an autistic proband (PMID 22542183). In addition, rare mutation in the KMT5B/SUV420H1 gene was also identified in PMID 22495306. Although population rate is not provided, many missense variants are listed in the NHLBI Exome Sequencing Project's Exome Variant Viewer. Two additional de novo LoF variants in this gene were identified in ASD probands from the Autism Sequencing Consortium (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified KMT5B/SUV420H1 as a gene meeting high statistical significance with a FDR ?0.01, meaning that this gene had a ?99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

CNVs associated with KMT5B(1 CNVs)
11q13.2 18 Deletion-Duplication 33  /  65
Submit New Gene

Report an Error