Human Gene Module / Chromosome 11 / KMT5B

KMT5Blysine methyltransferase 5B

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
15 / 21
Rare Variants / Common Variants
51 / 0
Aliases
KMT5B, CGI-85,  CGI85,  SUV420H1
Associated Syndromes
-
Chromosome Band
11q13.2
Associated Disorders
ASD, EPS
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). 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 KMT5B as a gene reaching exome-wide significance (P < 2.5E-06). 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.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBase
Mouse
Entrez GeneMouse Genome InformaticsAllen Brain Atlas
Fruit fly
Entrez Gene
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to KMT5B (21 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, epilepsy/seizures
10 Support Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model Guo H , et al. (2018) Yes -
11 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
12 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
13 Support Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders Wang T et al. (2020) Yes -
14 Support - Wang ZJ et al. (2021) Yes -
15 Support - Pode-Shakked B et al. (2021) No -
16 Support - Mahjani B et al. (2021) Yes -
17 Recent Recommendation - Paulsen B et al. (2022) Yes -
18 Support - Chen G et al. (2022) Yes -
19 Support - Eliyahu A et al. (2022) No Epilepsy/seizures
20 Support - Zhou X et al. (2022) Yes -
21 Support - Hulen J et al. (2022) No -
Rare Variants   (51)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo NA - 29276005 Faundes V , et al. (2017)
c.27+1G>A - splice_site_variant De novo NA - 33004838 Wang T et al. (2020)
c.-425+5G>A - splice_site_variant De novo NA - 35982159 Zhou X et al. (2022)
c.1843C>T p.Arg615Ter stop_gained De novo NA - 35982159 Zhou X et al. (2022)
c.-366del - frameshift_variant De novo NA - 29276005 Faundes V , et al. (2017)
c.560G>A p.Arg187Gln missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.973G>A p.Glu325Lys missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.220G>A p.Ala74Thr missense_variant De novo NA - 35982159 Zhou X et al. (2022)
c.1616G>A p.Arg539Gln missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1618C>T p.Arg540Trp missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2162G>A p.Arg721His missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2570G>A p.Arg857His missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2T>C p.Met1? initiator_codon_variant Unknown - - 33004838 Wang T et al. (2020)
c.559C>T p.Arg187Ter stop_gained De novo NA - 29276005 Faundes V , et al. (2017)
c.2656T>C p.Ter886GlnextTer25 stop_lost Unknown - - 33004838 Wang T et al. (2020)
c.1981G>T p.Val661Leu stop_gained De novo NA - 28554332 Bowling KM , et al. (2017)
c.715_717del p.Glu239del inframe_deletion De novo NA - 35982159 Zhou X et al. (2022)
c.87del p.Gln29HisfsTer12 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.234_235del p.Cys78Ter frameshift_variant De novo NA - 33004838 Wang T et al. (2020)
c.938G>A p.Gly313Glu missense_variant Unknown - Simplex 33004838 Wang T et al. (2020)
c.461+1G>A - splice_site_variant De novo NA Simplex 22542183 Iossifov I , et al. (2012)
c.676G>A p.Asp226Asn missense_variant De novo NA - 28191889 Stessman HA , et al. (2017)
c.983del p.Gly328AlafsTer31 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.788T>C p.Leu263Pro missense_variant De novo NA Simplex 35331928 Chen G et al. (2022)
c.-126_-123del - frameshift_variant De novo NA Simplex 35433545 Eliyahu A et al. (2022)
c.978-1G>A - splice_site_variant Familial Maternal Simplex 30564305 Guo H , et al. (2018)
c.541del p.His181MetfsTer32 frameshift_variant De novo NA - 35982159 Zhou X et al. (2022)
c.2347C>T p.Arg783Ter stop_gained De novo NA Simplex 25363760 De Rubeis S , et al. (2014)
c.1279del p.Glu427ArgfsTer22 frameshift_variant De novo NA - 33004838 Wang T et al. (2020)
c.1539G>A p.Ala513%3D synonymous_variant De novo NA Simplex 35982159 Zhou X et al. (2022)
c.340del p.Ser114GlnfsTer12 frameshift_variant Unknown - - 34615535 Mahjani B et al. (2021)
c.1150dup p.Thr384AsnfsTer11 frameshift_variant Unknown - - 34615535 Mahjani B et al. (2021)
c.2596T>C p.Ser866Pro missense_variant De novo NA Simplex 28263302 C Yuen RK et al. (2017)
c.264_265del p.Ala89SerfsTer13 frameshift_variant De novo NA - 33004838 Wang T et al. (2020)
c.791G>C p.Trp264Ser missense_variant De novo NA Simplex 22495306 Sanders SJ , et al. (2012)
c.572dup p.Leu192ValfsTer3 frameshift_variant Unknown - - 28191889 Stessman HA , et al. (2017)
c.2548A>G p.Ile850Val missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1572_1573del p.Ala525SerfsTer28 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.1538C>T p.Ala513Val missense_variant De novo NA Simplex 22495306 Sanders SJ , et al. (2012)
c.1619G>A p.Arg540Gln missense_variant Familial Maternal - 28191889 Stessman HA , et al. (2017)
c.725del p.Leu242HisfsTer30 frameshift_variant De novo NA - 28191889 Stessman HA , et al. (2017)
c.541C>G p.His181Asp missense_variant De novo NA Simplex 34580403 Pode-Shakked B et al. (2021)
c.833A>T p.Asn278Ile missense_variant De novo NA Simplex 34580403 Pode-Shakked B et al. (2021)
c.1557_1558del p.Asn520SerfsTer33 frameshift_variant De novo NA - 28191889 Stessman HA , et al. (2017)
c.459del p.Phe154SerfsTer4 frameshift_variant De novo NA Simplex 31981491 Satterstrom FK et al. (2020)
c.340del p.Ser114GlnfsTer12 frameshift_variant De novo NA Simplex 31981491 Satterstrom FK et al. (2020)
c.1150dup p.Thr384AsnfsTer10 frameshift_variant De novo NA Simplex 31981491 Satterstrom FK et al. (2020)
c.555_558del p.Leu186GlufsTer26 frameshift_variant De novo NA Simplex 25363760 De Rubeis S , et al. (2014)
c.-276-4_-276-1del - frameshift_variant Familial Maternal Multi-generational 31398340 Ruzzo EK , et al. (2019)
c.1205_1206insGCGTAAAA p.Lys403ArgfsTer11 frameshift_variant Familial Paternal Simplex 30564305 Guo H , et al. (2018)
NM_001300908.2:c.953_1028del;c.1157_1232del;c.1673_1748del p.Asn387CysfsTer37 frameshift_variant De novo NA Multiplex 28263302 C Yuen RK et al. (2017)
Common Variants  

No common variants reported.

SFARI Gene score
1

High Confidence

Score Delta: Score remained at 1

criteria met
See SFARI Gene'scoring criteria
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.

4/1/2021
1
icon
1

Score remained at 1

Description

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).

Reports Added
[Autism risk gene KMT5B deficiency in prefrontal cortex induces synaptic dysfunction and social deficits via alterations of DNA repair and gene transcription2021]
10/1/2020
1
icon
1

Score remained at 1

Description

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).

Reports Added
[Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders2020]
1/1/2020
1
icon
1

Score remained at 1

Description

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).

Reports Added
[Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism2020]
10/1/2019
1
icon
1

Score remained at 1

New Scoring Scheme
Description

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).

Reports Added
[New Scoring Scheme]
7/1/2019
1
icon
1

Score remained at 1

Description

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).

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
1/1/2019
1
icon
1

Score remained at 1

Description

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).

Reports Added
[Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.2018]
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).

Reports Added
[De novo mutations revealed by whole-exome sequencing are strongly associated with autism.2012] [De novo gene disruptions in children on the autistic spectrum.2012] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Incorporating Functional Information in Tests of Excess De Novo Mutational Load.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases.2017] [Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder2017] [Genomic diagnosis for children with intellectual disability and/or developmental delay.2017]
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).

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