Human Gene Module / Chromosome 7 / KMT2E

KMT2ELysine (K)-specific methyltransferase 2E

SFARI Gene Score
1S
High Confidence, Syndromic Criteria 1.1, Syndromic
Autism Reports / Total Reports
13 / 23
Rare Variants / Common Variants
85 / 1
Aliases
KMT2E, HDCMC04P,  MLL5,  NKp44L
Associated Syndromes
O'Donnell-Luria-Rodan syndrome, O'Donnell-Luria-Rodan syndrome, DD, epilepsy/seizu, O'Donnell-Luria-Rodan syndrome, DD, O'Donnell-Luria-Rodan syndrome, DD, ID, epilepsy/s, O'Donnell-Luria-Rodan syndrome, ASD, DD, ID
Chromosome Band
7q22.3
Associated Disorders
ID, EPS, ASD
Relevance to Autism

De novo frameshift variants in this gene have been identified in unrelated ASD cases from the Simons Simplex Collection (Iossifov et al., 2012; Dong et al., 2014).

Molecular Function

Histone methyltransferase that specifically mono- and dimethylates 'Lys-4' of histone H3 (H3K4me1 and H3K4me2). H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome InformaticsAllen Brain Atlas
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to KMT2E (23 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support De novo gene disruptions in children on the autistic spectrum Iossifov I , et al. (2012) Yes -
2 Primary De novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorder Dong S , et al. (2014) Yes -
3 Support De novo genic mutations among a Chinese autism spectrum disorder cohort Wang T , et al. (2016) Yes -
4 Support De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis Wang S , et al. (2018) No -
5 Support Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model Guo H , et al. (2018) Yes -
6 Recent Recommendation Identification of common genetic risk variants for autism spectrum disorder Grove J , et al. (2019) Yes -
7 Recent Recommendation Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy O'Donnell-Luria AH , et al. (2019) No -
8 Support Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes Feliciano P et al. (2019) Yes -
9 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
10 Support ODLURO syndrome: personal experience and review of the literature Conforti R et al. (2020) No ID, epilepsy/seizures
11 Support Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders Wang T et al. (2020) Yes -
12 Support - Li Y et al. (2021) No ASD, ID
13 Recent Recommendation - Velmans C et al. (2021) No ASD, ID
14 Support - Abreu NJ et al. (2022) No -
15 Support - Cao Z et al. (2022) No -
16 Support - Cătană A et al. (2022) Yes -
17 Support - Zhou X et al. (2022) Yes -
18 Support - Li YJ et al. (2023) Yes -
19 Support - Omri Bar et al. (2024) Yes OCD, ID, epilepsy/seizures
20 Support - Marketa Wayhelova et al. (2024) Yes -
21 Support - Mario Benvenuto et al. (2024) No -
22 Support - Alistair T Pagnamenta et al. (2024) No Autistic features
23 Support - Axel Schmidt et al. (2024) No -
Rare Variants   (85)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo - - 34321323 Velmans C et al. (2021)
c.1722+10G>A - intron_variant De novo - - 35982159 Zhou X et al. (2022)
c.72-3del - splice_site_variant Unknown - - 33004838 Wang T et al. (2020)
- - copy_number_loss De novo - - 31079897 O'Donnell-Luria AH , et al. (2019)
c.1130+1G>T - splice_site_variant Unknown - - 33004838 Wang T et al. (2020)
- - inversion De novo - Simplex 38776926 Alistair T Pagnamenta et al. (2024)
c.4279C>T p.Gln1427Ter stop_gained Unknown - - 33004838 Wang T et al. (2020)
c.2107G>T p.Glu703Ter stop_gained De novo - - 34321323 Velmans C et al. (2021)
c.532C>T p.Arg178Cys missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.3034C>T p.Gln1012Ter stop_gained De novo - - 34321323 Velmans C et al. (2021)
c.4279C>T p.Gln1427Ter stop_gained De novo - - 34321323 Velmans C et al. (2021)
c.1248+1G>T - splice_site_variant De novo - Simplex 35273928 Cao Z et al. (2022)
c.1465C>T p.Arg489Trp missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1547C>T p.Thr516Met missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1994G>A p.Arg665His missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2275C>T p.Arg759Cys missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2276G>A p.Arg759His missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.183_186+2del - splice_site_variant De novo - - 34321323 Velmans C et al. (2021)
c.3430G>A p.Gly1144Arg missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.3743C>T p.Pro1248Leu missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.3827G>C p.Arg1276Pro missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.4264C>T p.Arg1422Cys missense_variant Unknown - - 33004838 Wang T et al. (2020)
- - copy_number_loss De novo - Simplex 38776926 Alistair T Pagnamenta et al. (2024)
c.264A>G p.Glu88%3D synonymous_variant De novo - - 34321323 Velmans C et al. (2021)
c.186G>A p.Ala62%3D synonymous_variant De novo - Simplex 33681112 Li Y et al. (2021)
c.2414A>G p.Lys805Arg missense_variant De novo - - 31452935 Feliciano P et al. (2019)
c.2416G>A p.Glu806Lys missense_variant De novo - - 31452935 Feliciano P et al. (2019)
c.5417C>T p.Pro1806Leu missense_variant De novo - Simplex 33681112 Li Y et al. (2021)
c.556+1G>A - splice_site_variant De novo - - 31079897 O'Donnell-Luria AH , et al. (2019)
c.1130+2T>C - splice_site_variant De novo - - 31079897 O'Donnell-Luria AH , et al. (2019)
c.2116dup p.Thr706AsnfsTer9 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.76_77dup p.Ser27AsnfsTer3 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.2452C>T p.Arg818Ter stop_gained De novo - - 31079897 O'Donnell-Luria AH , et al. (2019)
c.2620C>T p.Arg874Ter stop_gained De novo - - 31079897 O'Donnell-Luria AH , et al. (2019)
c.2866dup p.Ser956LysfsTer11 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.3430G>A p.Gly1144Arg missense_variant De novo - Unknown 30257206 Wang S , et al. (2018)
c.2848-2A>C - splice_site_variant Unknown Not maternal - 34321323 Velmans C et al. (2021)
c.3070C>T p.Gln1024Ter stop_gained De novo - - 31079897 O'Donnell-Luria AH , et al. (2019)
c.3554C>G p.Ser1185Ter stop_gained De novo - - 31079897 O'Donnell-Luria AH , et al. (2019)
c.2051_2052dup p.Glu685Ter frameshift_variant De novo - - 34321323 Velmans C et al. (2021)
c.2714dup p.Met906TyrfsTer15 frameshift_variant De novo - - 34321323 Velmans C et al. (2021)
c.418G>A p.Val140Ile missense_variant De novo - - 31079897 O'Donnell-Luria AH , et al. (2019)
c.850T>C p.Tyr284His missense_variant De novo - - 31079897 O'Donnell-Luria AH , et al. (2019)
c.68_70delinsAAA p.Ser23_Glu24delinsTer stop_gained Unknown - - 33004838 Wang T et al. (2020)
c.2941_2944del p.Pro981LeufsTer6 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.498-11T>C - intron_variant Familial Paternal Simplex 35481221 Cătană A et al. (2022)
c.2720A>T p.Asp907Val missense_variant De novo - - 31079897 O'Donnell-Luria AH , et al. (2019)
c.4829dup p.Leu1610PhefsTer259 frameshift_variant De novo - - 34321323 Velmans C et al. (2021)
c.5054dup p.Pro1686SerfsTer183 frameshift_variant De novo - - 34321323 Velmans C et al. (2021)
c.768+1G>A - splice_site_variant Familial Paternal Multiplex 34321323 Velmans C et al. (2021)
c.186G>A p.Ala62= synonymous_variant De novo - Simplex 38674365 Mario Benvenuto et al. (2024)
c.4126C>T p.Pro1376Ser missense_variant De novo - - 31079897 O'Donnell-Luria AH , et al. (2019)
c.3527_3530del p.Thr1176ArgfsTer16 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.167del p.Tyr56SerfsTer34 frameshift_variant De novo - Simplex 25284784 Dong S , et al. (2014)
c.2261del p.Ser754Ter frameshift_variant De novo - - 31079897 O'Donnell-Luria AH , et al. (2019)
c.1646_1650del p.Ile549ArgfsTer6 frameshift_variant De novo - - 34321323 Velmans C et al. (2021)
c.3269C>T p.Ser1090Leu missense_variant Familial Maternal Simplex 30564305 Guo H , et al. (2018)
c.2164_2167del p.Lys722ValfsTer17 frameshift_variant De novo - - 34321323 Velmans C et al. (2021)
c.65del p.Gly22ValfsTer7 frameshift_variant Unknown Not maternal - 34321323 Velmans C et al. (2021)
c.280del p.Thr94LeufsTer25 frameshift_variant De novo - - 31079897 O'Donnell-Luria AH , et al. (2019)
c.3198del p.Trp1067GlyfsTer2 frameshift_variant De novo - Simplex 22542183 Iossifov I , et al. (2012)
c.997del p.Glu333ArgfsTer32 frameshift_variant De novo - - 31079897 O'Donnell-Luria AH , et al. (2019)
c.2936del p.Leu979TrpfsTer9 frameshift_variant De novo - - 31079897 O'Donnell-Luria AH , et al. (2019)
c.3672_3673del p.Tyr1224Ter frameshift_variant De novo - - 31079897 O'Donnell-Luria AH , et al. (2019)
c.1603del p.Leu535TyrfsTer15 frameshift_variant Unknown - - 31079897 O'Donnell-Luria AH , et al. (2019)
c.1812del p.Ile605SerfsTer41 frameshift_variant De novo - - 31079897 O'Donnell-Luria AH , et al. (2019)
c.4829dup p.Leu1610PhefsTer259 frameshift_variant De novo - - 31079897 O'Donnell-Luria AH , et al. (2019)
c.4872dup p.Val1625ArgfsTer244 frameshift_variant De novo - - 31079897 O'Donnell-Luria AH , et al. (2019)
c.3527_3530del p.Thr1176ArgfsTer16 frameshift_variant Familial Maternal - 27824329 Wang T , et al. (2016)
c.1099_1103dup p.Glu369SerfsTer25 frameshift_variant Familial Paternal - 34321323 Velmans C et al. (2021)
c.2602_2605del p.Thr868HisfsTer3 frameshift_variant De novo - - 31079897 O'Donnell-Luria AH , et al. (2019)
c.1773_1777del p.Lys593ArgfsTer17 frameshift_variant De novo - - 31079897 O'Donnell-Luria AH , et al. (2019)
c.1776_1780del p.Lys593ArgfsTer17 frameshift_variant De novo - - 31079897 O'Donnell-Luria AH , et al. (2019)
c.3494_3495del p.Arg1165ThrfsTer3 frameshift_variant De novo - - 31079897 O'Donnell-Luria AH , et al. (2019)
c.2334_2337del p.Tyr779AlafsTer41 frameshift_variant Unknown Not maternal - 35169466 Abreu NJ et al. (2022)
c.4485_4486del p.Gln1496LysfsTer39 frameshift_variant De novo - - 31079897 O'Donnell-Luria AH , et al. (2019)
c.549del p.Asn183LysfsTer33 frameshift_variant Familial Paternal Multiplex 32691224 Conforti R et al. (2020)
c.4743_4744del p.Phe1582TyrfsTer286 frameshift_variant De novo - Multiplex 39039281 Axel Schmidt et al. (2024)
c.2077_2093del p.Ile693TyrfsTer7 frameshift_variant De novo - Simplex 38321498 Marketa Wayhelova et al. (2024)
c.1239del p.Asn414MetfsTer4 frameshift_variant Unknown Not maternal - 31079897 O'Donnell-Luria AH , et al. (2019)
c.3198_3234del p.Trp1067GlnfsTer2 frameshift_variant Unknown Not maternal - 31079897 O'Donnell-Luria AH , et al. (2019)
c.5453_5460del p.Val1818AlafsTer48 frameshift_variant Unknown Not maternal - 31079897 O'Donnell-Luria AH , et al. (2019)
c.450dup p.Arg151Ter frameshift_variant Unknown Not maternal Multi-generational 31079897 O'Donnell-Luria AH , et al. (2019)
c.4397_4398insCACAGCATGGTTATCTTTC p.Pro1467ThrfsTer75 frameshift_variant De novo - - 31079897 O'Donnell-Luria AH , et al. (2019)
c.3337_3341delinsGTTTATGGAAA p.Arg1113_Gly1114delinsValTyrGlyAsn inframe_indel Familial Maternal Multiplex 38256266 Omri Bar et al. (2024)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.2196+1578A>G - intron_variant - - - 30804558 Grove J , et al. (2019)
SFARI Gene score
1S

High Confidence, Syndromic

Score Delta: Score remained at 1S

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.

S

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

4/1/2022
2S
icon
1

Decreased from 2S to 1

1/1/2021
2S
icon
2S

Decreased from 2S to 2S

Description

De novo loss-of-function frameshift variants in the KMT2E gene have been identified in two unrelated ASD cases from the Simons Simplex Collection (PMIDs 22542183, 25284784); no similar indels were observed in controls. A maternally-inherited frameshift variant in this gene was identified in a Chinese ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in Wang et al., 2016. An intronic polymorphism in the KMT2E gene (rs111931861) that was determined by Hi-C analysis to be a loss-of-function variant was found to be the index variant for a genome-wide significant locus (P = 3.53E-08) identified in a combined analysis of 18,381 ASD cases and 27,969 controls from iPSYCH and the Psychiatric Genomic Consortium (PGC) and five cohorts of European ancestry including a total of 2,119 additional ASD cases and 142,379 controls (Grove et al., 2019). A study including 31 distinct heterozygous variants in the KMT2E gene (28 ascertained from Matchmaker Exchange and three previously reported in ASD probands from the Simons Simplex Collection and the Autism Clinical and Genetic Resources in China cohort) and four individuals with microdeletions encompassing KMT2E identified a neurodevelopmental disorder characterized by developmental delay, intellectual disability, epilepsy, hypotonia, and either microcephaly or macrocephaly; a quarter of the 38 individuals in this cohort met criteria for autism spectrum disorder (ODonnell-Luria et al., 2019).

Reports Added
[Case Report: De novo Variants of KMT2E Cause O'Donnell-Luria-Rodan Syndrome: Additional Cases and Literature Review2021]
10/1/2020
2S
icon
2S

Decreased from 2S to 2S

Description

De novo loss-of-function frameshift variants in the KMT2E gene have been identified in two unrelated ASD cases from the Simons Simplex Collection (PMIDs 22542183, 25284784); no similar indels were observed in controls. A maternally-inherited frameshift variant in this gene was identified in a Chinese ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in Wang et al., 2016. An intronic polymorphism in the KMT2E gene (rs111931861) that was determined by Hi-C analysis to be a loss-of-function variant was found to be the index variant for a genome-wide significant locus (P = 3.53E-08) identified in a combined analysis of 18,381 ASD cases and 27,969 controls from iPSYCH and the Psychiatric Genomic Consortium (PGC) and five cohorts of European ancestry including a total of 2,119 additional ASD cases and 142,379 controls (Grove et al., 2019). A study including 31 distinct heterozygous variants in the KMT2E gene (28 ascertained from Matchmaker Exchange and three previously reported in ASD probands from the Simons Simplex Collection and the Autism Clinical and Genetic Resources in China cohort) and four individuals with microdeletions encompassing KMT2E identified a neurodevelopmental disorder characterized by developmental delay, intellectual disability, epilepsy, hypotonia, and either microcephaly or macrocephaly; a quarter of the 38 individuals in this cohort met criteria for autism spectrum disorder (ODonnell-Luria et al., 2019).

Reports Added
[Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders2020]
7/1/2020
2S
icon
2S

Decreased from 2S to 2S

Description

De novo loss-of-function frameshift variants in the KMT2E gene have been identified in two unrelated ASD cases from the Simons Simplex Collection (PMIDs 22542183, 25284784); no similar indels were observed in controls. A maternally-inherited frameshift variant in this gene was identified in a Chinese ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in Wang et al., 2016. An intronic polymorphism in the KMT2E gene (rs111931861) that was determined by Hi-C analysis to be a loss-of-function variant was found to be the index variant for a genome-wide significant locus (P = 3.53E-08) identified in a combined analysis of 18,381 ASD cases and 27,969 controls from iPSYCH and the Psychiatric Genomic Consortium (PGC) and five cohorts of European ancestry including a total of 2,119 additional ASD cases and 142,379 controls (Grove et al., 2019). A study including 31 distinct heterozygous variants in the KMT2E gene (28 ascertained from Matchmaker Exchange and three previously reported in ASD probands from the Simons Simplex Collection and the Autism Clinical and Genetic Resources in China cohort) and four individuals with microdeletions encompassing KMT2E identified a neurodevelopmental disorder characterized by developmental delay, intellectual disability, epilepsy, hypotonia, and either microcephaly or macrocephaly; a quarter of the 38 individuals in this cohort met criteria for autism spectrum disorder (ODonnell-Luria et al., 2019).

Reports Added
[ODLURO syndrome: personal experience and review of the literature2020]
1/1/2020
2S
icon
2S

Decreased from 2S to 2S

Description

De novo loss-of-function frameshift variants in the KMT2E gene have been identified in two unrelated ASD cases from the Simons Simplex Collection (PMIDs 22542183, 25284784); no similar indels were observed in controls. A maternally-inherited frameshift variant in this gene was identified in a Chinese ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in Wang et al., 2016. An intronic polymorphism in the KMT2E gene (rs111931861) that was determined by Hi-C analysis to be a loss-of-function variant was found to be the index variant for a genome-wide significant locus (P = 3.53E-08) identified in a combined analysis of 18,381 ASD cases and 27,969 controls from iPSYCH and the Psychiatric Genomic Consortium (PGC) and five cohorts of European ancestry including a total of 2,119 additional ASD cases and 142,379 controls (Grove et al., 2019). A study including 31 distinct heterozygous variants in the KMT2E gene (28 ascertained from Matchmaker Exchange and three previously reported in ASD probands from the Simons Simplex Collection and the Autism Clinical and Genetic Resources in China cohort) and four individuals with microdeletions encompassing KMT2E identified a neurodevelopmental disorder characterized by developmental delay, intellectual disability, epilepsy, hypotonia, and either microcephaly or macrocephaly; a quarter of the 38 individuals in this cohort met criteria for autism spectrum disorder (ODonnell-Luria et al., 2019).

Reports Added
[Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism2020]
10/1/2019
3S
icon
2S

Decreased from 3S to 2S

New Scoring Scheme
Description

De novo loss-of-function frameshift variants in the KMT2E gene have been identified in two unrelated ASD cases from the Simons Simplex Collection (PMIDs 22542183, 25284784); no similar indels were observed in controls. A maternally-inherited frameshift variant in this gene was identified in a Chinese ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in Wang et al., 2016. An intronic polymorphism in the KMT2E gene (rs111931861) that was determined by Hi-C analysis to be a loss-of-function variant was found to be the index variant for a genome-wide significant locus (P = 3.53E-08) identified in a combined analysis of 18,381 ASD cases and 27,969 controls from iPSYCH and the Psychiatric Genomic Consortium (PGC) and five cohorts of European ancestry including a total of 2,119 additional ASD cases and 142,379 controls (Grove et al., 2019). A study including 31 distinct heterozygous variants in the KMT2E gene (28 ascertained from Matchmaker Exchange and three previously reported in ASD probands from the Simons Simplex Collection and the Autism Clinical and Genetic Resources in China cohort) and four individuals with microdeletions encompassing KMT2E identified a neurodevelopmental disorder characterized by developmental delay, intellectual disability, epilepsy, hypotonia, and either microcephaly or macrocephaly; a quarter of the 38 individuals in this cohort met criteria for autism spectrum disorder (ODonnell-Luria et al., 2019).

Reports Added
[Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes2019] [New Scoring Scheme]
4/1/2019
3
icon
3

Decreased from 3 to 3

Description

De novo loss-of-function frameshift variants in the KMT2E gene have been identified in two unrelated ASD cases from the Simons Simplex Collection (PMIDs 22542183, 25284784); no similar indels were observed in controls. An intronic polymorphism in the KMT2E gene (rs111931861) that was determined by Hi-C analysis to be a loss-of-function variant was found to be the index variant for a genome-wide significant locus (P = 3.53E-08) identified in a combined analysis of 18,381 ASD cases and 27,969 controls from iPSYCH and the Psychiatric Genomic Consortium (PGC) and five cohorts of European ancestry including a total of 2,119 additional ASD cases and 142,379 controls (Grove et al., 2019).

Reports Added
[Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.2019]
1/1/2019
3
icon
3

Decreased from 3 to 3

Description

De novo loss-of-function frameshift variants in the KMT2E gene have been identified in two unrelated ASD cases from the Simons Simplex Collection (PMIDs 22542183, 25284784); no similar indels were observed in controls. An intronic polymorphism in the KMT2E gene (rs111931861) that was determined by Hi-C analysis to be a loss-of-function variant was found to be the index variant for a genome-wide significant locus (P = 3.53E-08) identified in a combined analysis of 18,381 ASD cases and 27,969 controls from iPSYCH and the Psychiatric Genomic Consortium (PGC) and five cohorts of European ancestry including a total of 2,119 additional ASD cases and 142,379 controls (Grove et al., 2019).

Reports Added
[Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.2018] [Identification of common genetic risk variants for autism spectrum disorder.2019]
10/1/2018
3
icon
3

Decreased from 3 to 3

Description

De novo loss-of-function frameshift variants in the KMT2E gene have been identified in two unrelated ASD cases from the Simons Simplex Collection (PMIDs 22542183, 25284784); no similar indels were observed in controls.

Reports Added
[De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis.2018]
10/1/2016
3
icon
3

Decreased from 3 to 3

Description

De novo loss-of-function frameshift variants in the KMT2E gene have been identified in two unrelated ASD cases from the Simons Simplex Collection (PMIDs 22542183, 25284784); no similar indels were observed in controls.

Reports Added
[De novo genic mutations among a Chinese autism spectrum disorder cohort.2016]
10/1/2014
icon
3

Increased from to 3

Description

De novo loss-of-function frameshift variants in the KMT2E gene have been identified in two unrelated ASD cases from the Simons Simplex Collection (PMIDs 22542183, 25284784); no similar indels were observed in controls.

Krishnan Probability Score

Score 0.49276089427939

Ranking 4417/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.99999999470269

Ranking 125/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.055167939906483

Ranking 48/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Larsen Cumulative Evidence Score

Score 22

Ranking 92/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Original Source
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
CDK11B cyclin-dependent kinase 11B Human Protein Binding 984 P21127
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