Human Gene Module / Chromosome 7 / KMT2E

KMT2ELysine (K)-specific methyltransferase 2E

Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
3 / 4
Rare Variants / Common Variants
4 / 0
Associated Syndromes
Genetic Category
Rare Single Gene Mutation
Chromosome Band
Associated Disorders
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.

Reports related to KMT2E (4 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 -
Rare Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.3197delC p.Ser1066fs frameshift_variant De novo - Simplex 22542183 Iossifov I , et al. (2012)
c.167delA p.Tyr56fs frameshift_variant De novo - Simplex 25284784 Dong S , et al. (2014)
c.3527_3530del p.Thr1176ArgfsTer16 frameshift_variant Familial Maternal - 27824329 Wang T , et al. (2016)
c.3430G>A p.Gly1144Arg missense_variant De novo - Unknown 30257206 Wang S , et al. (2018)
Common Variants  

No common variants reported.

SFARI Gene score

Suggestive Evidence


Score Delta: Score remained at 3.3


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.


Score remained at 3


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.


Increased from to 3


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: A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at
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 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: aned_exac_nonTCGA_z_pli_rec_null_data.txt
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
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.
CNVs associated with KMT2E(1 CNVs)
7q22.3 10 Deletion 19  /  14
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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