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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

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
De novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorder.
ASD
Support
Reanalysis of Trio Whole-Genome Sequencing Data Doubles the Yield in Autism Spectrum Disorder: De Novo Variants Present in Half
ASD
OCD, ID, epilepsy/seizures
Support
De novo genic mutations among a Chinese autism spectrum disorder cohort.
ASD
Support
Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders
ASD, DD
Support
De novo gene disruptions in children on the autistic spectrum.
ASD
Support
ODLURO syndrome: personal experience and review of the literature
O'Donnell-Luria-Rodan syndrome
ID, epilepsy/seizures
Support
Integrating de novo and inherited variants in 42
ASD
Support
Next-generation phenotyping integrated in a national framework for patients with ultrarare disorders improves genetic diagnostics and yields new molecular findings
DD
Support
Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism
ASD
Support
O'Donnel-Luria-Rodan Syndrome: New gene variant identified in Romania (A case report)
O'Donnell-Luria-Rodan syndrome, ASD, DD, ID
Support
The impact of inversions across 33,924 families with rare disease from a national genome sequencing project
DD, ID
Autistic features
Support
Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes
ASD
Support
Case Report: A Novel KMT2E Splice Site Variant as a Cause of O'Donnell-Luria-Rodan Syndrome in a Male Patient
O'Donnell-Luria-Rodan syndrome, DD, ID, epilepsy/s
Support
Phenotypic Description of A Patient with ODLURO Syndrome and Functional Characterization of the Pathogenetic Role of A Synonymous Variant c.186G>A in KMT2E Gene
O'Donnell-Luria-Rodan syndrome, DD
Support
Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
ASD
Support
Novel truncating variant in KMT2E associated with cerebellar hypoplasia and velopharyngeal dysfunction
ADHD, ID
Support
Exome sequencing improves the molecular diagnostics of paediatric unexplained neurodevelopmental disorders
ASD, ID
Support
De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis.
TS
Support
Case Report: De novo Variants of KMT2E Cause O'Donnell-Luria-Rodan Syndrome: Additional Cases and Literature Review
O'Donnell-Luria-Rodan syndrome, DD, epilepsy/seizu
ASD, ID
Recent Recommendation
Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.
Recent Recommendation
Identification of common genetic risk variants for autism spectrum disorder.
ASD
Recent Recommendation
O'Donnell-Luria-Rodan syndrome: description of a second multinational cohort and refinement of the phenotypic spectrum
O'Donnell-Luria-Rodan syndrome, DD
ASD, ID
Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN636R001 
 frameshift_variant 
 c.167del 
 p.Tyr56SerfsTer34 
 De novo 
  
 Simplex 
 GEN636R002 
 frameshift_variant 
 c.3198del 
 p.Trp1067GlyfsTer2 
 De novo 
  
 Simplex 
 GEN636R003 
 frameshift_variant 
 c.3527_3530del 
 p.Thr1176ArgfsTer16 
 Familial 
 Maternal 
  
 GEN636R004 
 missense_variant 
 c.3430G>A 
 p.Gly1144Arg 
 De novo 
  
 Unknown 
 GEN636R005 
 missense_variant 
 c.3269C>T 
 p.Ser1090Leu 
 Familial 
 Maternal 
 Simplex 
 GEN636R006 
 frameshift_variant 
 c.280del 
 p.Thr94LeufsTer25 
 De novo 
  
  
 GEN636R007 
 frameshift_variant 
 c.450dup 
 p.Arg151Ter 
 Unknown 
 Not maternal 
 Multi-generational 
 GEN636R008 
 splice_site_variant 
 c.556+1G>A 
  
 De novo 
  
  
 GEN636R009 
 frameshift_variant 
 c.997del 
 p.Glu333ArgfsTer32 
 De novo 
  
  
 GEN636R010 
 splice_site_variant 
 c.1130+2T>C 
  
 De novo 
  
  
 GEN636R011 
 frameshift_variant 
 c.1239del 
 p.Asn414MetfsTer4 
 Unknown 
 Not maternal 
  
 GEN636R012 
 frameshift_variant 
 c.1603del 
 p.Leu535TyrfsTer15 
 Unknown 
  
  
 GEN636R013 
 frameshift_variant 
 c.1773_1777del 
 p.Lys593ArgfsTer17 
 De novo 
  
  
 GEN636R014 
 frameshift_variant 
 c.1776_1780del 
 p.Lys593ArgfsTer17 
 De novo 
  
  
 GEN636R015 
 frameshift_variant 
 c.1812del 
 p.Ile605SerfsTer41 
 De novo 
  
  
 GEN636R016 
 frameshift_variant 
 c.2261del 
 p.Ser754Ter 
 De novo 
  
  
 GEN636R017 
 stop_gained 
 c.2452C>T 
 p.Arg818Ter 
 De novo 
  
  
 GEN636R018 
 frameshift_variant 
 c.2602_2605del 
 p.Thr868HisfsTer3 
 De novo 
  
  
 GEN636R019 
 stop_gained 
 c.2620C>T 
 p.Arg874Ter 
 De novo 
  
  
 GEN636R020 
 frameshift_variant 
 c.2936del 
 p.Leu979TrpfsTer9 
 De novo 
  
  
 GEN636R021 
 stop_gained 
 c.3070C>T 
 p.Gln1024Ter 
 De novo 
  
  
 GEN636R022 
 frameshift_variant 
 c.3198_3234del 
 p.Trp1067GlnfsTer2 
 Unknown 
 Not maternal 
  
 GEN636R023 
 frameshift_variant 
 c.3494_3495del 
 p.Arg1165ThrfsTer3 
 De novo 
  
  
 GEN636R024 
 stop_gained 
 c.3554C>G 
 p.Ser1185Ter 
 De novo 
  
  
 GEN636R025 
 frameshift_variant 
 c.3672_3673del 
 p.Tyr1224Ter 
 De novo 
  
  
 GEN636R026 
 frameshift_variant 
 c.4397_4398insCACAGCATGGTTATCTTTC 
 p.Pro1467ThrfsTer75 
 De novo 
  
  
 GEN636R027 
 frameshift_variant 
 c.4485_4486del 
 p.Gln1496LysfsTer39 
 De novo 
  
  
 GEN636R028 
 frameshift_variant 
 c.4829dup 
 p.Leu1610PhefsTer259 
 De novo 
  
  
 GEN636R029 
 frameshift_variant 
 c.4872dup 
 p.Val1625ArgfsTer244 
 De novo 
  
  
 GEN636R030 
 frameshift_variant 
 c.5453_5460del 
 p.Val1818AlafsTer48 
 Unknown 
 Not maternal 
  
 GEN636R031 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN636R032 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN636R033 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN636R034 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN636R035 
 missense_variant 
 c.418G>A 
 p.Val140Ile 
 De novo 
  
  
 GEN636R036 
 missense_variant 
 c.850T>C 
 p.Tyr284His 
 De novo 
  
  
 GEN636R037 
 missense_variant 
 c.2720A>T 
 p.Asp907Val 
 De novo 
  
  
 GEN636R038 
 missense_variant 
 c.4126C>T 
 p.Pro1376Ser 
 De novo 
  
  
 GEN636R039 
 missense_variant 
 c.2414A>G 
 p.Lys805Arg 
 De novo 
  
  
 GEN636R040 
 missense_variant 
 c.2416G>A 
 p.Glu806Lys 
 De novo 
  
  
 GEN636R041 
 frameshift_variant 
 c.549del 
 p.Asn183LysfsTer33 
 Familial 
 Paternal 
 Multiplex 
 GEN636R042 
 stop_gained 
 c.4279C>T 
 p.Gln1427Ter 
 Unknown 
  
  
 GEN636R043 
 frameshift_variant 
 c.3527_3530del 
 p.Thr1176ArgfsTer16 
 Unknown 
  
  
 GEN636R044 
 missense_variant 
 c.532C>T 
 p.Arg178Cys 
 Unknown 
  
  
 GEN636R045 
 missense_variant 
 c.1547C>T 
 p.Thr516Met 
 Unknown 
  
  
 GEN636R046 
 missense_variant 
 c.2275C>T 
 p.Arg759Cys 
 Unknown 
  
  
 GEN636R047 
 missense_variant 
 c.2275C>T 
 p.Arg759Cys 
 Unknown 
  
  
 GEN636R048 
 missense_variant 
 c.3430G>A 
 p.Gly1144Arg 
 Unknown 
  
  
 GEN636R049 
 missense_variant 
 c.3430G>A 
 p.Gly1144Arg 
 Unknown 
  
  
 GEN636R050 
 missense_variant 
 c.1465C>T 
 p.Arg489Trp 
 Unknown 
  
  
 GEN636R051 
 missense_variant 
 c.1994G>A 
 p.Arg665His 
 Unknown 
  
  
 GEN636R052 
 missense_variant 
 c.4264C>T 
 p.Arg1422Cys 
 Unknown 
  
  
 GEN636R053 
 missense_variant 
 c.3827G>C 
 p.Arg1276Pro 
 Unknown 
  
  
 GEN636R054 
 missense_variant 
 c.2276G>A 
 p.Arg759His 
 Unknown 
  
  
 GEN636R055 
 frameshift_variant 
 c.76_77dup 
 p.Ser27AsnfsTer3 
 Unknown 
  
  
 GEN636R056 
 stop_gained 
 c.68_70delinsAAA 
 p.Ser23_Glu24delinsTer 
 Unknown 
  
  
 GEN636R057 
 stop_gained 
 c.68_70delinsAAA 
 p.Ser23_Glu24delinsTer 
 Unknown 
  
  
 GEN636R058 
 stop_gained 
 c.68_70delinsAAA 
 p.Ser23_Glu24delinsTer 
 Unknown 
  
  
 GEN636R059 
 frameshift_variant 
 c.2941_2944del 
 p.Pro981LeufsTer6 
 Unknown 
  
  
 GEN636R060 
 frameshift_variant 
 c.2866dup 
 p.Ser956LysfsTer11 
 Unknown 
  
  
 GEN636R061 
 frameshift_variant 
 c.2116dup 
 p.Thr706AsnfsTer9 
 Unknown 
  
  
 GEN636R062 
 splice_site_variant 
 c.1130+1G>T 
  
 Unknown 
  
  
 GEN636R063 
 splice_site_variant 
 c.72-3del 
  
 Unknown 
  
  
 GEN636R064 
 frameshift_variant 
 c.3527_3530del 
 p.Thr1176ArgfsTer16 
 Unknown 
  
  
 GEN636R065 
 missense_variant 
 c.532C>T 
 p.Arg178Cys 
 Unknown 
  
  
 GEN636R066 
 missense_variant 
 c.3743C>T 
 p.Pro1248Leu 
 Unknown 
  
  
 GEN636R067 
 missense_variant 
 c.1547C>T 
 p.Thr516Met 
 Unknown 
  
  
 GEN636R068 
 missense_variant 
 c.2276G>A 
 p.Arg759His 
 Unknown 
  
  
 GEN636R069 
 missense_variant 
 c.5417C>T 
 p.Pro1806Leu 
 De novo 
  
 Simplex 
 GEN636R070 
 synonymous_variant 
 c.186G>A 
 p.Ala62%3D 
 De novo 
  
 Simplex 
 GEN636R071 
 frameshift_variant 
 c.2051_2052dup 
 p.Glu685Ter 
 De novo 
  
  
 GEN636R072 
 stop_gained 
 c.2107G>T 
 p.Glu703Ter 
 De novo 
  
  
 GEN636R073 
 stop_gained 
 c.3034C>T 
 p.Gln1012Ter 
 De novo 
  
  
 GEN636R074 
 stop_gained 
 c.4279C>T 
 p.Gln1427Ter 
 De novo 
  
  
 GEN636R075 
 frameshift_variant 
 c.65del 
 p.Gly22ValfsTer7 
 Unknown 
 Not maternal 
  
 GEN636R076 
 frameshift_variant 
 c.1099_1103dup 
 p.Glu369SerfsTer25 
 Familial 
 Paternal 
  
 GEN636R077 
 frameshift_variant 
 c.1646_1650del 
 p.Ile549ArgfsTer6 
 De novo 
  
  
 GEN636R078 
 frameshift_variant 
 c.2164_2167del 
 p.Lys722ValfsTer17 
 De novo 
  
  
 GEN636R079 
 frameshift_variant 
 c.2714dup 
 p.Met906TyrfsTer15 
 De novo 
  
  
 GEN636R080 
 frameshift_variant 
 c.4829dup 
 p.Leu1610PhefsTer259 
 De novo 
  
  
 GEN636R081 
 frameshift_variant 
 c.5054dup 
 p.Pro1686SerfsTer183 
 De novo 
  
  
 GEN636R082 
 splice_site_variant 
 c.183_186+2del 
  
 De novo 
  
  
 GEN636R083 
 synonymous_variant 
 c.264A>G 
 p.Glu88%3D 
 De novo 
  
  
 GEN636R084 
 splice_site_variant 
 c.768+1G>A 
  
 Familial 
 Paternal 
 Multiplex 
 GEN636R085 
 splice_site_variant 
 c.2848-2A>C 
  
 Unknown 
 Not maternal 
  
 GEN636R086 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN636R087 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN636R088 
 frameshift_variant 
 c.2334_2337del 
 p.Tyr779AlafsTer41 
 Unknown 
 Not maternal 
  
 GEN636R089 
 splice_site_variant 
 c.1248+1G>T 
  
 De novo 
  
 Simplex 
 GEN636R090 
 intron_variant 
 c.498-11T>C 
  
 Familial 
 Paternal 
 Simplex 
 GEN636R091 
 intron_variant 
 c.1722+10G>A 
  
 De novo 
  
  
 GEN636R092 
 inframe_indel 
 c.3337_3341delinsGTTTATGGAAA 
 p.Arg1113_Gly1114delinsValTyrGlyAsn 
 Familial 
 Maternal 
 Multiplex 
 GEN636R093 
 frameshift_variant 
 c.2077_2093del 
 p.Ile693TyrfsTer7 
 De novo 
  
 Simplex 
 GEN636R094 
 synonymous_variant 
 c.186G>A 
 p.Ala62= 
 De novo 
  
 Simplex 
 GEN636R095a 
 inversion 
  
  
 De novo 
  
 Simplex 
 GEN636R095b 
 copy_number_loss 
  
  
 De novo 
  
 Simplex 
 GEN636R095c 
 copy_number_loss 
  
  
 De novo 
  
 Simplex 
 GEN636R096 
 frameshift_variant 
 c.4743_4744del 
 p.Phe1582TyrfsTer286 
 De novo 
  
 Multiplex 
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
7
Deletion
 2
 
7
Deletion-Duplication
 28
 
7
Deletion-Duplication
 1
 
7
Deletion
 1
 
7
Deletion
 1
 
7
Deletion
 13
 
7
Deletion
 1
 

Model Summary

The Kmt2e haploinsufficiency model shows social deficits, repetitive behaviors and higher anxiety and depression. The model shows a decrease in neuronal activity in the amygdala, that is accompanied by an increase in neuronal size and number in the basolateral and basomedial amygdala.

References

Type
Title
Author, Year
Model Type: Genetic
Model Genotype: Heterozygous
Mutation: KMT2E-deficient mice were generated by using CRISPR/Cas9 approach that produced an 8-nucleotide deletion followed by a stop codon in exon 3 of KMT2E.
Allele Type: Knockout
Strain of Origin: C57BL/6J
Genetic Background: C57BL/6J
ES Cell Line: Not Specified
Mutant ES Cell Line:
Model Source: Dr. Zhang Yan (Shanghai Pasteur Institute of Chinese Academy of Sciences)
Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Neuronal number1
Increased
 Histology
 12 weeks
Neocortex morphology: size1
Decreased
 Histology
 12 weeks
Neuronal size1
Increased
 Histology
 12 weeks
Neuronal activation1
Decreased
 Positron emission tomography (PET) imaging
 8-16 weeks
Vertical jumping or back flipping1
Increased
 General observations
 8-16 weeks
Self grooming1
Increased
 General observations
 8-16 weeks
Social memory1
Decreased
 Three-chamber social approach test
 8-16 weeks
Social approach1
Decreased
 Partition test
 8-16 weeks
Social approach1
Decreased
 Three-chamber social approach test
 8-16 weeks
Depression1
Increased
 Sucrose preference test
 8-16 weeks
Anxiety1
Increased
 Open field test
 8-16 weeks
Targeted expression1
Abnormal
 Quantitative PCR (qRT-PCR)
 not specified
General locomotor activity: ambulatory activity1
 No change
 Partition test
 8-16 weeks
Grip strength1
 No change
 Inverted grid test
 8-16 weeks
Motor coordination and balance1
 No change
 Accelerating rotarod test
 8-16 weeks
Neuronal number1
 No change
 Histology
 12 weeks
Neuronal size1
 No change
 Histology
 12 weeks
Satiety response1
 No change
 Water intake measurements
 8-16 weeks
Repetitive digging1
 No change
 Marble-burying test
 8-16 weeks
 Not Reported:





Download KMT2E's Cytoscape file

Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
CDC7 cell division cycle 7 8317 O00311 IP; LC-MS/MS
Ding X , et al. 2015
CDK11B cyclin-dependent kinase 11B 984 P21127 IP; LC-MS/MS
Ding X , et al. 2015
CDK2 cyclin-dependent kinase 2 1017 P24941 IP; LC-MS/MS
Ding X , et al. 2015
DDX18 DEAD (Asp-Glu-Ala-Asp) box polypeptide 18 8886 Q9NVP1 IP; LC-MS/MS
Ding X , et al. 2015
DDX24 DEAD (Asp-Glu-Ala-Asp) box polypeptide 24 57062 Q9GZR7 IP; LC-MS/MS
Ding X , et al. 2015
DDX50 DEAD (Asp-Glu-Ala-Asp) box polypeptide 50 79009 Q9BQ39 IP; LC-MS/MS
Ding X , et al. 2015
DHX30 DEAH (Asp-Glu-Ala-His) box polypeptide 30 22907 Q7L2E3 IP; LC-MS/MS
Ding X , et al. 2015
GRWD1 glutamate-rich WD repeat containing 1 83743 Q9BQ67 IP; LC-MS/MS
Ding X , et al. 2015
HCFC1 host cell factor C1 (VP16-accessory protein) 3054 P51610 IP; LC-MS/MS
Ding X , et al. 2015
HDAC1 histone deacetylase 1 3065 Q13547 IP; LC-MS/MS
Ding X , et al. 2015
ILF2 interleukin enhancer binding factor 2 3608 Q12905 IP; LC-MS/MS
Ding X , et al. 2015
KPNA3 karyopherin alpha 3 (importin alpha 4) 3839 O00505 IP; LC-MS/MS
Ding X , et al. 2015
MCM3 minichromosome maintenance complex component 3 4172 P25205 IP; LC-MS/MS
Ding X , et al. 2015
OGT O-linked N-acetylglucosamine (GlcNAc) transferase 8473 O15294 IP/WB; In vivo ubiquitination assay; Co-localization; Size-exclusion chromatography (SEC); IP; LC-MS/MS
Ding X , et al. 2015
PLK1 polo-like kinase 1 5347 P53350 IP/WB; in vitro kinase assay; Co-localization
Zhao W , et al. 2016
RBBP4 retinoblastoma binding protein 4 5928 Q09028 IP; LC-MS/MS
Ding X , et al. 2015
RBBP6 retinoblastoma binding protein 6 5930 Q7Z6E9 IP; LC-MS/MS
Ding X , et al. 2015
RBM39 RNA binding motif protein 39 9584 Q14498 IP; LC-MS/MS
Ding X , et al. 2015
SART1 squamous cell carcinoma antigen recognized by T cells 9092 O43290 IP; LC-MS/MS
Ding X , et al. 2015
SIN3A SIN3 homolog A, transcription regulator (yeast) 25942 Q96ST3 IP; LC-MS/MS
Ding X , et al. 2015
SMYD3 SET and MYND domain containing 3 64754 Q9H7B4 IP; LC-MS/MS
Ding X , et al. 2015
TOP2A topoisomerase (DNA) II alpha 170kDa 7153 P11388 IP; LC-MS/MS
Ding X , et al. 2015
TRAF6 TNF receptor-associated factor 6, E3 ubiquitin protein ligase 7189 Q9Y4K3 IP; LC-MS/MS
Ding X , et al. 2015
TRIM25 tripartite motif containing 25 7706 Q14258 IP; LC-MS/MS
Ding X , et al. 2015
TUBG1 tubulin, gamma 1 7283 P23258 IP/WB; Rate-zonal centrifugation; Co-localization
Zhao W , et al. 2016
USP10 ubiquitin specific peptidase 10 9100 Q14694 IP; LC-MS/MS
Ding X , et al. 2015
USP7 ubiquitin specific peptidase 7 (herpes virus-associated) 7874 Q93009 IP/WB; Co-localization; Size-exclusion chromatography (SEC); IP; LC-MS/MS
Ding X , et al. 2015
VPS4A vacuolar protein sorting 4 homolog A (S. cerevisiae) 27183 Q9UN37 IP; LC-MS/MS
Ding X , et al. 2015
WDR12 WD repeat domain 12 55759 Q9GZL7 IP; LC-MS/MS
Ding X , et al. 2015
WDR6 WD repeat domain 6 11180 Q9NNW5 IP; LC-MS/MS
Ding X , et al. 2015
YY1 YY1 transcription factor 7528 P25490 IP; LC-MS/MS
Ding X , et al. 2015
ZNF768 zinc finger protein 768 79724 Q9H5H4 IP; LC-MS/MS
Ding X , et al. 2015

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