Developmental Brain Disorder Gene Database

LoF Variant Gene

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Tier

1

KMT2A

HGNC:7132 (protein-coding gene)

lysine methyltransferase 2A

Unique Cases:
60
Disorders:
ID, ASD, EP, CP
Last Updated:
November 4, 2024

Summary
Cases
Publications
External

Gene Summary:

DBD Genes Classification
KMT2A is a High Confidence candidate gene classified as Tier 1. Tier 1 genes have three or more de novo pathogenic loss-of-function variants.
Gene Function
Histone methyltransferase that plays an essential role in early development and hematopoiesis (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:26886794). Catalytic subunit of the MLL1/MLL complex, a multiprotein complex that mediates both methylation of 'Lys-4' of histone H3 (H3K4me) complex and acetylation of 'Lys-16' of histone H4 (H4K16ac) (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:2... (Source: Uniprot)
Previous symbols
MLL
Alias symbols
TRX1, HRX, ALL-1, HTRX1, CXXC7, MLL1A, MLL1, ALL1, HTRX
Chromosomal Location
11q23.3
Genomic Coordinates
GRCh37:chr11:118307205-118397539
GRCh38:chr11:118436492-118526832
Associated Disorders
Intellectual Disability, Autism, Epilepsy, Cerebral Palsy

Predictive Scores:

HI Score (Decipher)

17.01

pLI (gnomAD)

1.00

LOEUF (gnomAD)

0.07

Classifications from External Sources:

SFARI Score (SFARI)

1

DDG2P Classification (DDG2P)

Definitive

ClinGen Classification (ClinGen)

Definitive1

GenCC Classification (GenCC)

Definitive3 Supportive1 Strong1

Publications:

Chen M et. al., A novel de novo mutation (p.Pro1310Glnfs*46) in KMT2A caused Wiedemann-Steiner Syndrome in a Chinese boy with postnatal growth retardation: a case report., Mol Biol Rep, 2019
Jinxiu L et. al., Wiedemann-steiner syndrome with a de novo mutation in KMT2A: A case report., Medicine (Baltimore), 2020
Jezela-Stanek A et. al., The phenotype-driven computational analysis yields clinical diagnosis for patients with atypical manifestations of known intellectual disability syndromes., Mol Genet Genomic Med, 2020
Baer S et. al., Wiedemann-Steiner syndrome as a major cause of syndromic intellectual disability: A study of 33 French cases., Clin Genet, 2018
Homma TK et. al., Genetic Disorders in Prenatal Onset Syndromic Short Stature Identified by Exome Sequencing., J Pediatr, 2019
Dillon OJ et. al., Exome sequencing has higher diagnostic yield compared to simulated disease-specific panels in children with suspected monogenic disorders., Eur J Hum Genet, 2018
Helbig KL et. al., Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy., Genet Med, 2016
Lee H et. al., Clinical exome sequencing for genetic identification of rare Mendelian disorders., JAMA, 2014
Iossifov I et. al., The contribution of de novo coding mutations to autism spectrum disorder., Nature, 2014
Boonsawat P et. al., Elucidation of the phenotypic spectrum and genetic landscape in primary and secondary microcephaly., Genet Med, 2019
Trujillano D et. al., Clinical exome sequencing: results from 2819 samples reflecting 1000 families., Eur J Hum Genet, 2017
Deciphering Developmental Disorders Study. et. al., Large-scale discovery of novel genetic causes of developmental disorders., Nature, 2015
Coe BP et. al., Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity., Nat Genet, 2019
Dunkerton S et. al., A de novo Mutation in KMT2A (MLL) in monozygotic twins with Wiedemann-Steiner syndrome., Am J Med Genet A, 2015
Bogaert DJ et. al., Early-onset primary antibody deficiency resembling common variable immunodeficiency challenges the diagnosis of Wiedeman-Steiner and Roifman syndromes., Sci Rep, 2017
Zhang H et. al., A novel deletion mutation in KMT2A identified in a child with ID/DD and blood eosinophilia., BMC Med Genet, 2019
Ramirez-Montaño D et. al., Wiedemann-Steiner syndrome with a novel pathogenic variant in KMT2A: a case report., Colomb Med (Cali), 2019
Mendelsohn BA et. al., Advanced bone age in a girl with Wiedemann-Steiner syndrome and an exonic deletion in KMT2A (MLL)., Am J Med Genet A, 2014
Luo S et. al., Three de novo variants in KMT2A (MLL) identified by whole exome sequencing in patients with Wiedemann-Steiner syndrome., Mol Genet Genomic Med, 2021
Hiraide T et. al., Genetic and phenotypic analysis of 101 patients with developmental delay or intellectual disability using whole-exome sequencing., Clin Genet, 2021
Lindstrand A et. al., Genome sequencing is a sensitive first-line test to diagnose individuals with intellectual disability., Genet Med, 2022
et. al., , ,

NCBI: Gene

Integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
NCBI: Gene

Gene Reviews

An international point-of-care resource for busy clinicians, provides clinically relevant and medically actionable information for inherited conditions in a standardized journal-style format, covering diagnosis, management, and genetic counseling for patients and their families.
Gene Reviews

DECIPHER

DECIPHER (DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources) is an interactive web-based database which incorporates a suite of tools designed to aid the interpretation of genomic variants. DECIPHER enhances clinical diagnosis by retrieving information from a variety of bioinformatics resources relevant to the variant found in the patient.
DECIPHER

SFARI

SFARI Gene is an evolving online database designed to permit quick entrée into the genetics of autism, and to help researchers track the ever-expanding genetic risk factors that emerge in the literature.
SFARI

ClinGen

ClinGen is a National Institutes of Health (NIH)-funded resource dedicated to building an authoritative central resource that defines the clinical relevance of genes and variants for use in precision medicine and research.
ClinGen

GenCC

The GenCC DB provides information pertaining to the validity of gene-disease relationships, with a current focus on Mendelian diseases.
GenCC

gnomAD

The Genome Aggregation Database (gnomAD) is a resource developed by an international coalition of investigators, with the goal of aggregating and harmonizing both exome and genome sequencing data from a wide variety of large-scale sequencing projects, and making summary data available for the wider scientific community.
gnomAD
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