Gene: KMT2A

Alternate names for this Gene: ALL-1|CXXC7|HRX|HTRX1|MLL|MLL1|MLL1A|TRX1|WDSTS

Gene Summary: This gene encodes a transcriptional coactivator that plays an essential role in regulating gene expression during early development and hematopoiesis. The encoded protein contains multiple conserved functional domains. One of these domains, the SET domain, is responsible for its histone H3 lysine 4 (H3K4) methyltransferase activity which mediates chromatin modifications associated with epigenetic transcriptional activation. This protein is processed by the enzyme Taspase 1 into two fragments, MLL-C and MLL-N. These fragments reassociate and further assemble into different multiprotein complexes that regulate the transcription of specific target genes, including many of the HOX genes. Multiple chromosomal translocations involving this gene are the cause of certain acute lymphoid leukemias and acute myeloid leukemias. Alternate splicing results in multiple transcript variants.

Gene is located in Chromosome: 11

Location in Chromosome : 11q23.3

Description of this Gene: lysine methyltransferase 2A

Type of Gene: protein-coding

rs150800017 in KMT2A gene and Dysmorphic features PMID 8361504 1993 Rearrangement of the MLL gene in acute lymphoblastic and acute myeloid leukemias with 11q23 chromosomal translocations.

PMID 7802037 1994 "Hypertrichosis ""cubiti"" with facial asymmetry."

PMID 25929198 2015 A de novo Mutation in KMT2A (MLL) in monozygotic twins with Wiedemann-Steiner syndrome.

PMID 27777327 2017 Wiedemann-Steiner Syndrome With 2 Novel KMT2A Mutations.

PMID 23457195 2013 Primary mediastinal large B-cell lymphoma segregating in a family: exome sequencing identifies MLL as a candidate predisposition gene.

PMID 12453418 2002 MLL targets SET domain methyltransferase activity to Hox gene promoters.

PMID 24886118 2014 De Novo variants in the KMT2A (MLL) gene causing atypical Wiedemann-Steiner syndrome in two unrelated individuals identified by clinical exome sequencing.

PMID 7583381 1995 Abnormalities of chromosome band 11q23 and the MLL gene in pediatric myelomonocytic and monoblastic leukemias. Identification of the t(9;11) as an indicator of long survival.

PMID 25810209 2016 Delineation of clinical features in Wiedemann-Steiner syndrome caused by KMT2A mutations.

PMID 2738900 1989 Hypertrichosis cubiti (hairy elbows) and short stature: a recognisable association.

PMID 8634439 1996 Distribution of 11q23 breakpoints within the MLL breakpoint cluster region in de novo acute leukemia and in treatment-related acute myeloid leukemia: correlation with scaffold attachment regions and topoisomerase II consensus binding sites.

PMID 25724810 2015 Exome sequencing unravels unexpected differential diagnoses in individuals with the tentative diagnosis of Coffin-Siris and Nicolaides-Baraitser syndromes.

PMID 25186178 2014 Effective diagnosis of genetic disease by computational phenotype analysis of the disease-associated genome.

PMID 26795593 2016 Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy.

PMID 25574841 2015 Global transcriptional disturbances underlie Cornelia de Lange syndrome and related phenotypes.

PMID 22197486 2012 Deletion of KDM6A, a histone demethylase interacting with MLL2, in three patients with Kabuki syndrome.

PMID 28359930 2017 Wiedemann-Steiner syndrome: Novel pathogenic variant and review of literature.

PMID 22077973 2011 Whole-exome-sequencing identifies mutations in histone acetyltransferase gene KAT6B in individuals with the Say-Barber-Biesecker variant of Ohdo syndrome.

PMID 22795537 2012 De novo mutations in MLL cause Wiedemann-Steiner syndrome.

PMID 20711175 2010 Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome.

PMID 27759909 2017 Further delineation of the phenotype of truncating KMT2A mutations: The extended Wiedemann-Steiner syndrome.

PMID 20541448 2010 Multiple interactions recruit MLL1 and MLL1 fusion proteins to the HOXA9 locus in leukemogenesis.

rs1057518074 in KMT2A gene and Growth Deficiency and Mental Retardation with Facial Dysmorphism PMID 27441994 2017 Systematic reanalysis of clinical exome data yields additional diagnoses: implications for providers.

PMID 25724810 2015 Exome sequencing unravels unexpected differential diagnoses in individuals with the tentative diagnosis of Coffin-Siris and Nicolaides-Baraitser syndromes.

PMID 26633545 2016 Molecular diagnostic experience of whole-exome sequencing in adult patients.

rs1555044700 in KMT2A gene and Kabuki make-up syndrome PMID 29255178 2017 Patients with a Kabuki syndrome phenotype demonstrate DNA methylation abnormalities.

rs2017122 in KMT2A gene and Major Depressive Disorder PMID 27089181 2016 Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses.

rs1555046615 in KMT2A gene and Movement Disorders PMID 8634439 1996 Distribution of 11q23 breakpoints within the MLL breakpoint cluster region in de novo acute leukemia and in treatment-related acute myeloid leukemia: correlation with scaffold attachment regions and topoisomerase II consensus binding sites.

PMID 8361504 1993 Rearrangement of the MLL gene in acute lymphoblastic and acute myeloid leukemias with 11q23 chromosomal translocations.

PMID 28359930 2017 Wiedemann-Steiner syndrome: Novel pathogenic variant and review of literature.

PMID 27777327 2017 Wiedemann-Steiner Syndrome With 2 Novel KMT2A Mutations.

PMID 7802037 1994 "Hypertrichosis ""cubiti"" with facial asymmetry."

PMID 7583381 1995 Abnormalities of chromosome band 11q23 and the MLL gene in pediatric myelomonocytic and monoblastic leukemias. Identification of the t(9;11) as an indicator of long survival.

PMID 26795593 2016 Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy.

PMID 22795537 2012 De novo mutations in MLL cause Wiedemann-Steiner syndrome.

PMID 22197486 2012 Deletion of KDM6A, a histone demethylase interacting with MLL2, in three patients with Kabuki syndrome.

PMID 20711175 2010 Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome.

PMID 25810209 2016 Delineation of clinical features in Wiedemann-Steiner syndrome caused by KMT2A mutations.

PMID 22077973 2011 Whole-exome-sequencing identifies mutations in histone acetyltransferase gene KAT6B in individuals with the Say-Barber-Biesecker variant of Ohdo syndrome.

PMID 20541448 2010 Multiple interactions recruit MLL1 and MLL1 fusion proteins to the HOXA9 locus in leukemogenesis.

PMID 12453418 2002 MLL targets SET domain methyltransferase activity to Hox gene promoters.

PMID 25574841 2015 Global transcriptional disturbances underlie Cornelia de Lange syndrome and related phenotypes.

PMID 25186178 2014 Effective diagnosis of genetic disease by computational phenotype analysis of the disease-associated genome.

PMID 24886118 2014 De Novo variants in the KMT2A (MLL) gene causing atypical Wiedemann-Steiner syndrome in two unrelated individuals identified by clinical exome sequencing.

PMID 2738900 1989 Hypertrichosis cubiti (hairy elbows) and short stature: a recognisable association.

PMID 25724810 2015 Exome sequencing unravels unexpected differential diagnoses in individuals with the tentative diagnosis of Coffin-Siris and Nicolaides-Baraitser syndromes.

PMID 23457195 2013 Primary mediastinal large B-cell lymphoma segregating in a family: exome sequencing identifies MLL as a candidate predisposition gene.

PMID 25929198 2015 A de novo Mutation in KMT2A (MLL) in monozygotic twins with Wiedemann-Steiner syndrome.

PMID 27759909 2017 Further delineation of the phenotype of truncating KMT2A mutations: The extended Wiedemann-Steiner syndrome.

rs1555039606 in KMT2A gene and Multiple congenital anomalies PMID 8361504 1993 Rearrangement of the MLL gene in acute lymphoblastic and acute myeloid leukemias with 11q23 chromosomal translocations.

PMID 8634439 1996 Distribution of 11q23 breakpoints within the MLL breakpoint cluster region in de novo acute leukemia and in treatment-related acute myeloid leukemia: correlation with scaffold attachment regions and topoisomerase II consensus binding sites.

PMID 27759909 2017 Further delineation of the phenotype of truncating KMT2A mutations: The extended Wiedemann-Steiner syndrome.

PMID 7583381 1995 Abnormalities of chromosome band 11q23 and the MLL gene in pediatric myelomonocytic and monoblastic leukemias. Identification of the t(9;11) as an indicator of long survival.

PMID 7802037 1994 "Hypertrichosis ""cubiti"" with facial asymmetry."

PMID 23457195 2013 Primary mediastinal large B-cell lymphoma segregating in a family: exome sequencing identifies MLL as a candidate predisposition gene.

PMID 2738900 1989 Hypertrichosis cubiti (hairy elbows) and short stature: a recognisable association.

PMID 28359930 2017 Wiedemann-Steiner syndrome: Novel pathogenic variant and review of literature.

PMID 27777327 2017 Wiedemann-Steiner Syndrome With 2 Novel KMT2A Mutations.

PMID 26795593 2016 Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy.

PMID 25929198 2015 A de novo Mutation in KMT2A (MLL) in monozygotic twins with Wiedemann-Steiner syndrome.

PMID 22077973 2011 Whole-exome-sequencing identifies mutations in histone acetyltransferase gene KAT6B in individuals with the Say-Barber-Biesecker variant of Ohdo syndrome.

PMID 24886118 2014 De Novo variants in the KMT2A (MLL) gene causing atypical Wiedemann-Steiner syndrome in two unrelated individuals identified by clinical exome sequencing.

PMID 20541448 2010 Multiple interactions recruit MLL1 and MLL1 fusion proteins to the HOXA9 locus in leukemogenesis.

PMID 25574841 2015 Global transcriptional disturbances underlie Cornelia de Lange syndrome and related phenotypes.

PMID 25186178 2014 Effective diagnosis of genetic disease by computational phenotype analysis of the disease-associated genome.

PMID 22197486 2012 Deletion of KDM6A, a histone demethylase interacting with MLL2, in three patients with Kabuki syndrome.

PMID 25724810 2015 Exome sequencing unravels unexpected differential diagnoses in individuals with the tentative diagnosis of Coffin-Siris and Nicolaides-Baraitser syndromes.

PMID 25810209 2016 Delineation of clinical features in Wiedemann-Steiner syndrome caused by KMT2A mutations.

PMID 22795537 2012 De novo mutations in MLL cause Wiedemann-Steiner syndrome.

PMID 12453418 2002 MLL targets SET domain methyltransferase activity to Hox gene promoters.

PMID 20711175 2010 Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome.

rs1555036394 in KMT2A gene and Muscle hypotonia PMID 25810209 2016 Delineation of clinical features in Wiedemann-Steiner syndrome caused by KMT2A mutations.

PMID 22795537 2012 De novo mutations in MLL cause Wiedemann-Steiner syndrome.

PMID 25724810 2015 Exome sequencing unravels unexpected differential diagnoses in individuals with the tentative diagnosis of Coffin-Siris and Nicolaides-Baraitser syndromes.

PMID 24886118 2014 De Novo variants in the KMT2A (MLL) gene causing atypical Wiedemann-Steiner syndrome in two unrelated individuals identified by clinical exome sequencing.

PMID 23457195 2013 Primary mediastinal large B-cell lymphoma segregating in a family: exome sequencing identifies MLL as a candidate predisposition gene.

PMID 25186178 2014 Effective diagnosis of genetic disease by computational phenotype analysis of the disease-associated genome.

PMID 7583381 1995 Abnormalities of chromosome band 11q23 and the MLL gene in pediatric myelomonocytic and monoblastic leukemias. Identification of the t(9;11) as an indicator of long survival.

PMID 7802037 1994 "Hypertrichosis ""cubiti"" with facial asymmetry."

PMID 27777327 2017 Wiedemann-Steiner Syndrome With 2 Novel KMT2A Mutations.

PMID 25929198 2015 A de novo Mutation in KMT2A (MLL) in monozygotic twins with Wiedemann-Steiner syndrome.

PMID 22197486 2012 Deletion of KDM6A, a histone demethylase interacting with MLL2, in three patients with Kabuki syndrome.

PMID 2738900 1989 Hypertrichosis cubiti (hairy elbows) and short stature: a recognisable association.

PMID 25574841 2015 Global transcriptional disturbances underlie Cornelia de Lange syndrome and related phenotypes.

PMID 22077973 2011 Whole-exome-sequencing identifies mutations in histone acetyltransferase gene KAT6B in individuals with the Say-Barber-Biesecker variant of Ohdo syndrome.

PMID 26795593 2016 Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy.

PMID 20711175 2010 Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome.

PMID 20541448 2010 Multiple interactions recruit MLL1 and MLL1 fusion proteins to the HOXA9 locus in leukemogenesis.

PMID 12453418 2002 MLL targets SET domain methyltransferase activity to Hox gene promoters.

PMID 27759909 2017 Further delineation of the phenotype of truncating KMT2A mutations: The extended Wiedemann-Steiner syndrome.

PMID 8634439 1996 Distribution of 11q23 breakpoints within the MLL breakpoint cluster region in de novo acute leukemia and in treatment-related acute myeloid leukemia: correlation with scaffold attachment regions and topoisomerase II consensus binding sites.

PMID 8361504 1993 Rearrangement of the MLL gene in acute lymphoblastic and acute myeloid leukemias with 11q23 chromosomal translocations.

PMID 28359930 2017 Wiedemann-Steiner syndrome: Novel pathogenic variant and review of literature.

rs781978013 in KMT2A gene and Overgrowth PMID 27777327 2017 Wiedemann-Steiner Syndrome With 2 Novel KMT2A Mutations.

PMID 2738900 1989 Hypertrichosis cubiti (hairy elbows) and short stature: a recognisable association.

PMID 27759909 2017 Further delineation of the phenotype of truncating KMT2A mutations: The extended Wiedemann-Steiner syndrome.

PMID 26795593 2016 Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy.

PMID 8634439 1996 Distribution of 11q23 breakpoints within the MLL breakpoint cluster region in de novo acute leukemia and in treatment-related acute myeloid leukemia: correlation with scaffold attachment regions and topoisomerase II consensus binding sites.

PMID 28359930 2017 Wiedemann-Steiner syndrome: Novel pathogenic variant and review of literature.

PMID 25574841 2015 Global transcriptional disturbances underlie Cornelia de Lange syndrome and related phenotypes.

PMID 25929198 2015 A de novo Mutation in KMT2A (MLL) in monozygotic twins with Wiedemann-Steiner syndrome.

PMID 25724810 2015 Exome sequencing unravels unexpected differential diagnoses in individuals with the tentative diagnosis of Coffin-Siris and Nicolaides-Baraitser syndromes.

PMID 25186178 2014 Effective diagnosis of genetic disease by computational phenotype analysis of the disease-associated genome.

PMID 7583381 1995 Abnormalities of chromosome band 11q23 and the MLL gene in pediatric myelomonocytic and monoblastic leukemias. Identification of the t(9;11) as an indicator of long survival.

PMID 25810209 2016 Delineation of clinical features in Wiedemann-Steiner syndrome caused by KMT2A mutations.

PMID 24886118 2014 De Novo variants in the KMT2A (MLL) gene causing atypical Wiedemann-Steiner syndrome in two unrelated individuals identified by clinical exome sequencing.

PMID 20711175 2010 Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome.

PMID 23457195 2013 Primary mediastinal large B-cell lymphoma segregating in a family: exome sequencing identifies MLL as a candidate predisposition gene.

PMID 8361504 1993 Rearrangement of the MLL gene in acute lymphoblastic and acute myeloid leukemias with 11q23 chromosomal translocations.

PMID 20541448 2010 Multiple interactions recruit MLL1 and MLL1 fusion proteins to the HOXA9 locus in leukemogenesis.

PMID 22795537 2012 De novo mutations in MLL cause Wiedemann-Steiner syndrome.

PMID 7802037 1994 "Hypertrichosis ""cubiti"" with facial asymmetry."

PMID 22197486 2012 Deletion of KDM6A, a histone demethylase interacting with MLL2, in three patients with Kabuki syndrome.

PMID 12453418 2002 MLL targets SET domain methyltransferase activity to Hox gene promoters.

PMID 22077973 2011 Whole-exome-sequencing identifies mutations in histone acetyltransferase gene KAT6B in individuals with the Say-Barber-Biesecker variant of Ohdo syndrome.

rs74422681 in KMT2A gene and Red Blood Cell Count measurement PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs2017122 in KMT2A gene and Unipolar Depression PMID 27089181 2016 Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses.