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KMT2A lysine methyltransferase 2A [ Homo sapiens (human) ]

Gene ID: 4297, updated on 6-Jan-2019

Summary

Official Symbol
KMT2Aprovided by HGNC
Official Full Name
lysine methyltransferase 2Aprovided by HGNC
Primary source
HGNC:HGNC:7132
See related
Ensembl:ENSG00000118058 MIM:159555
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
HRX; MLL; MLL1; TRX1; ALL-1; CXXC7; HTRX1; MLL1A; WDSTS
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.[provided by RefSeq, Oct 2010]
Expression
Ubiquitous expression in ovary (RPKM 12.8), lymph node (RPKM 6.8) and 25 other tissues See more
Orthologs

Genomic context

See KMT2A in Genome Data Viewer
Location:
11q23.3
Exon count:
37
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 11 NC_000011.10 (118436490..118526832)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (118307205..118397539)

Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene ubiquitination factor E4A Neighboring gene uncharacterized LOC100131626 Neighboring gene ATP synthase membrane subunit g Neighboring gene uncharacterized LOC101929089 Neighboring gene tetratricopeptide repeat domain 36 Neighboring gene transmembrane protein 25 Neighboring gene intraflagellar transport 46 Neighboring gene ribosomal protein L5 pseudogene 30

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Wiedemann-Steiner syndrome
MedGen: C1854630 OMIM: 605130 GeneReviews: Not available
Compare labs

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated (2018-05-23)

ClinGen Genome Curation Page
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated (2018-05-23)

ClinGen Genome Curation PagePubMed

NHGRI GWAS Catalog

Description
Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.
NHGRI GWA Catalog

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
integrase gag-pol The IN catalytic core domain has a higher binding affinity (Kd) for PSIP1 (LEDGF/p75) than the physiological binding partner, KMT2A (MML1) PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • FLJ11783

Gene Ontology Provided by GOA

Function Evidence Code Pubs
AT DNA binding NAS
Non-traceable Author Statement
more info
PubMed 
DNA-binding transcription factor activity NAS
Non-traceable Author Statement
more info
PubMed 
DNA-binding transcription factor activity, RNA polymerase II-specific ISA
Inferred from Sequence Alignment
more info
 
DNA-binding transcription factor activity, RNA polymerase II-specific ISM
Inferred from Sequence Model
more info
PubMed 
RNA polymerase II distal enhancer sequence-specific DNA binding ISS
Inferred from Sequence or Structural Similarity
more info
 
histone methyltransferase activity (H3-K4 specific) EXP
Inferred from Experiment
more info
PubMed 
histone methyltransferase activity (H3-K4 specific) IDA
Inferred from Direct Assay
more info
PubMed 
histone methyltransferase activity (H3-K4 specific) IMP
Inferred from Mutant Phenotype
more info
PubMed 
histone-lysine N-methyltransferase activity TAS
Traceable Author Statement
more info
 
identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
lysine-acetylated histone binding IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein homodimerization activity IDA
Inferred from Direct Assay
more info
PubMed 
transcription regulatory region DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
unmethylated CpG binding IDA
Inferred from Direct Assay
more info
PubMed 
zinc ion binding IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
apoptotic process IEA
Inferred from Electronic Annotation
more info
 
circadian regulation of gene expression ISS
Inferred from Sequence or Structural Similarity
more info
 
embryonic hemopoiesis TAS
Traceable Author Statement
more info
PubMed 
histone H3-K4 methylation IDA
Inferred from Direct Assay
more info
PubMed 
histone H3-K4 methylation IMP
Inferred from Mutant Phenotype
more info
PubMed 
histone H3-K4 trimethylation IDA
Inferred from Direct Assay
more info
PubMed 
histone H4-K16 acetylation IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of DNA methylation IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of cellular response to drug IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of histone H3-K4 methylation ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of transcription by RNA polymerase II IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of transcription, DNA-templated IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of transporter activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein-containing complex assembly IDA
Inferred from Direct Assay
more info
PubMed 
regulation of hematopoietic stem cell differentiation TAS
Traceable Author Statement
more info
 
regulation of histone H3-K14 acetylation ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of histone H3-K9 acetylation ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of megakaryocyte differentiation TAS
Traceable Author Statement
more info
 
transcription by RNA polymerase II TAS
Traceable Author Statement
more info
PubMed 
Component Evidence Code Pubs
MLL1 complex IDA
Inferred from Direct Assay
more info
PubMed 
cytosol IDA
Inferred from Direct Assay
more info
 
histone methyltransferase complex IDA
Inferred from Direct Assay
more info
PubMed 
nucleoplasm IDA
Inferred from Direct Assay
more info
 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 
nucleus NAS
Non-traceable Author Statement
more info
PubMed 

General protein information

Preferred Names
histone-lysine N-methyltransferase 2A
Names
CXXC-type zinc finger protein 7
lysine (K)-specific methyltransferase 2A
lysine N-methyltransferase 2A
mixed lineage leukemia 1
myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila)
trithorax-like protein
zinc finger protein HRX
NP_001184033.1
NP_005924.2
XP_006718902.2
XP_011541131.1
XP_011541132.1
XP_011541133.1
XP_011541135.1

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_027813.1 RefSeqGene

    Range
    5001..95335
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_613

mRNA and Protein(s)

  1. NM_001197104.1NP_001184033.1  histone-lysine N-methyltransferase 2A isoform 1 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AP000941, AP001267, BC065385, D14540, L04731
    Consensus CDS
    CCDS55791.1
    UniProtKB/Swiss-Prot
    Q03164
    Related
    ENSP00000436786.1, ENST00000534358.6
    Conserved Domains (11) summary
    cd05493
    Location:16501780
    Bromo_ALL-1; Bromodomain, ALL-1 like proteins. ALL-1 is a vertebrate homologue of Drosophila trithorax and is often affected in chromosomal rearrangements that are linked to acute leukemias, such as acute lymphocytic leukemia (ALL). Bromodomains are found in many ...
    smart00542
    Location:36723755
    FYRC; FY-rich domain, C-terminal region
    smart00317
    Location:38343954
    SET; SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain
    smart00508
    Location:39563972
    PostSET; Cysteine-rich motif following a subset of SET domains
    COG2940
    Location:38283972
    SET; SET domain-containing protein (function unknown) [General function prediction only]
    pfam02008
    Location:11471194
    zf-CXXC; CXXC zinc finger domain
    cd15588
    Location:14331479
    PHD1_KMT2A; PHD finger 1 found in histone-lysine N-methyltransferase 2A (KMT2A)
    cd15590
    Location:14811530
    PHD2_KMT2A; PHD finger 2 found in histone-lysine N-methyltransferase 2A (KMT2A)
    cd15592
    Location:15681627
    PHD3_KMT2A; PHD finger 3 found in histone-lysine N-methyltransferase 2A (KMT2A)
    cd15693
    Location:18741986
    ePHD_KMT2A; Extended PHD finger found in histone-lysine N-methyltransferase 2A (KMT2A)
    pfam05964
    Location:20282074
    FYRN; F/Y-rich N-terminus
  2. NM_005933.3NP_005924.2  histone-lysine N-methyltransferase 2A isoform 2 precursor

    See identical proteins and their annotated locations for NP_005924.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate in-frame splice site in the coding region, compared to variant 1. This results in a shorter protein (isoform 2), compared to isoform 1.
    Source sequence(s)
    AB209508, AP000941, AP001267, BC065385, D14540
    Consensus CDS
    CCDS31686.1
    UniProtKB/Swiss-Prot
    Q03164
    Related
    ENSP00000374157.5, ENST00000389506.10
    Conserved Domains (11) summary
    cd05493
    Location:16471777
    Bromo_ALL-1; Bromodomain, ALL-1 like proteins. ALL-1 is a vertebrate homologue of Drosophila trithorax and is often affected in chromosomal rearrangements that are linked to acute leukemias, such as acute lymphocytic leukemia (ALL). Bromodomains are found in many ...
    smart00542
    Location:36693752
    FYRC; FY-rich domain, C-terminal region
    smart00317
    Location:38313951
    SET; SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain
    smart00508
    Location:39533969
    PostSET; Cysteine-rich motif following a subset of SET domains
    COG2940
    Location:38253969
    SET; SET domain-containing protein (function unknown) [General function prediction only]
    pfam02008
    Location:11471194
    zf-CXXC; CXXC zinc finger domain
    cd15588
    Location:14331479
    PHD1_KMT2A; PHD finger 1 found in histone-lysine N-methyltransferase 2A (KMT2A)
    cd15590
    Location:14811530
    PHD2_KMT2A; PHD finger 2 found in histone-lysine N-methyltransferase 2A (KMT2A)
    cd15592
    Location:15681624
    PHD3_KMT2A; PHD finger 3 found in histone-lysine N-methyltransferase 2A (KMT2A)
    cd15693
    Location:18711983
    ePHD_KMT2A; Extended PHD finger found in histone-lysine N-methyltransferase 2A (KMT2A)
    pfam05964
    Location:20252071
    FYRN; F/Y-rich N-terminus

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000011.10 Reference GRCh38.p12 Primary Assembly

    Range
    118436490..118526832
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011542829.2XP_011541131.1  histone-lysine N-methyltransferase 2A isoform X1

    Conserved Domains (11) summary
    cd05493
    Location:16831813
    Bromo_ALL-1; Bromodomain, ALL-1 like proteins. ALL-1 is a vertebrate homologue of Drosophila trithorax and is often affected in chromosomal rearrangements that are linked to acute leukemias, such as acute lymphocytic leukemia (ALL). Bromodomains are found in many ...
    smart00542
    Location:37053788
    FYRC; FY-rich domain, C-terminal region
    smart00317
    Location:38673987
    SET; SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain
    smart00508
    Location:39894005
    PostSET; Cysteine-rich motif following a subset of SET domains
    COG2940
    Location:38614005
    SET; SET domain-containing protein (function unknown) [General function prediction only]
    pfam02008
    Location:11801227
    zf-CXXC; CXXC zinc finger domain
    cd15588
    Location:14661512
    PHD1_KMT2A; PHD finger 1 found in histone-lysine N-methyltransferase 2A (KMT2A)
    cd15590
    Location:15141563
    PHD2_KMT2A; PHD finger 2 found in histone-lysine N-methyltransferase 2A (KMT2A)
    cd15592
    Location:16011660
    PHD3_KMT2A; PHD finger 3 found in histone-lysine N-methyltransferase 2A (KMT2A)
    cd15693
    Location:19072019
    ePHD_KMT2A; Extended PHD finger found in histone-lysine N-methyltransferase 2A (KMT2A)
    pfam05964
    Location:20612107
    FYRN; F/Y-rich N-terminus
  2. XM_011542831.2XP_011541133.1  histone-lysine N-methyltransferase 2A isoform X3

    Related
    ENSP00000496927.1, ENST00000649699.1
    Conserved Domains (11) summary
    cd05493
    Location:16801810
    Bromo_ALL-1; Bromodomain, ALL-1 like proteins. ALL-1 is a vertebrate homologue of Drosophila trithorax and is often affected in chromosomal rearrangements that are linked to acute leukemias, such as acute lymphocytic leukemia (ALL). Bromodomains are found in many ...
    smart00542
    Location:37023785
    FYRC; FY-rich domain, C-terminal region
    smart00317
    Location:38643984
    SET; SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain
    smart00508
    Location:39864002
    PostSET; Cysteine-rich motif following a subset of SET domains
    COG2940
    Location:38584002
    SET; SET domain-containing protein (function unknown) [General function prediction only]
    pfam02008
    Location:11801227
    zf-CXXC; CXXC zinc finger domain
    cd15588
    Location:14661512
    PHD1_KMT2A; PHD finger 1 found in histone-lysine N-methyltransferase 2A (KMT2A)
    cd15590
    Location:15141563
    PHD2_KMT2A; PHD finger 2 found in histone-lysine N-methyltransferase 2A (KMT2A)
    cd15592
    Location:16011657
    PHD3_KMT2A; PHD finger 3 found in histone-lysine N-methyltransferase 2A (KMT2A)
    cd15693
    Location:19042016
    ePHD_KMT2A; Extended PHD finger found in histone-lysine N-methyltransferase 2A (KMT2A)
    pfam05964
    Location:20582104
    FYRN; F/Y-rich N-terminus
  3. XM_011542830.2XP_011541132.1  histone-lysine N-methyltransferase 2A isoform X2

    Conserved Domains (11) summary
    cd05493
    Location:16821812
    Bromo_ALL-1; Bromodomain, ALL-1 like proteins. ALL-1 is a vertebrate homologue of Drosophila trithorax and is often affected in chromosomal rearrangements that are linked to acute leukemias, such as acute lymphocytic leukemia (ALL). Bromodomains are found in many ...
    smart00542
    Location:37043787
    FYRC; FY-rich domain, C-terminal region
    smart00317
    Location:38663986
    SET; SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain
    smart00508
    Location:39884004
    PostSET; Cysteine-rich motif following a subset of SET domains
    COG2940
    Location:38604004
    SET; SET domain-containing protein (function unknown) [General function prediction only]
    pfam02008
    Location:11801227
    zf-CXXC; CXXC zinc finger domain
    cd15588
    Location:14661512
    PHD1_KMT2A; PHD finger 1 found in histone-lysine N-methyltransferase 2A (KMT2A)
    cd15590
    Location:15141562
    PHD2_KMT2A; PHD finger 2 found in histone-lysine N-methyltransferase 2A (KMT2A)
    cd15592
    Location:16001659
    PHD3_KMT2A; PHD finger 3 found in histone-lysine N-methyltransferase 2A (KMT2A)
    cd15693
    Location:19062018
    ePHD_KMT2A; Extended PHD finger found in histone-lysine N-methyltransferase 2A (KMT2A)
    pfam05964
    Location:20602106
    FYRN; F/Y-rich N-terminus
  4. XM_011542833.2XP_011541135.1  histone-lysine N-methyltransferase 2A isoform X4

    Conserved Domains (11) summary
    cd05493
    Location:844974
    Bromo_ALL-1; Bromodomain, ALL-1 like proteins. ALL-1 is a vertebrate homologue of Drosophila trithorax and is often affected in chromosomal rearrangements that are linked to acute leukemias, such as acute lymphocytic leukemia (ALL). Bromodomains are found in many ...
    smart00542
    Location:28662949
    FYRC; FY-rich domain, C-terminal region
    smart00317
    Location:30283148
    SET; SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain
    smart00508
    Location:31503166
    PostSET; Cysteine-rich motif following a subset of SET domains
    COG2940
    Location:30143166
    SET; SET domain-containing protein (function unknown) [General function prediction only]
    pfam02008
    Location:341388
    zf-CXXC; CXXC zinc finger domain
    cd15588
    Location:627673
    PHD1_KMT2A; PHD finger 1 found in histone-lysine N-methyltransferase 2A (KMT2A)
    cd15590
    Location:675724
    PHD2_KMT2A; PHD finger 2 found in histone-lysine N-methyltransferase 2A (KMT2A)
    cd15592
    Location:762821
    PHD3_KMT2A; PHD finger 3 found in histone-lysine N-methyltransferase 2A (KMT2A)
    cd15693
    Location:10681180
    ePHD_KMT2A; Extended PHD finger found in histone-lysine N-methyltransferase 2A (KMT2A)
    pfam05964
    Location:12221268
    FYRN; F/Y-rich N-terminus
  5. XM_006718839.3XP_006718902.2  histone-lysine N-methyltransferase 2A isoform X5

    Conserved Domains (11) summary
    cd05493
    Location:811941
    Bromo_ALL-1; Bromodomain, ALL-1 like proteins. ALL-1 is a vertebrate homologue of Drosophila trithorax and is often affected in chromosomal rearrangements that are linked to acute leukemias, such as acute lymphocytic leukemia (ALL). Bromodomains are found in many ...
    smart00542
    Location:28332916
    FYRC; FY-rich domain, C-terminal region
    smart00317
    Location:29953115
    SET; SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain
    smart00508
    Location:31173133
    PostSET; Cysteine-rich motif following a subset of SET domains
    COG2940
    Location:29813133
    SET; SET domain-containing protein (function unknown) [General function prediction only]
    pfam02008
    Location:308355
    zf-CXXC; CXXC zinc finger domain
    cd15588
    Location:594640
    PHD1_KMT2A; PHD finger 1 found in histone-lysine N-methyltransferase 2A (KMT2A)
    cd15590
    Location:642691
    PHD2_KMT2A; PHD finger 2 found in histone-lysine N-methyltransferase 2A (KMT2A)
    cd15592
    Location:729788
    PHD3_KMT2A; PHD finger 3 found in histone-lysine N-methyltransferase 2A (KMT2A)
    cd15693
    Location:10351147
    ePHD_KMT2A; Extended PHD finger found in histone-lysine N-methyltransferase 2A (KMT2A)
    pfam05964
    Location:11891235
    FYRN; F/Y-rich N-terminus

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_024891.2: Suppressed sequence

    Description
    NM_024891.2: This RefSeq was permanently suppressed because it is primarily intronic sequence.
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