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    KMT2D lysine methyltransferase 2D [ Homo sapiens (human) ]

    Gene ID: 8085, updated on 3-Nov-2024

    Summary

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    Official Symbol
    KMT2Dprovided by HGNC
    Official Full Name
    lysine methyltransferase 2Dprovided by HGNC
    Primary source
    HGNC:HGNC:7133
    See related
    Ensembl:ENSG00000167548 MIM:602113; AllianceGenome:HGNC:7133
    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
    ALR; KMS; MLL2; MLL4; AAD10; BCAHH; KABUK1; TNRC21; CAGL114
    Summary
    The protein encoded by this gene is a histone methyltransferase that methylates the Lys-4 position of histone H3. The encoded protein is part of a large protein complex called ASCOM, which has been shown to be a transcriptional regulator of the beta-globin and estrogen receptor genes. Mutations in this gene have been shown to be a cause of Kabuki syndrome. [provided by RefSeq, Oct 2010]
    Expression
    Ubiquitous expression in bone marrow (RPKM 10.0), skin (RPKM 5.8) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See KMT2D in Genome Data Viewer
    Location:
    12q13.12
    Exon count:
    55
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (49018978..49060794, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (48981150..49022967, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (49412761..49454577, complement)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene Sharpr-MPRA regulatory region 4123 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4419 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4420 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6301 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4421 Neighboring gene Sharpr-MPRA regulatory region 2140 Neighboring gene Sharpr-MPRA regulatory region 4008 Neighboring gene DDN and PRKAG1 antisense RNA 1 Neighboring gene dendrin Neighboring gene protein kinase AMP-activated non-catalytic subunit gamma 1 Neighboring gene Sharpr-MPRA regulatory region 4712 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:49411600-49412190 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6302 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr12:49442744-49443943 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:49443977-49444477 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4422 Neighboring gene Sharpr-MPRA regulatory region 5975 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4423 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6303 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6304 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4424 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6305 Neighboring gene RHEB like 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6306 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6307 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:49485416-49485598 Neighboring gene uncharacterized LOC105369759 Neighboring gene GATA motif-containing MPRA enhancer 293 Neighboring gene desert hedgehog signaling molecule

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues 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

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    Related articles in PubMed

    1. Genetic mutational status of genes regulating epigenetics: Role of the histone methyltransferase KMT2D in triple negative breast tumors. Morcillo-Garcia S, et al. PLoS One, 2019. PMID 30990809, Free PMC Article
    2. Growth pattern in Kabuki syndrome with a KMT2D mutation. Schott DA, et al. Am J Med Genet A, 2016 Dec. PMID 27530205
    3. Refining the clinical phenotype associated with missense variants in exons 38 and 39 of KMT2D. Tharreau M, et al. Am J Med Genet A, 2022 May. PMID 35060672
    4. Systemic lupus erythematosus: A new autoimmune disorder in Kabuki syndrome. Arsov T, et al. Eur J Med Genet, 2019 Jun. PMID 30213761
    5. Kabuki syndrome with midgut malrotation and hyperinsulinemic hypoglycemia: A rare co-occurrence from Thailand. Phetthong T, et al. Am J Med Genet A, 2020 Aug. PMID 32525229

    See all (270) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The histone methyltransferase KMT2D maintains cellular glucocorticoid responsiveness by shielding the glucocorticoid receptor from degradation.
      Title: The histone methyltransferase KMT2D maintains cellular glucocorticoid responsiveness by shielding the glucocorticoid receptor from degradation.
    2. Histone-methyltransferase KMT2D deficiency impairs the Fanconi anemia/BRCA pathway upon glycolytic inhibition in squamous cell carcinoma.
      Title: Histone-methyltransferase KMT2D deficiency impairs the Fanconi anemia/BRCA pathway upon glycolytic inhibition in squamous cell carcinoma.
    3. PI 3-Kinase and the Histone Methyl-Transferase KMT2D Collaborate to Induce Arp2/3-Dependent Migration of Mammary Epithelial Cells.
      Title: PI 3-Kinase and the Histone Methyl-Transferase KMT2D Collaborate to Induce Arp2/3-Dependent Migration of Mammary Epithelial Cells.
    4. Lysine Methyltransferase 2D Regulates Immune Response and Metastasis in Head and Neck Cancer.
      Title: Lysine Methyltransferase 2D Regulates Immune Response and Metastasis in Head and Neck Cancer.
    5. DNA methylation profiling in Kabuki syndrome: reclassification of germline KMT2D VUS and sensitivity in validating postzygotic mosaicism.
      Title: DNA methylation profiling in Kabuki syndrome: reclassification of germline KMT2D VUS and sensitivity in validating postzygotic mosaicism.
    6. Macular dystrophy in Kabuki syndrome due to de novo KMT2D variants: refining the phenotype with multimodal imaging and follow-up over 10 years: insight into pathophysiology.
      Title: Macular dystrophy in Kabuki syndrome due to de novo KMT2D variants: refining the phenotype with multimodal imaging and follow-up over 10 years: insight into pathophysiology.
    7. [Clinical and genetic characteristics of four children with Kabuki syndrome due to de novo variants of KMT2D gene].
      Title: [Clinical and genetic characteristics of four children with Kabuki syndrome due to de novo variants of KMT2D gene].
    8. KMT2D Deficiency Causes Sensorineural Hearing Loss in Mice and Humans.
      Title: KMT2D Deficiency Causes Sensorineural Hearing Loss in Mice and Humans.
    9. Hearing characteristics and otoradiological abnormalities in three patients with novel pathogenic variants of KMT2D-related Kabuki syndrome.
      Title: Hearing characteristics and otoradiological abnormalities in three patients with novel pathogenic variants of KMT2D-related Kabuki syndrome.
    10. EBF2 Links KMT2D-Mediated H3K4me1 to Suppress Pancreatic Cancer Progression via Upregulating KLLN.
      Title: EBF2 Links KMT2D-Mediated H3K4me1 to Suppress Pancreatic Cancer Progression via Upregulating KLLN.
    Submit: New GeneRIF Correction See all GeneRIFs (170)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2020-01-23)

    ClinGen Genome Curation Page
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated 2020-01-23)

    ClinGen Genome Curation PagePubMed

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables DNA binding NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables histone H3K4 methyltransferase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables histone H3K4 methyltransferase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables histone H3K4 methyltransferase activity TAS
    Traceable Author Statement
    more info
    		  
    enables histone H3K4 monomethyltransferase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H3K4 trimethyltransferase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables transcription cis-regulatory region binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables transcription coactivator activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in beta-catenin-TCF complex assembly TAS
    Traceable Author Statement
    more info
    		  
    involved_in heterochromatin formation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in methylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in oocyte growth ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in oogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of cell population proliferation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of intracellular estrogen receptor signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of transcription by RNA polymerase II IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of transcription by RNA polymerase II IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of DNA-templated transcription NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in response to estrogen IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    part_of MLL3/4 complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of MLL3/4 complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of MLL3/4 complex IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleus NAS
    Non-traceable Author Statement
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    histone-lysine N-methyltransferase 2D
    Names
    ALL1-related protein
    Kabuki make-up syndrome
    histone-lysine N-methyltransferase MLL2
    lysine (K)-specific methyltransferase 2D
    lysine N-methyltransferase 2D
    myeloid/lymphoid or mixed-lineage leukemia 2
    trinucleotide repeat containing 21
    NP_003473.3

    NCBI Reference Sequences (RefSeq)

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    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_027827.1 RefSeqGene

      Range
      5001..41350
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_003482.4 → NP_003473.3  histone-lysine N-methyltransferase 2D

      See identical proteins and their annotated locations for NP_003473.3

      Status: REVIEWED

      Source sequence(s)
      AC011603
      Consensus CDS
      CCDS44873.1
      UniProtKB/Swiss-Prot
      O14686, O14687
      UniProtKB/TrEMBL
      A0A8I5KSG1
      Related
      ENSP00000301067.7, ENST00000301067.12
      Conserved Domains (11) summary
      smart00398
      Location:2021 → 2072
      HMG; high mobility group
      smart00542
      Location:5240 → 5327
      FYRC; FY-rich domain, C-terminal region
      smart00317
      Location:5397 → 5519
      SET; SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain
      cd15509
      Location:228 → 273
      PHD1_KMT2C_like; PHD finger 1 found in Histone-lysine N-methyltransferase 2C (KMT2C) and 2D (KMT2D)
      cd15513
      Location:1429 → 1475
      PHD5_KMT2C_like; PHD finger 5 found in Histone-lysine N-methyltransferase 2C (KMT2C) and PHD finger 4 found in KMT2D
      cd15597
      Location:1378 → 1428
      PHD3_KMT2D; PHD finger 3 found in Histone-lysine N-methyltransferase 2D (KMT2D)
      cd15601
      Location:1506 → 1556
      PHD5_KMT2D; PHD finger 5 found in Histone-lysine N-methyltransferase 2D (KMT2D)
      cd15695
      Location:134 → 217
      ePHD1_KMT2D; Extended PHD finger 1 found in histone-lysine N-methyltransferase 2D (KMT2D)
      cd15698
      Location:5032 → 5138
      ePHD2_KMT2D; Extended PHD finger 2 found in histone-lysine N-methyltransferase 2D (KMT2D)
      pfam05964
      Location:5182 → 5232
      FYRN; F/Y-rich N-terminus
      cl22851
      Location:275 → 320
      PHD_SF; PHD finger superfamily

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      49018978..49060794 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      48981150..49022967 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O14686.2 GenPept UniProtKB/Swiss-Prot:O14686

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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