• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
KMT2D (HGNC:7133) HGNC Entrez Ensembl OMIM Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
lysine methyltransferase 2D
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
TNRC21, MLL2
Alias symbols
ALR, MLL4, CAGL114
%HI
17.49(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.1(Read more about gnomAD LOEUF score)
Cytoband
12q13.12
Genomic Coordinates
GRCh37/hg19: chr12:49412761-49454577 NCBI Ensembl UCSC
GRCh38/hg38: chr12:49018978-49060794 NCBI Ensembl UCSC
MANE Select Transcript
NM_003482.4 ENST00000301067.12 (Read more about MANE Select)
Function
Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) (PubMed:25561738). Part of chromatin remodeling machinery predominantly forms H3K4me1 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:25561738, PubMed:17500065). Acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription (PubMed:16603732). {ECO:0000269|... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-21328
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
01/23/2020

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 20711175
    Ng et al. described ten patients with Kabuki syndrome and "de novo" LoF mutations in KMT2D gene.
  • PUBMED: 21671394
    Hannibal et al. described 25 patients with Kabuki syndrome and "de novo" LoF mutations which were located all over KMT2D gene. The majority of variants found to cause Kabuki syndrome were novel nonsense or frameshift mutations.
  • PUBMED: 21607748
    Li et al. described eleven patients with Kabuki syndrome and "de novo" LoF mutations at KMT2D gene: Three nonsense mutations, two splice-site mutations, six small deletions or insertions.
HI Evidence Comments:
Associated with Kabuki syndrome. A large number of truncating mutations scattered throughout the gene have been described in the literature (see HGMD). Mutation spectrum includes nonsense, splicing, indels, and frameshift changes, and intragenic exonic deletions. Since 2010, several individuals with KMT2D de novo LoF mutations were described (first time: PMID 20711175). More recent publications related to Kabuki syndrome and KMT2D are PMIDs 23535010; 27302555; 28295206; 30107592.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
Focal duplications involving KMT2D have not been described.

Genomic View

Select assembly: (NC_000012.11) (NC_000012.12)