• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
KMT2B (HGNC:15840) HGNC Entrez Ensembl OMIM Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
lysine methyltransferase 2B
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
KIAA0304, MLL2, TRX2, HRX2, WBP7, MLL1B, MLL4, CXXC10
%HI
0(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.07(Read more about gnomAD LOEUF score)
Cytoband
19q13.12
Genomic Coordinates
GRCh37/hg19: chr19:36208905-36229779 NCBI Ensembl UCSC
GRCh38/hg38: chr19:35718003-35738878 NCBI Ensembl UCSC
MANE Select Transcript
NM_014727.3 ENST00000420124.4 (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) via a non-processive mechanism. Part of chromatin remodeling machinery predominantly forms H3K4me1 and H3K4me2 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:25561738, PubMed:17707229). Likely plays a redundant role with KMT2C in enriching H3K4me1 marks on primed and active enhancer elements (PubM... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-37515
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
05/11/2017

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 27839873
    Zech et al (2016) used whole-exome sequencing of parent-child trios to identify loss-of-function sequence mutations in KMT2B, resulting in early-onset generalized dystonia. In vitro functional studies demonstrated a reduction in mRNA levels, consistent with a haploinsufficient effect. Three of the four affected probands had de novo mutations, with one inherited. The family in which the mutation was inherited showed variable expressivity in carriers, as the father and grandfather had less severe dystonia. Other features reported in several individuals were microcephaly and mild intellectual disability.
  • PUBMED: 27992417
    Meyer et al (2016) describe 10 individuals with microdeletions of various sizes identified by microarray studies presenting with childhood onset dystonia. The smallest region of overlap encompassed two genes, ZBTB32 and KMT2B, and all deletions were de novo. Seven additional individuals with dystonia were found to have loss-of-function sequence mutation in KMT2B, three of which were inherited. Interestingly, those individuals with missense mutations were affected at a later age of onset than those with mutations predicted to truncate or elongate the protein. The subject with the smallest deletion of ~600 kb was originally reported in Dale et al (2012, PMID: 22515636).

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000019.9) (NC_000019.10)