KMT2B |
- 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:
- dystonia 28, childhood-onset Monarch
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)