• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
KMT2A (HGNC:7132) HGNC Entrez Ensembl OMIM Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
lysine methyltransferase 2A
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
MLL
Alias symbols
TRX1, HRX, ALL-1, HTRX1, CXXC7, MLL1A, MLL1, ALL1, HTRX
%HI
17.01(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
11q23.3
Genomic Coordinates
GRCh37/hg19: chr11:118307207-118397547 NCBI Ensembl UCSC
GRCh38/hg38: chr11:118436492-118526832 NCBI Ensembl UCSC
MANE Select Transcript
NM_001197104.2 ENST00000534358.8 (Read more about MANE Select)
Function
Histone methyltransferase that plays an essential role in early development and hematopoiesis (PubMed:15960975, PubMed:12453419, PubMed:15960975, PubMed:19556245, PubMed:19187761, PubMed:20677832, PubMed:21220120, PubMed:26886794). Catalytic subunit of the MLL1/MLL complex, a multiprotein complex that mediates both methylation of 'Lys- 4' of histone H3 (H3K4me) complex and acetylation of 'Lys-16' of histone H4 (H4K16ac) (PubMed:15960975, PubMed:12453419, PubMed:15960975, PubMed:19556245, PubMed:... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-14169
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
05/23/2018

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • Wiedemann-Steiner Syndrome (WDSTS) Monarch
HI Evidence:
  • PUBMED: 22795537
    Jones et al. 2012: Describes mutations in MLL (currently known as KMT2A) in 5 of 6 individuals with hairy elbows, short stature, facial dysmorphism, and developmental delay (Wiedemann-Steiner syndrome). All five mutations were de novo; four were frameshift mutations thought to result in premature truncation, and one was a nonsense mutation. None of the observed mutations were present in dbSNP, had been observed by the 1000 Genomes Project, or were detected in 600 unrelated control exome profiles. The variants were confirmed with Sanger sequencing in the respective probands. In order "to establish whether the mutant MLL(KMT2A) alleles were subject to nonsense-mediated decay, the authors used a quantitative real-time PCR approach...to assess the total abundance of MLL(KMT2A) transcripts in primary skin fibroblast cells derived from individual WSS-3, heterozygous for the c.6913del allele. The authors observed that the level of MLL(KMT2A) transcript was reduced in comparison to unrelated healthy controls, consistent with the notion that transcripts arising from the mutant MLL(KMT2A) alleles are subject to nonsense-mediated decay."
  • PUBMED: 24818805
    Mendelsohn et al. 2014 identified a de novo intragenic deletion of exons 2-10 within the KMT2A (MLL) gene by whole exome sequencing. Patient presented with mild developmental delay, short stature, dysmorphic facial features, advanced bone age, renal anomalies and hypertrichosis. However, this patient has generalized hypertrichosis unlike previously reported Wiedemann-Steiner syndrome (WDSTS) patients with hypertrichosis cubiti as reported by Jones et al. further expanding the variable patterns of hypertrichosis and first reported Wiedemann-Steiner syndrome due to exonic deletion.
  • PUBMED: 27759909
    Sun et al. 2016 describe two males with de novo nonsense mutations in the KMT2A gene detected by whole exome sequencing. Both nonsense mutations were absent in the 1000 genomes project ExAC, EVS and in an inhouse database. Most of the males phenotype was concordant with WDSTS however, both lacked hypertrichosis cubiti but did show generalized hypertrichosis. A comparison of the two reported patients to previously reported and a common phenotype that included postnatal growth retardation, developmental delay, intellectual disability, distinct dysmorphic features and generalized hypertrichosis.
HI Evidence Comments:
Additional supporting articles are included below: PMID: 25533962 Fitgerald et al. (2015) PMID:118397539 Miyake et al. (2016) PMID: 27777327 Ko et al.( 2017), PMID: 27848944 Truijillano et al. (2017), PMID: 29574747 Baer et al. (2018), Although no complete gene deletions have been described in the literature, nonsense, frameshift, exonic deletions and splice site mutations have been described in the literature.

Triplosensitivity (TS) Score Details

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

Genomic View

Select assembly: (NC_000011.9) (NC_000011.10)