DOT1L

Chr 19p13.3

DOT1 like histone lysine methyltransferase

Aliases:: KIAA1814, DOT1, KMT4
MANE:: ENST00000398665.8

OMIM: 607375 ↗NCBI: 84444 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

DOT1L · Q8TEK3

v62025-08-01

Predicted Aligned Error matrix for DOT1L — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

52.5/ 100

Low

1,537 residues

Confidence breakdown

Very high(≥ 90)18%
Confident(70–90)13%
Low(50–70)4%
Very low(< 50)65%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Disease associations (Open Targets)

Nil-Deshwar neurodevelopmental syndrome
0.63
hereditary disease
0.34
atrial fibrillation
0.34
neuroblastoma
0.33
neurodegenerative disease
0.30
atrial flutter
0.28
Abnormality of the skeletal system
0.27
osteoarthritis, knee
0.27
cardiac arrhythmia
0.26
coronary atherosclerosis
0.24

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Histone-lysine N-methyltransferase, H3 lysine-79 specific

Histone methyltransferase that methylates 'Lys-79' of histone H3 (PubMed:12123582, PubMed:38503750, PubMed:38129415). Histones in nucleosomes are preferred as substrate compared to free histones (PubMed:12123582, PubMed:38503750). Binds to DNA (PubMed:12628190, PubMed:38503750). Together with MLLT3/AF9, is involved in SCNN1A transcriptional repression following H3K79 hypermethylation at the promoter (By similarity)