ASH1L
Chr 1ADASH1 like histone lysine methyltransferase
Also known as: ASH1, ASH1L1, KMT2H, MRD52
The protein is a trithorax group transcriptional activator that localizes to nuclear speckles and cell-cell tight junctions, containing AT hooks, a SET domain, PHD-finger motif, and bromodomain. Loss-of-function mutations cause autosomal dominant intellectual developmental disorder (intellectual developmental disorder, autosomal dominant 52). The gene is highly intolerant to loss-of-function variants, consistent with haploinsufficiency as the pathogenic mechanism.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Highly missense-constrained (top ~0.1%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
ASH1L · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools