ASH1L

Summary

ASH1L (ASH1 like histone lysine methyltransferase, HGNC:19088) is a protein-coding gene on chromosome 1q22, encoding Histone-lysine N-methyltransferase ASH1L (Q9NR48). Histone methyltransferase specifically trimethylating ‘Lys-36’ of histone H3 forming H3K36me3. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a member of the trithorax group of transcriptional activators. The protein contains four AT hooks, a SET domain, a PHD-finger motif, and a bromodomain. It is localized to many small speckles in the nucleus, and also to cell-cell tight junctions.

Source: NCBI Gene 55870 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic complex neurodevelopmental disorder (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 27
• Clinical variants (ClinVar): 979 total — 66 pathogenic, 31 likely-pathogenic
• Phenotypes (HPO): 59
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_018489

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19088
Approved symbol	ASH1L
Name	ASH1 like histone lysine methyltransferase
Location	1q22
Locus type	gene with protein product
Status	Approved
Aliases	huASH1, ASH1, ASH1L1, KMT2H
Ensembl gene	ENSG00000116539
Ensembl biotype	protein_coding
OMIM	607999
Entrez	55870

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 9 protein_coding, 5 nonsense_mediated_decay, 3 retained_intron

ENST00000368346, ENST00000392403, ENST00000477427, ENST00000478837, ENST00000492987, ENST00000548566, ENST00000548830, ENST00000676814, ENST00000677042, ENST00000677213, ENST00000677825, ENST00000677992, ENST00000678117, ENST00000678699, ENST00000679097, ENST00000679133, ENST00000679333

RefSeq mRNA: 2 — MANE Select: NM_018489 NM_001366177, NM_018489

CCDS: CCDS1113, CCDS91067

Canonical transcript exons

ENST00000392403 — 28 exons

Exon	Start	End
ENSE00000558165	155477886	155482449
ENSE00000961130	155438327	155439068
ENSE00000961131	155415744	155415923
ENSE00000961132	155395459	155395553
ENSE00000961134	155378503	155378548
ENSE00000961135	155378281	155378389
ENSE00000961136	155370777	155370983
ENSE00000961137	155370504	155370650
ENSE00000961138	155360301	155360409
ENSE00000961139	155357585	155357749
ENSE00000961140	155357316	155357410
ENSE00001054201	155339328	155339368
ENSE00001054203	155341936	155342102
ENSE00001054204	155349542	155349596
ENSE00001054205	155349327	155349459
ENSE00001054206	155338089	155338390
ENSE00001054208	155354473	155354630
ENSE00001054210	155352706	155352858
ENSE00001054214	155343314	155343486
ENSE00001171548	155459797	155459898
ENSE00001446940	155335268	155337751
ENSE00001446941	155521100	155521618
ENSE00001446942	155562153	155562803
ENSE00001511687	155380043	155380116
ENSE00002356147	155347656	155347904
ENSE00002362078	155346383	155346469
ENSE00003514406	155343604	155343742
ENSE00003597204	155344183	155344273

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 98.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.7628 / max 108.5483, expressed in 1565 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14970	5.7628	1565

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	98.22	gold quality
pylorus	UBERON:0001166	98.07	gold quality
cardia of stomach	UBERON:0001162	97.85	gold quality
cerebellar vermis	UBERON:0004720	97.66	gold quality
middle temporal gyrus	UBERON:0002771	97.64	gold quality
nipple	UBERON:0002030	97.48	gold quality
postcentral gyrus	UBERON:0002581	97.27	gold quality
visceral pleura	UBERON:0002401	97.21	gold quality
renal medulla	UBERON:0000362	97.01	gold quality
parietal lobe	UBERON:0001872	97.01	gold quality
endothelial cell	CL:0000115	96.95	gold quality
lateral globus pallidus	UBERON:0002476	96.89	gold quality
entorhinal cortex	UBERON:0002728	96.75	gold quality
medial globus pallidus	UBERON:0002477	96.08	gold quality
globus pallidus	UBERON:0001875	96.06	gold quality
primary visual cortex	UBERON:0002436	95.78	gold quality
parietal pleura	UBERON:0002400	95.74	gold quality
pleura	UBERON:0000977	95.67	gold quality
urethra	UBERON:0000057	95.65	gold quality
substantia nigra pars reticulata	UBERON:0001966	95.64	gold quality
inferior vagus X ganglion	UBERON:0005363	95.52	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.47	gold quality
superior surface of tongue	UBERON:0007371	95.47	gold quality
trigeminal ganglion	UBERON:0001675	95.42	gold quality
substantia nigra pars compacta	UBERON:0001965	95.42	gold quality
superior frontal gyrus	UBERON:0002661	95.41	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.39	gold quality
superficial temporal artery	UBERON:0001614	95.15	gold quality
dorsal root ganglion	UBERON:0000044	95.04	gold quality
seminal vesicle	UBERON:0000998	95.04	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
NRXN1	Repression
NTRK2	Activation
TGFB1	Unknown
TIMP1	Unknown

Upstream regulators (CollecTRI, top): GLI3, NEUROG3

miRNA regulators (miRDB)

247 targeting ASH1L, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-557	99.96	70.01	1640

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 28)

• These data suggest that ASH1L occupies most, if not all, active genes and methylates histone H3 in a nonredundant fashion at a subset of genes. (PMID:17923682)
• human ASH1L specifically methylates histone H3 Lys-36. (PMID:21239497)
• ASH1 and MLL1 synergize in activation of Hox genes. (PMID:22140534)
• Long Non-coding RNA, DBE-T recruits the Trithorax group protein Ash1L to the FSHD locus, driving histone H3 lysine 36 dimethylation, chromatin remodeling, and 4q35 gene transcription. (PMID:22541069)
• induction of Cdk5 activity is a novel mechanism through which hASH1 may regulate migration in lung carcinogenesis (PMID:22696682)
• all of the H3K36-specific methyltransferases, including ASH1L, HYPB, NSD1, and NSD2 were inhibited by ubH2A, whereas the other histone methyltransferases, including PRC2, G9a, and Pr-Set7 were not affected by ubH2A. (PMID:24019522)
• Our results uncover a novel regulatory cascade orchestrated by Ash1l with RAR and provide insights into mechanisms underlying the establishment of the transcriptional activation that counteracts Polycomb silencing (PMID:24244179)
• These data demonstrate that miR-142-3p downregulation has a role in thyroid tumorigenesis, by regulating ASH1L and MLL1. (PMID:25238203)
• Both ASH1L and SETD2 are H3K36 specific methyltransferases but only SETD2 can trimethylate this mark. (PMID:26002201)
• Structural features were identified in ASH1L related to its’ function and enzymatic activity. (PMID:26292256)
• Epigenetic regulators play vital roles in cancer pathogenesis and represent a new frontier in therapeutic targeting. Our studies provide basic mechanistic insight into the role of H3K36me2 in transcription activation and MLL leukemia pathogenesis and implicate ASH1L histone methyltransferase as a promising target for novel molecular therapy. (PMID:27154821)
• Our data suggest a role for ASH1L, a methyl transferase protein and member of the trithorax (Trx) family, in regulation of the HBB gene and as a potential modifier of beta-thalassaemia severity. (PMID:27434206)
• suppresses matrix metalloproteinase through mitogen-activated protein kinase signaling pathway in pulpitis (PMID:28041684)
• There has been increasing evidence that heterozygous mutation of ASH1L is associated with ID and autism spectrum disorders. We suggest that ASH1L abnormalities may cause a novel MCA/ID syndrome. (PMID:28394464)
• DDB2 promotes cyclobutane pyrimidine dimer excision by recruiting the histone methyltransferase ASH1L, which methylates lysine 4 of histone H3. In turn, methylated H3 facilitates the docking of the XPC complex to nucleosomal histone octamers. (PMID:29109511)
• Study shows that mutations associated with acute myelogenous leukemia (AML) result both in loss of miR-142-3p function and in decreased miR-142-5p expression. During hematopoietic maturation, loss of Mir142 increased ASH1L protein expression and consequently resulted in the aberrant maintenance of Hoxa gene expression in myeloid-committed hematopoietic progenitors. (PMID:29724719)
• A novel loss of function mutation in ASH1L was identified in a patient with an emergent neurodevelopmental syndrome. (PMID:29753921)
• ASH1L activation by MRG15 represents a delicate regulatory mechanism for how a cofactor activates an SET domain HMTase by releasing autoinhibition (PMID:30827841)
• Ash1L stimulates H3K36 methyltransferase activity through Mrg15 binding (PMID:30827843)
• Mutations in ASH1L confer susceptibility to Tourette syndrome. (PMID:31673123)
• Novel role of ASH1L histone methyltransferase in anaplastic thyroid carcinoma. (PMID:32398261)
• ASH1L mutation caused seizures and intellectual disability in twin sisters. (PMID:34373061)
• Deficiency of autism risk factor ASH1L in prefrontal cortex induces epigenetic aberrations and seizures. (PMID:34782621)
• Exploration of INSM1 and hASH1 as additional markers in lung cytology samples of high-grade neuroendocrine carcinoma with indeterminate neuroendocrine differentiation. (PMID:35147301)
• ASH1L may contribute to the risk of Tourette syndrome: Combination of family-based analysis and case-control study. (PMID:35307981)
• MRG15 activates histone methyltransferase activity of ASH1L by recruiting it to the nucleosomes. (PMID:37527654)
• The ASH1L-AS1-ASH1L axis controls NME1-mediated activation of the RAS signaling in gastric cancer. (PMID:37805663)
• ASH1L guards cis-regulatory elements against cyclobutane pyrimidine dimer induction. (PMID:38884271)

Cross-species orthologs

17 orthologs

Organism	Symbol	Gene ID
danio_rerio	ash1l	ENSDARG00000070981
mus_musculus	Ash1l	ENSMUSG00000028053
rattus_norvegicus	Ash1l	ENSRNOG00000020386
drosophila_melanogaster	ash1	FBGN0005386
drosophila_melanogaster	Set2	FBGN0030486
drosophila_melanogaster	CG4565	FBGN0037841
drosophila_melanogaster	G9a	FBGN0040372
caenorhabditis_elegans	set-32	WBGENE00008062
caenorhabditis_elegans		WBGENE00008206
caenorhabditis_elegans		WBGENE00008527
caenorhabditis_elegans	met-1	WBGENE00016603
caenorhabditis_elegans		WBGENE00018023
caenorhabditis_elegans		WBGENE00019584
caenorhabditis_elegans		WBGENE00019690
caenorhabditis_elegans		WBGENE00020006
caenorhabditis_elegans		WBGENE00020919
caenorhabditis_elegans		WBGENE00021282

Paralogs (19): KMT2C (ENSG00000055609), SETD1A (ENSG00000099381), SUV39H1 (ENSG00000101945), EZH2 (ENSG00000106462), EZH1 (ENSG00000108799), NSD2 (ENSG00000109685), KMT2A (ENSG00000118058), SETDB2 (ENSG00000136169), SETD1B (ENSG00000139718), SETDB1 (ENSG00000143379), NSD3 (ENSG00000147548), SETBP1 (ENSG00000152217), SUV39H2 (ENSG00000152455), NSD1 (ENSG00000165671), KMT2D (ENSG00000167548), EHMT1 (ENSG00000181090), SETD2 (ENSG00000181555), EHMT2 (ENSG00000204371), KMT2B (ENSG00000272333)

Protein

Protein identifiers

Histone-lysine N-methyltransferase ASH1L — Q9NR48 (reviewed: Q9NR48)

Alternative names: ASH1-like protein, Absent small and homeotic disks protein 1 homolog, Lysine N-methyltransferase 2H

All UniProt accessions (10): Q9NR48, A0A7I2V316, A0A7I2V3D6, A0A7I2V4H9, A0A7I2V4K0, A0A7I2V542, A0A7I2YQL4, A0A7I2YQU9, F8VWK7, H0YI82

UniProt curated annotations — full annotation on UniProt →

Function. Histone methyltransferase specifically trimethylating ‘Lys-36’ of histone H3 forming H3K36me3. Also monomethylates ‘Lys-9’ of histone H3 (H3K9me1) in vitro. The physiological significance of the H3K9me1 activity is unclear.

Subcellular location. Nucleus. Cell junction. Tight junction. Chromosome.

Tissue specificity. Widely expressed, with highest level in brain, heart and kidney.

Post-translational modifications. Methylated at Gln-1220 by N6AMT1.

Disease relevance. Intellectual developmental disorder, autosomal dominant 52 (MRD52) [MIM:617796] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. SET2 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NR48-1	1	yes
Q9NR48-2	2

RefSeq proteins (2): NP_001353106, NP_060959* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001025	BAH_dom	Domain
IPR001214	SET_dom	Domain
IPR001487	Bromodomain	Domain
IPR001965	Znf_PHD	Domain
IPR003616	Post-SET_dom	Domain
IPR006560	AWS_dom	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017956	AT_hook_DNA-bd_motif	Conserved_site
IPR019786	Zinc_finger_PHD-type_CS	Conserved_site
IPR036427	Bromodomain-like_sf	Homologous_superfamily
IPR043151	BAH_sf	Homologous_superfamily
IPR043319	PHD_ASH1L	Domain
IPR043320	Bromo_ASH1L	Domain
IPR046341	SET_dom_sf	Homologous_superfamily

Pfam: PF00439, PF00856, PF01426, PF17907, PF20826

Enzyme classification (BRENDA):

• EC 2.1.1.357 — [histone H3]-lysine36 N-dimethyltransferase (BRENDA: 4 organisms, 14 substrates, 5 inhibitors, 4 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

3 substrates with measured Km, best-characterized 3. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
S-ADENOSYL-L-METHIONINE	0.0028–0.0038	2
CHICKEN NUCLEOSOME	0.0003	1
RECOMBINANT NUCLEOSOME	—	1

Catalyzed reactions (Rhea), 2 shown:

• L-lysyl(9)-[histone H3] + S-adenosyl-L-methionine = N(6)-methyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-homocysteine + H(+) (RHEA:60280)
• L-lysyl(36)-[histone H3] + 3 S-adenosyl-L-methionine = N(6),N(6),N(6)-trimethyl-L-lysyl(36)-[histone H3] + 3 S-adenosyl-L-homocysteine + 3 H(+) (RHEA:60324)

UniProt features (108 total): compositionally biased region 23, region of interest 17, helix 16, strand 14, sequence variant 12, modified residue 8, domain 5, DNA-binding region 3, cross-link 2, sequence conflict 2, turn 2, chain 1, splice variant 1, mutagenesis site 1, zinc finger region 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
8VLF	X-RAY DIFFRACTION	1.34
6WZW	X-RAY DIFFRACTION	1.69
6X0P	X-RAY DIFFRACTION	1.69
8VLD	X-RAY DIFFRACTION	1.92
4YNM	X-RAY DIFFRACTION	2.19
4YPE	X-RAY DIFFRACTION	2.2
4YPA	X-RAY DIFFRACTION	2.3
8VLH	X-RAY DIFFRACTION	2.4
3MQM	X-RAY DIFFRACTION	2.54
4YPU	X-RAY DIFFRACTION	2.6
6INE	X-RAY DIFFRACTION	2.6
3OPE	X-RAY DIFFRACTION	2.9
4YNP	X-RAY DIFFRACTION	2.9
6AGO	X-RAY DIFFRACTION	3.1
7Y0I	SOLUTION NMR
8ZXC	SOLUTION NMR

Predicted structure (AlphaFold)

No AlphaFold model available for Q9NR48 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (10): 22, 375, 1162, 1170, 1220, 2317, 2319, 2323, 34, 425

Mutagenesis-validated functional residues (1):

Position	Phenotype
1220	abolishes methylation by n6amt1.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-3214841	PKMTs methylate histone lysines
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-4839726	Chromatin organization

MSigDB gene sets: 409 (showing top): GOBP_SINGLE_FERTILIZATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_INFLAMMATORY_RESPONSE, CMYB_01, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, KEGG_TIGHT_JUNCTION, MOTAMED_RESPONSE_TO_ANDROGEN_DN, GOBP_NEGATIVE_REGULATION_OF_ACUTE_INFLAMMATORY_RESPONSE, BILD_SRC_ONCOGENIC_SIGNATURE, YY1_Q6, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE, NFKB_Q6, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_ACUTE_INFLAMMATORY_RESPONSE, GOBP_DECIDUALIZATION

GO Biological Process (21): MAPK cascade (GO:0000165), skeletal system development (GO:0001501), negative regulation of acute inflammatory response (GO:0002674), regulation of DNA-templated transcription (GO:0006355), transcription by RNA polymerase II (GO:0006366), inflammatory response (GO:0006954), single fertilization (GO:0007338), post-embryonic development (GO:0009791), flagellated sperm motility (GO:0030317), methylation (GO:0032259), negative regulation of MAPK cascade (GO:0043409), positive regulation of transcription by RNA polymerase II (GO:0045944), decidualization (GO:0046697), uterus morphogenesis (GO:0061038), tarsal gland development (GO:1903699), uterine gland development (GO:1903709), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338), regulation of gene expression (GO:0010468), sebaceous gland development (GO:0048733), negative regulation of inflammatory response (GO:0050728)

GO Molecular Function (15): DNA binding (GO:0003677), chromatin binding (GO:0003682), zinc ion binding (GO:0008270), histone H3K4 methyltransferase activity (GO:0042800), histone H3K9 methyltransferase activity (GO:0046974), histone H3K36 methyltransferase activity (GO:0046975), histone H3 methyltransferase activity (GO:0140938), histone H3K9 monomethyltransferase activity (GO:0140948), histone H3K36 trimethyltransferase activity (GO:0140955), protein binding (GO:0005515), methyltransferase activity (GO:0008168), transferase activity (GO:0016740), histone methyltransferase activity (GO:0042054), metal ion binding (GO:0046872), histone H3K9me2 methyltransferase activity (GO:0140947)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), Golgi apparatus (GO:0005794), bicellular tight junction (GO:0005923), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Chromatin modifying enzymes	1
Chromatin organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein-lysine N-methyltransferase activity	3
histone H3 methyltransferase activity	3
DNA-templated transcription	2
developmental process involved in reproduction	2
gland development	2
binding	2
histone H3K9 methyltransferase activity	2
intracellular membrane-bounded organelle	2
intracellular signaling cassette	1
system development	1
acute inflammatory response	1
regulation of acute inflammatory response	1
negative regulation of inflammatory response	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
defense response	1
fertilization	1
multicellular organism development	1
multicellular organismal process	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
metabolic process	1
MAPK cascade	1
regulation of MAPK cascade	1
negative regulation of intracellular signal transduction	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
maternal placenta development	1
tissue development	1
animal organ morphogenesis	1
uterus development	1
sebaceous gland development	1
cellular component organization	1
chromatin organization	1
gene expression	1
regulation of macromolecule biosynthetic process	1
skin development	1
nucleic acid binding	1

Protein interactions and networks

STRING

2646 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASH1L	GON4L	Q3T8J9	944
ASH1L	YY1AP1	Q9H869	939
ASH1L	CGN	Q9P2M7	847
ASH1L	SMYD2	Q9NRG4	679
ASH1L	MORF4L1	Q9UBU8	676
ASH1L	SETD3	Q86TU7	675
ASH1L	KMT5B	Q4FZB7	646
ASH1L	BRD1	O95696	632
ASH1L	RBBP5	Q15291	626
ASH1L	SETD7	Q8WTS6	602
ASH1L	DOT1L	Q8TEK3	602
ASH1L	WDR5	P61964	590
ASH1L	SMYD3	Q9H7B4	574
ASH1L	TJP1	Q07157	573
ASH1L	DNMT3B	Q9UBC3	538

IntAct

50 interactions, top by confidence:

A	B	Type	Score
MORF4L1	SIN3B	psi-mi:“MI:0914”(association)	0.730
RBBP7	HAT1	psi-mi:“MI:0914”(association)	0.730
MORF4L2	YEATS4	psi-mi:“MI:0914”(association)	0.640
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
RBBP4	TNRC18	psi-mi:“MI:0914”(association)	0.530
THAP7	RPS27A	psi-mi:“MI:0914”(association)	0.530
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.530
ASH1L	MESD	psi-mi:“MI:0915”(physical association)	0.400
ASH1L	ARPC1B	psi-mi:“MI:0915”(physical association)	0.400
ASH1L	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
ASH1L	PLEC	psi-mi:“MI:0915”(physical association)	0.400
ASH1L	OXTR	psi-mi:“MI:0915”(physical association)	0.370
ASH1L	SMAD7	psi-mi:“MI:0915”(physical association)	0.370
DCAF4	IGLL5	psi-mi:“MI:0914”(association)	0.350
CSNK2A2	VWA8	psi-mi:“MI:0914”(association)	0.350
PIPSL	C1orf226	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
LURAP1	CIBAR1	psi-mi:“MI:0914”(association)	0.350
MCC	CIBAR1	psi-mi:“MI:0914”(association)	0.350
MAGEA9	CIBAR1	psi-mi:“MI:0914”(association)	0.350
NOP2	ZNF320	psi-mi:“MI:0914”(association)	0.350
NXF2B	MEIOC	psi-mi:“MI:0914”(association)	0.350
RPL28	GTPBP10	psi-mi:“MI:0914”(association)	0.350
OASL	ZNF316	psi-mi:“MI:0914”(association)	0.350
RPL15	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
CDX1	ZNF724	psi-mi:“MI:0914”(association)	0.350
FGFBP1	ZNF724	psi-mi:“MI:0914”(association)	0.350
PNMA8A	AP3B1	psi-mi:“MI:0914”(association)	0.350

BioGRID (93): ASH1L (Affinity Capture-MS), ASH1L (Affinity Capture-MS), ASH1L (Affinity Capture-MS), ASH1L (Affinity Capture-MS), ASH1L (Affinity Capture-MS), ASH1L (Affinity Capture-MS), ASH1L (Affinity Capture-MS), ASH1L (Affinity Capture-MS), ASH1L (Affinity Capture-MS), ASH1L (Affinity Capture-MS), ASH1L (Affinity Capture-MS), ASH1L (Affinity Capture-RNA), ASH1L (Proximity Label-MS), ASH1L (Affinity Capture-RNA), ASH1L (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GTH6, A0A1D5RMD1, A1KXM5, A2AEY4, A6NCI8, A6QQS3, A7KBS4, C4P6S0, O94713, P0C9Z7, P53963, P53976, Q0P670, Q0VAV2, Q10668, Q196W1, Q2KHR3, Q2YDJ5, Q32MG2, Q3V0A6, Q3V3Q4, Q4V8E9, Q5JRM2, Q68FV4, Q6AXV6, Q6AYN3, Q6NS59, Q7TSG5, Q80VJ6, Q80Y39, Q80YD3, Q810T2, Q86XD8, Q8C5U4, Q8CH19, Q8IWI9, Q8K4E0, Q8NDH2, Q8NEV8, Q8NFU7

Diamond homologs: A2VE56, A5DDB7, A8MW92, O44498, P36124, Q08923, Q10362, Q1MTR4, Q3UG20, Q4V9H5, Q5F3G6, Q6BNY5, Q6C0K9, Q8BLG0, Q8CCJ9, Q8IZD2, Q99MY8, Q9BVI0, Q9NR48, Q9U263, Q9VGA4, Q9Y7V2, A0A1L7TZE5, A7E2Z2, A8XI75, C6KTD2, E9Q5F9, G5EEU2, O14026, O43463, O54864, O60016, O64827, O82175, P20659, P38827, P42124, P45975, P46995, P55200

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
NEUROG3	“down-regulates quantity by repression”	ASH1L	“transcriptional regulation”
ASH1L	“down-regulates quantity by repression”	NRXN1	“transcriptional regulation”
ASH1L	“up-regulates quantity by expression”	NTRK2	“transcriptional regulation”
ASH1L	“up-regulates activity”	H3C1	trimethylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 66 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
HATs acetylate histones	6	11.9×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

979 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	66
Likely pathogenic	31
Uncertain significance	642
Likely benign	139
Benign	21

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1047928	NM_018489.3(ASH1L):c.1013C>A (p.Ser338Ter)	Pathogenic
1176209	NM_018489.3(ASH1L):c.2770_2783del (p.Ser924fs)	Pathogenic
1216975	NM_018489.3(ASH1L):c.790G>T (p.Gly264Ter)	Pathogenic
1317483	NM_018489.3(ASH1L):c.6826C>T (p.Arg2276Ter)	Pathogenic
1334992	NM_018489.3(ASH1L):c.7558_7559dup (p.Tyr2521fs)	Pathogenic
1700066	NM_018489.3(ASH1L):c.5502dup (p.Leu1835fs)	Pathogenic
1706432	NM_018489.3(ASH1L):c.7603C>T (p.Arg2535Ter)	Pathogenic
1710352	NM_018489.3(ASH1L):c.491del (p.Arg164fs)	Pathogenic
1997605	NM_018489.3(ASH1L):c.6502G>T (p.Glu2168Ter)	Pathogenic
2298244	NM_018489.3(ASH1L):c.1984_1985del (p.Ile662fs)	Pathogenic
2442664	NM_018489.3(ASH1L):c.7098G>A (p.Trp2366Ter)	Pathogenic
2497754	NM_018489.3(ASH1L):c.160C>T (p.Arg54Ter)	Pathogenic
2503251	NM_018489.3(ASH1L):c.7252C>T (p.Arg2418Ter)	Pathogenic
2543541	NM_018489.3(ASH1L):c.6366C>A (p.Cys2122Ter)	Pathogenic
2570737	NM_018489.3(ASH1L):c.4656_4659del (p.Glu1553fs)	Pathogenic
2573017	NM_018489.3(ASH1L):c.5325C>A (p.Cys1775Ter)	Pathogenic
2582343	NM_018489.3(ASH1L):c.6640C>T (p.Arg2214Ter)	Pathogenic
2626868	NM_018489.3(ASH1L):c.5569_5585del (p.Pro1857fs)	Pathogenic
2627116	NM_018489.3(ASH1L):c.1959del (p.Lys653fs)	Pathogenic
2627827	NM_018489.3(ASH1L):c.3860_3861del (p.Phe1287fs)	Pathogenic
2692609	NM_018489.3(ASH1L):c.2113C>T (p.Gln705Ter)	Pathogenic
3130304	NM_018489.3(ASH1L):c.1651G>T (p.Gly551Ter)	Pathogenic
3254699	NM_018489.3(ASH1L):c.2966_2969del (p.Met989fs)	Pathogenic
3254705	NM_018489.3(ASH1L):c.7021dup (p.Gln2341fs)	Pathogenic
3254958	NM_018489.3(ASH1L):c.3937C>T (p.Arg1313Ter)	Pathogenic
3370481	NM_018489.3(ASH1L):c.3916C>T (p.Arg1306Ter)	Pathogenic
3382380	NM_018489.3(ASH1L):c.7189C>T (p.Arg2397Ter)	Pathogenic
3384137	NM_018489.3(ASH1L):c.2905_2908del (p.Lys969fs)	Pathogenic
3390586	NM_018489.3(ASH1L):c.4024C>T (p.Arg1342Ter)	Pathogenic
3435994	NM_018489.3(ASH1L):c.6436C>T (p.Arg2146Ter)	Pathogenic

SpliceAI

5735 predictions. Top by Δscore:

Variant	Effect	Δscore
1:155339326:A:AC	donor_gain	1.0000
1:155339326:ACCGT:A	donor_gain	1.0000
1:155339327:C:CC	donor_gain	1.0000
1:155339327:CCGTC:C	donor_gain	1.0000
1:155339364:TGAGG:T	acceptor_gain	1.0000
1:155339365:GAGG:G	acceptor_gain	1.0000
1:155339367:GG:G	acceptor_gain	1.0000
1:155339367:GGC:G	acceptor_loss	1.0000
1:155339368:GC:G	acceptor_loss	1.0000
1:155339369:C:CC	acceptor_gain	1.0000
1:155339370:T:A	acceptor_loss	1.0000
1:155341931:CTCA:C	donor_loss	1.0000
1:155341932:TCA:T	donor_loss	1.0000
1:155341933:CA:C	donor_loss	1.0000
1:155341934:A:AC	donor_gain	1.0000
1:155341935:C:CC	donor_gain	1.0000
1:155342099:CTCC:C	acceptor_gain	1.0000
1:155342100:TCC:T	acceptor_gain	1.0000
1:155342101:CC:C	acceptor_gain	1.0000
1:155342101:CCC:C	acceptor_gain	1.0000
1:155342102:CC:C	acceptor_gain	1.0000
1:155342103:C:CC	acceptor_gain	1.0000
1:155342104:T:C	acceptor_loss	1.0000
1:155342116:CAG:C	acceptor_gain	1.0000
1:155343483:CTCT:C	acceptor_gain	1.0000
1:155343485:CT:C	acceptor_gain	1.0000
1:155343600:GTACT:G	donor_loss	1.0000
1:155343601:TACTT:T	donor_loss	1.0000
1:155343602:A:AC	donor_gain	1.0000
1:155343602:AC:A	donor_loss	1.0000

AlphaMissense

19514 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:155338115:A:G	L2931P	1.000
1:155342102:C:T	G2770E	1.000
1:155343314:C:G	G2770R	1.000
1:155343314:C:T	G2770R	1.000
1:155343379:T:A	E2748V	1.000
1:155343466:C:A	G2719V	1.000
1:155343466:C:T	G2719D	1.000
1:155343467:C:G	G2719R	1.000
1:155343472:G:T	A2717D	1.000
1:155343617:A:G	W2708R	1.000
1:155343617:A:T	W2708R	1.000
1:155343619:A:G	L2707P	1.000
1:155343631:C:G	R2703P	1.000
1:155346405:C:G	C2628S	1.000
1:155346406:A:G	C2628R	1.000
1:155346406:A:T	C2628S	1.000
1:155346413:A:C	C2625W	1.000
1:155346414:C:G	C2625S	1.000
1:155346414:C:T	C2625Y	1.000
1:155346415:A:G	C2625R	1.000
1:155346415:A:T	C2625S	1.000
1:155346449:A:C	C2613W	1.000
1:155346451:A:G	C2613R	1.000
1:155346458:G:C	H2610Q	1.000
1:155346458:G:T	H2610Q	1.000
1:155346462:T:G	Q2609P	1.000
1:155346464:C:A	W2608C	1.000
1:155346464:C:G	W2608C	1.000
1:155346466:A:G	W2608R	1.000
1:155346466:A:T	W2608R	1.000

dbSNP variants (sampled 300 via entrez): RS1000034706 (1:155418459 A>C), RS1000058487 (1:155496452 C>T), RS1000096410 (1:155525982 A>G), RS1000096454 (1:155545668 C>T), RS1000098786 (1:155402359 C>T), RS1000107278 (1:155482695 T>C), RS1000109814 (1:155418767 G>A), RS1000113537 (1:155527249 TCCA>T), RS1000116244 (1:155392704 G>A), RS1000120789 (1:155473158 C>T), RS1000140154 (1:155352315 A>G), RS1000146790 (1:155449361 T>C), RS1000156303 (1:155373753 G>A), RS1000164469 (1:155507812 C>G), RS1000187210 (1:155515091 G>A)

Disease associations

OMIM: gene MIM:607999 | disease phenotypes: MIM:617796

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability, autosomal dominant 52	Strong	Autosomal dominant
autosomal dominant non-syndromic intellectual disability	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
syndromic complex neurodevelopmental disorder	Definitive	AD

Mondo (7): intellectual disability, autosomal dominant 52 (MONDO:0030918), intellectual disability (MONDO:0001071), syndromic complex neurodevelopmental disorder (MONDO:0800439), autism spectrum disorder (MONDO:0005258), neurodevelopmental disorder (MONDO:0700092), congenital heart disease (MONDO:0005453), autosomal dominant non-syndromic intellectual disability (MONDO:0015802)

Orphanet (3): Rare genetic intellectual disability (Orphanet:183757), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

59 total (30 of 59 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000194	Open mouth
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000268	Dolichocephaly
HP:0000294	Low anterior hairline
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000322	Short philtrum
HP:0000369	Low-set ears
HP:0000407	Sensorineural hearing impairment
HP:0000426	Prominent nasal bridge
HP:0000444	Convex nasal ridge
HP:0000448	Prominent nose
HP:0000463	Anteverted nares
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000540	Hypermetropia
HP:0000664	Synophrys
HP:0000666	Horizontal nystagmus
HP:0000729	Autistic behavior
HP:0000733	Motor stereotypy
HP:0000737	Irritability
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0000752	Hyperactivity
HP:0000768	Pectus carinatum

GWAS associations

27 associations (top):

Study	Trait	p-value
GCST002928_2	Nickel levels	5.000000e-07
GCST003218_2	Non-cardia gastric cancer	2.000000e-19
GCST003744_5	Chronic periodontitis (mean interproximal clinical attachment level)	5.000000e-07
GCST004131_70	Inflammatory bowel disease	6.000000e-08
GCST004132_44	Crohn’s disease	2.000000e-07
GCST007294_124	Body fat distribution (trunk fat ratio)	8.000000e-35
GCST007294_3	Body fat distribution (trunk fat ratio)	6.000000e-21
GCST007294_50	Body fat distribution (trunk fat ratio)	1.000000e-15
GCST007295_17	Body fat distribution (leg fat ratio)	3.000000e-13
GCST007295_37	Body fat distribution (leg fat ratio)	7.000000e-17
GCST007295_72	Body fat distribution (leg fat ratio)	1.000000e-28
GCST007881_2	Dementia with Lewy bodies	1.000000e-09
GCST010696_19	Cortical thickness (min-P)	2.000000e-10
GCST010697_10	Cortical surface area (min-P)	3.000000e-10
GCST010698_59	Subcortical volume (min-P)	9.000000e-10
GCST010699_20	Brain morphology (min-P)	7.000000e-10
GCST010700_5	Cortical thickness (MOSTest)	8.000000e-17
GCST010701_66	Cortical surface area (MOSTest)	1.000000e-09
GCST010702_43	Subcortical volume (MOSTest)	3.000000e-10
GCST010703_253	Brain morphology (MOSTest)	4.000000e-14
GCST012431_1	Parkinson’s disease	1.000000e-09
GCST90002385_95	High light scatter reticulocyte count	3.000000e-36
GCST90002386_377	High light scatter reticulocyte percentage of red cells	2.000000e-40
GCST90002405_84	Reticulocyte count	4.000000e-42
GCST90002406_106	Reticulocyte fraction of red cells	5.000000e-50
GCST90020025_1217	Waist-to-hip ratio adjusted for BMI	7.000000e-10
GCST90020027_1802	Waist-hip index	2.000000e-10

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007780	periodontal measurement
EFO:0004341	body fat distribution
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0007986	reticulocyte count
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3588739 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 2.1.1.43 Histone methyltransferases (HMTs)

ChEMBL bioactivities

62 potent at pChembl≥5 of 112 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.03	IC50	94	nM	CHEMBL6165353
6.96	IC50	110	nM	CHEMBL6145608
6.96	IC50	110	nM	CHEMBL6144101
6.96	IC50	110	nM	CHEMBL6102285
6.92	IC50	120	nM	CHEMBL6161638
6.85	IC50	140	nM	CHEMBL6146517
6.82	IC50	150	nM	CHEMBL6102285
6.82	IC50	150	nM	CHEMBL6165353
6.80	IC50	160	nM	CHEMBL6144101
6.80	IC50	160	nM	CHEMBL6146228
6.77	IC50	170	nM	CHEMBL6145608
6.77	IC50	170	nM	CHEMBL6160988
6.75	IC50	180	nM	CHEMBL6142945
6.75	IC50	180	nM	CHEMBL6147246
6.75	Kd	179	nM	CHEMBL6165353
6.72	IC50	190	nM	CHEMBL6145086
6.71	IC50	197	nM	CHEMBL6141624
6.68	IC50	210	nM	CHEMBL6133537
6.66	IC50	220	nM	CHEMBL6146517
6.66	IC50	220	nM	CHEMBL6143264
6.58	IC50	260	nM	CHEMBL6143922
6.55	IC50	280	nM	CHEMBL6141839
6.51	IC50	310	nM	CHEMBL6133192
6.51	IC50	310	nM	CHEMBL6150238
6.51	IC50	310	nM	CHEMBL6167146
6.51	IC50	310	nM	CHEMBL6132754
6.50	IC50	320	nM	CHEMBL6103249
6.42	IC50	380	nM	CHEMBL6163648
6.41	IC50	390	nM	CHEMBL6133063
6.36	IC50	439	nM	CHEMBL4531716
6.33	IC50	470	nM	CHEMBL6163991
6.31	IC50	490	nM	CHEMBL6146639
6.30	IC50	500	nM	CHEMBL6142111
6.28	IC50	520	nM	CHEMBL4531716
6.28	IC50	530	nM	CHEMBL6143581
6.27	IC50	540	nM	CHEMBL6153004
6.26	IC50	550	nM	CHEMBL6103111
6.25	IC50	560	nM	CHEMBL6143305
6.22	IC50	600	nM	CHEMBL5077328
6.21	IC50	610	nM	CHEMBL6150683
6.19	IC50	640	nM	CHEMBL6102565
6.12	IC50	750	nM	CHEMBL6165380
6.11	Kd	780	nM	CHEMBL5077328
6.11	IC50	770	nM	CHEMBL6144826
6.10	IC50	790	nM	CHEMBL5410484
6.10	IC50	790	nM	CHEMBL5085204
6.09	IC50	810	nM	CHEMBL6161262
6.08	IC50	833	nM	CHEMBL5085204
6.08	IC50	830	nM	CHEMBL5085204
6.05	Kd	890	nM	CHEMBL5085204

PubChem BioAssay actives

6 with measured affinity, of 104 total; 4 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[[3-(3-carbamothioylphenyl)-1-[1-(trifluoromethylsulfonyl)piperidin-4-yl]indol-6-yl]methyl]azetidine-3-carboxamide	2115839: Inhibition of N-terminal ASH1L SET domain (2069 to 2288) (unknown origin) extracted from Escherichia coli BL21 incubated for 60 mins by ITC analysis	ic50	0.6000	uM
N-[[3-(3-carbamothioylphenyl)-1-[1-(trifluoromethylsulfonyl)piperidin-4-yl]indol-6-yl]methyl]-1-methylazetidine-3-carboxamide	2115839: Inhibition of N-terminal ASH1L SET domain (2069 to 2288) (unknown origin) extracted from Escherichia coli BL21 incubated for 60 mins by ITC analysis	ic50	0.7900	uM
N-[[3-(3-carbamothioylphenyl)-1-[4-(trifluoromethylsulfonyl)cyclohexyl]indol-6-yl]methyl]-1-methylazetidine-3-carboxamide	2026849: Inhibition of N-terminal Mocr-tagged ASH1L (2069 to 2288 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) by ITC analysis	ic50	0.7900	uM
3-[6-(aminomethyl)-1-(2-hydroxyethyl)indol-3-yl]benzenecarbothioamide	2128865: Inhibition of N-terminal ASH1L SET domain (2069 to 2288) (unknown origin) extracted from Escherichia coli BL21 (DE3)	ic50	4.0000	uM

CTD chemical–gene interactions

31 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects expression, decreases expression	5
Benzo(a)pyrene	increases expression, increases methylation	2
Formaldehyde	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Cadmium Chloride	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	decreases methylation	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
bis-N,N-dimethylamino-2-(N-methylpyrrolyl)methyl cyclopentadienyl titanium (IV)	decreases expression	1
Acetaminophen	increases expression	1
Ethanol	decreases expression	1
Atrazine	increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Doxorubicin	decreases expression	1
Methapyrilene	decreases methylation	1
Methyl Methanesulfonate	increases expression	1
Nickel	decreases expression	1
Plant Extracts	increases expression	1
Xylitol	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1

ChEMBL screening assays

65 unique, capped per target: 63 binding, 1 admet, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3592414	Binding	Inhibition of ASH1L (unknown origin) at 1 uM after 1 hr by filter-based assay	Discovery of A-893, A New Cell-Active Benzoxazinone Inhibitor of Lysine Methyltransferase SMYD2. — ACS Med Chem Lett
CHEMBL4416350	ADMET	Inhibition of human ASH1L expressed in Escherichia coli assessed as reduction in methylated polynucleosome level using polynucleosome as substrate in presence of [3H] SAM incubated for 15 mins by scintillation counting	High-Affinity Alkynyl Bisubstrate Inhibitors of Nicotinamide N-Methyltransferase (NNMT). — J Med Chem
CHEMBL5723063	Functional	Affinity Biochemical interaction: (Histone methyltransferase radioactivity assay) EUB0001089a ASH1L	Affinity Biochemical Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1K5	Abcam HeLa ASH1L KO	Cancer cell line	Female
CVCL_D6XJ	GM28328	Transformed cell line	Male
CVCL_D7KK	Ubigene A-549 ASH1L KO	Cancer cell line	Male
CVCL_SD61	HAP1 ASH1L (-) 1	Cancer cell line	Male
CVCL_SD62	HAP1 ASH1L (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

197 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders