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 (top 5% of genes corpus-wide)
• Clinical variants (ClinVar): 1,108 total — 67 pathogenic, 42 likely-pathogenic (top 3% of genes corpus-wide)
• Regional missense constraint (gnomAD): 4 of 13 regions constrained (≈3% of expected missense variation)
• GTEx eGene: eQTL in 9 tissues, sQTL in 2 (q < 0.05)
• Phenotypes (HPO): 59
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.10 (highly constrained)
• 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: 20 — 9 protein_coding, 8 nonsense_mediated_decay, 3 retained_intron

MANE Select: ENST00000392403

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 2, TSL 4: 1, TSL 5: 3

ENST00000392403, ENST00000368346, ENST00000477427, ENST00000478837, ENST00000492987, ENST00000548566, ENST00000548830, ENST00000676814, ENST00000677042, ENST00000677213, ENST00000677825, ENST00000677992, ENST00000678117, ENST00000678699, ENST00000679097, ENST00000679133, ENST00000679333, ENST00000978115, ENST00000978116, ENST00001009748

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
ENSE00001511687	155380043	155380116
ENSE00002356147	155347656	155347904
ENSE00002362078	155346383	155346469
ENSE00003514406	155343604	155343742
ENSE00003597204	155344183	155344273
ENSE00004805939	155562153	155562803

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.

Highest expression (Bgee): Brodmann (1909) area 23, pylorus, cardia of stomach, cerebellar vermis, middle temporal gyrus.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ASH1L is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 9 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

11 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Breast Mammary Tissue	eqtl	1.1e-06	+0.15	1:155587180:G:A
Adipose Subcutaneous	eqtl	1.4e-06	+0.11	1:155688550:T:C
Adipose Visceral Omentum	eqtl	4.8e-06	+0.16	1:155645024:A:C
Thyroid	eqtl	7.2e-04	+0.10	1:156061029:C:A
Heart Atrial Appendage	sqtl	7.3e-03	-2.45	1:156236390:C:T
Testis	eqtl	1.3e-02	+0.36	1:155073926:G:T
Artery Tibial	eqtl	1.3e-02	+0.07	1:156494753:C:G
Brain Frontal Cortex BA9	eqtl	3.3e-02	+0.47	1:155066655:AG:A
Colon Sigmoid	sqtl	3.4e-02	-1.13	1:156079040:C:T
Artery Aorta	eqtl	4.2e-02	-0.07	1:155093940:G:A
Cells EBV-transformed lymphocytes	eqtl	4.9e-02	-0.33	1:154580954:C:A

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
14970	5.7628	1565

Top tissues by expression

showing 100 of 288 tissues 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
germinal epithelium of ovary	UBERON:0001304	94.96	gold quality
jejunum	UBERON:0002115	94.87	gold quality
tibia	UBERON:0000979	94.75	gold quality
sperm	CL:0000019	94.73	gold quality
amniotic fluid	UBERON:0000173	94.72	gold quality
occipital lobe	UBERON:0002021	94.71	gold quality
subthalamic nucleus	UBERON:0001906	94.61	gold quality
mammary duct	UBERON:0001765	94.33	gold quality
tendon	UBERON:0000043	94.30	gold quality
ventral tegmental area	UBERON:0002691	94.25	gold quality
skin of hip	UBERON:0001554	94.24	gold quality
parotid gland	UBERON:0001831	94.21	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.18	gold quality
tendon of biceps brachii	UBERON:0008188	94.17	gold quality
corpus callosum	UBERON:0002336	93.99	gold quality
jejunal mucosa	UBERON:0000399	93.96	gold quality
epithelium of nasopharynx	UBERON:0001951	93.94	gold quality
pericardium	UBERON:0002407	93.88	gold quality
pigmented layer of retina	UBERON:0001782	93.80	gold quality
biceps brachii	UBERON:0001507	93.79	gold quality
gingival epithelium	UBERON:0001949	93.78	gold quality
saphenous vein	UBERON:0007318	93.73	gold quality
superior vestibular nucleus	UBERON:0007227	93.68	gold quality
calcaneal tendon	UBERON:0003701	93.58	gold quality
colonic epithelium	UBERON:0000397	93.45	gold quality
body of tongue	UBERON:0011876	93.30	gold quality
cerebellar cortex	UBERON:0002129	93.19	gold quality
pons	UBERON:0000988	93.15	gold quality
caput epididymis	UBERON:0004358	93.15	gold quality
cerebellar hemisphere	UBERON:0002245	93.13	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.13	gold quality
synovial joint	UBERON:0002217	93.10	gold quality
pharyngeal mucosa	UBERON:0000355	92.98	gold quality
colonic mucosa	UBERON:0000317	92.85	gold quality
secondary oocyte	CL:0000655	92.79	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.79	gold quality
palpebral conjunctiva	UBERON:0001812	92.69	gold quality
cerebellum	UBERON:0002037	92.68	gold quality
temporal lobe	UBERON:0001871	92.60	gold quality
penis	UBERON:0000989	92.59	gold quality
vena cava	UBERON:0004087	92.58	gold quality
tongue	UBERON:0001723	92.52	gold quality
cortical plate	UBERON:0005343	92.44	gold quality
tonsil	UBERON:0002372	92.28	gold quality
gingiva	UBERON:0001828	92.22	gold quality
corpus epididymis	UBERON:0004359	92.13	gold quality
trabecular bone tissue	UBERON:0002483	91.91	gold quality
cauda epididymis	UBERON:0004360	91.87	gold quality
oral cavity	UBERON:0000167	91.84	gold quality
mucosa of paranasal sinus	UBERON:0005030	91.69	gold quality
mammary gland	UBERON:0001911	91.60	gold quality
gastrocnemius	UBERON:0001388	91.52	gold quality
thoracic mammary gland	UBERON:0005200	91.52	gold quality
heart right ventricle	UBERON:0002080	91.50	gold quality
dorsal plus ventral thalamus	UBERON:0001897	91.48	gold quality
ovary	UBERON:0000992	91.40	gold quality
left ovary	UBERON:0002119	91.34	gold quality
ventricular zone	UBERON:0003053	91.30	gold quality
muscle of leg	UBERON:0001383	91.28	gold quality
popliteal artery	UBERON:0002250	91.27	gold quality
tibial artery	UBERON:0007610	91.27	gold quality
nucleus accumbens	UBERON:0001882	91.24	gold quality
bronchial epithelial cell	CL:0002328	91.23	gold quality
cerebral cortex	UBERON:0000956	91.23	gold quality
tibial nerve	UBERON:0001323	91.18	gold quality
fundus of stomach	UBERON:0001160	91.17	gold quality
right ovary	UBERON:0002118	91.17	gold quality
telencephalon	UBERON:0001893	91.15	gold quality
neocortex	UBERON:0001950	91.14	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.11	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Cerebellum	tissue	113.6	not detected
Cerebral cortex	tissue	79.8	low
Occipital cortex	tissue	79.8
Motor cortex	tissue	79.5
Somatosensory cortex	tissue	79.0
Prefrontal cortex	tissue	76.9
Putamen	tissue	76.1
Hippocampal formation	tissue	72.1
Entorhinal cortex	tissue	72.1
Retrosplenial cortex	tissue	70.6
Retrosplenial and cingulate cortex	tissue	70.5
Midbrain	tissue	69.4
Thalamus	tissue	68.6
Insular cortex	tissue	66.9
Temporal cortex	tissue	66.8
Basal ganglia	tissue	66.7	medium
Pons	tissue	66.5
Superior colliculi	tissue	66.4
Ventral forebrain	tissue	65.8
Hypothalamus	tissue	65.0
Olfactory bulb	tissue	64.6
Substantia nigra	tissue	64.3
Septum	tissue	63.2
Periaqueductal gray	tissue	62.1
Medulla oblongata	tissue	61.6
Amygdala	tissue	60.8
Spinal cord	tissue	60.7
Corpus callosum	tissue	60.7
Postcentral gyrus	tissue	44.6
Nucleus accumbens	tissue	41.3
Hippocampus	tissue	40.7	not detected
Locus coeruleus	tissue	31.1
Skeletal muscle	tissue	28.4	not detected
Choroid plexus	tissue	26.7
Retina	tissue	24.2
Caudate putamen	tissue	23.9
Tongue	tissue	22.7
Frontal cortex	tissue	20.8
Epididymis	tissue	19.6	medium
Skin 1	tissue	19.3	low
Vagina	tissue	18.0	low
Ovary	tissue	17.9	low
Pituitary gland	tissue	17.6
Parathyroid gland	tissue	17.1	medium
Breast	tissue	15.7
Thyroid gland	tissue	14.8	not detected
Prostate	tissue	14.7	low
Seminal vesicle	tissue	14.5	not detected
Salivary gland	tissue	14.0	medium
Cervix	tissue	13.5	medium
Endometrium 1	tissue	13.5	not detected
Adipose tissue	tissue	13.2	not detected
Kidney	tissue	13.0	not detected
Adrenal gland	tissue	12.1	medium
Smooth muscle	tissue	11.9	not detected
Heart muscle	tissue	11.8	not detected
Thymus	tissue	11.3
Stomach 1	tissue	11.2	not detected
Bone marrow	tissue	11.2	low
Rectum	tissue	10.8	low

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Subiculum (68.5), Dorsal hippocampus (66.2), Ventral hippocampus (63.3), Dorsal spinal cord (60.7), White matter (60.7).

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)

Targeting ASH1L by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 247 miRNAs:

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

gnomAD constraint: pLI 1, LOEUF 0.104, missense Z 4.8 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000392403 splits into 13 regions with different missense tolerance; 4 are missense-constrained (≈3% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
1:155,337,663–155,339,344	154 / 165.0	0.93	no
1:155,339,345–155,346,456	179 / 293.8	0.61	no
1:155,346,457–155,347,684	2 / 18.5	0.11	yes (p 1.2e-04)
1:155,347,685–155,360,373	309 / 435.1	0.71	no
1:155,360,374–155,370,564	7 / 42.5	0.16	yes (p 5.0e-08)
1:155,370,565–155,415,904	193 / 311.6	0.62	no
1:155,415,905–155,479,230	789 / 897.6	0.88	no
1:155,479,231–155,479,280	2 / 20.2	0.10	yes (p 5.1e-05)
1:155,479,281–155,479,679	157 / 154.6	1.02	no
1:155,479,680–155,479,775	13 / 38.5	0.34	yes (p 3.9e-05)
1:155,479,776–155,481,648	715 / 721.0	0.99	no
1:155,481,649–155,521,253	277 / 367.7	0.75	no
1:155,521,254–155,521,519	115 / 101.5	1.13	no
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

21 orthologs

Organism	Symbol	Gene ID
danio_rerio	ash1l	ENSDARG00000070981
mus_musculus	Ash1l	ENSMUSG00000028053
rattus_norvegicus	Ash1l	ENSRNOG00000020386
drosophila_melanogaster	ash1	FBGN0005386
drosophila_melanogaster	trr	FBGN0023518
drosophila_melanogaster	Set2	FBGN0030486
drosophila_melanogaster	CG4565	FBGN0037841
drosophila_melanogaster	G9a	FBGN0040372
drosophila_melanogaster	egg	FBGN0086908
caenorhabditis_elegans	set-32	WBGENE00008062
caenorhabditis_elegans		WBGENE00008206
caenorhabditis_elegans		WBGENE00008527
caenorhabditis_elegans		WBGENE00011729
caenorhabditis_elegans	met-1	WBGENE00016603
caenorhabditis_elegans		WBGENE00018023
caenorhabditis_elegans		WBGENE00019584
caenorhabditis_elegans		WBGENE00019690
caenorhabditis_elegans		WBGENE00019883
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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2183158) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 48 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal sternum morphology	1
increased rib number	1
abnormal uterus morphology	1
decreased body weight	1
decreased body size	1
abnormal coat appearance	1
postnatal growth retardation	1
reduced male fertility	1
female infertility	1
increased susceptibility to bacterial infection	1
increased IgM level	1
increased IgA level	1
increased basophil cell number	1
abnormal epididymis morphology	1
small uterus	1
abnormal cauda epididymis morphology	1
abnormal sperm number	1
glomerulonephritis	1
abnormal vas deferens morphology	1
increased heart weight	1
increased susceptibility to induced arthritis	1
increased autoantibody level	1
abnormal decidualization	1
increased eosinophil cell number	1
blepharitis	1

+23 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5RB81	100.0%	Diamond
Macaca fascicularis	Q4R381	99.9%	Diamond
Cryptococcus deneoformans JEC21	P0CO28	99.8%	Diamond
Cryptococcus deneoformans B-3501A	P0CO29	99.8%	Diamond
Bos taurus	Q2NL30	99.3%	Diamond
Oryza sativa Japonica Group	Q10MI4	98.7%	Diamond
Oryza sativa Indica Group	Q84UI6	98.7%	Diamond
Xenopus tropicalis	Q28D84	97.7%	Diamond
Xenopus laevis	Q98SM3	97.7%	Diamond
Zea mays	Q8S4P4	89.5%	Diamond
Gallus gallus	Q5F3W5	78.7%	Diamond
Aspergillus oryzae RIB40	Q2UTN6	76.3%	Diamond
Aspergillus nidulans FGSC A4	Q5ASA5	76.3%	Diamond
Aspergillus fumigatus Af293	Q4WTT2	75.7%	Diamond
Neurospora crassa OR74A	Q7RZU4	73.6%	Diamond
Chaetomium globosum CBS 148.51	Q2H988	72.9%	Diamond
Coccidioides immitis RS	Q1DU03	71.1%	Diamond
Saccharomyces cerevisiae S288C	P38827	70.7%	Diamond
Ricinus communis	B9RU15	69.6%	Diamond
Caenorhabditis briggsae	A8XI75	69.3%	Diamond
Fusarium graminearum PH-1	Q4I5R3	69.2%	Diamond
Arabidopsis thaliana	P0CB22	69.1%	Diamond
Nakaseomyces glabratus CBS 138	Q6FKB1	69.1%	Diamond
Candida albicans SC5314	Q5ABG1	63.0%	Diamond
Dictyostelium discoideum	Q54HS3	62.5%	Diamond
Kluyveromyces lactis NRRL Y-1140	Q6CIT4	61.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MSTO1	protein-coding	55154
ASH1L-AS1	ncRNA	645676
RUSC1	protein-coding	23623
RUSC1-AS1	ncRNA	284618
MIR555	ncRNA	693140
FDPS	protein-coding	2224
PKLR	protein-coding	5313
HCN3	protein-coding	57657
CLK2	protein-coding	1196

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): A0A7I2V316, A0A7I2V3D6, A0A7I2V4H9, A0A7I2V4K0, A0A7I2V542, A0A7I2YQL4, A0A7I2YQU9, F8VWK7, H0YI82, Q9NR48

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)

• 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 (143 total): strand 31, helix 31, compositionally biased region 23, region of interest 17, sequence variant 12, modified residue 8, domain 5, turn 5, DNA-binding region 3, cross-link 2, sequence conflict 2, chain 1, splice variant 1, mutagenesis site 1, zinc finger region 1

Structure

Experimental structures (PDB)

16 structures by resolution:

PDB	Title	Method	Resolution (Å)
8VLF	Crystal structure of Ash1L PHD finger in complex with histone H3K4me3	X-RAY DIFFRACTION	1.34
6WZW	Ash1L SET domain in complex with AS-85	X-RAY DIFFRACTION	1.69
6X0P	Ash1L SET domain Q2265A mutant in complex with AS-5	X-RAY DIFFRACTION	1.69
8VLD	Crystal structure of Ash1L PHD finger in complex with histone H3K4me2	X-RAY DIFFRACTION	1.92
4YNM	ASH1L wild-type SET domain in complex with S-adenosyl methionine (SAM)	X-RAY DIFFRACTION	2.19
4YPE	ASH1L SET domain H2193F mutant in complex with S-adenosyl methionine (SAM)	X-RAY DIFFRACTION	2.2
4YPA	ASH1L SET domain Q2265A mutant in complex with S-adenosyl methionine (SAM)	X-RAY DIFFRACTION	2.3
8VLH	Crystal structure of Ash1L PHD-BAH domains	X-RAY DIFFRACTION	2.4
3MQM	Crystal Structure of the Bromodomain of human ASH1L	X-RAY DIFFRACTION	2.54
4YPU	ASH1L SET domain K2264L mutant in complex with S-adenosyl methionine (SAM)	X-RAY DIFFRACTION	2.6
6INE	Crystal Structure of human ASH1L-MRG15 complex	X-RAY DIFFRACTION	2.6
3OPE	Structural Basis of Auto-inhibitory mechanism of Histone methyltransferase	X-RAY DIFFRACTION	2.9
4YNP	ASH1L SET domain S2259M mutant in complex with S-adenosyl methionine (SAM)	X-RAY DIFFRACTION	2.9
6AGO	Crystal structure of MRG15-ASH1L Histone methyltransferase complex	X-RAY DIFFRACTION	3.1
7Y0I	Solution structures of ASH1L PHD domain in complex with H3K4me2 peptide	SOLUTION NMR
8ZXC	NMR solution structures of ASH1L BRD-PHD domain in complex with H3K4me2 peptide	SOLUTION NMR

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted intracellular proteins, Disease related genes, Potential drug targets, Human disease related genes, Mental and behavioural disorders

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus; nucleoplasm; nuclear bodies

Antibody reliability (HPA): IH approved · IF approved

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)

Type	Positions
Phosphoserine	22, 1162, 1170
N6-acetyllysine	375, 2317, 2319, 2323
N5-methylglutamine	1220
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	34, 425

Mutagenesis-validated functional residues (1)

Position	Phenotype
1220	abolishes methylation by n6amt1.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

ID	Pathway	Evidence
R-HSA-3214841	PKMTs methylate histone lysines	curated
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 (5): DNA-templated transcription (GO:0006351), regulation of DNA-templated transcription (GO:0006355), methylation (GO:0032259), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338)

GO Molecular Function (14): 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)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), bicellular tight junction (GO:0005923), nuclear body (GO:0016604)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Chromatin modifying enzymes	1
Chromatin organization	1

GO top-level categories

28 GO namespaces:

Category	Terms
protein-lysine N-methyltransferase activity	3
histone H3 methyltransferase activity	3
binding	2
intracellular membraneless organelle	2
gene expression	1
RNA biosynthetic process	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
metabolic process	1
cellular component organization	1
chromatin organization	1
nucleic acid binding	1
transition metal ion binding	1
histone methyltransferase activity	1
histone H3K9 methyltransferase activity	1
histone H3K36 methyltransferase activity	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
protein methyltransferase activity	1
histone modifying activity	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
apical junction complex	1
tight junction	1
nucleoplasm	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 24 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
nuclear body	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
histone H3K36 methyltransferase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,674 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASH1L	GON4L	Q3T8J9	936
ASH1L	YY1AP1	Q9H869	932
ASH1L	CGN	Q9P2M7	761
ASH1L	SMYD2	Q9NRG4	665
ASH1L	SETD3	Q86TU7	664
ASH1L	KMT5B	Q4FZB7	641
ASH1L	H3-3A	P06351	619
ASH1L	H3C14	Q71DI3	619
ASH1L	H3-5	Q6NXT2	619
ASH1L	H3C1	P02295	619
ASH1L	H3-4	Q16695	619
ASH1L	H3-7	Q5TEC6	619
ASH1L	DOT1L	Q8TEK3	604
ASH1L	PRDM2	Q13029	602
ASH1L	SETD7	Q8WTS6	590

IntAct

Human interaction partners of ASH1L in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

10 partners by confidence:

Partner	Interaction type	MIscore	Records
ARPC1B	physical association	0.400	1
H2BC9	physical association	0.400	1
MESD	physical association	0.400	1
PLEC	physical association	0.400	1
OXTR	physical association	0.370	1
SMAD7	physical association	0.370	1
APP	physical association	0.000	2
DSCR9	physical association	0.000	1
EPHA1	physical association	0.000	1
VPS26C	physical association	0.000	1

BioGRID (96 interactions; top human partners by supporting records): MORF4L1 (Affinity Capture-MS; 10 records), MORF4L2 (Affinity Capture-MS; 7 records), RBBP4 (Affinity Capture-MS; 3 records), THAP7 (Affinity Capture-MS; 3 records), CDX1 (Affinity Capture-MS; 2 records), HIST1H3A (Biochemical Activity; 2 records), NXF2 (Affinity Capture-MS; 2 records), RBBP7 (Affinity Capture-MS; 2 records), AGR2 (Proximity Label-MS), AKAP8 (Affinity Capture-Western), APP (Two-hybrid), ARPC1B (Cross-Linking-MS (XL-MS)), ATG16L1 (Proximity Label-MS), BRD4 (Affinity Capture-MS), BRPF3 (Affinity Capture-MS)

SIGNOR signaling

4 signaling 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

Disease & clinical

Genetic variants

Variant evidence for ASH1L: 1,108 ClinVar records (109 pathogenic / likely pathogenic); 27 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

1,108 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	67
Likely pathogenic	42
Uncertain significance	714
Likely benign	173
Benign	23

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 109 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
625522	NM_018489.3(ASH1L):c.3664_3667del (p.Lys1222fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
1706432	NM_018489.3(ASH1L):c.7603C>T (p.Arg2535Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
620260	NM_018489.3(ASH1L):c.4579C>T (p.Arg1527Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
3384137	NM_018489.3(ASH1L):c.2905_2908del (p.Lys969fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
3390586	NM_018489.3(ASH1L):c.4024C>T (p.Arg1342Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
3436077	NM_018489.3(ASH1L):c.8500C>T (p.Arg2834Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
4075766	NM_018489.3(ASH1L):c.6178-2A>G	Pathogenic	criteria provided, multiple submitters, no conflicts	2
444180	NM_018489.3(ASH1L):c.4651_4654del (p.Asn1551fs)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
1334572	NM_018489.3(ASH1L):c.5269C>T (p.Arg1757Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
3255379	NM_018489.3(ASH1L):c.1948del (p.Gly651fs)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
817414	NM_018489.3(ASH1L):c.4224_4225del (p.Tyr1409fs)	Pathogenic	criteria provided, single submitter	2
633562	NM_018489.3(ASH1L):c.1632del (p.Lys544fs)	Pathogenic	criteria provided, single submitter	1
633576	NM_018489.3(ASH1L):c.5506C>T (p.Gln1836Ter)	Pathogenic	criteria provided, single submitter	1
662987	NM_018489.3(ASH1L):c.2991_2992del (p.Leu998fs)	Pathogenic	criteria provided, single submitter	1
817705	NM_018489.3(ASH1L):c.1880_1881dup (p.Gly628fs)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore ASH1L’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 33 predictions of 3,258):

Position(s)	Effect	Δscore	Sites
1:155339369–155339370	acceptor_loss	1.0000	5
1:155341934–155341935	donor_loss	1.0000	4
1:155342103–155342104	acceptor_loss	1.0000	5
1:155343602–155343603	donor_loss	1.0000	3
1:155343743–155343744	acceptor_loss	1.0000	5
1:155343754–155343755	acceptor_gain	1.0000	2
1:155346470–155346471	acceptor_loss	1.0000	3
1:155347905–155347906	acceptor_loss	1.0000	2
1:155349325–155349326	donor_loss	1.0000	3
1:155349331	donor_gain	1.0000

AlphaMissense

6,100 missense substitutions predicted likely pathogenic (of 19,514 scored), across 1,292 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M989	9	0.991	1.000
M2599	9	0.991	1.000
M2231	9	0.980	1.000
M2214	9	0.914	0.993
M2188	9	0.901	0.987
M2117	9	0.895	0.995
D1206	8	0.999	1.000
D2210	8	0.999	1.000
H2223	8	0.999	1.000
D2259	8	0.998	1.000
H2610	8	0.998	1.000
S1040	8	0.997	1.000
D2055	8	0.997	1.000
D2788	8	0.996	0.999
H2730	8	0.994	0.999
N1207	8	0.993	1.000
H1485	8	0.993	0.999
F2262	8	0.993	1.000
D2942	8	0.993	0.998
D1200	8	0.992	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.61e-05
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000415

Disease associations

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

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
intellectual disability, autosomal dominant 52	Strong	Autosomal dominant	4
autosomal dominant non-syndromic intellectual disability	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
syndromic complex neurodevelopmental disorder	Definitive	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (7 panels, 7 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

7 panels:

Panel	Rating
DDG2P	green
Early onset or syndromic epilepsy	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Paediatric disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (5): intellectual disability, autosomal dominant 52 (MONDO:0030918), neurodevelopmental disorder (MONDO:0700092), intellectual disability (MONDO:0001071), syndromic complex neurodevelopmental disorder (MONDO:0800439), autosomal dominant non-syndromic intellectual disability (MONDO:0015802)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

59 phenotypes (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
HP:0000821	Hypothyroidism
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001262	Excessive daytime somnolence
HP:0001263	Global developmental delay
HP:0001344	Absent speech
HP:0001518	Small for gestational age
HP:0001623	Breech presentation
HP:0002188	Delayed CNS myelination
HP:0002360	Sleep disturbance
HP:0002714	Downturned corners of mouth
HP:0002938	Lumbar hyperlordosis
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0003691	Scapular winging
HP:0004602	Cervical C2/C3 vertebral fusion
HP:0004626	Lumbar scoliosis
HP:0005280	Depressed nasal bridge
HP:0006610	Wide intermamillary distance
HP:0008071	Maternal hypertension
HP:0008689	Bilateral cryptorchidism
HP:0008770	Obsessive-compulsive trait
HP:0008936	Axial hypotonia
HP:0010722	Asymmetry of the ears
HP:0011856	Pica
HP:0011968	Feeding difficulties
HP:0012450	Chronic constipation
HP:0025502	Overweight

GWAS associations

27 associations:

Study	Trait	p-value
GCST90002406_190	Reticulocyte fraction of red cells	5e-50
GCST90002405_34	Reticulocyte count	4e-42
GCST90002386_409	High light scatter reticulocyte percentage of red cells	2e-40
GCST90002385_32	High light scatter reticulocyte count	3e-36
GCST007294_150	Body fat distribution (trunk fat ratio)	8e-35
GCST007295_72	Body fat distribution (leg fat ratio)	1e-28
GCST007294_159	Body fat distribution (trunk fat ratio)	6e-21
GCST003218_2	Non-cardia gastric cancer	2e-19
GCST007295_112	Body fat distribution (leg fat ratio)	7e-17
GCST010700_5	Cortical thickness (MOSTest)	8e-17
GCST007294_25	Body fat distribution (trunk fat ratio)	1e-15
GCST010703_205	Brain morphology (MOSTest)	4e-14
GCST007295_17	Body fat distribution (leg fat ratio)	3e-13
GCST010696_10	Cortical thickness (min-P)	2e-10
GCST90020027_55	Waist-hip index	2e-10
GCST010697_21	Cortical surface area (min-P)	3e-10
GCST010702_25	Subcortical volume (MOSTest)	3e-10
GCST010699_50	Brain morphology (min-P)	7e-10
GCST90020025_167	Waist-to-hip ratio adjusted for BMI	7e-10
GCST010698_84	Subcortical volume (min-P)	9e-10
GCST007881_2	Dementia with Lewy bodies	1e-9
GCST010701_97	Cortical surface area (MOSTest)	1e-9
GCST012431_1	Parkinson’s disease	1e-9
GCST004131_70	Inflammatory bowel disease	6e-8
GCST004132_19	Crohn’s disease	2e-7
GCST002928_18	Nickel levels	5e-7
GCST003744_5	Chronic periodontitis (mean interproximal clinical attachment level)	5e-7

EFO canonical traits (from GWAS)

6 canonical traits:

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

2 disease descriptors:

Descriptor	Name	Tree numbers
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 (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Histone methyltransferases (HMTs)

Binding affinities (BindingDB)

46 measured of 48 human assays (48 total across all organisms); most potent 46 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL6145608	IC50	110 nM
CHEMBL6144101	IC50	110 nM
CHEMBL6102285	IC50	110 nM
CHEMBL6165353	IC50	120 nM
CHEMBL6146517	IC50	140 nM
CHEMBL6146228	IC50	160 nM
CHEMBL6160988	IC50	170 nM
CHEMBL6142945	IC50	180 nM
CHEMBL6147246	IC50	180 nM
CHEMBL6145086	IC50	190 nM
CHEMBL6141624	IC50	197 nM
CHEMBL6133537	IC50	210 nM
CHEMBL6143264	IC50	220 nM
CHEMBL6143922	IC50	260 nM
CHEMBL6141839	IC50	280 nM
CHEMBL6133192	IC50	310 nM
CHEMBL6150238	IC50	310 nM
CHEMBL6167146	IC50	310 nM
CHEMBL6132754	IC50	310 nM
CHEMBL6103249	IC50	320 nM
CHEMBL6163648	IC50	380 nM
CHEMBL6133063	IC50	390 nM
CHEMBL4531716	IC50	439 nM
CHEMBL6163991	IC50	470 nM
CHEMBL6146639	IC50	490 nM
CHEMBL6142111	IC50	500 nM
CHEMBL6143581	IC50	530 nM
CHEMBL6153004	IC50	540 nM
CHEMBL6103111	IC50	550 nM
CHEMBL6143305	IC50	560 nM
CHEMBL5077328	IC50	600 nM
CHEMBL6150683	IC50	610 nM
CHEMBL6102565	IC50	640 nM
CHEMBL6165380	IC50	750 nM
CHEMBL6144826	IC50	770 nM
CHEMBL5410484	IC50	790 nM
CHEMBL5085204	IC50	790 nM
CHEMBL6161262	IC50	810 nM
CHEMBL6120558	IC50	1700 nM
CHEMBL4546073	IC50	4000 nM
CHEMBL4591248	IC50	7600 nM
CHEMBL6151260	IC50	8600 nM
CHEMBL4551717	IC50	15000 nM
CHEMBL4556344	IC50	23000 nM
CHEMBL4580008	IC50	50000 nM
CHEMBL5619490	IC50	72000 nM

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

58 with measured affinity, of 160 total; 42 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-[2-[2-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methylcarbamoyl]-7-azaspiro[3.5]nonan-7-yl]ethyl]-1,3-thiazole-2-carboxamide;hydrochloride	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.0940	uM
N-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methyl]-7-[2-(pyridine-3-carbonylamino)ethyl]-7-azaspiro[3.5]nonane-2-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.1100	uM
N-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methyl]-7-[2-(furan-2-carbonylamino)ethyl]-7-azaspiro[3.5]nonane-2-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.1100	uM
N-[2-[2-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methylcarbamoyl]-7-azaspiro[3.5]nonan-7-yl]ethyl]-1,3-thiazole-4-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.1100	uM
N-[2-[2-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methylcarbamoyl]-7-azaspiro[3.5]nonan-7-yl]ethyl]-1,3-thiazole-2-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.1200	uM
N-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methyl]-7-[2-(thiophene-2-carbonylamino)ethyl]-7-azaspiro[3.5]nonane-2-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.1400	uM
N-[2-[2-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methylcarbamoyl]-7-azaspiro[3.5]nonan-7-yl]ethyl]-1,3-thiazole-5-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.1600	uM
N-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methyl]-7-[2-(pyridine-4-carbonylamino)ethyl]-7-azaspiro[3.5]nonane-2-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.1700	uM
N-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methyl]-7-[2-[(4-fluorobenzoyl)amino]ethyl]-7-azaspiro[3.5]nonane-2-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.1800	uM
N-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methyl]-7-[2-[(2-fluoropyridine-4-carbonyl)amino]ethyl]-7-azaspiro[3.5]nonane-2-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.1800	uM
N-[2-[2-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methylcarbamoyl]-7-azaspiro[3.5]nonan-7-yl]ethyl]-1,3-oxazole-5-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.1900	uM
N-[6-[[3-(3-carbamothioylphenyl)-7-chloro-1-(1-methylsulfonylpiperidin-4-yl)indol-6-yl]methylamino]-6-oxohexyl]-3’,6’-dihydroxy-3-oxospiro[2-benzofuran-1,9’-xanthene]-5-carboxamide	2219219: Binding affinity to ASH1L SET domain (2046 to 2330 residues)(unknown origin) assessed as dissociation constant incubated for 1 hr by FP assay	ic50	0.1970	uM
N-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methyl]-7-[2-(1,3-thiazol-5-ylmethoxy)ethyl]-7-azaspiro[3.5]nonane-2-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.2100	uM
7-(2-acetamidoethyl)-N-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methyl]-7-azaspiro[3.5]nonane-2-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.2200	uM
N-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methyl]-7-[2-(3,3,3-trifluoropropanoylamino)ethyl]-7-azaspiro[3.5]nonane-2-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.2600	uM
N-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methyl]-7-(2-cyclobutyloxyethyl)-7-azaspiro[3.5]nonane-2-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.2800	uM
N-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methyl]-7-[2-(furan-2-ylmethoxy)ethyl]-7-azaspiro[3.5]nonane-2-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.3100	uM
N-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methyl]-7-[2-(pyridin-4-ylmethoxy)ethyl]-7-azaspiro[3.5]nonane-2-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.3100	uM
N-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methyl]-7-[2-(cyclopentanecarbonylamino)ethyl]-7-azaspiro[3.5]nonane-2-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.3100	uM
N-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methyl]-7-[2-(3-propoxypropanoylamino)ethyl]-7-azaspiro[3.5]nonane-2-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.3100	uM
N-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methyl]-7-[2-[(2,2,2-trifluoroacetyl)amino]ethyl]-7-azaspiro[3.5]nonane-2-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.3200	uM
N-[2-[2-[[3-(3-carbamothioylphenyl)-1-(oxan-4-yl)indol-6-yl]methylcarbamoyl]-7-azaspiro[3.5]nonan-7-yl]ethyl]-1,3-thiazole-2-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.3800	uM
N-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methyl]-7-[2-(1,3-thiazol-5-yl)ethyl]-7-azaspiro[3.5]nonane-2-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.3900	uM
N-[[3-(3-carbamothioylphenyl)-1-(1-methylsulfonylpiperidin-4-yl)indol-6-yl]methyl]-2-(1H-imidazol-5-yl)acetamide	2219219: Binding affinity to ASH1L SET domain (2046 to 2330 residues)(unknown origin) assessed as dissociation constant incubated for 1 hr by FP assay	ic50	0.4390	uM
N-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methyl]-7-[2-(pyridin-2-ylmethoxy)ethyl]-7-azaspiro[3.5]nonane-2-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.4700	uM
N-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methyl]-2-[2-(1,3-thiazol-5-ylmethoxy)ethyl]-2-azaspiro[3.3]heptane-6-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.4900	uM
N-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methyl]-7-[2-(thiophen-2-ylmethoxy)ethyl]-7-azaspiro[3.5]nonane-2-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.5000	uM
N-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methyl]-7-[3-(4-fluoroanilino)-3-oxopropyl]-7-azaspiro[3.5]nonane-2-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.5300	uM
N-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methyl]-7-azaspiro[3.5]nonane-2-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.5400	uM
N-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methyl]-7-[2-(oxolane-2-carbonylamino)ethyl]-7-azaspiro[3.5]nonane-2-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.5500	uM
7-(2-butoxyethyl)-N-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methyl]-7-azaspiro[3.5]nonane-2-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.5600	uM
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
2-(2-butoxyethyl)-N-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methyl]-2-azaspiro[3.3]heptane-6-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.6100	uM
N-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methyl]-2-azaspiro[3.3]heptane-6-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.6400	uM
N-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methyl]-7-[2-(cyclobutylmethoxy)ethyl]-7-azaspiro[3.5]nonane-2-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.7500	uM
N-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methyl]-2-[2-(cyclobutylmethoxy)ethyl]-2-azaspiro[3.3]heptane-6-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.7700	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
N-[[3-(3-carbamothioylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methyl]-7-[2-[2-(1-methylcyclopropyl)ethoxy]ethyl]-7-azaspiro[3.5]nonane-2-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	0.8100	uM
N-[[3-(3-carbamothioylphenyl)-1-(1-methylsulfonylpiperidin-4-yl)indol-6-yl]methyl]-2-azaspiro[3.3]heptane-6-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	1.7000	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
N-[2-[2-[[3-(3-carbamoylphenyl)-7-chloro-1-(oxan-4-yl)indol-6-yl]methylcarbamoyl]-7-azaspiro[3.5]nonan-7-yl]ethyl]-1,3-thiazole-2-carboxamide	2219221: Inhibition of ASH1L SET domain (2046 to 2330 residues)(unknown origin) incubated for 1 hr by FP assay	ic50	8.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	5
Benzo(a)pyrene	increases methylation, increases expression	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	affects binding, increases reaction	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
Air Pollutants	increases expression, increases abundance	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
Ozone	increases abundance, increases expression	1
Plant Extracts	increases 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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 204 trials:

NCT	Phase	Status	Title
NCT05657860	Phase 4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	Phase 4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	Phase 4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	Phase 4	RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	Phase 3	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	Phase 2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	Phase 2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	Phase 2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	Phase 2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	Phase 1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	Phase 1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	Phase 1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	Phase 1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	Phase 1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	Phase 2/3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	Phase 1/2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	Early Phase 1	TERMINATED	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
NCT02862808	Not specified	COMPLETED	Molecular Diagnosis of Syndromic or Isolated Severe Intellectual Disability Using Whole Exome Sequencing : a Pilot Study
NCT02881333	Not specified	UNKNOWN	Various Type of Genetic Events in Patients With Intellectual Disability
NCT02889068	Not specified	COMPLETED	Targeted Next Generation Sequencing and Intellectual Disability
NCT02914951	Not specified	ENROLLING_BY_INVITATION	Cognitive-Behavioral Therapy for Irritability in Children With Autism Spectrum Disorder and Intellectual Disability
NCT02919826	Not specified	COMPLETED	Dialectical Behaviour Group Therapy for Adults With Intellectual Disabilities
NCT02934854	Not specified	WITHDRAWN	Biomarker for Creatine Deficiency Syndromes (BioCDS)
NCT03033797	Not specified	UNKNOWN	Augmentative and Alternative Communication in Games With Virtual Reality in Intellectual Disabilities
NCT03135236	Not specified	COMPLETED	Parents as the Primary Sexuality Educators for Their Young Adults With Down Syndrome
NCT03139760	Not specified	COMPLETED	POWERSforID: A Telehealth Weight Management System for Adults With Intellectual Disability
NCT03203226	Not specified	COMPLETED	The Feldenkrais Method for People With Intellectual Disability
NCT03212092	Not specified	COMPLETED	Reducing Aggression Among People With an Intellectual Disability
NCT03218462	Not specified	COMPLETED	Effect of Sensory Adapted Dental Environment on Dental Anxiety of Children With Intellectual and Developmental Disabilities
NCT03234231	Not specified	UNKNOWN	Supervised Brushing Programme for Intellectual Disabled Students
NCT03348124	Not specified	UNKNOWN	Prevention Among Young People With Intellectual Disability
NCT03424772	Not specified	UNKNOWN	Whole Genome Sequencing in the Detection of Rare Undiagnosed Genetic Diseases in Children in China
NCT03426059	Not specified	COMPLETED	Mapping the Phenotype in Adults With Phelan-McDermid Syndrome
NCT03492060	Not specified	RECRUITING	Longitudinal Study of Neurogenetic Disorders
NCT03501914	Not specified	COMPLETED	A Pilot Trial of Mindfulness Based Intervention Program for People With Intellectual Disabilities in a Low Income Setting
NCT03522337	Not specified	COMPLETED	Oral Health Promotion Among Preschool Children With Special Needs
NCT03525431	Not specified	COMPLETED	Clinical Utility of Pediatric Whole Exome Sequencing

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for ASH1L across ~30M SureChEMBL compounds — explore on Sugi Predict.