CHD8

Summary

CHD8 (chromodomain helicase DNA binding protein 8, HGNC:20153) is a protein-coding gene on chromosome 14q11.2, encoding ATP-dependent chromatin remodeler CHD8 (Q9HCK8). ATP-dependent chromatin-remodeling factor, it slides nucleosomes along DNA; nucleosome sliding requires ATP. It is a selective cancer dependency (DepMap: 20.2% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a member of the chromodomain-helicase-DNA binding protein family, which is characterized by a SNF2-like domain and two chromatin organization modifier domains. The encoded protein also contains brahma and kismet domains, which are common to the subfamily of chromodomain-helicase-DNA binding proteins to which this protein belongs. This gene has been shown to function in several processes that include transcriptional regulation, epigenetic remodeling, promotion of cell proliferation, and regulation of RNA synthesis. Allelic variants of this gene are associated with autism spectrum disorder. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 57680 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 1,878 total — 139 pathogenic, 76 likely-pathogenic
• Phenotypes (HPO): 97
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 20.2% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 15 downstream targets (CollecTRI)
• MANE Select transcript: NM_001170629

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20153
Approved symbol	CHD8
Name	chromodomain helicase DNA binding protein 8
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1564, DUPLIN
Ensembl gene	ENSG00000100888
Ensembl biotype	protein_coding
OMIM	610528
Entrez	57680

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 15 protein_coding, 10 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000430710, ENST00000553283, ENST00000553622, ENST00000553651, ENST00000553870, ENST00000554384, ENST00000555301, ENST00000555935, ENST00000555962, ENST00000556833, ENST00000557329, ENST00000557364, ENST00000557727, ENST00000642518, ENST00000642914, ENST00000643048, ENST00000643469, ENST00000645140, ENST00000645206, ENST00000645929, ENST00000646063, ENST00000646340, ENST00000646558, ENST00000646647, ENST00000864429, ENST00000934460, ENST00000934461

RefSeq mRNA: 2 — MANE Select: NM_001170629 NM_001170629, NM_020920

CCDS: CCDS45081, CCDS53885

Canonical transcript exons

ENST00000646647 — 38 exons

Exon	Start	End
ENSE00000653222	21400875	21401071
ENSE00000653232	21414301	21414418
ENSE00000653233	21414938	21414993
ENSE00000653240	21415574	21415642
ENSE00000653248	21415725	21415907
ENSE00000889091	21394912	21395119
ENSE00000889094	21400413	21400612
ENSE00000889097	21406856	21407032
ENSE00000889098	21408312	21408555
ENSE00000889099	21408704	21408825
ENSE00000940587	21412913	21412996
ENSE00001096823	21392507	21392809
ENSE00001096825	21391833	21391946
ENSE00001096832	21391463	21391642
ENSE00001096834	21393106	21393254
ENSE00001096837	21394277	21394485
ENSE00001096840	21390947	21391063
ENSE00001096842	21393476	21394195
ENSE00001207501	21403453	21403663
ENSE00001207619	21401403	21401513
ENSE00001418360	21426128	21426242
ENSE00001422532	21427869	21428254
ENSE00001424069	21428964	21429335
ENSE00001673287	21405721	21405864
ENSE00001737016	21405209	21405464
ENSE00001739488	21403017	21403212
ENSE00002446410	21430801	21431858
ENSE00003488804	21395298	21395352
ENSE00003505651	21395817	21395892
ENSE00003554772	21397823	21397952
ENSE00003567094	21401957	21402136
ENSE00003577915	21399602	21399705
ENSE00003594715	21409851	21409988
ENSE00003665557	21402336	21402503
ENSE00003688540	21400151	21400307
ENSE00003694144	21399981	21400070
ENSE00003830160	21385199	21386176
ENSE00003897064	21456032	21456123

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 97.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.4318 / max 215.6569, expressed in 1805 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
142169	12.3299	1785
142167	2.9041	1458
142168	2.1977	1340

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	97.06	gold quality
ventricular zone	UBERON:0003053	95.44	gold quality
cortical plate	UBERON:0005343	94.28	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.08	gold quality
cerebellar hemisphere	UBERON:0002245	94.04	gold quality
cerebellar cortex	UBERON:0002129	94.02	gold quality
granulocyte	CL:0000094	93.90	gold quality
cerebellum	UBERON:0002037	93.74	gold quality
ganglionic eminence	UBERON:0004023	93.37	gold quality
skin of leg	UBERON:0001511	93.29	gold quality
lower esophagus mucosa	UBERON:0035834	93.13	gold quality
skin of abdomen	UBERON:0001416	93.06	gold quality
colonic epithelium	UBERON:0000397	92.67	gold quality
adenohypophysis	UBERON:0002196	92.48	gold quality
pituitary gland	UBERON:0000007	92.17	gold quality
spleen	UBERON:0002106	91.99	gold quality
calcaneal tendon	UBERON:0003701	91.89	gold quality
mucosa of transverse colon	UBERON:0004991	91.54	gold quality
bone marrow cell	CL:0002092	91.52	gold quality
zone of skin	UBERON:0000014	91.51	gold quality
nipple	UBERON:0002030	91.50	gold quality
right frontal lobe	UBERON:0002810	91.44	gold quality
secondary oocyte	CL:0000655	91.27	gold quality
adrenal tissue	UBERON:0018303	91.14	gold quality
right uterine tube	UBERON:0001302	91.12	gold quality
right lobe of thyroid gland	UBERON:0001119	90.94	gold quality
right ovary	UBERON:0002118	90.89	gold quality
paraflocculus	UBERON:0005351	90.80	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.79	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.63	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.15

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

15 targets.

Target	Regulation
ASCL1	Repression
BRCA1	Unknown
CCNE2	Activation
DCX	Repression
HOXA2	Unknown
MAP2	Repression
MYC	Unknown
NEFM	Repression
NEUROD4	Repression
NEUROG1	Repression
SOX11	Repression
SOX2	Repression
SOX3	Repression
SOX7	Repression
TYMS	Unknown

Upstream regulators (CollecTRI, top): GLI3, KMT2A

miRNA regulators (miRDB)

39 targeting CHD8, 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-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-365A-3P	99.43	70.02	836
HSA-MIR-365B-3P	99.43	70.02	836
HSA-MIR-4480	99.42	66.02	735
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-1843	98.97	66.07	838
HSA-MIR-4802-5P	98.97	66.26	833
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-7114-5P	98.51	67.87	1349
HSA-MIR-541-5P	98.24	67.77	1181
HSA-MIR-6801-3P	98.04	64.64	805
HSA-MIR-6810-3P	97.96	64.57	1023
HSA-MIR-3159	97.94	66.79	1098
HSA-MIR-7111-3P	97.80	66.75	1467
HSA-MIR-6783-5P	97.67	67.21	1528
HSA-MIR-4723-3P	97.67	65.91	1017
HSA-MIR-4640-5P	97.42	66.33	1543
HSA-MIR-6769B-3P	97.41	65.53	1036
HSA-MIR-3183	97.40	65.68	978

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 20.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Staf activates U6 transcription from a preassembled chromatin template in vitro and associates with several proteins linked to chromatin modification, among them chromodomain-helicase-DNA binding protein 8 (CHD8). (PMID:17938208)
• CHD8 is an ATP-dependent chromatin remodeling factor that regulates beta-catenin target genes (PMID:18378692)
• CHD8 interacts with elongating RNA polymerase II and controls expression of CCNE2 and TYMS genes. (PMID:19255092)
• Results show that Depletion of CHD8 enhances HOXA2 expression and a loss of the WDR5/Ash2L/RbBP5 subcomplex. (PMID:20085832)
• This study provides evidence of a novel interaction between BRCA1 and beta-catenin, and that loss of BRCA1 leads to impaired expression of the nuclear form of beta-catenin, which may contribute to the pathogenesis of breast cancer. (PMID:20215423)
• The recruitment of AR to the TMPRSS2 promoter in response to androgen treatment requires CHD8. (PMID:20308527)
• Disruption of the direct CHD7-CHD8 interaction might chang the conformation of a putative large complex and could be a disease mechanism in CHARGE syndrome. (PMID:20453063)
• CHD8 promotes the association of beta-catenin and histone H1, with formation of the trimeric complex on chromatin being required for inhibition of beta-catenin-dependent transactivation. (PMID:22083958)
• results from de novo events and a large parallel case-control study provide strong evidence in favour of CHD8 and KATNAL2 as genuine autism risk factors (PMID:22495311)
• Loss of CHD8 expression is associated with aggressiveness in gastric cancer. (PMID:23835524)
• Genes that regulate chromatin were mutated in CpG island methylator phenotype 1 colorectal carcinoma; the highest rates of mutation were observed in CHD7 and CHD8. (PMID:24211491)
• CHD8 is required for E2F-dependent transcription activation of S-phase genes (PMID:24265227)
• indings suggest that CHD8 disruptions represent a specific pathway in the development of Autism spectrum disorder (ASD) and define a distinct ASD subtype. Common phenotypic features include increased head size; a facial phenotype marked by prominent forehead, wide-set eyes, and pointed chin; as well as increased rates of GI complaints and marked sleep dysfunction. (PMID:24998929)
• Recurrent approximately 100 Kb microdeletion in the chromosomal region 14q11.2, involving CHD8 gene, is associated with autism and macrocephaly. (PMID:25257502)
• CHD8 precipitates a network of gene-expression changes involved in neurodevelopmental pathways in which many autism spectrum disorder-associated genes may converge on shared mechanisms of pathogenesis (PMID:25294932)
• In the first detailed analysis in cancer, a marked loss of CHD8 expression and increased BORIS/CTCF ratio indicate frequent disruption of CTCF and its effector genes in PCa. (PMID:25499215)
• Loss of CHD8 contributes to autism spectrum disorder by perturbing an ancient gene regulatory network during human brain development. (PMID:25752243)
• Taken together our data demonstrate that CHD8 is involved in late stages of progesterone receptor enhancers activation. (PMID:25894978)
• CHD8 insufficiency results in altered gene expression of coding genes and noncoding RNAs. The changes among protein-coding genes involved genes that are enriched in neuronal development and in previously identified autism candidate genes. (PMID:25989142)
• Study provides evidence that links the CHD8 chromatin remodeler to the cancer maintenance functions of BRD4 and NSD3. (PMID:26626481)
• Review of 16 other CHD8 mutation cases suggests that clinical features and their severity vary considerably across individuals; however, these data support a CHD8 mutation syndrome, further highlighting the importance of genomic medicine to guide clinical assessment and treatment (PMID:26789910)
• present observation and published data suggest that phenotype present in patients with duplication of 14q11.2 region, encompassing the SUPT16H and CHD8 genes, resemble in some extend features described in cases carrying microdeletion of that genomic region (PMID:26834018)
• Our clinical case supports the hypothesis that CHD8 may play a central role in neuronal cell development and Autism spectrum disorders risk (PMID:26921529)
• SHANK3, CHD8, and ADNP had distinctly higher scores than all other genes in the dataset describing the genes associated with autism spectrum disorders. (PMID:27790361)
• Data suggest that CHD6 and CHD7 both bind with high affinity to short linker DNA, whereas CHD8 requires longer DNA for binding; thus, CHD8 slides nucleosomes into positions with more flanking linker DNA than CHD7; CHD6 disrupts nucleosomes in a distinct non-sliding manner. (PMID:28533432)
• rare CNVR at 14q11 encompassing the chromatin modifier CHD8 was significantly associated with sporadic CRC risk. Copy number loss at CHD8 altered expressions of genes implicated in colorectal tumourigenesis. (PMID:29079706)
• The Autism spectrum disorder candidate genes SATB2, CHD8 and EHMT1 show enriched expression in neurons, especially inhibitory neurons (PMID:29317598)
• We suggested that this constituted a new multiple congenital anomaly-intellectual disability syndrome due to defects in CHD8 and/or SUPT16H..The identification of multiple patients with the same genetic defect and characteristic clinical phenotype, confirms our suggestion that this is a syndromic disorder caused by haploinsufficiency or heterozygous loss of function of CHD8. (PMID:30670789)
• Our study shows that haploinsufficiency of CHD8 is associated with a distinctive OGID syndrome with pronounced autistic traits and supports a sex-dependent penetrance of CHD8 PTVs in humans. (PMID:31001818)
• Clinical Phenotypes of Carriers of Mutations in CHD8 or Its Conserved Target Genes. (PMID:31526516)
• CHD8 causes an overgrowth phenotype, and should be considered in the differential diagnosis of patients presenting with increased height and/or head circumference in association with intellectual disability (PMID:31721432)
• De Novo Damaging DNA Coding Mutations Are Associated With Obsessive-Compulsive Disorder and Overlap With Tourette’s Disorder and Autism. (PMID:31771860)
• Neurodevelopmental phenotype associated with CHD8-SUPT16H duplication. (PMID:31823155)
• this study adds to the ASD-associated loss-of-function mutations in CHD8 and highlights the clinical importance of the HELIC domain of CHD8. (PMID:31980904)
• Oligodendrocyte dysfunction due to Chd8 mutation gives rise to behavioral deficits in mice. (PMID:32142125)
• The human chd8 gene is transcribed from two distant upstream promoters. (PMID:32854944)
• Heterozygous nonsense variant of CHD8 in a patient with forme-fruste Marfan syndrome and intellectual disability. (PMID:32951261)
• High glucose-ROS conditions enhance the progression in cholangiocarcinoma via upregulation of MAN2A2 and CHD8. (PMID:33141432)
• Childhood-onset progressive dystonia associated with pathogenic truncating variants in CHD8. (PMID:34415117)
• The Mechanisms of CHD8 in Neurodevelopment and Autism Spectrum Disorders. (PMID:34440307)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	chd8	ENSDARG00000075543
mus_musculus	Chd8	ENSMUSG00000053754
rattus_norvegicus	Chd8	ENSRNOG00000025011

Paralogs (30): HLTF (ENSG00000071794), SMARCA2 (ENSG00000080503), SRCAP (ENSG00000080603), ATRX (ENSG00000085224), RAD54L (ENSG00000085999), BTAF1 (ENSG00000095564), SMARCA1 (ENSG00000102038), CHD4 (ENSG00000111642), CHD5 (ENSG00000116254), TTF2 (ENSG00000116830), HELLS (ENSG00000119969), ZRANB3 (ENSG00000121988), CHD6 (ENSG00000124177), SMARCA4 (ENSG00000127616), INO80 (ENSG00000128908), CHD1L (ENSG00000131778), SMARCAL1 (ENSG00000138375), SHPRH (ENSG00000146414), SMARCA5 (ENSG00000153147), CHD1 (ENSG00000153922), SMARCAD1 (ENSG00000163104), RAD54L2 (ENSG00000164080), CHD3 (ENSG00000170004), CHD7 (ENSG00000171316), CHD2 (ENSG00000173575), CHD9 (ENSG00000177200), EP400 (ENSG00000183495), ERCC6L (ENSG00000186871), RAD54B (ENSG00000197275), ERCC6 (ENSG00000225830)

Protein

Protein identifiers

ATP-dependent chromatin remodeler CHD8 — Q9HCK8 (reviewed: Q9HCK8)

Alternative names: Chromo domain-containing protein 8

All UniProt accessions (9): Q9HCK8, A0A2R8Y4P3, A0A2R8Y808, A0A2R8Y840, A0A2R8YFI9, A0A2R8YFT4, G3V303, H0YJA4, H0YJG4

UniProt curated annotations — full annotation on UniProt →

Function. ATP-dependent chromatin-remodeling factor, it slides nucleosomes along DNA; nucleosome sliding requires ATP. Acts as a transcription repressor by remodeling chromatin structure and recruiting histone H1 to target genes. Suppresses p53/TP53-mediated apoptosis by recruiting histone H1 and preventing p53/TP53 transactivation activity. Acts as a negative regulator of Wnt signaling pathway by regulating beta-catenin (CTNNB1) activity. Negatively regulates CTNNB1-targeted gene expression by being recruited specifically to the promoter regions of several CTNNB1 responsive genes. Involved in both enhancer blocking and epigenetic remodeling at chromatin boundary via its interaction with CTCF. Acts as a suppressor of STAT3 activity by suppressing the LIF-induced STAT3 transcriptional activity. Also acts as a transcription activator via its interaction with ZNF143 by participating in efficient U6 RNA polymerase III transcription. Regulates alternative splicing of a core group of genes involved in neuronal differentiation, cell cycle and DNA repair. Enables H3K36me3-coupled transcription elongation and co-transcriptional RNA processing likely via interaction with HNRNPL.

Subunit / interactions. Interacts with p53/TP53, histone H1, CTNNB1, CTCF and PIAS3. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BACC1, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Interacts with CHD7. Interacts with FAM124B. Interacts with TLK2. Interacts with HNRNPL in an RNA-dependent manner.

Subcellular location. Nucleus.

Post-translational modifications. Sumoylated.

Disease relevance. Intellectual developmental disorder with autism and macrocephaly (IDDAM) [MIM:615032] An autosomal dominant disorder characterized by impaired intellectual development, a highly penetrant autism spectrum phenotype, and macrocephaly. Other common features include tall stature, gastrointestinal symptoms, distinct facial features, sleep problems, and attention problems. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Miscellaneous. Its gene is located in the 14q11.2 region of the genome which is associated with developmental delay, cognitive impairment and similar minor anomalies in some children, suggesting that it may be a good candidate for the phenotype.

Similarity. Belongs to the SNF2/RAD54 helicase family. CHD8 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9HCK8-1	1	yes
Q9HCK8-2	2

RefSeq proteins (2): NP_001164100, NP_065971 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000330	SNF2_N	Domain
IPR000953	Chromo/chromo_shadow_dom	Domain
IPR001650	Helicase_C-like	Domain
IPR006576	BRK_domain	Domain
IPR014001	Helicase_ATP-bd	Domain
IPR016197	Chromo-like_dom_sf	Homologous_superfamily
IPR023780	Chromo_domain	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR034724	CHD8	Family
IPR037259	BRK_sf	Homologous_superfamily
IPR038718	SNF2-like_sf	Homologous_superfamily
IPR049730	SNF2/RAD54-like_C	Domain
IPR051493	CHD	Family
IPR056342	HTH_CHD6-9	Domain

Pfam: PF00176, PF00271, PF00385, PF07533, PF23078

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (72 total): modified residue 22, compositionally biased region 15, region of interest 10, domain 4, sequence conflict 4, cross-link 3, strand 3, helix 3, sequence variant 2, chain 1, short sequence motif 1, binding site 1, splice variant 1, mutagenesis site 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2CKA	SOLUTION NMR
2DL6	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HCK8-F1	55.17	0.06

Functional residue map

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

Ligand- & substrate-binding residues (1): 836–843

Post-translational modifications (25): 432, 553, 562, 1420, 1424, 1976, 1978, 1993, 1995, 2008, 2046, 2051, 2069, 2071, 2182, 2200, 2202, 2204, 2211, 2215 …

Mutagenesis-validated functional residues (1):

Position	Phenotype
842	abolishes atpase activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-3769402	Deactivation of the beta-catenin transactivating complex
R-HSA-9943962	CHD6, CHD7, CHD8, CHD9 subfamily

MSigDB gene sets: 370 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_BEHAVIOR, GOZGIT_ESR1_TARGETS_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_TRANSCRIPTION_BY_RNA_POLYMERASE_III, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_1, GOBP_STARTLE_RESPONSE, GOBP_DIGESTIVE_SYSTEM_DEVELOPMENT, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_PREPULSE_INHIBITION, GOBP_BIOLOGICAL_PROCESS_INVOLVED_IN_INTRASPECIES_INTERACTION_BETWEEN_ORGANISMS, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_TRANS, GOBP_HEAD_DEVELOPMENT

GO Biological Process (19): negative regulation of transcription by RNA polymerase II (GO:0000122), in utero embryonic development (GO:0001701), chromatin remodeling (GO:0006338), mRNA processing (GO:0006397), brain development (GO:0007420), Wnt signaling pathway (GO:0016055), social behavior (GO:0035176), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of transcription by RNA polymerase III (GO:0045945), digestive tract development (GO:0048565), prepulse inhibition (GO:0060134), negative regulation of canonical Wnt signaling pathway (GO:0090090), negative regulation of fibroblast apoptotic process (GO:2000270), startle response (GO:0001964), chromatin organization (GO:0006325), negative regulation of Wnt signaling pathway (GO:0030178), negative regulation of apoptotic process (GO:0043066)

GO Molecular Function (15): p53 binding (GO:0002039), DNA binding (GO:0003677), DNA helicase activity (GO:0003678), chromatin binding (GO:0003682), ATP binding (GO:0005524), beta-catenin binding (GO:0008013), ATP hydrolysis activity (GO:0016887), histone binding (GO:0042393), histone H3K4me3 reader activity (GO:0140002), ATP-dependent chromatin remodeler activity (GO:0140658), nucleotide binding (GO:0000166), helicase activity (GO:0004386), protein binding (GO:0005515), ATP-dependent activity, acting on DNA (GO:0008094), hydrolase activity (GO:0016787)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), protein-containing complex (GO:0032991), MLL1 complex (GO:0071339)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
TCF dependent signaling in response to WNT	1
CHD chromatin remodelers	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	3
ATP-dependent activity	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
DNA-templated transcription	2
regulation of DNA-templated transcription	2
positive regulation of DNA-templated transcription	2
ATP-dependent activity, acting on DNA	2
binding	2
cellular anatomical structure	2
negative regulation of DNA-templated transcription	1
chordate embryonic development	1
chromatin organization	1
RNA processing	1
mRNA metabolic process	1
central nervous system development	1
animal organ development	1
head development	1
cell surface receptor signaling pathway	1
behavior	1
biological process involved in intraspecies interaction between organisms	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
regulation of transcription by RNA polymerase III	1
transcription by RNA polymerase III	1
tube development	1
digestive system development	1
startle response	1
negative regulation of response to external stimulus	1
negative regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
negative regulation of apoptotic process	1
fibroblast apoptotic process	1
regulation of fibroblast apoptotic process	1
response to external stimulus	1
neuromuscular process	1
cellular component organization	1
negative regulation of signal transduction	1
Wnt signaling pathway	1

Protein interactions and networks

STRING

4240 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHD8	CHD7	Q9P2D1	912
CHD8	CTCF	P49711	904
CHD8	CTNNB1	P35222	873
CHD8	BRD4	O60885	862
CHD8	MAFG	O15525	826
CHD8	DNMT3B	Q9UBC3	792
CHD8	PTK6	Q13882	782
CHD8	FAM124B	Q9H5Z6	760
CHD8	ZNF143	P52747	745
CHD8	WDR5	P61964	735
CHD8	CHD1	O14646	696
CHD8	SCN2A	Q99250	696
CHD8	KATNAL2	Q8IYT4	677
CHD8	ADNP	Q9H2P0	667
CHD8	SUPT16H	Q9Y5B9	660

IntAct

142 interactions, top by confidence:

A	B	Type	Score
PSMC3	PSMD9	psi-mi:“MI:0914”(association)	0.940
TLK2	DYNLL1	psi-mi:“MI:0914”(association)	0.890
KPNA6	RNMT	psi-mi:“MI:0914”(association)	0.800
HSPB2	BAG3	psi-mi:“MI:0914”(association)	0.670
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
PSMC3	PSMD12	psi-mi:“MI:0914”(association)	0.640
YAF2	E2F6	psi-mi:“MI:0914”(association)	0.640
IKZF5	CCNB1	psi-mi:“MI:0914”(association)	0.640
CHD8	WDR5	psi-mi:“MI:0914”(association)	0.620
CHD8	WDR5	psi-mi:“MI:0915”(physical association)	0.620
YY1	YY2	psi-mi:“MI:0914”(association)	0.570
KPNB1	POM121C	psi-mi:“MI:0914”(association)	0.530
NFATC2IP	ZNHIT1	psi-mi:“MI:0914”(association)	0.530
ZBTB7A	CHD8	psi-mi:“MI:0915”(physical association)	0.510
CHD8	ACOT7	psi-mi:“MI:0914”(association)	0.500
ACOT7	CHD8	psi-mi:“MI:0915”(physical association)	0.500
RBBP5	CHD8	psi-mi:“MI:0915”(physical association)	0.500
CHD8	ASH2L	psi-mi:“MI:0915”(physical association)	0.500
CHD8	CTCF	psi-mi:“MI:0915”(physical association)	0.460
CHD8	CTCF	psi-mi:“MI:0403”(colocalization)	0.460
CTCF	CHD8	psi-mi:“MI:0403”(colocalization)	0.460
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410

BioGRID (409): CHD8 (Affinity Capture-RNA), CHD8 (Affinity Capture-MS), CHD8 (Affinity Capture-MS), CHD8 (Affinity Capture-MS), CHD8 (Affinity Capture-MS), CHD8 (Affinity Capture-MS), CHD8 (Affinity Capture-MS), CHD8 (Affinity Capture-MS), CHD8 (Co-fractionation), CHD8 (Co-fractionation), CHD8 (Proximity Label-MS), CDC27 (Affinity Capture-MS), KPNA1 (Affinity Capture-MS), UHRF1BP1L (Affinity Capture-MS), KPNA6 (Affinity Capture-MS)

ESM2 similar proteins: A1Z9E2, B0R0I6, B5DE69, G5ED89, O94842, P25425, P32519, P34333, P34447, Q02086, Q08CM4, Q09XV5, Q0IHV2, Q0P5K4, Q0V9U1, Q15723, Q28BL7, Q3TUF7, Q571G4, Q5E9U0, Q5F3U0, Q5R6A9, Q5RBN8, Q5RCV7, Q60775, Q641Z1, Q6DJM6, Q6IQU7, Q6MZP7, Q7Z589, Q7ZUV7, Q7ZX03, Q86NP2, Q8AYC1, Q8BIH0, Q8BMB0, Q8BU11, Q8CHI8, Q8IRW8, Q8WNV2

Diamond homologs: A0A0P0WGX7, A2A8L1, A2BGR3, A3KFM7, A6QQR4, A7Z019, A9X4T1, B0R0I6, B0XPE7, B3NAN8, B4GS98, B5BT18, B5DE69, B6ZLK2, D3Z9Z9, D3ZA12, D3ZD32, E1B7X9, F1Q8K0, F4I2H2, F4IV45, F4J9M5, F4JY24, F4K128, F4KBP5, F8VPZ5, G5EBZ4, G5EF53, O12944, O13682, O14139, O14646, O14981, O43065, O76460, P0CO16, P0CO17, P28370, P31380, P32333

SIGNOR signaling

15 interactions.

A	Effect	B	Mechanism
CHD8	down-regulates	CTNNB1	binding
CHD8	“up-regulates quantity by expression”	CCNE2	“transcriptional regulation”
CHD8	“up-regulates quantity by expression”	TYMS	“transcriptional regulation”
CHD8	“up-regulates activity”	“RNA Polymerase II”	binding
CHD8	“up-regulates activity”	“MLL/SET subcomplex”	binding
CHD8	“down-regulates quantity”	ASCL1	“transcriptional regulation”
CHD8	“down-regulates quantity”	DCX	“transcriptional regulation”
CHD8	“down-regulates quantity”	MAP2	“transcriptional regulation”
CHD8	“down-regulates quantity”	NEFM	“transcriptional regulation”
CHD8	“down-regulates quantity”	NEUROD4	“transcriptional regulation”
CHD8	“down-regulates quantity”	NEUROG1	“transcriptional regulation”
CHD8	“down-regulates quantity”	SOX3	“transcriptional regulation”
CHD8	“down-regulates quantity”	SOX2	“transcriptional regulation”
CHD8	“down-regulates quantity”	SOX7	“transcriptional regulation”
CHD8	“down-regulates quantity”	SOX11	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 169 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
NS1 Mediated Effects on Host Pathways	6	14.9×	2e-04
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	5	13.1×	1e-03
Influenza Infection	8	12.2×	2e-05
Maturation of DENV proteins	6	11.0×	6e-04
SARS-CoV-1-host interactions	7	10.7×	2e-04
mRNA Splicing	11	10.5×	8e-07
Antimicrobial mechanism of IFN-stimulated genes	6	10.3×	9e-04
SPOP-mediated proteasomal degradation of PD-L1(CD274)	5	9.9×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
NLS-bearing protein import into nucleus	6	33.7×	2e-05
transcription initiation-coupled chromatin remodeling	5	13.4×	5e-03
mRNA transcription by RNA polymerase II	5	11.6×	8e-03
protein import into nucleus	9	9.1×	2e-04
mRNA splicing, via spliceosome	11	7.0×	1e-04
chromatin remodeling	11	5.6×	8e-04
mRNA processing	9	5.0×	9e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

1878 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	139
Likely pathogenic	76
Uncertain significance	835
Likely benign	535
Benign	83

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1048638	NM_001170629.2(CHD8):c.3331_3332del (p.Glu1111fs)	Pathogenic
1064594	NM_001170629.2(CHD8):c.3308-1G>C	Pathogenic
1075073	NC_000014.8:g.(?21756136)(22005055_?)del	Pathogenic
1075533	NM_001170629.2(CHD8):c.1444C>T (p.Arg482Ter)	Pathogenic
1172605	NM_001170629.2(CHD8):c.5061del (p.Phe1687fs)	Pathogenic
1201424	NM_001170629.2(CHD8):c.4429C>T (p.Arg1477Ter)	Pathogenic
1212794	NM_001170629.2(CHD8):c.4210C>T (p.Gln1404Ter)	Pathogenic
1213586	NM_001170629.2(CHD8):c.1951C>T (p.Arg651Trp)	Pathogenic
1216758	NM_001170629.2(CHD8):c.4800del (p.Gly1602fs)	Pathogenic
1297051	NM_001170629.2(CHD8):c.5646_5647del (p.Arg1882fs)	Pathogenic
1328373	NM_001170629.2(CHD8):c.4875G>A (p.Trp1625Ter)	Pathogenic
1453599	NM_001170629.2(CHD8):c.5947_5951dup (p.Leu1985fs)	Pathogenic
1685628	NM_001170629.2(CHD8):c.6002del (p.Pro2001fs)	Pathogenic
1685629	NM_001170629.2(CHD8):c.4440G>T (p.Glu1480Asp)	Pathogenic
1687035	NM_001170629.2(CHD8):c.2065G>T (p.Glu689Ter)	Pathogenic
1687036	NM_001170629.2(CHD8):c.4818-1G>A	Pathogenic
1687037	NM_001170629.2(CHD8):c.3502T>A (p.Tyr1168Asn)	Pathogenic
1699389	NM_001170629.2(CHD8):c.3308-2A>G	Pathogenic
1699404	NM_001170629.2(CHD8):c.5744del (p.Pro1915fs)	Pathogenic
1699441	NM_001170629.2(CHD8):c.3790_3796del (p.Glu1264fs)	Pathogenic
1700165	NM_001170629.2(CHD8):c.2841_2845delinsATC (p.Asp948fs)	Pathogenic
1708479	NM_001170629.2(CHD8):c.6527G>A (p.Trp2176Ter)	Pathogenic
1709073	NM_001170629.2(CHD8):c.1473_1477delinsAGGAA (p.Ser491_Val492delinsArgGly)	Pathogenic
1800961	NM_001170629.2(CHD8):c.4384C>T (p.Arg1462Ter)	Pathogenic
1802536	NM_001170629.2(CHD8):c.2025-1G>C	Pathogenic
1805207	NM_001170629.2(CHD8):c.2199_2200del (p.His734fs)	Pathogenic
1978411	NM_001170629.2(CHD8):c.5240_5243del (p.Ala1747fs)	Pathogenic
1995321	NM_001170629.2(CHD8):c.5547del (p.Phe1850fs)	Pathogenic
2004103	NM_001170629.2(CHD8):c.961del (p.Leu321fs)	Pathogenic
2011071	NM_001170629.2(CHD8):c.2532del (p.Gln845fs)	Pathogenic

SpliceAI

4746 predictions. Top by Δscore:

Variant	Effect	Δscore
14:21391064:C:CC	acceptor_gain	1.0000
14:21391828:CTCA:C	donor_loss	1.0000
14:21391830:CA:C	donor_loss	1.0000
14:21391831:A:AC	donor_gain	1.0000
14:21391832:C:CC	donor_gain	1.0000
14:21391832:CCT:C	donor_gain	1.0000
14:21392501:GCTTA:G	donor_loss	1.0000
14:21392502:CTTA:C	donor_loss	1.0000
14:21392503:TTAC:T	donor_loss	1.0000
14:21392504:TACA:T	donor_loss	1.0000
14:21392505:A:AC	donor_gain	1.0000
14:21392505:AC:A	donor_loss	1.0000
14:21392505:ACAT:A	donor_gain	1.0000
14:21392506:C:CC	donor_gain	1.0000
14:21392506:C:CG	donor_loss	1.0000
14:21392506:CA:C	donor_gain	1.0000
14:21392506:CAT:C	donor_gain	1.0000
14:21392506:CATC:C	donor_gain	1.0000
14:21392506:CATCT:C	donor_gain	1.0000
14:21392508:T:TA	donor_gain	1.0000
14:21392525:AAACT:A	donor_gain	1.0000
14:21392530:C:CA	donor_gain	1.0000
14:21392805:CGATC:C	acceptor_gain	1.0000
14:21392808:TC:T	acceptor_gain	1.0000
14:21392809:CC:C	acceptor_gain	1.0000
14:21393134:T:A	donor_gain	1.0000
14:21393474:A:AC	donor_gain	1.0000
14:21393475:C:CC	donor_gain	1.0000
14:21393475:CTTAG:C	donor_gain	1.0000
14:21393479:G:C	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000033647 (14:21387252 G>A), RS1000044155 (14:21440736 G>C,T), RS1000065547 (14:21432810 T>A), RS1000135734 (14:21430492 T>G), RS1000187163 (14:21438055 A>C,G), RS1000218545 (14:21456376 C>G), RS1000230766 (14:21445974 T>C), RS1000235150 (14:21426812 T>C), RS1000277012 (14:21450591 T>C), RS1000297745 (14:21396351 G>C), RS1000377731 (14:21394352 T>C), RS1000384707 (14:21401391 G>T), RS1000430174 (14:21388966 G>A), RS1000460739 (14:21444686 T>A), RS1000504067 (14:21433070 G>A,C,T)

Disease associations

OMIM: gene MIM:610528 | disease phenotypes: MIM:615032, MIM:608194, MIM:613826, MIM:209850, MIM:308350

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability	Strong	Autosomal dominant
intellectual developmental disorder with autism and macrocephaly	Strong	Autosomal dominant
autism	Strong	Autosomal dominant
congenital myasthenic syndrome	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Definitive	AD

Mondo (11): intellectual developmental disorder with autism and macrocephaly (MONDO:0014017), intellectual disability (MONDO:0001071), neurodevelopmental disorder (MONDO:0700092), cone-rod dystrophy 13 (MONDO:0011987), Leber congenital amaurosis 6 (MONDO:0013446), complex neurodevelopmental disorder (MONDO:0100038), autism spectrum disorder (MONDO:0005258), autism (MONDO:0005260), genetic developmental and epileptic encephalopathy (MONDO:0100062), congenital ptosis (MONDO:0008340), congenital myasthenic syndrome (MONDO:0018940)

Orphanet (8): CHD8 overgrowth syndrome (Orphanet:642675), Cone rod dystrophy (Orphanet:1872), Leber congenital amaurosis (Orphanet:65), Non-specific syndromic intellectual disability (Orphanet:528084), Rare genetic intellectual disability (Orphanet:183757), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Autism (Orphanet:106), Congenital ptosis (Orphanet:91411)

HPO phenotypes

97 total (30 of 97 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000053	Macroorchidism
HP:0000098	Tall stature
HP:0000194	Open mouth
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000303	Mandibular prognathia
HP:0000307	Pointed chin
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000336	Prominent supraorbital ridges
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000400	Macrotia
HP:0000431	Wide nasal bridge
HP:0000445	Wide nose
HP:0000494	Downslanted palpebral fissures
HP:0000508	Ptosis
HP:0000565	Esotropia
HP:0000666	Horizontal nystagmus
HP:0000709	Psychosis
HP:0000716	Depression
HP:0000717	Autism
HP:0000718	Aggressive behavior
HP:0000736	Short attention span
HP:0000739	Anxiety

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST008839_536	Height	1.000000e-26
GCST012227_599	Hip circumference adjusted for BMI	4.000000e-11
GCST90000025_526	Appendicular lean mass	1.000000e-19

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference
EFO:0004980	appendicular lean mass

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D020294	Myasthenic Syndromes, Congenital	C10.668.758.800; C16.320.590
D065886	Neurodevelopmental Disorders	F03.625
C567698	Cone-Rod Dystrophy 13 (supp.)
C565327	Leber Congenital Amaurosis 6 (supp.)
C566737	Ptosis, Hereditary Congenital 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066165 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.70	Kd	20	nM	MOLIBRESIB
7.52	IC50	30	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 7 total; 1 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179128: Binding affinity against CHD8 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases abundance	3
Benzo(a)pyrene	affects methylation, decreases methylation	2
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	increases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, affects expression, affects oxidation, increases abundance	1
lead acetate	increases expression, affects cotreatment, decreases expression	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects reaction, decreases activity, affects response to substance	1
arsenite	decreases reaction, affects binding	1
coumarin	affects phosphorylation	1
methacrylaldehyde	affects cotreatment, affects expression, affects oxidation, increases abundance	1
beta-methylcholine	affects expression	1
Decitabine	increases expression	1
Glyphosate	decreases expression	1
Acrolein	affects oxidation, increases abundance, affects cotreatment, affects expression	1
Air Pollutants	affects oxidation, increases abundance, affects cotreatment, affects expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Vehicle Emissions	decreases expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Dexamethasone	affects cotreatment, increases expression	1
Chlorpyrifos	affects response to substance	1
Indomethacin	affects cotreatment, increases expression	1
Ozone	affects cotreatment, affects expression, affects oxidation, increases abundance	1
Ribonucleotides	affects binding	1
Tretinoin	increases expression	1
1-Methyl-3-isobutylxanthine	increases expression, affects cotreatment	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697182	Binding	Inhibition of CHD8 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Cellosaurus cell lines

9 cell lines: 6 cancer cell line, 2 transformed cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B8DP	Abcam HCT 116 CHD8 KO	Cancer cell line	Male
CVCL_B9FX	Abcam A-549 CHD8 KO	Cancer cell line	Male
CVCL_C8DW	SDQLCHi051-A	Induced pluripotent stem cell	Male
CVCL_D2EE	Abcam MCF-7 CHD8 KO	Cancer cell line	Female
CVCL_D7MG	Ubigene A-549 CHD8 KO	Cancer cell line	Male
CVCL_D8IX	Ubigene HCT 116 CHD8 KO	Cancer cell line	Male
CVCL_D9BX	Ubigene HEK293 CHD8 KO	Transformed cell line	Female
CVCL_E0A5	Ubigene HeLa CHD8 KO	Cancer cell line	Female
CVCL_E1FN	Abcam HEK293 CHD8 KO	Transformed cell line	Female

Clinical trials (associated diseases)

401 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
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
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