CHD2

Summary

CHD2 (chromodomain helicase DNA binding protein 2, HGNC:1917) is a protein-coding gene on chromosome 15q26.1, encoding ATP-dependent chromatin remodeler CHD2 (O14647). ATP-dependent chromatin-remodeling factor that specifically binds to the promoter of target genes, leading to chromatin remodeling, possibly by promoting deposition of histone H3.3. It is haploinsufficient (ClinGen: sufficient evidence).

The CHD family of proteins is characterized by the presence of chromo (chromatin organization modifier) domains and SNF2-related helicase/ATPase domains. CHD genes alter gene expression possibly by modification of chromatin structure thus altering access of the transcriptional apparatus to its chromosomal DNA template. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

Source: NCBI Gene 1106 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 9
• Clinical variants (ClinVar): 2,566 total — 258 pathogenic, 121 likely-pathogenic
• Phenotypes (HPO): 74
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 4 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001271

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1917
Approved symbol	CHD2
Name	chromodomain helicase DNA binding protein 2
Location	15q26.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ38614, DKFZp547I1315, DKFZp781D1727, DKFZp686E01200
Ensembl gene	ENSG00000173575
Ensembl biotype	protein_coding
OMIM	602119
Entrez	1106

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 11 protein_coding, 11 nonsense_mediated_decay, 8 protein_coding_CDS_not_defined, 4 retained_intron

ENST00000394196, ENST00000420239, ENST00000625243, ENST00000625463, ENST00000625662, ENST00000625990, ENST00000626782, ENST00000626874, ENST00000627185, ENST00000627200, ENST00000627460, ENST00000627622, ENST00000628118, ENST00000628181, ENST00000628375, ENST00000629104, ENST00000629136, ENST00000629346, ENST00000630016, ENST00000630790, ENST00000630813, ENST00000635856, ENST00000635922, ENST00000636306, ENST00000636410, ENST00000636861, ENST00000636881, ENST00000637572, ENST00000637613, ENST00000637789, ENST00000700549, ENST00000700550, ENST00000700551, ENST00000700552

RefSeq mRNA: 2 — MANE Select: NM_001271 NM_001042572, NM_001271

CCDS: CCDS10374, CCDS45356

Canonical transcript exons

ENST00000394196 — 39 exons

Exon	Start	End
ENSE00001097738	92996957	92997095
ENSE00001097753	93009145	93009323
ENSE00001097770	92991476	92991517
ENSE00001097780	92980815	92980911
ENSE00001097827	92985498	92985673
ENSE00001097839	92984330	92984500
ENSE00001097848	92992859	92992998
ENSE00001097863	92981365	92981457
ENSE00001097892	92979135	92979283
ENSE00001179524	93014696	93014909
ENSE00001179528	93012345	93012444
ENSE00001255131	92971765	92971927
ENSE00001255136	92967325	92967513
ENSE00001255168	92948952	92949076
ENSE00001314469	93004617	93004751
ENSE00001517729	93024372	93027996
ENSE00001517730	93020012	93020258
ENSE00002434605	92978234	92978383
ENSE00002469647	92997253	92997403
ENSE00003459914	92927244	92927330
ENSE00003475931	92945821	92945865
ENSE00003481778	92953357	92953573
ENSE00003503542	92998499	92998621
ENSE00003503986	92956459	92956649
ENSE00003511443	92942843	92943068
ENSE00003535318	92974879	92974950
ENSE00003552452	92901167	92901299
ENSE00003564518	92939578	92939718
ENSE00003565364	92941822	92941955
ENSE00003587375	93002177	93002317
ENSE00003587849	92955423	92955512
ENSE00003593607	92946038	92946216
ENSE00003659253	92972265	92972417
ENSE00003673545	93000512	93000640
ENSE00003756424	92937518	92937625
ENSE00003757930	92924321	92924552
ENSE00003774486	92944415	92944515
ENSE00003774778	92929030	92929091
ENSE00003980129	92900324	92900824

Expression profiles

Bgee: expression breadth ubiquitous, 268 present calls, max score 99.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 66.9330 / max 2887.9604, expressed in 1821 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
148642	66.4678	1820
148654	0.2848	100
148647	0.1804	83

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.22	gold quality
sural nerve	UBERON:0015488	99.20	gold quality
colonic epithelium	UBERON:0000397	98.25	gold quality
adrenal tissue	UBERON:0018303	97.81	gold quality
ventricular zone	UBERON:0003053	97.71	gold quality
ganglionic eminence	UBERON:0004023	97.40	gold quality
mucosa of stomach	UBERON:0001199	96.85	gold quality
cortical plate	UBERON:0005343	96.64	gold quality
cerebellar hemisphere	UBERON:0002245	96.19	gold quality
right uterine tube	UBERON:0001302	96.14	gold quality
cerebellar cortex	UBERON:0002129	96.05	gold quality
left ovary	UBERON:0002119	96.03	gold quality
left lobe of thyroid gland	UBERON:0001120	96.01	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.97	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.91	gold quality
monocyte	CL:0000576	95.74	gold quality
tendon	UBERON:0000043	95.74	gold quality
right lung	UBERON:0002167	95.64	gold quality
skin of leg	UBERON:0001511	95.58	gold quality
thyroid gland	UBERON:0002046	95.45	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.42	gold quality
skin of abdomen	UBERON:0001416	95.41	gold quality
tonsil	UBERON:0002372	95.40	gold quality
upper lobe of left lung	UBERON:0008952	95.37	gold quality
right ovary	UBERON:0002118	95.29	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.17	gold quality
right lobe of thyroid gland	UBERON:0001119	95.04	gold quality
upper lobe of lung	UBERON:0008948	94.96	gold quality
minor salivary gland	UBERON:0001830	94.88	gold quality
endothelial cell	CL:0000115	94.84	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	19.34
E-GEOD-106540	no	1167.20
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

188 targeting CHD2, 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-6740-5P	100.00	65.64	932
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-5193	100.00	67.26	1744
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-150-5P	99.99	66.69	1976
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-6753-3P	99.93	66.57	637

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 28)

• detected a homozygous deletion of chromosomal region 15q26.2 in the cell line HDLM2 encompasing RGMA and CHD2 (PMID:17606441)
• De novo CHD2 and SYNGAP1 mutations are new causes of epileptic encephalopathies, accounting for 1.2% and 1% of cases, respectively. (PMID:23708187)
• De novo loss-of-function mutations in CHD2 are a cause of epileptic encephalopathy with generalized seizures. (PMID:24207121)
• Genetic variants of BCL2, GNAO1, and CHD2 are associated with non-obstructive azoospermia risk. (PMID:24549219)
• Our findings suggest that CHD2 mutations are important in the etiological spectrum of Lennox-Gastaut syndrome. (PMID:24614520)
• CHD1 and CHD2 act as positive regulators of HIV-1 gene expression. (PMID:25297984)
• Human CHD2 is a chromatin assembly ATPase regulated by its chromatin- and DNA-binding domains. (PMID:25384982)
• The phenotypic spectrum of CHD2 encephalopathy has distinctive features of myoclonic epilepsy with marked photosensitivity. (PMID:25672921)
• CHD2 mutation is the first identified cause of the archetypal generalized photosensitive epilepsy syndrome (PMID:25783594)
• CHD2 is a cancer driver and has a role as chromatin remodeler in chronic lymphocytic leukemia. (PMID:26031915)
• CHD2 mutations are responsible in rare cases for generalized epilepsy with myoclonic-atonic seizures. (PMID:26262932)
• study reports monozygotic twins with a global neurodevelopmental delay associated with an autism spectrum disorder, hypotonia, postnatal microcephaly, stereotypic movements and circadian rhythm alterations in association with late-onset epilepsy; identified a CHD2 mutation, previously described in association with a phenotypic spectrum overlapping our patients’ phenotype (PMID:26754451)
• Results indicate a PARP1-dependent mechanism that regulates non-homologous end-joining through localized chromatin expansion and deposition of the histone variant H3.3 by CHD2 at DNA breaks promoting DNA repair. (PMID:26895424)
• Germline mosaicism resulted in a CHD2 gene missense variant and the development of autism spectrum disorder in two siblings. (PMID:28960266)
• CHD2 mutation is associated with neurodevelopmental disorders. (PMID:29740950)
• DNA helicases CHD2 and CHD7 could reduce BAP1 promoter activity, likely through unwinding its G4 structures. (PMID:29787736)
• Study finds that Q1392TfsX17 maybe the hot-spot mutation of CHD2 and that West syndrome could be a new phenotype of CHD2 mutation. (PMID:31677157)
• A regulatory role for CHD2 in myelopoiesis. (PMID:31900031)
• CHD2 encodes a member of the chromodomain helicase DNA-binding (CHD) family involved in chromatin remodeling. This observation adds schizophrenia to the phenotypic spectrum of chromodomain remodeling disorders, which may lead to innovative therapeutic approaches. (PMID:31914951)
• CHD1 and SPOP synergistically protect prostate epithelial cells from DNA damage. (PMID:33022763)
• CHD2-Related CNS Pathologies. (PMID:33435571)
• Novel Loss-of-Function Variants in CHD2 Cause Childhood-Onset Epileptic Encephalopathy in Chinese Patients. (PMID:35627293)
• Regulation of human cortical interneuron development by the chromatin remodeling protein CHD2. (PMID:36115870)
• CircCHD2/miR-200b-3p/HLF Axis Promotes Liver Cirrhosis. (PMID:36374958)
• Role of CircCHD2 in the pathogenesis of gestational diabetes mellitus by regulating autophagy via miR-33b-3p/ULK1 axis. (PMID:38039841)
• Low-grade parental gonosomal mosaicism in CHD2 siblings with Smith-Magenis-like syndrome. (PMID:38385826)
• Clinical analysis of five CHD2 gene mutations in Chinese children with epilepsy. (PMID:39068850)
• Diagnostic utility of DNA methylation analysis in genetically unsolved pediatric epilepsies and CHD2 episignature refinement. (PMID:39107278)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	chd2	ENSDARG00000060687
mus_musculus	Chd2	ENSMUSG00000078671
rattus_norvegicus	Chd2	ENSRNOG00000012716

Paralogs (30): HLTF (ENSG00000071794), SMARCA2 (ENSG00000080503), SRCAP (ENSG00000080603), ATRX (ENSG00000085224), RAD54L (ENSG00000085999), BTAF1 (ENSG00000095564), CHD8 (ENSG00000100888), 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), CHD9 (ENSG00000177200), EP400 (ENSG00000183495), ERCC6L (ENSG00000186871), RAD54B (ENSG00000197275), ERCC6 (ENSG00000225830)

Protein

Protein identifiers

ATP-dependent chromatin remodeler CHD2 — O14647 (reviewed: O14647)

Alternative names: Chromo domain-containing protein 2

All UniProt accessions (20): O14647, A0A0D9SEH6, A0A0D9SEP7, A0A0D9SET4, A0A0D9SEU0, A0A0D9SF92, A0A0D9SFA3, A0A0D9SFV4, A0A0D9SFV8, A0A0D9SGA6, A0A0D9SGK0, A0A1B0GTM9, A0A1B0GTU9, A0A1B0GU59, A0A8V8TPT9, A0A8V8TQC6, A0A8V8TQD9, A0A8V8TR03, A0A8V8TRB2, B7Z3I4

UniProt curated annotations — full annotation on UniProt →

Function. ATP-dependent chromatin-remodeling factor that specifically binds to the promoter of target genes, leading to chromatin remodeling, possibly by promoting deposition of histone H3.3. Involved in myogenesis via interaction with MYOD1: binds to myogenic gene regulatory sequences and mediates incorporation of histone H3.3 prior to the onset of myogenic gene expression, promoting their expression.

Subunit / interactions. Interacts with MYOD1. Interacts with histone H3.3.

Subcellular location. Nucleus.

Disease relevance. Developmental and epileptic encephalopathy 94 (DEE94) [MIM:615369] A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE94 is an autosomal dominant, severe form characterized by onset of multiple seizure types in the first few years of life. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The CHD1 helical C-terminal domain (CHCT) may bind DNA and nucleosomes.

Similarity. Belongs to the SNF2/RAD54 helicase family.

Isoforms (3)

UniProt ID	Names	Canonical?
O14647-1	1	yes
O14647-2	2
O14647-3	3

RefSeq proteins (2): NP_001036037, NP_001262* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000330	SNF2_N	Domain
IPR000953	Chromo/chromo_shadow_dom	Domain
IPR001650	Helicase_C-like	Domain
IPR014001	Helicase_ATP-bd	Domain
IPR016197	Chromo-like_dom_sf	Homologous_superfamily
IPR023779	Chromodomain_CS	Conserved_site
IPR023780	Chromo_domain	Domain
IPR025260	CHD1-like_C	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR038718	SNF2-like_sf	Homologous_superfamily
IPR040793	CDH1_2_SANT_HL1	Domain
IPR049730	SNF2/RAD54-like_C	Domain
IPR056302	CHD1-2/Hrp3_HTH	Domain

Pfam: PF00176, PF00271, PF00385, PF13907, PF18375, PF23588

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (48 total): compositionally biased region 16, modified residue 9, region of interest 6, sequence variant 6, domain 4, splice variant 3, chain 1, short sequence motif 1, binding site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14647-F1	60.81	0.07

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): 509–516

Post-translational modifications (9): 207, 208, 240, 242, 1085, 1087, 1365, 1386, 1807

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9943411	CHD1 and CHD2 subfamily

MSigDB gene sets: 487 (showing top): E2F_Q4, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, FREAC2_01, HNF3ALPHA_Q6, CCAWYNNGAAR_UNKNOWN, RORA1_01, SP3_Q3, TGACCTY_ERR1_Q2, CEBPB_01, GOBP_HEMATOPOIETIC_STEM_CELL_DIFFERENTIATION, SRF_Q5_01, NKX61_01, EVI1_05, TCF4_Q5, CDP_01

GO Biological Process (7): DNA damage response (GO:0006974), muscle organ development (GO:0007517), gene expression (GO:0010467), nucleosome organization (GO:0034728), hematopoietic stem cell differentiation (GO:0060218), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338)

GO Molecular Function (12): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA binding (GO:0003677), chromatin binding (GO:0003682), RNA binding (GO:0003723), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), histone binding (GO:0042393), ATP-dependent chromatin remodeler activity (GO:0140658), nucleotide binding (GO:0000166), helicase activity (GO:0004386), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
CHD chromatin remodelers	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chromatin remodeling	2
nucleic acid binding	2
binding	2
ATP-dependent activity	2
cellular response to stress	1
animal organ development	1
muscle structure development	1
macromolecule biosynthetic process	1
protein-DNA complex organization	1
hematopoietic progenitor cell differentiation	1
stem cell differentiation	1
cellular component organization	1
chromatin organization	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
protein binding	1
DNA binding	1
ATP-dependent activity, acting on DNA	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
nucleic acid conformation isomerase activity	1
catalytic activity, acting on a nucleic acid	1
catalytic activity	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2253 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHD2	ZNF618	Q5T7W0	521
CHD2	SPATA12	Q7Z6I5	479
CHD2	FAM174B	Q3ZCQ3	437
CHD2	TP53	P04637	433
CHD2	RGMA	Q96B86	368
CHD2	SNX16	P57768	365
CHD2	BCL2	P10415	359
CHD2	DCHS1	Q96JQ0	348
CHD2	DYNC1H1	Q14204	338
CHD2	MCTP2	Q6DN12	332
CHD2	ANKRD34A	Q69YU3	318
CHD2	CBX3	Q13185	307
CHD2	FAT4	Q6V0I7	297
CHD2	POGZ	Q7Z3K3	295
CHD2	RBM25	P49756	291

IntAct

62 interactions, top by confidence:

A	B	Type	Score
CHD2	TRIM41	psi-mi:“MI:0915”(physical association)	0.670
TRIM41	CHD2	psi-mi:“MI:0915”(physical association)	0.670
BEND7	CHD2	psi-mi:“MI:0915”(physical association)	0.560
CHD2	TEKT1	psi-mi:“MI:0915”(physical association)	0.560
THAP1	CHD2	psi-mi:“MI:0915”(physical association)	0.560
CHD2	MID2	psi-mi:“MI:0915”(physical association)	0.560
TEKT1	CHD2	psi-mi:“MI:0915”(physical association)	0.560
MID2	CHD2	psi-mi:“MI:0915”(physical association)	0.560
CHD2	THAP1	psi-mi:“MI:0915”(physical association)	0.560
CHD2	BEND7	psi-mi:“MI:0915”(physical association)	0.560
N	RBM47	psi-mi:“MI:0914”(association)	0.530
ABT1	ZNF316	psi-mi:“MI:0914”(association)	0.530
FGF11	CHD1	psi-mi:“MI:0914”(association)	0.530
SRPK2	CHD2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
H2BC12L	CHD2	psi-mi:“MI:0915”(physical association)	0.400
CHD2	SMC1A	psi-mi:“MI:0915”(physical association)	0.400
CHD2	FLNA	psi-mi:“MI:0915”(physical association)	0.400
TARDBP	CHD2	psi-mi:“MI:0915”(physical association)	0.400
C9orf72	CHD2	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
KMT5C	CBX4	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350

BioGRID (77): MID2 (Two-hybrid), THAP1 (Two-hybrid), TEKT1 (Two-hybrid), TRIM41 (Two-hybrid), BEND7 (Two-hybrid), CHD2 (Affinity Capture-MS), CHD2 (Co-fractionation), CHD2 (Co-fractionation), CHD2 (Co-fractionation), CHD2 (Co-fractionation), TRIM41 (Two-hybrid), CHD2 (Affinity Capture-MS), CHD2 (Affinity Capture-RNA), CHD2 (Affinity Capture-MS), CHD2 (Affinity Capture-MS)

ESM2 similar proteins: A1Z9L3, A2A4P0, A2QIL2, A3KFM7, A3KMI0, B2RR83, B6ZLK2, D3ZA12, D4A2Z8, E9PZM4, F4IJV4, F4ILR7, F4JY24, F4K2E9, O14646, O14647, O18017, O42643, O45244, O60231, P24384, P34498, P40201, P93008, Q05B79, Q09530, Q10752, Q14562, Q17R09, Q38953, Q4TVV3, Q53RK8, Q54F05, Q5R746, Q5RAZ4, Q5ZI74, Q6P158, Q6P5D3, Q6PGC1, Q767K6

Diamond homologs: A2A8L1, A2AJK6, A3KFM7, A7Z019, A9X4T1, B0R061, B0R0I6, B4KHL5, B5DE69, B6ZLK2, D3Z9Z9, D3ZA12, D3ZD32, E1B7X9, E7F1C4, E9PZM4, F4IHS2, F4IV45, F4IV99, F4J9M5, F4JTF6, F4JY24, F4K128, F4KBP5, F8VPZ5, G5EBZ4, G5EDG2, G5EF53, O14139, O14646, O14647, O16102, O42861, O60264, O74842, O94421, O97159, P22082, P25439, P28370

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
PARP1	“up-regulates quantity”	CHD2	binding
CHD2	“up-regulates quantity”	H3-3A	relocalization
CHD2	“up-regulates quantity”	XRCC4	relocalization
CHD2	up-regulates	DNA_repair
CHD2	“up-regulates activity”	MYOD1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 45 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.

GO biological processes:

GO term	Partners	Fold	FDR
RNA splicing	6	13.2×	2e-03
DNA repair	7	11.2×	1e-03
protein stabilization	6	10.0×	4e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 4 cancer types — BLCA, CLLSLL, GIST, PRCC.

Clinical variants and AI predictions

ClinVar

2566 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	258
Likely pathogenic	121
Uncertain significance	928
Likely benign	908
Benign	138

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1048635	NM_001271.4(CHD2):c.1387C>T (p.Gln463Ter)	Pathogenic
1057862	NM_001271.4(CHD2):c.2698C>G (p.Arg900Gly)	Pathogenic
1065604	NM_001271.4(CHD2):c.4349del (p.Gly1450fs)	Pathogenic
1067558	NM_001271.4(CHD2):c.1052+2T>C	Pathogenic
1068680	NM_001271.4(CHD2):c.2888_2889insAT (p.Phe963fs)	Pathogenic
1069342	NC_000015.9:g.(?93514985)(93518190_?)del	Pathogenic
1069402	NM_001271.4(CHD2):c.4184_4187del (p.Lys1395fs)	Pathogenic
1069910	NM_001271.4(CHD2):c.2587_2591del (p.Phe863fs)	Pathogenic
1071676	NM_001271.4(CHD2):c.2536C>T (p.Arg846Ter)	Pathogenic
1071922	NM_001271.4(CHD2):c.3638_3644delinsAAAATGCACAGAAATGTCATCAAGAGGTTAANNNNNNNNNNATGCATTTCCCCAGTAGATGGGTCCTTGTACACCAAGACTTTTTGTTCGTCTTTGTACCAGAGTTTAGCCAAAG (p.Ser1213_Val1215delinsTer)	Pathogenic
1073543	NM_001271.4(CHD2):c.3355_3356del (p.Arg1119fs)	Pathogenic
1074629	NM_001271.4(CHD2):c.2826_2827insTGGC (p.Met943fs)	Pathogenic
1076209	NM_001271.4(CHD2):c.938_948del (p.Gly313fs)	Pathogenic
1076494	NM_001271.4(CHD2):c.1880_1883del (p.Ser627fs)	Pathogenic
1076495	NM_001271.4(CHD2):c.4949dup (p.Gly1651fs)	Pathogenic
1076544	NM_001271.4(CHD2):c.3323_3324del (p.Asp1107_Ser1108insTer)	Pathogenic
1188134	NM_001271.4(CHD2):c.4935del (p.Lys1645fs)	Pathogenic
1213090	NM_001271.4(CHD2):c.2189+1G>T	Pathogenic
1219194	NM_001271.4(CHD2):c.4176_4177del (p.Lys1393fs)	Pathogenic
1319260	NM_001271.4(CHD2):c.1459del (p.Tyr487fs)	Pathogenic
1334432	NM_001271.4(CHD2):c.1053-1G>C	Pathogenic
1335189	NM_001271.4(CHD2):c.3786_3787del (p.Val1263fs)	Pathogenic
1351835	NM_001271.4(CHD2):c.3100G>T (p.Glu1034Ter)	Pathogenic
1352740	NM_001271.4(CHD2):c.1787_1788del (p.Thr595_Tyr596insTer)	Pathogenic
1353592	NC_000015.9:g.(?93444468)(93583743_?)del	Pathogenic
1359923	NM_001271.4(CHD2):c.3412del (p.Arg1138fs)	Pathogenic
1365520	NM_001271.4(CHD2):c.4304del (p.Ser1434_Ser1435insTer)	Pathogenic
1370206	NM_001271.4(CHD2):c.294+3A>G	Pathogenic
1370712	NM_001271.4(CHD2):c.1833G>A (p.Trp611Ter)	Pathogenic
1379909	NM_001271.4(CHD2):c.5153+1G>T	Pathogenic

SpliceAI

1032 predictions. Top by Δscore:

Variant	Effect	Δscore
15:92886255:G:GG	donor_gain	1.0000
15:92891998:CTGCA:C	acceptor_loss	1.0000
15:92891999:TGCAG:T	acceptor_loss	1.0000
15:92892000:GCAGA:G	acceptor_loss	1.0000
15:92892002:A:AG	acceptor_gain	1.0000
15:92892002:AG:A	acceptor_loss	1.0000
15:92892003:G:GA	acceptor_gain	1.0000
15:92892003:GA:G	acceptor_gain	1.0000
15:92892003:GAA:G	acceptor_gain	1.0000
15:92892003:GAAA:G	acceptor_gain	1.0000
15:92892003:GAAAT:G	acceptor_gain	1.0000
15:92892068:ATTTA:A	donor_gain	1.0000
15:92892069:TTTA:T	donor_gain	1.0000
15:92892070:TTA:T	donor_gain	1.0000
15:92892071:TA:T	donor_gain	1.0000
15:92892071:TAG:T	donor_loss	1.0000
15:92892073:G:A	donor_loss	1.0000
15:92892073:G:GG	donor_gain	1.0000
15:92892074:T:G	donor_loss	1.0000
15:92892075:AA:A	donor_loss	1.0000
15:92924313:A:AG	acceptor_gain	1.0000
15:92924314:A:G	acceptor_gain	1.0000
15:92924315:A:AG	acceptor_gain	1.0000
15:92924317:T:G	acceptor_gain	1.0000
15:92924318:A:AG	acceptor_gain	1.0000
15:92924319:A:AG	acceptor_gain	1.0000
15:92924320:G:GA	acceptor_gain	1.0000
15:92924320:GT:G	acceptor_gain	1.0000
15:92924320:GTC:G	acceptor_gain	1.0000
15:92924529:G:GT	donor_gain	1.0000

AlphaMissense

12137 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:92927247:T:A	W100R	1.000
15:92927247:T:C	W100R	1.000
15:92927278:G:C	R110T	1.000
15:92927278:G:T	R110M	1.000
15:92927279:G:C	R110S	1.000
15:92927279:G:T	R110S	1.000
15:92942947:T:A	W311R	1.000
15:92942947:T:C	W311R	1.000
15:92942948:G:C	W311S	1.000
15:92942949:G:C	W311C	1.000
15:92942949:G:T	W311C	1.000
15:92946088:T:A	W417R	1.000
15:92946088:T:C	W417R	1.000
15:92949045:G:C	G491R	1.000
15:92953371:T:A	I506N	1.000
15:92953374:T:C	L507P	1.000
15:92953376:G:C	A508P	1.000
15:92953377:C:A	A508D	1.000
15:92953379:G:C	D509H	1.000
15:92953380:A:T	D509V	1.000
15:92953382:G:A	E510K	1.000
15:92953383:A:T	E510V	1.000
15:92953386:T:A	M511K	1.000
15:92953386:T:C	M511T	1.000
15:92953386:T:G	M511R	1.000
15:92953387:G:A	M511I	1.000
15:92953387:G:C	M511I	1.000
15:92953387:G:T	M511I	1.000
15:92953388:G:C	G512R	1.000
15:92953388:G:T	G512C	1.000

dbSNP variants (sampled 300 via entrez): RS1000025751 (15:92903204 T>C), RS1000109474 (15:92969317 G>A), RS1000117273 (15:93018838 T>C,G), RS1000152328 (15:93020233 C>G,T), RS1000157537 (15:92901140 C>T), RS1000169959 (15:93023428 T>G), RS1000183757 (15:92952930 C>G), RS1000186431 (15:92936268 G>T), RS1000189353 (15:93017425 A>T), RS1000229586 (15:92932603 T>A,C), RS1000246457 (15:92980507 A>G), RS1000258691 (15:92899828 TAAA>T), RS1000266845 (15:92941284 G>A,C), RS1000281760 (15:92932788 C>G,T), RS1000291898 (15:93001161 C>A,T)

Disease associations

OMIM: gene MIM:602119 | disease phenotypes: MIM:615369, MIM:616421, MIM:606369, MIM:308350, MIM:117100, MIM:617159

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy 94	Definitive	Autosomal dominant
myoclonic-astatic epilepsy	Supportive	Unknown
Lennox-Gastaut syndrome	Supportive	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 (18): developmental and epileptic encephalopathy 94 (MONDO:0014150), neurodevelopmental disorder (MONDO:0700092), intellectual disability (MONDO:0001071), epilepsy with myoclonic atonic seizures (MONDO:0014633), autism spectrum disorder (MONDO:0005258), prostate cancer (MONDO:0008315), developmental and epileptic encephalopathy (MONDO:0100620), Lennox-Gastaut syndrome (MONDO:0016532), complex neurodevelopmental disorder (MONDO:0100038), breast ductal adenocarcinoma (MONDO:0005590), teratoma (MONDO:0002601), developmental and epileptic encephalopathy, 1 (MONDO:0010632), epilepsy (MONDO:0005027), microcephaly (MONDO:0001149), self-limited epilepsy with centrotemporal spikes (MONDO:0007295)

Orphanet (9): Epilepsy with myoclonic-atonic seizures (Orphanet:1942), Lennox-Gastaut syndrome (Orphanet:2382), Familial prostate cancer (Orphanet:1331), Non-specific syndromic intellectual disability (Orphanet:528084), Self-limited epilepsy with centrotemporal spikes (Orphanet:1945), Cleft lip/palate (Orphanet:199306), CHD4-related neurodevelopmental disorder (Orphanet:653712), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

74 total (30 of 74 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000154	Wide mouth
HP:0000179	Thick lower lip vermilion
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000289	Broad philtrum
HP:0000343	Long philtrum
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000568	Microphthalmia
HP:0000708	Atypical behavior
HP:0000709	Psychosis
HP:0000718	Aggressive behavior
HP:0000729	Autistic behavior
HP:0000737	Irritability
HP:0000741	Apathy
HP:0000750	Delayed speech and language development
HP:0000752	Hyperactivity
HP:0001159	Syndactyly
HP:0001249	Intellectual disability
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001268	Mental deterioration
HP:0001298	Encephalopathy
HP:0001326	EEG with irregular generalized spike and wave complexes
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0001999	Abnormal facial shape
HP:0002069	Bilateral tonic-clonic seizure

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002337_14	Amyotrophic lateral sclerosis (sporadic)	3.000000e-06
GCST006626_24	Pulse pressure	9.000000e-12
GCST006902_10	Adolescent idiopathic scoliosis	1.000000e-06
GCST009391_1015	Metabolite levels	2.000000e-06
GCST009391_762	Metabolite levels	7.000000e-06
GCST011494_68	Daytime nap	1.000000e-07
GCST90002390_429	Mean corpuscular hemoglobin	2.000000e-11
GCST90002392_441	Mean corpuscular volume	8.000000e-12
GCST90002397_269	Mean spheric corpuscular volume	3.000000e-10

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0010360	lysophosphatidylcholine 18:1 measurement
EFO:0010391	sphingomyelin 16:0 measurement
EFO:0007828	daytime rest measurement
EFO:0004527	mean corpuscular hemoglobin

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D004827	Epilepsy	C10.228.140.490
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065768	Lennox Gastaut Syndrome	C10.228.140.490.493.750; C16.320.495
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D065886	Neurodevelopmental Disorders	F03.625
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
D013724	Teratoma	C04.557.465.910

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs28458425	CHD2		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, affects cotreatment, increases expression, decreases expression	11
trichostatin A	affects cotreatment, decreases expression, affects expression	3
Cyclosporine	increases expression	3
bisphenol A	decreases methylation, increases methylation	2
sodium arsenite	decreases expression, increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
Aflatoxin B1	increases methylation, decreases methylation	2
Cadmium Chloride	increases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
TAK-243	decreases sumoylation	1
methylmercuric chloride	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
quercitrin	decreases expression	1
arsenite	decreases reaction, affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
14-deoxy-11,12-didehydroandrographolide	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
eprenetapopt	affects expression, affects reaction	1
NSC 689534	affects binding, increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Bortezomib	increases expression	1

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_SI89	HAP1 CHD2 (-) 1	Cancer cell line	Male
CVCL_SI90	HAP1 CHD2 (-) 2	Cancer cell line	Male
CVCL_SI91	HAP1 CHD2 (-) 3	Cancer cell line	Male
CVCL_SI92	HAP1 CHD2 (-) 4	Cancer cell line	Male
CVCL_VE77	PFIZi029-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03779672	PHASE4	COMPLETED	Memantine for Epileptic Encephalopathy
NCT01370486	PHASE4	WITHDRAWN	Melatonin Versus Placebo in the Lennox-Gastaut Syndrome: Neurophysiological and Neuropsychological Effects
NCT02731300	PHASE4	COMPLETED	Transcranial Direct Current Stimulation, Treatment of Childhood Drug-Resistant Lennox-Gastaut Syndrome, A Pilot Study
NCT04133480	PHASE4	WITHDRAWN	Investigation of Cognitive Outcomes With Cannabidiol Oral Solution
NCT05044819	PHASE4	ACTIVE_NOT_RECRUITING	Assessment of Potential for Chronic Liver Injury in Participants Treated With Epidiolex (Cannabidiol) Oral Solution
NCT06924827	PHASE4	NOT_YET_RECRUITING	A Study to Investigate the Transition of Children From ‘Artisanal Cannabidiol (CBD) to Epidiolex
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
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
NCT00004776	PHASE3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Oral Topiramate for Lennox-Gastaut Syndrome
NCT01146951	PHASE3	COMPLETED	A Placebo-Controlled, Double-Blind Comparative Study of E2080 in Lennox-Gastaut Syndrome Patients (Study E2080-J081-304)
NCT01151540	PHASE3	COMPLETED	A Long Term Extension Study of E2080 in Lennox-Gastaut Patients
NCT01160770	PHASE3	COMPLETED	Safety and Effectiveness of Open-Label Clobazam in Subjects With Lennox-Gastaut Syndrome
NCT01405053	PHASE3	COMPLETED	Study of Rufinamide in Pediatric Subjects 1 to Less Than 4 Years of Age With Lennox-Gastaut Syndrome Inadequately Controlled With Other Anti-epileptic Drugs
NCT02224560	PHASE3	COMPLETED	Efficacy and Safety of GWP42003-P for Seizures Associated With Lennox-Gastaut Syndrome in Children and Adults
NCT02224573	PHASE3	COMPLETED	An Open Label Extension Study of Cannabidiol (GWP42003-P) in Children and Adults With Dravet or Lennox-Gastaut Syndromes
NCT02224690	PHASE3	COMPLETED	A Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P; CBD) as Adjunctive Treatment for Seizures Associated With Lennox-Gastaut Syndrome in Children and Adults
NCT02318537	PHASE3	WITHDRAWN	Cannabidiol Oral Solution as an Adjunctive Therapy for Treatment of Participants With Inadequately Controlled Lennox-Gastaut Syndrome
NCT02834793	PHASE3	TERMINATED	Study of Perampanel as Adjunctive Treatment for Inadequately Controlled Seizures Associated With Lennox-Gastaut Syndrome
NCT03355209	PHASE3	COMPLETED	A Study to Investigate the Efficacy and Safety of ZX008 (Fenfluramine Hydrochloride) as an Adjunctive Therapy in Children and Adults With Lennox-Gastaut Syndrome
NCT03936777	PHASE3	COMPLETED	A Study to Investigate the Long-Term Safety of ZX008 (Fenfluramine Hydrochloride) Oral Solution in Children and Adults With Epileptic Encephalopathy Including Dravet Syndrome and Lennox-Gastaut Syndrome
NCT04611438	PHASE3	UNKNOWN	Research on Cognitive Effect of Cannabidiol on Dravet Syndrome and Lennox-Gastaut SyndromeGastaut Syndrome
NCT04938427	PHASE3	COMPLETED	A Study of Soticlestat as an Add-on Therapy in Children, Teenagers, and Adults With Lennox-Gastaut Syndrome
NCT05066217	PHASE3	RECRUITING	An Efficacy and Safety Study of Clemizole HCl in Patients With Lennox-Gastaut Syndrome
NCT05163314	PHASE3	TERMINATED	A Study of Soticlestat as an Add-on Therapy in Children and Adults With Dravet Syndrome or Lennox-Gastaut Syndrome
NCT05219617	PHASE3	RECRUITING	Investigate Efficacy and Safety of Carisbamate as Adjunctive Treatment for Seizures Associated With LGS in Children and Adults
NCT06422377	PHASE3	TERMINATED	A Study Evaluating Soticlestat in Participants With Dravet Syndrome or Lennox-Gastaut Syndrome Who Have Been Exposed to Fenfluramine
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02655198	PHASE2	UNKNOWN	Add-on Therapy With Low Dose Fenfluramine in Lennox Gastaut Epilepsy
NCT03635073	PHASE2	TERMINATED	A Study of Soticlestat in Adults and Children With Rare Epilepsies
NCT03650452	PHASE2	COMPLETED	A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of TAK-935 (OV935) as an Adjunctive Therapy in Pediatric Participants With Developmental and/or Epileptic Encephalopathies
NCT05339126	PHASE2	ACTIVE_NOT_RECRUITING	RNS System LGS Feasibility Study
NCT05626634	PHASE2	COMPLETED	Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy