CHD5

Summary

CHD5 (chromodomain helicase DNA binding protein 5, HGNC:16816) is a protein-coding gene on chromosome 1p36.31, encoding ATP-dependent chromatin remodeler CHD5 (Q8TDI0). ATP-dependent chromatin-remodeling factor that binds DNA through histones and regulates gene transcription.

This gene encodes a member of the chromodomain helicase DNA-binding protein family. Members of this family are characterized by a chromodomain, a helicase ATP-binding domain and an additional functional domain. This gene encodes a neuron-specific protein that may function in chromatin remodeling and gene transcription. This gene is a potential tumor suppressor gene that may play a role in the development of neuroblastoma.

Source: NCBI Gene 26038 — RefSeq curated summary.

At a glance

• Gene–disease (curated): parenti-mignot neurodevelopmental syndrome (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 561 total — 9 pathogenic, 28 likely-pathogenic
• MANE Select transcript: NM_015557

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16816
Approved symbol	CHD5
Name	chromodomain helicase DNA binding protein 5
Location	1p36.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000116254
Ensembl biotype	protein_coding
OMIM	610771
Entrez	26038

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 nonsense_mediated_decay, 2 protein_coding

ENST00000262450, ENST00000377999, ENST00000462991, ENST00000475121, ENST00000491020, ENST00000496404

RefSeq mRNA: 1 — MANE Select: NM_015557 NM_015557

CCDS: CCDS57

Canonical transcript exons

ENST00000262450 — 42 exons

Exon	Start	End
ENSE00003460858	6124517	6124661
ENSE00003473165	6149246	6149412
ENSE00003476087	6125524	6125612
ENSE00003484903	6142414	6142605
ENSE00003487979	6106395	6106509
ENSE00003497393	6134128	6134259
ENSE00003497624	6146665	6146871
ENSE00003503861	6151032	6151155
ENSE00003509557	6110394	6110526
ENSE00003512526	6128046	6128218
ENSE00003515415	6168150	6168277
ENSE00003529809	6128499	6128609
ENSE00003535657	6121494	6121573
ENSE00003536305	6142128	6142328
ENSE00003542604	6106616	6106779
ENSE00003551672	6126572	6126746
ENSE00003558616	6159336	6159515
ENSE00003559681	6130204	6130328
ENSE00003567515	6143823	6143931
ENSE00003572111	6154660	6154898
ENSE00003572475	6123948	6124107
ENSE00003574650	6179945	6180321
ENSE00003574772	6134718	6134859
ENSE00003583454	6136517	6136638
ENSE00003592037	6112909	6112998
ENSE00003593925	6112140	6112277
ENSE00003596442	6135230	6135403
ENSE00003597382	6144024	6144155
ENSE00003603242	6146212	6146423
ENSE00003610596	6101787	6105427
ENSE00003619995	6121105	6121237
ENSE00003623878	6125100	6125233
ENSE00003624662	6111775	6111883
ENSE00003626498	6136728	6136865
ENSE00003650481	6128838	6129069
ENSE00003651772	6106234	6106287
ENSE00003664810	6152412	6152536
ENSE00003665634	6148854	6149075
ENSE00003669874	6109795	6109990
ENSE00003684103	6131631	6131748
ENSE00003686441	6125766	6125858
ENSE00003691668	6155599	6155717

Expression profiles

Bgee: expression breadth ubiquitous, 193 present calls, max score 97.02.

FANTOM5 (CAGE): breadth broad, TPM avg 4.7690 / max 875.5705, expressed in 334 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
9987	2.7716	289
9983	0.7424	121
9985	0.6714	140
9982	0.2714	75
9984	0.1466	67
201332	0.1012	40
9976	0.0379	19
201333	0.0139	13
9986	0.0127	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	97.02	gold quality
right frontal lobe	UBERON:0002810	95.40	gold quality
male germ cell	CL:0000015	94.11	gold quality
cingulate cortex	UBERON:0003027	93.56	gold quality
anterior cingulate cortex	UBERON:0009835	93.54	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.48	gold quality
Brodmann (1909) area 10	UBERON:0013541	93.48	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.43	gold quality
frontal cortex	UBERON:0001870	92.84	gold quality
prefrontal cortex	UBERON:0000451	92.44	gold quality
neocortex	UBERON:0001950	92.35	gold quality
pituitary gland	UBERON:0000007	92.26	gold quality
left testis	UBERON:0004533	92.26	gold quality
right testis	UBERON:0004534	92.00	gold quality
primary visual cortex	UBERON:0002436	91.54	gold quality
Brodmann (1909) area 46	UBERON:0006483	91.53	gold quality
adenohypophysis	UBERON:0002196	91.48	gold quality
cerebral cortex	UBERON:0000956	91.43	gold quality
superior frontal gyrus	UBERON:0002661	91.33	gold quality
frontal pole	UBERON:0002795	90.71	gold quality
postcentral gyrus	UBERON:0002581	90.21	gold quality
amygdala	UBERON:0001876	90.08	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.84	gold quality
parietal lobe	UBERON:0001872	89.81	gold quality
orbitofrontal cortex	UBERON:0004167	89.64	gold quality
occipital lobe	UBERON:0002021	89.56	gold quality
testis	UBERON:0000473	89.31	gold quality
temporal lobe	UBERON:0001871	89.28	gold quality
middle temporal gyrus	UBERON:0002771	89.06	gold quality
CA1 field of hippocampus	UBERON:0003881	88.85	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	8.50
E-ANND-3	yes	3.41

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

140 targeting CHD5, 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-6833-3P	100.00	70.63	3197
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833

Literature-anchored findings (GeneRIF, showing 40)

• CDH5 may play a role in the development of the nervous system, and it may also play a role in the pathogenesis of neural tumors. (PMID:12592387)
• Study demonstrates that Chd5 functions as a tumor suppressor in vivo and implicates deletion of CHD5 in human cancer. (PMID:17289567)
• A recent functional study identified chromodomain helicase DNA-binding protein 5 (CHD5) as a novel tumor suppressor mapping to 1p36. [REVIEW] (PMID:18413720)
• CHD5 is the strongest candidate tumor suppressor gene that is deleted from 1p36.31 in neuroblastomas, and inactivation of the second allele may occur by an epigenetic mechanism. (PMID:18577749)
• the DNA methylation profiles of CHD family members (CHD1-9) in different tumor types. (PMID:18698156)
• study demonstrated the existence of somatic mutations and methylation of CHD5 in primary epithelial ovarian cancers; CHD5 may play a role as a tumor suppressor gene in ovarian cancer (PMID:18953434)
• CHD5 is a tumor suppressor gene epigenetically down-regulated in gastric cancer (PMID:19840376)
• Data show a strong association of CHD5 expression with favorable prognostic variables (age at diagnosis <12 months, low clinical stage, and favorable histology), overall survival and event-free survival. (PMID:20950435)
• As only one of the 47 families studied has the CHD5 rs7513548 SNP variant, it appears to be a rare event and further screening of melanoma families is required to confirm whether or not CHD5 is involved in melanoma pathogenesis. (PMID:21250965)
• data suggest that CHD5 is a tumor suppressor gene that is epigenetically downregulated in laryngeal squamous cell carcinoma. (PMID:21636313)
• CHD5 is downregulated in a certain number of ovarian cancers and appears to be an adverse predictor candidate of ovarian cancer disease-free and total survival. (PMID:21860208)
• CHD5 is a potential tumor suppressor gene that is inactivated via an epigenetic mechanism in lung cancer. (PMID:22186629)
• the association of between miR-211-regulated CHD5 expression and CHD5 function in colorectal tumorigenesis (PMID:22235338)
• We conclude that (i) somatically acquired CHD5 mutations are rare in primary NBs, so inactivation probably occurs by deletion and epigenetic silencing. (PMID:22294723)
• Studies identified three genes, CHD5, PAFAH1B1, and NME1, strongly associated with patient outcome. (PMID:22328561)
• study concludes that down-regulation of CHD5, mediated at least in part by promoter methylation, contributes to the development and progression of human breast cancer (PMID:22569290)
• Decreased expression of chromodomain helicase DNA-binding protein 5 is associated with primary gallbladder carcinoma (PMID:22855185)
• In this Caucasian population, endometriosis seems to be associated with the tumor-suppressor gene CHD5. Our findings support recent data, suggesting that the 1p36 region plays an important role in endometrios. (PMID:22910690)
• CHD% protein mediates the p53-dependent senescence program triggered by decreased JMJD2A levels. (PMID:23168260)
• CHD5 might act as a tumor suppressor in glioma (PMID:23707602)
• These findings provide insights into the regulatory role of CHD5 during neurogenesis and suggest how inactivation of this candidate tumor suppressor might contribute to neuroblastoma. (PMID:23948251)
• CHD5 activity is regulated by DNA methylation and repressive histone modifications. CHD5 likely acts as a tumor-suppressor gene in early colorectal carcinogenesis. (PMID:24243398)
• Low CHD5 expression activates the DNA damage response and predicts poor outcome in patients undergoing adjuvant therapy for resected pancreatic cancer. (PMID:24276239)
• repression of CHD5 gene expression in human leukemia is mediated in part by DNA methylation of its promoter. (PMID:24454811)
• CHD5 is a potential tumour suppressor gene epigenetically silenced in hepatocellular carcinoma. (PMID:24529164)
• The tumor suppressor chromodomain helicase DNA-binding protein 5 (CHD5) remodels nucleosomes by unwrapping. (PMID:24923445)
• Study shows that CHD5 is a Nucleosome remodeling and deacetylase complex-associated transcriptional repressor and identifies WEE1 as one of the CHD5-regulated genes that may link CHD5 to tumor suppression. (PMID:25247294)
• Authors identified the CHD5 as a direct target of miR-454. CHD5 was downregulated in HCC tissues and cell lines and the expression level of CHD5 was inversely correlated with the expression of miR-454 in HCC tissues. (PMID:26287602)
• Data show a mutual suppression regulation between chromodomain helicase DNA binding protein 5 (CHD5) and enhancer of zeste homolog 2 (EZH2, which may provide new insights into their potential therapeutic significance for hepatocellular carcinoma (HCC). (PMID:26517514)
• CHD5 methylation of rectal cancer has a great effect in influencing its clinical and pathological features. (PMID:26753653)
• Data show that chromodomain helicase DNA binding protein 5 (CHD5) acted as a functional tumor suppressor and was frequently silenced by promoter CpG methylation in renal cell carcinoma (RCC). (PMID:26943038)
• CHD5 may act as a tumor suppressor gene in NSCLC. (PMID:28400267)
• CHD5 was identified as a direct target of miR-454. CHD5 was downregulated in GC tissues/cell lines and the expresssion of CHD5 inversely correlated with the level of miR-454 in GC tissues. Taken together, these observations indicate that HDAC3 is associated with GC cell growth via the miR-454-mediated targeting of CHD5. (PMID:29115379)
• Our results suggest that the rare CHD5 gene haplotype and alcohol intake contribute to the risk of hepatocellular carcinoma (PMID:29907144)
• SLC16A1-AS1 enhances radiosensitivity and represses cell proliferation and invasion by regulating the miR-301b-3p/CHD5 axis in hepatocellular carcinoma. (PMID:32748357)
• Chromodomain Helicase DNA-Binding Protein 5 Inhibits Renal Cell Carcinoma Tumorigenesis by Activation of the p53 and RB Pathways. (PMID:33062682)
• Missense and truncating variants in CHD5 in a dominant neurodevelopmental disorder with intellectual disability, behavioral disturbances, and epilepsy. (PMID:33944996)
• CHD5 inhibits metastasis of neuroblastoma. (PMID:34789839)
• mRNA expression and epigenetic-based role of chromodomain helicase DNA-binding 5 in hepatocellular carcinoma. (PMID:35808817)
• Pan-Cancer Analysis Identifies CHD5 as a Potential Biomarker for Glioma. (PMID:35955624)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	chd5	ENSDARG00000105083
mus_musculus	Chd5	ENSMUSG00000005045
rattus_norvegicus	Chd5	ENSRNOG00000011268

Paralogs (30): HLTF (ENSG00000071794), SMARCA2 (ENSG00000080503), SRCAP (ENSG00000080603), ATRX (ENSG00000085224), RAD54L (ENSG00000085999), BTAF1 (ENSG00000095564), CHD8 (ENSG00000100888), SMARCA1 (ENSG00000102038), CHD4 (ENSG00000111642), 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 CHD5 — Q8TDI0 (reviewed: Q8TDI0)

Alternative names: Chromo domain-containing protein 5

All UniProt accessions (6): Q8TDI0, F2Z2R5, F6T542, K7EMC0, K7EMY3, K7ESA5

UniProt curated annotations — full annotation on UniProt →

Function. ATP-dependent chromatin-remodeling factor that binds DNA through histones and regulates gene transcription. May specifically recognize and bind trimethylated ‘Lys-27’ (H3K27me3) and non-methylated ‘Lys-4’ of histone H3. Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin. Plays a role in the development of the nervous system by activating the expression of genes promoting neuron terminal differentiation. In parallel, it may also positively regulate the trimethylation of histone H3 at ‘Lys-27’ thereby specifically repressing genes that promote the differentiation into non-neuronal cell lineages. Regulates the expression of genes involved in cell proliferation and differentiation. Downstream activated genes may include CDKN2A that positively regulates the p53/TP53 pathway, which in turn, prevents cell proliferation. In spermatogenesis, it probably regulates histone hyperacetylation and the replacement of histones by transition proteins in chromatin, a crucial step in the condensation of spermatid chromatin and the production of functional spermatozoa.

Subunit / interactions. Component of the nucleosome remodeling and deacetylase (NuRD) repressor complex, composed of core proteins MTA1, MTA2, MTA3, RBBP4, RBBP7, HDAC1, HDAC2, MBD2, MBD3, and peripherally associated proteins CDK2AP1, CDK2AP2, GATAD2A, GATAD2B, CHD3, CHD4 and CHD5. The exact stoichiometry of the NuRD complex is unknown, and some subunits such as MBD2 and MBD3, GATAD2A and GATAD2B, and CHD3, CHD4 and CHD5 define mutually exclusive NuRD complexes. Interacts with HDAC2.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Preferentially expressed in total brain, fetal brain, and cerebellum. It is also moderately expressed in the adrenal gland and detected in testis.

Post-translational modifications. Methylated at Gln-1390 by N6AMT1.

Disease relevance. Defects in CHD5 may be a cause of the development of cancers from epithelial, neural and hematopoietic origin. CHD5 is one of the missing genes in the del(1p36), a deletion which is extremely common in this type of cancers. A decrease of its expression, results in increased susceptibility of cells to Ras-mediated transformation in vitro and in vivo. Parenti-Mignot neurodevelopmental syndrome (PMNDS) [MIM:619873] An autosomal dominant neurodevelopmental disorder characterized by intellectual disability, speech delay, motor delay, behavioral problems, and epilepsy. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The PHD domains mediate specific binding to histone H3 unmethylated at ‘Lys-4’ and may preferentially recruit the protein to transcriptionally inactive genes. The chromo domains mediate specific binding to histone H3 trimethylated at ‘Lys-27’ (H3K27me3) and may be required in neuron differentiation for proper gene regulation.

Similarity. Belongs to the SNF2/RAD54 helicase family.

RefSeq proteins (1): NP_056372* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000330	SNF2_N	Domain
IPR000953	Chromo/chromo_shadow_dom	Domain
IPR001650	Helicase_C-like	Domain
IPR001965	Znf_PHD	Domain
IPR002464	DNA/RNA_helicase_DEAH_CS	Conserved_site
IPR009462	CHD_II_SANT-like	Domain
IPR009463	DUF1087	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR012957	CHD_C2	Domain
IPR012958	CHD_N	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR014001	Helicase_ATP-bd	Domain
IPR016197	Chromo-like_dom_sf	Homologous_superfamily
IPR019786	Zinc_finger_PHD-type_CS	Conserved_site
IPR019787	Znf_PHD-finger	Domain
IPR023780	Chromo_domain	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR028727	DEXHc_CHD5	Domain
IPR038718	SNF2-like_sf	Homologous_superfamily
IPR049730	SNF2/RAD54-like_C	Domain

Pfam: PF00176, PF00271, PF00385, PF00628, PF06461, PF06465, PF08073, PF08074

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (76 total): sequence variant 19, compositionally biased region 13, helix 10, region of interest 9, strand 9, domain 4, mutagenesis site 3, modified residue 2, zinc finger region 2, turn 2, chain 1, short sequence motif 1, binding site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6GUU	X-RAY DIFFRACTION	2.95

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TDI0-F1	62.87	0.16

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): 725–732

Post-translational modifications (2): 1390, 1554

Mutagenesis-validated functional residues (3):

Position	Phenotype
518	reduced affinity for trimethylated histone h3k27me3.
619	reduced affinity for trimethylated histone h3k27me3.
1390	abolishes methylation by n6amt1.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9937850	NuRD complex assembly
R-HSA-9940951	Interaction of NuRD complexes with transcription factors

MSigDB gene sets: 221 (showing top): BENPORATH_ES_WITH_H3K27ME3, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, WHITE_NEUROBLASTOMA_WITH_1P36.3_DELETION, GOBP_NEUROGENESIS, GOBP_MALE_GAMETE_GENERATION, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_FOREBRAIN_GENERATION_OF_NEURONS, GOBP_POSITIVE_REGULATION_OF_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR, GOBP_CEREBRAL_CORTEX_NEURON_DIFFERENTIATION, GOBP_NUCLEUS_ORGANIZATION, GOBP_CENTRAL_NERVOUS_SYSTEM_NEURON_DIFFERENTIATION, AAAGGGA_MIR204_MIR211, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_SPERMATID_NUCLEUS_DIFFERENTIATION, GOBP_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR

GO Biological Process (10): chromatin remodeling (GO:0006338), regulation of transcription by RNA polymerase II (GO:0006357), negative regulation of cell population proliferation (GO:0008285), cerebral cortex neuron differentiation (GO:0021895), sperm DNA condensation (GO:0035092), positive regulation of signal transduction by p53 class mediator (GO:1901798), chromatin organization (GO:0006325), spermatogenesis (GO:0007283), nervous system development (GO:0007399), cell differentiation (GO:0030154)

GO Molecular Function (12): DNA binding (GO:0003677), chromatin binding (GO:0003682), ATP binding (GO:0005524), zinc ion binding (GO:0008270), ATP hydrolysis activity (GO:0016887), histone binding (GO:0042393), histone H3K27me3 reader activity (GO:0061628), ATP-dependent chromatin remodeler activity (GO:0140658), nucleotide binding (GO:0000166), helicase activity (GO:0004386), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (9): chromatin (GO:0000785), heterochromatin (GO:0000792), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), membrane (GO:0016020), NuRD complex (GO:0016581), nuclear speck (GO:0016607), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
CHD3, CHD4, CHD5 subfamily	1
NuRD complex assembly	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
chromatin organization	2
ATP-dependent activity	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
forebrain neuron differentiation	1
spermatid nucleus differentiation	1
signal transduction by p53 class mediator	1
regulation of signal transduction by p53 class mediator	1
positive regulation of intracellular signal transduction	1
cellular component organization	1
developmental process involved in reproduction	1
male gamete generation	1
system development	1
cellular developmental process	1
nucleic acid binding	1
binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transition metal ion binding	1
ribonucleoside triphosphate phosphatase activity	1
protein binding	1
histone H3 reader activity	1
DNA binding	1
chromatin remodeling	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
cation binding	1
chromosome	1
chromatin	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1

Protein interactions and networks

STRING

2733 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHD5	CDH5	P33151	613
CHD5	MTA1	Q13330	563
CHD5	TNP1	P09430	504
CHD5	LOX	P28300	493
CHD5	CDKN2A	P42771	488
CHD5	PRM2	P04554	425
CHD5	CAMTA1	Q9Y6Y1	389
CHD5	GATAD2A	Q86YP4	355
CHD5	BRDT	Q58F21	347
CHD5	TNP2	Q05952	344
CHD5	GATAD2B	Q8WXI9	327
CHD5	ACTR8	Q9H981	318
CHD5	BACC1	Q8IXM2	313
CHD5	PCDHGA8	Q9Y5G5	304
CHD5	PCDHGA5	Q9Y5G8	300

IntAct

58 interactions, top by confidence:

A	B	Type	Score
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
RBBP7	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
GATAD2B	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
HDAC1	TNRC18	psi-mi:“MI:0914”(association)	0.790
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
GATAD2A	CDK2AP1	psi-mi:“MI:0914”(association)	0.730
CDK2AP1	MTA2	psi-mi:“MI:0914”(association)	0.730
HDAC1	ZNF609	psi-mi:“MI:0914”(association)	0.730
RBBP7	HAT1	psi-mi:“MI:0914”(association)	0.730
MBD3	CDK2AP1	psi-mi:“MI:0914”(association)	0.730
ZNF219	CDK2AP1	psi-mi:“MI:0914”(association)	0.640
GATAD2B	MTA2	psi-mi:“MI:0914”(association)	0.640
CSNK2A2	PES1	psi-mi:“MI:0914”(association)	0.640
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
EGFR	CHD5	psi-mi:“MI:0915”(physical association)	0.550
CHAF1B	H4C16	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
RBBP4	TNRC18	psi-mi:“MI:0914”(association)	0.530
RBBP7	SMARCA5	psi-mi:“MI:0914”(association)	0.530
RBBP7	EPOP	psi-mi:“MI:0914”(association)	0.530
MBD3L1	CDK2AP1	psi-mi:“MI:0914”(association)	0.530

BioGRID (111): CHD5 (Affinity Capture-MS), CHD5 (Affinity Capture-MS), CHD5 (Affinity Capture-MS), MTA2 (Affinity Capture-Western), HDAC1 (Affinity Capture-Western), RBBP7 (Affinity Capture-Western), MBD3 (Affinity Capture-Western), HIST3H3 (Affinity Capture-Western), CHD4 (Affinity Capture-Western), GATAD2B (Affinity Capture-MS), RBBP7 (Affinity Capture-MS), RBBP4 (Affinity Capture-MS), MTA1 (Affinity Capture-MS), GATAD2A (Affinity Capture-MS), MBD2 (Affinity Capture-MS)

ESM2 similar proteins: A2A8L1, A2BGR3, A3KFM7, A7E320, B2RRD7, D3ZA12, D3ZD32, E1B7X9, E7EZF3, F4J9M5, F4JTF6, F4K128, F8VPZ5, G5EBZ4, G5EDG2, O14139, O75164, O97159, P32657, P34305, P38144, P55201, Q03468, Q12873, Q14839, Q22516, Q27746, Q4P3S3, Q5RD88, Q640I9, Q6P1G2, Q6P5D3, Q6PDQ2, Q6ZRS2, Q7G8Y3, Q7TMI3, Q7TPK1, Q7Z478, Q8BRB7, Q8TD26

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

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 57 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
Regulation of TP53 Activity through Acetylation	7	74.4×	6e-10
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	7	62.0×	1e-09
RNA Polymerase I Transcription Initiation	8	41.7×	1e-09
NuRD complex assembly	11	36.1×	2e-12
Regulation of PTEN gene transcription	8	33.2×	4e-09
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	9	31.9×	9e-10
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	8	27.2×	2e-08
Interaction of NuRD complexes with transcription factors	9	26.6×	2e-09

GO biological processes:

GO term	Partners	Fold	FDR
regulation of stem cell differentiation	7	101.2×	7e-11
DNA methylation-dependent constitutive heterochromatin formation	5	51.3×	4e-06
chromatin remodeling	10	13.8×	3e-07
nucleosome assembly	5	13.2×	2e-03
chromatin organization	6	11.2×	9e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	28
Uncertain significance	423
Likely benign	52
Benign	19

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
2022088	NM_015557.3(CHD5):c.3684del (p.Asn1229fs)	Pathogenic
2104557	NM_015557.3(CHD5):c.5830C>T (p.Gln1944Ter)	Pathogenic
2181026	NM_015557.3(CHD5):c.1370_1371insAG (p.Cys457Ter)	Pathogenic
3376973	NM_015557.3(CHD5):c.1721del (p.Leu574fs)	Pathogenic
3901205	NM_015557.3(CHD5):c.3056del (p.Leu1019fs)	Pathogenic
4075496	NM_015557.3(CHD5):c.4180C>T (p.Arg1394Ter)	Pathogenic
4536260	NM_015557.3(CHD5):c.2129G>A (p.Trp710Ter)	Pathogenic
4813050	NM_015557.3(CHD5):c.457G>T (p.Glu153Ter)	Pathogenic
58041	GRCh38/hg38 1p36.32-36.31(chr1:4799319-6129675)x3	Pathogenic
1213025	NM_015557.3(CHD5):c.2792G>A (p.Arg931Gln)	Likely pathogenic
1321987	NM_015557.3(CHD5):c.4171+5G>A	Likely pathogenic
2444409	NM_015557.3(CHD5):c.4572C>A (p.Tyr1524Ter)	Likely pathogenic
2497742	NM_015557.3(CHD5):c.1490_1496del (p.Leu497fs)	Likely pathogenic
2663914	NM_015557.3(CHD5):c.2795T>G (p.Leu932Arg)	Likely pathogenic
2691722	NM_015557.3(CHD5):c.3988C>T (p.Gln1330Ter)	Likely pathogenic
3024552	NM_015557.3(CHD5):c.3187G>A (p.Glu1063Lys)	Likely pathogenic
3251189	NM_015557.3(CHD5):c.1590+1G>T	Likely pathogenic
3251946	NM_015557.3(CHD5):c.5596_5597delinsTT (p.Glu1866Leu)	Likely pathogenic
3375462	NM_015557.3(CHD5):c.139C>T (p.Leu47Phe)	Likely pathogenic
3376984	NM_015557.3(CHD5):c.3305C>A (p.Ala1102Glu)	Likely pathogenic
3382657	NM_015557.3(CHD5):c.2552G>A (p.Arg851His)	Likely pathogenic
3767292	NM_015557.3(CHD5):c.5556del (p.Ala1853fs)	Likely pathogenic
3832812	NM_015557.3(CHD5):c.3370C>T (p.Pro1124Ser)	Likely pathogenic
4813049	NM_015557.3(CHD5):c.840dup (p.Ile281fs)	Likely pathogenic
4813468	NM_015557.3(CHD5):c.3366G>C (p.Trp1122Cys)	Likely pathogenic
4819624	NM_015557.3(CHD5):c.3397C>T (p.Arg1133Cys)	Likely pathogenic
4820088	NM_015557.3(CHD5):c.2514del (p.Ile839fs)	Likely pathogenic
995776	NM_015557.3(CHD5):c.612dup (p.Ser205fs)	Likely pathogenic
995778	NM_015557.3(CHD5):c.1279G>A (p.Glu427Lys)	Likely pathogenic
995779	NM_015557.3(CHD5):c.1786C>T (p.Arg596Ter)	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

13034 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:6106671:T:A	E1896V	1.000
1:6106755:A:G	L1868P	1.000
1:6106758:A:G	L1867P	1.000
1:6106767:A:G	L1864P	1.000
1:6106776:A:G	L1861P	1.000
1:6109803:A:G	L1857P	1.000
1:6109806:A:T	V1856D	1.000
1:6109815:G:T	A1853D	1.000
1:6109848:A:G	L1842P	1.000
1:6109858:G:C	H1839D	1.000
1:6109859:G:C	S1838R	1.000
1:6109859:G:T	S1838R	1.000
1:6109861:T:G	S1838R	1.000
1:6109869:A:G	L1835P	1.000
1:6109956:A:G	L1806P	1.000
1:6109986:A:G	L1796P	1.000
1:6109989:A:G	L1795P	1.000
1:6110397:A:C	F1793L	1.000
1:6110397:A:T	F1793L	1.000
1:6110399:A:G	F1793L	1.000
1:6110401:C:A	R1792M	1.000
1:6110410:A:G	L1789P	1.000
1:6110508:C:A	W1756C	1.000
1:6110508:C:G	W1756C	1.000
1:6110510:A:G	W1756R	1.000
1:6110510:A:T	W1756R	1.000
1:6111793:A:G	L1744P	1.000
1:6111802:T:A	D1741V	1.000
1:6111867:C:A	W1719C	1.000
1:6111867:C:G	W1719C	1.000

dbSNP variants (sampled 300 via entrez): RS1000066166 (1:6166820 T>C), RS1000147571 (1:6170661 G>A), RS1000196057 (1:6131757 G>T), RS1000215266 (1:6121936 T>C,G), RS1000325045 (1:6162521 G>A,C), RS1000368757 (1:6116718 A>T), RS1000375405 (1:6175618 T>C), RS1000382138 (1:6152453 G>A), RS1000423395 (1:6165916 T>C), RS1000426104 (1:6157863 C>T), RS1000435247 (1:6170454 G>A), RS1000483715 (1:6136956 C>A,T), RS1000499832 (1:6122888 G>A), RS1000510648 (1:6133018 C>A), RS1000533254 (1:6126103 G>A)

Disease associations

OMIM: gene MIM:610771 | disease phenotypes: MIM:619873, MIM:610805, MIM:617183

GenCC curated gene-disease

Disease	Classification	Inheritance
parenti-mignot neurodevelopmental syndrome	Strong	Autosomal dominant
schizophrenia	Limited	Unknown

Mondo (7): parenti-mignot neurodevelopmental syndrome (MONDO:0859249), congenital heart disease (MONDO:0005453), congenital anomaly of kidney and urinary tract (MONDO:0019719), neurodevelopmental disorder (MONDO:0700092), Harel-Yoon syndrome (MONDO:0014958), intellectual disability (MONDO:0001071), schizophrenia (MONDO:0005090)

Orphanet (3): Renal or urinary tract malformation (Orphanet:93545), Ocular anomalies-axonal neuropathy-developmental delay syndrome (Orphanet:496790), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
C566906	Cakut (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
aristolochic acid I	increases expression	1
fluorene-9-bisphenol	increases expression	1
propionaldehyde	increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	affects methylation	1
pentanal	increases expression	1
ICG 001	increases expression	1
(+)-JQ1 compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Aldehydes	increases expression	1
Cisplatin	decreases expression	1
Dinitrochlorobenzene	affects binding	1
Estradiol	increases expression	1
Lead	affects expression	1
Methapyrilene	increases methylation	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Acrylamide	decreases expression	1
S-Nitrosoglutathione	affects expression	1

Cellosaurus cell lines

6 cell lines: 3 embryonic stem cell, 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A0R4	SEES3-1V human CHD5, clone1	Embryonic stem cell	Male
CVCL_A0R5	SEES3-1V human CHD5, clone2	Embryonic stem cell	Male
CVCL_A0R6	SEES3-1V human CHD5, clone3	Embryonic stem cell	Male
CVCL_B8DM	Abcam HCT 116 CHD5 KO	Cancer cell line	Male
CVCL_B8U4	Abcam MCF-7 CHD5 KO	Cancer cell line	Female
CVCL_B9FV	Abcam A-549 CHD5 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety