CHD1

gene
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Summary

CHD1 (chromodomain helicase DNA binding protein 1, HGNC:1915) is a protein-coding gene on chromosome 5q15-q21.1, encoding ATP-dependent chromatin remodeler CHD1 (O14646). ATP-dependent chromatin-remodeling factor which functions as substrate recognition component of the transcription regulatory histone acetylation (HAT) complex SAGA.

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.

Source: NCBI Gene 1105 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): Pilarowski-Bjornsson syndrome (Strong, GenCC) — +1 more curated relationship
  • GWAS associations: 9
  • Clinical variants (ClinVar): 481 total — 3 pathogenic, 8 likely-pathogenic
  • Phenotypes (HPO): 27
  • Druggable target: yes
  • MANE Select transcript: NM_001270

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:1915
Approved symbolCHD1
Namechromodomain helicase DNA binding protein 1
Location5q15-q21.1
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000153922
Ensembl biotypeprotein_coding
OMIM602118
Entrez1105

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 8 retained_intron, 4 protein_coding, 3 nonsense_mediated_decay

ENST00000414220, ENST00000505657, ENST00000505982, ENST00000508756, ENST00000511067, ENST00000511628, ENST00000512392, ENST00000512844, ENST00000513064, ENST00000514344, ENST00000614616, ENST00000706140, ENST00000706141, ENST00000926040, ENST00000926041

RefSeq mRNA: 3 — MANE Select: NM_001270 NM_001270, NM_001364113, NM_001376194

CCDS: CCDS34204, CCDS93752

Canonical transcript exons

ENST00000614616 — 36 exons

ExonStartEnd
ENSE000020817249887068798870803
ENSE000035147239886975498869882
ENSE000036460279886849598868635
ENSE000037915429886340898863586
ENSE000039947919888127998881375
ENSE000039947939889719398897320
ENSE000039947949885997298860068
ENSE000039947989889948098899705
ENSE000039948009889825698898434
ENSE000039948019890118698901335
ENSE000039948029885398598856725
ENSE000039948069890290098902964
ENSE000039948079892853998929007
ENSE000039948089887359398873723
ENSE000039948099887955298879728
ENSE000039948109888907698889238
ENSE000039948129887639898876558
ENSE000039948159892633498926534
ENSE000039948179887205198872201
ENSE000039948249887241798872555
ENSE000039948259889622698896442
ENSE000039948279890489798905098
ENSE000039948289888557898885649
ENSE000039948299888308898883237
ENSE000039948309885818098858390
ENSE000039948319885896498859015
ENSE000039948329888197598882123
ENSE000039948339887507298875113
ENSE000039948349890081198901082
ENSE000039948419889341698893606
ENSE000039948429888107698881171
ENSE000039948439889866498898764
ENSE000039948449888808898888240
ENSE000039948479890379298903908
ENSE000039948499889252598892713
ENSE000039948509889459798894686

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 96.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.3039 / max 1000.0594, expressed in 1805 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter IDTPM avgSamples expressed
6274123.36761800
627422.48091143
627371.4093460
627430.9731509
627380.7672235
627390.4906200
627400.3592166
627440.182465
627360.165263
627300.108336

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
calcaneal tendonUBERON:000370196.31gold quality
cauda epididymisUBERON:000436095.93gold quality
adrenal tissueUBERON:001830395.47gold quality
colonic epitheliumUBERON:000039795.46gold quality
bone marrowUBERON:000237195.02gold quality
thymusUBERON:000237094.28gold quality
monocyteCL:000057694.12gold quality
mononuclear cellCL:000084294.05gold quality
left ovaryUBERON:000211993.98gold quality
ventricular zoneUBERON:000305393.96gold quality
leukocyteCL:000073893.91gold quality
caput epididymisUBERON:000435893.87gold quality
right ovaryUBERON:000211893.74gold quality
right testisUBERON:000453493.59gold quality
left uterine tubeUBERON:000130393.57gold quality
left testisUBERON:000453393.50gold quality
corpus epididymisUBERON:000435993.32gold quality
peritoneumUBERON:000235893.27gold quality
omental fat padUBERON:001041493.27gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047393.13gold quality
cartilage tissueUBERON:000241892.99gold quality
testisUBERON:000047392.93gold quality
ovaryUBERON:000099292.91gold quality
right lungUBERON:000216792.83gold quality
mucosa of sigmoid colonUBERON:000499392.60gold quality
adipose tissue of abdominal regionUBERON:000780892.60gold quality
superficial temporal arteryUBERON:000161492.47gold quality
mammary ductUBERON:000176592.47gold quality
tibial nerveUBERON:000132392.33gold quality
bone marrow cellCL:000209292.25gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-MTAB-6379no1255.45
E-GEOD-106540no852.58
E-ANND-3no0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI3, KMT2A, NKX3-1, SMARCA1, SMARCA5, SSRP1

miRNA regulators (miRDB)

191 targeting CHD1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-3163100.0077.238605
HSA-MIR-30A-5P100.0076.313233
HSA-MIR-30B-5P100.0076.293248
HSA-MIR-30C-5P100.0076.293248
HSA-MIR-30D-5P100.0076.323233
HSA-MIR-30E-5P100.0076.323242
HSA-MIR-4262100.0073.263931
HSA-MIR-4425100.0067.591049
HSA-LET-7A-3P100.0074.033932
HSA-LET-7B-3P100.0074.083913
HSA-LET-7F-1-3P100.0074.023928
HSA-MIR-98-3P100.0074.083907
HSA-MIR-3613-3P100.0076.367965
HSA-MIR-656-3P100.0072.152788
HSA-MIR-4682100.0068.891258
HSA-MIR-4747-5P100.0067.902681
HSA-MIR-5196-5P100.0067.982761
HSA-MIR-513A-5P100.0069.772465
HSA-MIR-5011-5P100.0083.465820
HSA-MIR-3667-3P99.9967.171636
HSA-MIR-181A-5P99.9972.962995
HSA-MIR-181B-5P99.9972.972996
HSA-MIR-181C-5P99.9972.952996
HSA-MIR-181D-5P99.9973.042997
HSA-MIR-548C-3P99.9974.017587
HSA-MIR-34A-5P99.9971.211784
HSA-MIR-449A99.9971.051776
HSA-MIR-1213699.9872.815713
HSA-MIR-548N99.9871.944170
HSA-MIR-480399.9871.993117

Literature-anchored findings (GeneRIF, showing 40)

  • associates with NCoR and histone deacetylase as well as with RNA splicing proteins (PMID:12890497)
  • yeast and human CHD1 have diverged in their ability to discriminate covalently modified histones and link histone modification-recognition and non-covalent chromatin remodeling activities within a single human protein (PMID:16263726)
  • the structure of the tandem arrangement of the human CHD1 chromodomains, and its interactions with histone tails (PMID:16372014)
  • analysis of chromodomains in human and fungal Chd1 (PMID:17098252)
  • overexpression of CHD1L could sustain tumor cell survival by preventing Nur77-mediated apoptosis (PMID:19441106)
  • CENP-H-containing complex facilitates deposition of newly synthesized CENP-A into centromeric chromatin in cooperation with FACT and CHD1. (PMID:19625449)
  • Mediator coactivator complex, which controls PIC assembly, is also necessary for CHD1 recruitment (PMID:21979373)
  • that hPaf1/PD2 in association with MLL1 regulates methylation of H3K4 residues, as well as interacts and regulates nuclear shuttling of chromatin remodeling protein CHD1, facilitating its function in pancreatic cancer cells (PMID:22046413)
  • CHD1, was the most “dietary sensitive” genes, as methylation of their promoters was associated with intakes of at least two out of the eight dietary methyl factors examined. (PMID:22048254)
  • findings collectively suggest that distinct CHD1-associated alterations of genomic structure evolve during and are required for the development of prostate cancer (PMID:22139082)
  • findings suggest that CHD1 deletion may underlie cell invasiveness in a subset of prostate cancers, and indicate a possible novel role of altered chromatin remodeling in prostate tumorigenesis (PMID:22179824)
  • CHD1 is the 5q21 tumor suppressor gene in prostate cancer (PMID:23492366)
  • Data indicate that chromodomain-helicase-DNA-binding protein CHD1, neoplasm protein GREB1 and karyopherin alpha 2 protein KPNA2 as critical mediators of miR-26a and miR-26b elicited cell growth. (PMID:24735615)
  • The double chromodomains of CHD1 adopt an ‘open pocket’ to interact with the free N-terminal amine of H3K4, and the open pocket permits the NS1 mimic to bind in a distinct conformation. (PMID:24853335)
  • results demonstrate the ability of confocal microscopy and FISH to identify the cell-to-cell differences in common gene fusions such as TMPRSS2-ERG that may arise independently within the same tumor focus (PMID:25175909)
  • CHD1 and CHD2 act as positive regulators of HIV-1 gene expression. (PMID:25297984)
  • identify coordinate loss of MAP3K7 and CHD1 as a unique driver of aggressive prostate cancer development (PMID:25770290)
  • We have identified CHD1 as the RUNX1 fusion partner in acute myeloid leukemia with t(5;21)(q21;q22). (PMID:25879624)
  • These data link the assembly of methylated KDM1A and CHD1 with AR-dependent transcription and genomic translocations, thereby providing mechanistic insight into the formation of TMPRSS2-ERG gene fusions during prostate-tumor evolution. (PMID:26751641)
  • These results indicate that CHD1 is a positive regulator of influenza virus multiplication and suggest a role for chromatin remodeling in the control of the influenza virus life cycle. (PMID:26792750)
  • The authors have identified an additional conserved domain C-terminal to the SANT-SLIDE domain and determined its structure by multidimensional heteronuclear NMR spectroscopy. They have termed this domain the CHD1 helical C-terminal (CHCT) domain as it is comprised of five alpha-helices arranged in a variant helical bundle topology. (PMID:27591891)
  • examined the role of CHD1 in DNA double-strand break (DSB) repair in prostate cancer cells; findings show that CHD1 is required for the recruitment of CtIP to chromatin and subsequent end resection during DNA DSB repair; data support a role for CHD1 in opening the chromatin around the DSB to facilitate the recruitment of homologous recombination (HR) proteins (PMID:27596623)
  • In PTEN-deficient prostate and breast cancers, CHD1 depletion profoundly and specifically suppressed cell proliferation, cell survival and tumorigenic potential. (PMID:28166537)
  • CHD1 loss is associated with an increased sensitivity to PARP inhibition and anti-cancer drugs that induce DNA intercross-strand links in prostate tumors. (PMID:28383660)
  • CHD1 is required for the induction of osteoblast-specific gene expression, extracellular-matrix mineralization and ectopic bone formation in vivo. Genome-wide occupancy analyses revealed increased CHD1 occupancy around the transcriptional start site of differentiation-activated genes. (PMID:28475736)
  • Increased CHD1L protein expression was significantly associated with poor overall survival in pancreatic cancer patients. (PMID:28646284)
  • Our results suggest that variants in CHD1 can lead to diverse phenotypic outcomes; however, the neurodevelopmental phenotype appears to be limited to patients with missense variants, which is compatible with a dominant negative mechanism of disease. (PMID:28866611)
  • CHD1 facilitates substrate handover from XPC to the downstream TFIIH (transcription factor IIH). (PMID:29018037)
  • Identified a unique N-terminal region of CHD1 that inhibits the DNA binding, ATPase, and chromatin assembly and remodeling activities of CHD1. CHD1 lacking the N terminus was more active in rescuing the defects in gammaH2AX formation and CtIP recruitment in CHD1-KO cells than full-length CHD1, suggesting the N terminus is a negative regulator in cells. (PMID:29529298)
  • SPOP-mutated mCRPCs are strongly enriched for CHD1 loss. These tumors appear highly sensitive to abiraterone treatment. (PMID:30068710)
  • CHD1 functions as a tumor suppressor in the prostate by constraining AR binding/function to limit tumor progression. (PMID:30930119)
  • The chromatin remodeler Chd1 regulates cohesin in budding yeast and humans. (PMID:31222142)
  • Loss of CHD1 Promotes Heterogeneous Mechanisms of Resistance to AR-Targeted Therapy via Chromatin Dysregulation. (PMID:32220301)
  • CHD1 loss negatively influences metastasis-free survival in R0-resected prostate cancer patients and promotes spontaneous metastasis in vivo. (PMID:33414516)
  • The Chromatin Remodeling Complex CHD1 Regulates the Primitive State of Mesenchymal Stromal Cells to Control Their Stem Cell Supporting Activity. (PMID:33593142)
  • MAP3K7 Loss Drives Enhanced Androgen Signaling and Independently Confers Risk of Recurrence in Prostate Cancer with Joint Loss of CHD1. (PMID:33846123)
  • Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex. (PMID:34424918)
  • SPOP and CHD1 alterations in prostate cancer: Relationship with PTEN loss, tumor grade, perineural infiltration, and PSA recurrence. (PMID:34533858)
  • CHD1 Promotes Sensitivity to Aurora Kinase Inhibitors by Suppressing Interaction of AURKA with Its Coactivator TPX2. (PMID:35771632)
  • MiR-30a-5p/CHD1 axis enhances cisplatin sensitivity of ovarian cancer cells via inactivating the Wnt/beta-catenin pathway. (PMID:36206129)

Cross-species orthologs

3 orthologs

OrganismSymbolGene ID
danio_reriochd1ENSDARG00000103787
mus_musculusChd1ENSMUSG00000023852
rattus_norvegicusChd1ENSRNOG00000014434

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), 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 CHD1O14646 (reviewed: O14646)

Alternative names: Chromo domain-containing protein 1

All UniProt accessions (5): O14646, A0A087WVF4, A0A994J7K7, H0Y8V4, H0Y8Z0

UniProt curated annotations — full annotation on UniProt →

Function. ATP-dependent chromatin-remodeling factor which functions as substrate recognition component of the transcription regulatory histone acetylation (HAT) complex SAGA. Regulates polymerase II transcription. Also required for efficient transcription by RNA polymerase I, and more specifically the polymerase I transcription termination step. Regulates negatively DNA replication. Not only involved in transcription-related chromatin-remodeling, but also required to maintain a specific chromatin configuration across the genome. Is also associated with histone deacetylase (HDAC) activity. Required for the bridging of SNF2, the FACT complex, the PAF complex as well as the U2 snRNP complex to H3K4me3. Functions to modulate the efficiency of pre-mRNA splicing in part through physical bridging of spliceosomal components to H3K4me3. Required for maintaining open chromatin and pluripotency in embryonic stem cells.

Subunit / interactions. Component of the SAGA complex. Interacts with BCLAF1, NCoR, SRP20 and SAFB. Specifically interacts with methylated H3K4me2 and H3K4me3. Interacts with the FACT complex, the PAF complex and the U2 snRNP. Interacts directly with PAF1, SFA3A1, SFA3A2, SFA3A3, SNF2 and SSRP1.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed in many tissues including in the brain, where the highest level of expression is found in the cerebellum and basal ganglia.

Disease relevance. Pilarowski-Bjornsson syndrome (PILBOS) [MIM:617682] An autosomal dominant disorder characterized by developmental delay, speech apraxia, intellectual disability, autism, and facial dysmorphic features. Some patients may have seizures. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The 2 chromodomains are involved in the binding to the histone H3 methyllysine at position 4 (H3K4me3). The CHD1 helical C-terminal domain (CHCT) binds DNA and nucleosomes.

Similarity. Belongs to the SNF2/RAD54 helicase family.

Isoforms (2)

UniProt IDNamesCanonical?
O14646-11yes
O14646-22

RefSeq proteins (3): NP_001261, NP_001351042, NP_001363123 (=MANE)

Domains & families (InterPro)

IDNameType
IPR000330SNF2_NDomain
IPR000953Chromo/chromo_shadow_domDomain
IPR001650Helicase_C-likeDomain
IPR014001Helicase_ATP-bdDomain
IPR016197Chromo-like_dom_sfHomologous_superfamily
IPR023779Chromodomain_CSConserved_site
IPR023780Chromo_domainDomain
IPR025260CHD1-like_CDomain
IPR027417P-loop_NTPaseHomologous_superfamily
IPR038718SNF2-like_sfHomologous_superfamily
IPR040793CDH1_2_SANT_HL1Domain
IPR049730SNF2/RAD54-like_CDomain
IPR056302CHD1-2/Hrp3_HTHDomain

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

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (106 total): modified residue 27, helix 22, compositionally biased region 15, strand 11, region of interest 6, sequence variant 5, domain 4, mutagenesis site 4, turn 4, repeat 3, chain 1, short sequence motif 1, binding site 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

18 structures.

PDBMethodResolution (Å)
9T9FX-RAY DIFFRACTION1.35
9T9HX-RAY DIFFRACTION1.45
9T9IX-RAY DIFFRACTION1.55
5AFWX-RAY DIFFRACTION1.6
4B4CX-RAY DIFFRACTION1.62
9T9EX-RAY DIFFRACTION1.7
9T9GX-RAY DIFFRACTION1.7
4O42X-RAY DIFFRACTION1.87
4NW2X-RAY DIFFRACTION1.9
2B2YX-RAY DIFFRACTION2.35
2B2WX-RAY DIFFRACTION2.4
2B2TX-RAY DIFFRACTION2.45
2B2VX-RAY DIFFRACTION2.65
2B2UX-RAY DIFFRACTION2.95
8UMGX-RAY DIFFRACTION3.1
9EARELECTRON MICROSCOPY3.1
9NH8ELECTRON MICROSCOPY3.2
2N39SOLUTION NMR

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-O14646-F162.630.09

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): 506–513

Post-translational modifications (27): 1688, 215, 216, 237, 241, 250, 252, 471, 1025, 1040, 1081, 1085, 1096, 1098, 1100, 1102, 1161, 1353, 1355, 1356 …

Mutagenesis-validated functional residues (4):

PositionPhenotype
1418–1425abolishes dna-binding.
1429–1436abolishes dna-binding.
1491–1495abolishes dna-binding.
1498–1503abolishes dna-binding.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

IDPathway
R-HSA-9018519Estrogen-dependent gene expression
R-HSA-9943411CHD1 and CHD2 subfamily

MSigDB gene sets: 337 (showing top): YAGI_AML_WITH_INV_16_TRANSLOCATION, MODULE_255, GOBP_HOST_MEDIATED_ACTIVATION_OF_VIRAL_TRANSCRIPTION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MODULE_317, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM, BROWNE_HCMV_INFECTION_16HR_UP, FOXO1_01, GOBP_HOST_MEDIATED_PERTURBATION_OF_VIRAL_PROCESS, FOSTER_TOLERANT_MACROPHAGE_UP, GENTILE_UV_RESPONSE_CLUSTER_D2, BLALOCK_ALZHEIMERS_DISEASE_UP, HFH8_01, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN

GO Biological Process (4): chromatin remodeling (GO:0006338), nucleosome organization (GO:0034728), host-mediated activation of viral transcription (GO:0043923), chromatin organization (GO:0006325)

GO Molecular Function (11): DNA binding (GO:0003677), chromatin binding (GO:0003682), ATP binding (GO:0005524), 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), hydrolase activity (GO:0016787)

GO Cellular Component (5): nuclear chromosome (GO:0000228), chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

CategoryPathways
ESR-mediated signaling1
CHD chromatin remodelers1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure3
chromatin remodeling2
binding2
ATP-dependent activity2
chromosome2
nuclear lumen2
chromatin organization1
protein-DNA complex organization1
host-mediated perturbation of viral transcription1
host-mediated activation of viral process1
cellular component organization1
nucleic acid binding1
adenyl ribonucleotide binding1
purine ribonucleoside triphosphate binding1
ribonucleoside triphosphate phosphatase activity1
protein binding1
histone H3 reader activity1
DNA binding1
ATP-dependent activity, acting on DNA1
nucleoside phosphate binding1
heterocyclic compound binding1
nucleic acid conformation isomerase activity1
catalytic activity, acting on a nucleic acid1
catalytic activity1
nucleus1
intracellular membrane-bounded organelle1
intracellular anatomical structure1

Protein interactions and networks

STRING

4002 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
CHD1RTF1Q92541922
CHD1H3-3AP06351881
CHD1H3C14Q71DI3881
CHD1H3-5Q6NXT2881
CHD1H3C1P02295881
CHD1H3-4Q16695881
CHD1H3-7Q5TEC6881
CHD1SUPT16HQ9Y5B9751
CHD1SUPT5HO00267743
CHD1SETD2Q9BYW2737
CHD1H2AZ1P0C0S5736
CHD1CHD6Q8TD26727
CHD1BPTFQ12830715
CHD1H2BC21Q16778700
CHD1CHD8Q9HCK8696

IntAct

47 interactions, top by confidence:

ABTypeScore
KDM1ACHD1psi-mi:“MI:0914”(association)0.700
CHD1KDM1Apsi-mi:“MI:0407”(direct interaction)0.700
KDM1ACHD1psi-mi:“MI:0915”(physical association)0.700
CHD1KDM1Apsi-mi:“MI:0915”(physical association)0.700
NNOP56psi-mi:“MI:0914”(association)0.530
NRBM47psi-mi:“MI:0914”(association)0.530
EPB41L1AP3B1psi-mi:“MI:0914”(association)0.530
FGF11CHD1psi-mi:“MI:0914”(association)0.530
EHMT2CHD1psi-mi:“MI:0914”(association)0.500
NS1CHD1psi-mi:“MI:0914”(association)0.500
NS1CHD1psi-mi:“MI:0915”(physical association)0.500
CHD1psi-mi:“MI:0407”(direct interaction)0.440
CHD1psi-mi:“MI:0915”(physical association)0.400
TAF4psi-mi:“MI:0914”(association)0.350
KDM1AKIF2Apsi-mi:“MI:0914”(association)0.350
RRP1BZNF785psi-mi:“MI:0914”(association)0.350
MecomESYT2psi-mi:“MI:0914”(association)0.350
ESR1ESYT2psi-mi:“MI:0914”(association)0.350
LRRK2psi-mi:“MI:0914”(association)0.350
BMXSMAPpsi-mi:“MI:0914”(association)0.350
DOCK9CHD1psi-mi:“MI:0914”(association)0.350
NRBM47psi-mi:“MI:0914”(association)0.350

BioGRID (175): CHD1 (Affinity Capture-MS), CHD1 (Protein-peptide), CHD1 (Affinity Capture-MS), CHD1 (Affinity Capture-MS), CHD1 (Affinity Capture-MS), CHD1 (Co-fractionation), CHD1 (Co-fractionation), CHD1 (Co-fractionation), CHD1 (Co-fractionation), CHD1 (Affinity Capture-MS), CHD1 (Affinity Capture-MS), CHD1 (Affinity Capture-MS), CHD1 (Affinity Capture-MS), CHD1 (Affinity Capture-MS), CHD1 (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: 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

1 interactions.

AEffectBMechanism
CHD1“up-regulates activity”SF3abinding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic3
Likely pathogenic8
Uncertain significance357
Likely benign52
Benign10

Top pathogenic / likely-pathogenic (11)

Variant IDHGVSClassification
4088180NM_001270.4(CHD1):c.3888dup (p.Pro1297fs)Pathogenic
438819NM_001270.4(CHD1):c.1853G>A (p.Arg618Gln)Pathogenic
438821NM_001270.4(CHD1):c.1379G>A (p.Arg460Lys)Pathogenic
1710449NM_001270.4(CHD1):c.1978A>G (p.Ile660Val)Likely pathogenic
2429179NM_001270.4(CHD1):c.3133G>A (p.Glu1045Lys)Likely pathogenic
2442344NM_001270.4(CHD1):c.643dup (p.Ser215fs)Likely pathogenic
2582374NM_001270.4(CHD1):c.2569-11A>GLikely pathogenic
3065580NM_001270.4(CHD1):c.490del (p.Ser164fs)Likely pathogenic
3254730NM_001270.4(CHD1):c.2112dup (p.Ser705fs)Likely pathogenic
3383426NM_001270.4(CHD1):c.1132_1144del (p.Gln378fs)Likely pathogenic
4819013NM_001270.4(CHD1):c.1101del (p.Pro368fs)Likely pathogenic

SpliceAI

5020 predictions. Top by Δscore:

VariantEffectΔscore
5:98858388:CAT:Cacceptor_gain1.0000
5:98858960:ATAC:Adonor_loss1.0000
5:98858961:TA:Tdonor_loss1.0000
5:98858962:ACCTG:Adonor_loss1.0000
5:98860069:C:CCacceptor_gain1.0000
5:98860079:T:Cacceptor_gain1.0000
5:98863406:A:ACdonor_gain1.0000
5:98863407:C:CCdonor_gain1.0000
5:98863407:CTTT:Cdonor_gain1.0000
5:98863585:CA:Cacceptor_gain1.0000
5:98863588:T:Cacceptor_gain1.0000
5:98868489:GCTTA:Gdonor_loss1.0000
5:98868490:CTTA:Cdonor_loss1.0000
5:98868491:TTACA:Tdonor_loss1.0000
5:98868492:TA:Tdonor_loss1.0000
5:98868493:A:ACdonor_gain1.0000
5:98868493:A:Cdonor_loss1.0000
5:98868494:C:CAdonor_loss1.0000
5:98868494:C:CCdonor_gain1.0000
5:98868494:CA:Cdonor_gain1.0000
5:98868494:CAA:Cdonor_gain1.0000
5:98868494:CAAT:Cdonor_gain1.0000
5:98868494:CAATG:Cdonor_gain1.0000
5:98868631:CTCAA:Cacceptor_gain1.0000
5:98868632:TCAA:Tacceptor_gain1.0000
5:98868633:CAA:Cacceptor_gain1.0000
5:98868633:CAAC:Cacceptor_gain1.0000
5:98868634:AA:Aacceptor_gain1.0000
5:98868634:AACT:Aacceptor_loss1.0000
5:98868635:ACTAA:Aacceptor_loss1.0000

AlphaMissense

11382 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
5:98859997:G:TA1500D1.000
5:98859998:C:GA1500P1.000
5:98860002:C:AK1498N1.000
5:98860002:C:GK1498N1.000
5:98860004:T:CK1498E1.000
5:98860007:A:CY1497D1.000
5:98860007:A:TY1497N1.000
5:98860009:A:GL1496S1.000
5:98860016:G:CH1494D1.000
5:98860017:T:AL1493F1.000
5:98860017:T:GL1493F1.000
5:98860018:A:GL1493S1.000
5:98860032:A:CF1488L1.000
5:98860032:A:TF1488L1.000
5:98860033:A:GF1488S1.000
5:98860034:A:GF1488L1.000
5:98860039:G:AT1486I1.000
5:98860041:A:CF1485L1.000
5:98860041:A:TF1485L1.000
5:98860042:A:CF1485C1.000
5:98860042:A:GF1485S1.000
5:98860043:A:CF1485V1.000
5:98860043:A:GF1485L1.000
5:98860043:A:TF1485I1.000
5:98860048:G:AS1483F1.000
5:98860049:A:GS1483P1.000
5:98860051:A:TV1482E1.000
5:98860053:A:CF1481L1.000
5:98860053:A:TF1481L1.000
5:98860054:A:CF1481C1.000

dbSNP variants (sampled 300 via entrez): RS1000040891 (5:98904357 T>A,C), RS1000048149 (5:98892234 T>C), RS1000062578 (5:98910352 G>A), RS1000140444 (5:98913486 A>T), RS1000178679 (5:98910162 T>C), RS1000242887 (5:98866901 G>C), RS1000248631 (5:98855261 A>G), RS1000294089 (5:98854321 A>T), RS1000326016 (5:98905137 T>A,C), RS1000357799 (5:98861894 A>C,G), RS1000393804 (5:98885302 G>C), RS1000394655 (5:98872873 A>G), RS1000409709 (5:98921429 G>A), RS1000459011 (5:98879781 A>C,G,T), RS1000461968 (5:98921667 T>C)

Disease associations

OMIM: gene MIM:602118 | disease phenotypes: MIM:617682, MIM:617862

GenCC curated gene-disease

DiseaseClassificationInheritance
Pilarowski-Bjornsson syndromeStrongAutosomal dominant
complex neurodevelopmental disorderLimitedAutosomal recessive

ClinGen Gene-Disease Validity (1)

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

DiseaseClassificationInheritance
complex neurodevelopmental disorderLimitedAD

Mondo (4): Pilarowski-Bjornsson syndrome (MONDO:0060568), neurodevelopmental disorder (MONDO:0700092), complex neurodevelopmental disorder (MONDO:0100038), neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy (MONDO:0060640)

Orphanet (2): Intellectual disability-autism-speech apraxia-craniofacial dysmorphism syndrome (Orphanet:529965), Non-specific syndromic intellectual disability (Orphanet:528084)

HPO phenotypes

27 total (27 of 27 shown, HPO-id order):

HPOTerm
HP:0000006Autosomal dominant inheritance
HP:0000256Macrocephaly
HP:0000307Pointed chin
HP:0000494Downslanted palpebral fissures
HP:0000527Long eyelashes
HP:0000574Thick eyebrow
HP:0000629Periorbital fullness
HP:0000717Autism
HP:0000729Autistic behavior
HP:0000733Motor stereotypy
HP:0001211Abnormal fingertip morphology
HP:0001212Prominent fingertip pads
HP:0001249Intellectual disability
HP:0001250Seizure
HP:0001252Hypotonia
HP:0001263Global developmental delay
HP:0001290Generalized hypotonia
HP:0002007Frontal bossing
HP:0002721Immunodeficiency
HP:0003593Infantile onset
HP:0007874Almond-shaped palpebral fissure
HP:0008897Postnatal growth retardation
HP:0010648Dermal translucency
HP:0011098Speech apraxia
HP:0011229Broad eyebrow
HP:0011800Midface retrusion
HP:0012393Allergy

GWAS associations

9 associations (top):

StudyTraitp-value
GCST001304_1Renal sinus fat7.000000e-06
GCST002127_15Periodontitis (Mean PAL)9.000000e-06
GCST004600_155Eosinophil percentage of white cells2.000000e-13
GCST004606_120Eosinophil count1.000000e-10
GCST004617_100Eosinophil percentage of granulocytes2.000000e-13
GCST004623_5Neutrophil percentage of granulocytes3.000000e-12
GCST004631_30Basophil percentage of white cells6.000000e-10
GCST90002382_111Eosinophil percentage of white cells3.000000e-18
GCST90002396_307Mean reticulocyte volume7.000000e-13

EFO canonical traits (7, from GWAS)

EFO IDTrait name
EFO:0004864renal sinus adipose tissue measurement
EFO:0007991eosinophil percentage of leukocytes
EFO:0004842eosinophil count
EFO:0007996eosinophil percentage of granulocytes
EFO:0007994neutrophil percentage of granulocytes
EFO:0007992basophil percentage of leukocytes
EFO:0010701mean reticulocyte volume

MeSH disease descriptors (1)

DescriptorNameTree numbers
D065886Neurodevelopmental DisordersF03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523123 (SINGLE PROTEIN)

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

ChEMBL bioactivities

32 potent at pChembl≥5 of 57 total, top 32 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
6.40IC50400nMCHEMBL6162155
6.21IC50620nMCHEMBL6167419
6.12IC50760nMCHEMBL6166574
6.10IC50800nMCHEMBL6147437
6.10IC50800nMCHEMBL6170691
6.00Kd1000nMCHEMBL6151379
6.00IC501000nMCHEMBL6165658
5.89IC501300nMCHEMBL6161222
5.85IC501400nMCHEMBL6159947
5.80IC501600nMCHEMBL6171654
5.80IC501600nMCHEMBL6146090
5.77IC501700nMCHEMBL6164059
5.77IC501700nMCHEMBL6170209
5.75IC501800nMCHEMBL6163641
5.72IC501920nMCHEMBL6163845
5.62IC502400nMCHEMBL6146760
5.57IC502700nMCHEMBL6160342
5.40IC504000nMCHEMBL6150008
5.39IC504100nMCHEMBL6169498
5.37Kd4300nMCHEMBL6170209
5.31IC504900nMCHEMBL1829307
5.30IC505000nMCHEMBL6165257
5.30IC505000nMCHEMBL6170545
5.30IC505000nMCHEMBL6163786
5.23IC505900nMCHEMBL6174769
5.23IC505900nMCHEMBL6152866
5.22IC506000nMCHEMBL6173559
5.19IC506400nMCHEMBL6151379
5.19IC506400nMCHEMBL6169721
5.16IC507000nMCHEMBL6165999
5.05IC509000nMCHEMBL6161724
5.00IC501e+04nMCHEMBL6170241

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Valproic Aciddecreases expression, increases expression, increases methylation4
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxidedecreases expression3
bisphenol Aincreases methylation, affects cotreatment, decreases expression2
Formaldehydedecreases expression2
Indomethacindecreases expression, affects cotreatment2
Tobacco Smoke Pollutionincreases expression2
Cyclosporineincreases expression2
aristolochic acid Idecreases expression1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamidedecreases expression1
GSK-J4increases expression1
FR900359affects phosphorylation1
bisphenol Faffects cotreatment, decreases expression1
TAK-243decreases sumoylation1
dicrotophosdecreases expression1
tris(1,3-dichloro-2-propyl)phosphateincreases expression1
sodium arseniteincreases reaction, affects binding1
cobaltous chlorideincreases expression1
coumarinaffects phosphorylation1
beta-methylcholineaffects expression1
pinosylvinincreases expression1
di-n-butylphosphoric acidaffects expression1
perfluorooctane sulfonic aciddecreases expression1
K 7174increases expression1
bisphenol Saffects cotreatment, decreases expression1
jinfukangdecreases expression1
Irinotecandecreases expression1
Resveratrolaffects cotreatment, increases expression1
Air Pollutantsincreases abundance, decreases expression1
Caffeineaffects phosphorylation1
Dexamethasoneaffects cotreatment, decreases expression1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL4377349BindingBinding affinity to CHD1 (unknown origin) assessed as induction of thermal shifts at 20 uM measured for 25 mins by SYPRO orange dye thermal shift assayDiscovery of a Potent and Selective Fragment-like Inhibitor of Methyllysine Reader Protein Spindlin 1 (SPIN1). — J Med Chem

Cellosaurus cell lines

7 cell lines: 3 embryonic stem cell, 3 cancer cell line, 1 transformed cell line

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

CellosaurusNameCategorySex
CVCL_A0Q8SEES3-1V human CHD1, clone1Embryonic stem cellMale
CVCL_A0Q9SEES3-1V human CHD1, clone2Embryonic stem cellMale
CVCL_A0R0SEES3-1V human CHD1, clone3Embryonic stem cellMale
CVCL_B2UBAbcam HEK293T CHD1 KOTransformed cell lineFemale
CVCL_C0UVKUCaP13Cancer cell lineMale
CVCL_SI85HAP1 CHD1 (-) 1Cancer cell lineMale
CVCL_SI86HAP1 CHD1 (-) 2Cancer cell lineMale

Clinical trials (associated diseases)

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

TrialPhaseStatusTitle
NCT04586348PHASE4UNKNOWNPrenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115PHASE4UNKNOWNDouble-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,
NCT02559102PHASE3COMPLETEDDexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079PHASE3COMPLETEDStudy of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480PHASE3RECRUITINGReducing Missed Appointments
NCT07377032PHASE3RECRUITINGTAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959PHASE2COMPLETEDSulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348PHASE2RECRUITINGSertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372PHASE2COMPLETEDSafety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191PHASE1COMPLETEDNeuroModulation Technique Treatment of Autism
NCT04475848PHASE1COMPLETEDA Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398PHASE1COMPLETEDIAMA-6 Oral Dose Study in Healthy Adults
NCT06310681Not specifiedCOMPLETEDPilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049Not specifiedNOT_YET_RECRUITINGCognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder
NCT01783041PHASE2/PHASE3COMPLETEDEffect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385PHASE2/PHASE3RECRUITINGFetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098EARLY_PHASE1NOT_YET_RECRUITINGCentral Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783Not specifiedCOMPLETEDCYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504Not specifiedRECRUITINGStudying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784Not specifiedUNKNOWNHigh Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791Not specifiedCOMPLETEDNutrition and Pregnancy Intervention Study
NCT01942525Not specifiedUNKNOWNInfluence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170Not specifiedCOMPLETEDEtiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649Not specifiedACTIVE_NOT_RECRUITINGEnhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191Not specifiedTERMINATEDBiomarkers, Neurodevelopment and Preterm Infants
NCT02690675Not specifiedCOMPLETEDIron Supplement Effect on Child Development
NCT02694003Not specifiedCOMPLETEDBetter Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894Not specifiedCOMPLETEDFamily Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674Not specifiedUNKNOWNGood Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157Not specifiedCOMPLETEDAnalyzing Retinal Microanatomy in ROP
NCT02898298Not specifiedCOMPLETEDPositive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780Not specifiedUNKNOWNIntroduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293Not specifiedCOMPLETEDn-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644Not specifiedCOMPLETEDImproving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991Not specifiedUNKNOWNEarly Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189Not specifiedTERMINATEDEffect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028Not specifiedCOMPLETEDDevelopmental Origins of Mental Health Disorders
NCT03148782Not specifiedCOMPLETEDBrain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104Not specifiedCOMPLETEDNeurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375Not specifiedRECRUITINGSQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism