CHD4
CHD4 (ATP-dependent chromatin remodeler CHD4) is a protein that switches other genes on and off. The public catalogues list it as an oncogene driver and a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Endometrial cancer, Colorectal cancer, Renal cell carcinoma and 5 more.
Overview
ATP-dependent chromatin-remodeling factor that binds and distorts nucleosomal DNA. Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin. Localises to acetylated damaged chromatin in a ZMYND8-dependent manner, to promote transcriptional repression and double-strand break repair by homologous recombination.
Open Targets scores its association with cancer at 0.75 (direct and indirect evidence; datatypes literature 0.98, affected pathway 0.28, genetic association 0.00, somatic mutation 0.95). IntOGen calls it a driver in 9 cohorts (6 activating, 3 loss-of-function), covering Acute Lymphoblastic Leukaemia, Renal Clear Cell Carcinoma, Colon Adenocarcinoma, Head and Neck Squamous Cell Carcinoma, Neuroblastoma, Endometrial Carcinoma and others.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · CHD4 (ATP-dependent chromatin remodeler CHD4) is a protein that switches other genes on and off. The public catalogues list it as an oncogene driver and a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Endometrial cancer, Colorectal cancer, Renal cell carcinoma and 5 more.
- 1 · What it is
CHD4 (ATP-dependent chromatin remodeler CHD4) is a protein that switches other genes on and off. The public catalogues list it as an oncogene driver and a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Endometrial cancer, Colorectal cancer, Renal cell carcinoma and 5 more.
- 2 · What goes wrong in cancer
ATP-dependent chromatin-remodeling factor that binds and distorts nucleosomal DNA. Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin.
- 3 · How drugs use it
No product in this corpus aims at CHD4 yet. Transcription factors have no pocket to plug, so drugs either degrade them or block the partner protein they need to dock on DNA.
External identifiers
Sources: HGNC HGNC:1919 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q14839 (protein name, function text, keywords and locations (REST API)); Open Targets ENSG00000111642 (association with cancer (MONDO_0004992) 0.75; per-cancer scores at or above 0.5: colorectal cancer 0.57, gastric cancer 0.52, endometrial cancer 0.55, melanoma 0.52, skin cancer 0.53 (GraphQL API, CC0)); IntOGen CHD4 (driver in 9 cohorts (Act 6, LoF 3); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
ATP-dependent chromatin-remodeling factor that binds and distorts nucleosomal DNA. Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin. Localises to acetylated damaged chromatin in a ZMYND8-dependent manner, to promote transcriptional repression and double-strand break repair by homologous recombination. Involved in neurogenesis. Location: Nucleus; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome (UniProt). Locus 12p13.31 (HGNC).
- Endometrial cancer: Open Targets association 0.55 with endometrial cancer (MONDO_0011962); IntOGen driver in 3 cohorts (UCEC)
- Colorectal cancer: Open Targets association 0.57 with colorectal cancer (MONDO_0005575); IntOGen driver in 1 cohort (COAD)
- Renal cell carcinoma: IntOGen driver in 1 cohort (CCRCC)
- Head and neck squamous cell carcinoma: IntOGen driver in 1 cohort (HNSC)
- Skin cancer: Open Targets association 0.53 with skin cancer (MONDO_0002898)
- Gastric & gastro-oesophageal junction cancer: Open Targets association 0.52 with gastric cancer (MONDO_0001056)
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it an activating (Act) driver in 6 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 3 cohorts. Evidence tier "cohort-driver" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery for this target: (TITLE:"CHD4" OR ABSTRACT:"CHD4" OR TITLE:"chromodomain helicase DNA binding protein 4" OR ABSTRACT:"chromodomain helicase DNA binding protein 4" OR TITLE:"ATP-dependent chromatin remodeler CHD4" OR ABSTRACT:"ATP-dependent chromatin remodeler CHD4" OR TITLE:"Mi-2b" OR ABSTRACT:"Mi-2b" OR TITLE:"Mi2-BETA" OR ABSTRACT:"Mi2-BETA") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about CHD4, not a curated reading list.
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