ATRX
ATRX (Chromatin remodeler ATRX) is a protein that switches other genes on and off. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor, a biomarker and a DNA repair gene, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Sarcomas, Neuroendocrine tumours, Adrenocortical carcinoma and 5 more.
Overview
Involved in transcriptional regulation and chromatin remodeling. Facilitates DNA replication in multiple cellular environments and is required for efficient replication of a subset of genomic loci. Binds to DNA tandem repeat sequences in both telomeres and euchromatin and in vitro binds DNA quadruplex structures.
CIViC holds 11 clinical evidence items and 0 assertions across 6 variants, naming Temozolomide, Olaparib, Talazoparib and Cisplatin and others. Open Targets scores its association with cancer at 0.82 (direct and indirect evidence; datatypes literature 0.98, affected pathway 0.61, genetic association 0.72, somatic mutation 0.98). IntOGen calls it a driver in 27 cohorts (2 activating, 25 loss-of-function), covering Adrenocortical Carcinoma, Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma, Glioblastoma, Glioblastoma Multiforme, High-Grade Glioma, NOS, Low-Grade Glioma, NOS 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 · ATRX (Chromatin remodeler ATRX) is a protein that switches other genes on and off. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor, a biomarker and a DNA repair gene, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Sarcomas, Neuroendocrine tumours, Adrenocortical carcinoma and 5 more.
- 1 · What it is
ATRX (Chromatin remodeler ATRX) is a protein that switches other genes on and off. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor, a biomarker and a DNA repair gene, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Sarcomas, Neuroendocrine tumours, Adrenocortical carcinoma and 5 more.
- 2 · What goes wrong in cancer
Involved in transcriptional regulation and chromatin remodeling. Facilitates DNA replication in multiple cellular environments and is required for efficient replication of a subset of genomic loci.
- 3 · How drugs use it
No product in this corpus aims at ATRX 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:886 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P46100 (protein name, function text, keywords and locations (REST API)); CIViC gene ATRX (11 evidence items, 0 assertions, 6 variants; diseases: Glioblastoma, Malignant Astrocytoma, Neuroblastoma, Osteosarcoma, Cancer and 1 more (GraphQL API, CC0)); Open Targets ENSG00000085224 (association with cancer (MONDO_0004992) 0.82; per-cancer scores at or above 0.5: colorectal cancer 0.56, renal cell carcinoma 0.60, melanoma 0.59, glioblastoma 0.63, sarcoma 0.70, neuroendocrine neoplasm 0.63 (GraphQL API, CC0)); IntOGen ATRX (driver in 27 cohorts (Act 2, LoF 25); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Involved in transcriptional regulation and chromatin remodeling. Facilitates DNA replication in multiple cellular environments and is required for efficient replication of a subset of genomic loci. Binds to DNA tandem repeat sequences in both telomeres and euchromatin and in vitro binds DNA quadruplex structures. May help stabilising G-rich regions into regular chromatin structures by remodeling G4 DNA and incorporating H3.3-containing nucleosomes. Catalytic component of the chromatin remodeling complex ATRX:DAXX which has ATP-dependent DNA translocase activity and catalyses the replication-independent deposition of histone H3.3 in pericentric DNA repeats outside S-phase and telomeres, and the in vitro remodeling of H3.3-containing nucleosomes. Its heterochromatin targeting is proposed to involve a combinatorial readout of histone H3 modifications (specifically methylation states of H3K9 and H3K4) and association with CBX5. Location: Nucleus; Chromosome, telomere; Nucleus, PML body (UniProt). Locus Xq21.1 (HGNC).
- Sarcomas: Open Targets association 0.70 with sarcoma (MONDO_0005089); IntOGen driver in 5 cohorts (LMS, SARCNOS, SOFT_TISSUE)
- Neuroendocrine tumours: Open Targets association 0.63 with neuroendocrine neoplasm (MONDO_0019496); IntOGen driver in 1 cohort (PANET)
- Adrenocortical carcinoma: IntOGen driver in 3 cohorts (ACC)
- Renal cell carcinoma: Open Targets association 0.60 with renal cell carcinoma (MONDO_0005086)
- Ovarian cancer: IntOGen driver in 1 cohort (OVT)
- Breast cancer: Open Targets association 0.56 with breast cancer (MONDO_0007254)
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: CIViC lists 10 therapies; IntOGen calls it an activating (Act) driver in 2 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 25 cohorts; CIViC holds 11 clinical evidence items on its variants; UniProt keyword "DNA repair". Evidence tier "clinical-evidence" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
- Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Malignant Astrocytoma; High-Grade Glioma, NOS; Low-Grade Glioma, NOS.
Latest papers
topQuery for this target: (TITLE:"ATRX" OR ABSTRACT:"ATRX" OR TITLE:"ATRX chromatin remodeler" OR ABSTRACT:"ATRX chromatin remodeler" OR TITLE:"Chromatin remodeler ATRX" OR ABSTRACT:"Chromatin remodeler ATRX" OR TITLE:"XH2" OR ABSTRACT:"XH2" OR TITLE:"RAD54" OR ABSTRACT:"RAD54" OR TITLE:"MRX52" OR ABSTRACT:"MRX52") 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 ATRX, not a curated reading list.
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