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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.
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.
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.
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.
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.
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.
Tumour-specific alteration: the catalogues call it an oncogene driver (IntOGen cohort analysis finds it activated more often than chance) and a tumour suppressor (IntOGen finds it knocked out more often than chance), so the direction differs between cohorts but the alteration is somatic either way; what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA ATRX: RNA low tissue specificity; high antibody staining in 36 normal tissues; highest cancer staining melanoma (6 of 12 high). Distribution: 8 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Sarcomas (soft tissue, bone, GIST), Neuroendocrine tumours, Adrenocortical carcinoma, Renal cell carcinoma, Ovarian cancer, Breast cancer (all types), Colorectal cancer and more); Open Targets associates it with 4 specific cancer types at or above 0.5 (alpha thalassemia-X-linked intellectual disability syndrome, adrenal cortex carcinoma, leiomyosarcoma, glioblastoma). (Rule 6 of scripts/fetch-target-specificity.ts.)
Sources: UniProt P46100; CIViC gene ATRX; IntOGen ATRX; Human Protein Atlas ATRX tissue; Open Targets ENSG00000085224 associations
First described 1994. Earliest sequence paper UniProt cites for the protein: Stayton C.L. et al, Hum. Mol. Genet, 1994, "Cloning and characterization of a new human Xq13 gene, encoding a putative helicase". Source.
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)
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).
RNA: low tissue specificity, detected in all normal tissues.
Medium: Cervix, Endometrium, Lymph node, Prostate, Seminal vesicle, Small intestine, Testis.
Medium only: liver cancer, pancreatic cancer, prostate cancer.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
Query 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.
Shares Telomere maintenance & replicative immortality, Adrenocortical carcinoma, Neuroendocrine tumours, Skin cancer (all types).
Shares Adrenocortical carcinoma, Neuroendocrine tumours, Skin cancer (all types), CIViC.
Shares Telomere maintenance & replicative immortality, Skin cancer (all types), CIViC, IntOGen.
Shares Adrenocortical carcinoma, Sarcomas (soft tissue, bone, GIST), CIViC, IntOGen.
Shares Adrenocortical carcinoma, Renal cell carcinoma, CIViC, IntOGen.
Shares Adrenocortical carcinoma, IntOGen, Open Targets Platform.
Shares Adrenocortical carcinoma, CIViC, IntOGen, Ovarian cancer.
Shares Adrenocortical carcinoma, Renal cell carcinoma, CIViC, IntOGen.