RUNX1
RUNX1 (Runt-related transcription factor 1) 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 fusion partner, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Leukaemia, Myeloproliferative neoplasms, Non-Hodgkin lymphoma and 5 more.
Overview
Forms the heterodimeric complex core-binding factor (CBF) with CBFB. RUNX members modulate the transcription of their target genes through recognising the core consensus binding sequence 5'-TGTGGT-3', or very rarely, 5'-TGCGGT-3', within their regulatory regions via their runt domain, while CBFB is a non-DNA-binding regulatory subunit that allosterically enhances the sequence-specific DNA-binding capacity of RUNX. The heterodimers bind to the core site of a number of enhancers and promoters, including murine leukaemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL3 and GM-CSF promoters.
CIViC holds 18 clinical evidence items and 0 assertions across 13 variants, naming Cytarabine. Open Targets scores its association with cancer at 0.86 (direct and indirect evidence; datatypes genetic literature 0.83, affected pathway 0.44, literature 1.00, genetic association 0.83, somatic mutation 0.94, animal model 0.80). IntOGen calls it a driver in 7 cohorts (1 activating, 6 loss-of-function), covering Adenoid Cystic Carcinoma, Acute Lymphoblastic Leukaemia, Acute Myeloid Leukaemia, Invasive Breast Carcinoma, Glioblastoma Multiforme.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · RUNX1 (Runt-related transcription factor 1) 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 fusion partner, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Leukaemia, Myeloproliferative neoplasms, Non-Hodgkin lymphoma and 5 more.
- 1 · What it is
RUNX1 (Runt-related transcription factor 1) 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 fusion partner, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Leukaemia, Myeloproliferative neoplasms, Non-Hodgkin lymphoma and 5 more.
- 2 · What goes wrong in cancer
Forms the heterodimeric complex core-binding factor (CBF) with CBFB.
- 3 · How drugs use it
No product in this corpus aims at RUNX1 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:10471 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q01196 (protein name, function text, keywords and locations (REST API)); CIViC gene RUNX1 (18 evidence items, 0 assertions, 13 variants; diseases: Acute Myeloid Leukaemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukaemia (GraphQL API, CC0)); Open Targets ENSG00000159216 (association with cancer (MONDO_0004992) 0.86; per-cancer scores at or above 0.5: ovarian cancer 0.51, acute myeloid leukaemia 0.78, acute lymphoblastic leukaemia 0.61, non-Hodgkin lymphoma 0.63, myeloproliferative neoplasm 0.83, breast cancer 0.55 (GraphQL API, CC0)); IntOGen RUNX1 (driver in 7 cohorts (Act 1, LoF 6); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Forms the heterodimeric complex core-binding factor (CBF) with CBFB. RUNX members modulate the transcription of their target genes through recognising the core consensus binding sequence 5'-TGTGGT-3', or very rarely, 5'-TGCGGT-3', within their regulatory regions via their runt domain, while CBFB is a non-DNA-binding regulatory subunit that allosterically enhances the sequence-specific DNA-binding capacity of RUNX. The heterodimers bind to the core site of a number of enhancers and promoters, including murine leukaemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL3 and GM-CSF promoters. Essential for the development of normal haematopoiesis. Acts synergistically with ELF4 to transactivate the IL-3 promoter and with ELF2 to transactivate the BLK promoter. Inhibits KAT6B-dependent transcriptional activation. Location: Nucleus (UniProt). Locus 21q22.12 (HGNC).
- Leukaemia: Open Targets association 0.84 with leukaemia (MONDO_0005059)
- Myeloproliferative neoplasms: Open Targets association 0.83 with myeloproliferative neoplasm (MONDO_0020076)
- Non-Hodgkin lymphoma: Open Targets association 0.63 with non-Hodgkin lymphoma (MONDO_0018908)
- Myelodysplastic syndromes / neoplasms: CIViC evidence names this disease
- Breast cancer: Open Targets association 0.55 with breast cancer (MONDO_0007254); IntOGen driver in 2 cohorts (BRCA)
- Salivary gland cancers: IntOGen driver in 1 cohort (ACYC)
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 1 therapies; IntOGen calls it an activating (Act) driver in 1 cohort; IntOGen calls it a loss-of-function (LoF) driver in 6 cohorts; CIViC holds 18 clinical evidence items on its variants; UniProt disease notes describe a translocation or gene fusion involving the gene. Evidence tier "clinical-evidence" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery for this target: (TITLE:"RUNX1" OR ABSTRACT:"RUNX1" OR TITLE:"RUNX family transcription factor 1" OR ABSTRACT:"RUNX family transcription factor 1" OR TITLE:"Runt-related transcription factor 1" OR ABSTRACT:"Runt-related transcription factor 1" OR TITLE:"PEBP2A2" OR ABSTRACT:"PEBP2A2" OR TITLE:"AMLCR1" OR ABSTRACT:"AMLCR1" OR TITLE:"AML1" OR ABSTRACT:"AML1") 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 RUNX1, not a curated reading list.
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