TFEB
TFEB (Transcription factor EB) is a protein that switches other genes on and off. The public catalogues list it as a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Skin cancer, Breast cancer and Melanoma.
Overview
Transcription factor that acts as a master regulator of lysosomal biogenesis, autophagy, lysosomal exocytosis, lipid catabolism, energy metabolism and immune response. Specifically recognises and binds E-box sequences (5'-CANNTG-3'); efficient DNA-binding requires dimerisation with itself or with another MiT/TFE family member such as TFE3 or MITF. Involved in the cellular response to amino acid availability by acting downstream of MTOR: in the presence of nutrients, TFEB phosphorylation by MTOR promotes its cytosolic retention and subsequent inactivation.
CIViC holds 1 clinical evidence item and 0 assertions across 4 variants. Open Targets scores its association with cancer at 0.67 (direct and indirect evidence; datatypes literature 0.99, animal model 0.33, genetic association 0.34, somatic mutation 0.97).
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · TFEB (Transcription factor EB) is a protein that switches other genes on and off. The public catalogues list it as a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Skin cancer, Breast cancer and Melanoma.
- 1 · What it is
TFEB (Transcription factor EB) is a protein that switches other genes on and off. The public catalogues list it as a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Skin cancer, Breast cancer and Melanoma.
- 2 · What goes wrong in cancer
Transcription factor that acts as a master regulator of lysosomal biogenesis, autophagy, lysosomal exocytosis, lipid catabolism, energy metabolism and immune response.
- 3 · How drugs use it
No product in this corpus aims at TFEB 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:11753 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P19484 (protein name, function text, keywords and locations (REST API)); CIViC gene TFEB (1 evidence items, 0 assertions, 4 variants; diseases: Renal Cell Carcinoma With MiT Translocations (GraphQL API, CC0)); Open Targets ENSG00000112561 (association with cancer (MONDO_0004992) 0.67; per-cancer scores at or above 0.5: melanoma 0.53, skin cancer 0.51, breast cancer 0.51 (GraphQL API, CC0))
Biology
Transcription factor that acts as a master regulator of lysosomal biogenesis, autophagy, lysosomal exocytosis, lipid catabolism, energy metabolism and immune response. Specifically recognises and binds E-box sequences (5'-CANNTG-3'); efficient DNA-binding requires dimerisation with itself or with another MiT/TFE family member such as TFE3 or MITF. Involved in the cellular response to amino acid availability by acting downstream of MTOR: in the presence of nutrients, TFEB phosphorylation by MTOR promotes its cytosolic retention and subsequent inactivation. Upon starvation or lysosomal stress, inhibition of MTOR induces TFEB dephosphorylation, resulting in nuclear localisation and transcription factor activity. Specifically recognises and binds the CLEAR-box sequence (5'-GTCACGTGAC-3') present in the regulatory region of many lysosomal genes, leading to activate their expression, thereby playing a central role in expression of lysosomal genes. Regulates lysosomal positioning in response to nutrient deprivation by promoting the expression of PIP4P1. Location: Nucleus; Cytoplasm, cytosol; Lysosome membrane (UniProt). Locus 6p21.1 (HGNC).
- Skin cancer: Open Targets association 0.51 with skin cancer (MONDO_0002898)
- Breast cancer: Open Targets association 0.51 with breast cancer (MONDO_0007254)
- Melanoma: Open Targets association 0.53 with melanoma (MONDO_0005105)
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 holds 1 clinical evidence items on its variants. 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: Renal Cell Carcinoma With MiT Translocations.
Latest papers
topQuery for this target: (TITLE:"TFEB" OR ABSTRACT:"TFEB" OR TITLE:"transcription factor EB" OR ABSTRACT:"transcription factor EB" OR TITLE:"Transcription factor EB" OR ABSTRACT:"Transcription factor EB" OR TITLE:"TCFEB" OR ABSTRACT:"TCFEB" OR TITLE:"bHLHe35" OR ABSTRACT:"bHLHe35") 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 TFEB, not a curated reading list.