TFEB (transcription factor EB)
2004-05-01 Roland P Kuiper   AffiliationDept of Human Genetics-417, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands
Identity
HGNC
LOCATION
6p21.1
LOCUSID
ALIAS
ALPHATFEB,BHLHE35,TCFEB
FUSION GENES
DNA/RNA

Genomic organization of TFEB gene.
Description
TFEB gene contains 8 coding exons and 7 alternative first exons that are differentially expressed.
Transcription
Alternative first exon usage points towards the existence of up to seven alternative promoters. Alternative splicing of exon 3 (encoding an acidic activation domain) similar to the closely related TFE3, TFEC, and MiTF genes.
Proteins

Functional domains in the TFEB protein.
Description
490 amino acids; 65 kDa; N-terminal Gln-rich stretch (Gln, exon 2), N-term acidic transcriptional activation domain (AAD, exon 3), basic helix-loop-helix region (bHLH, exon 6-8), leucine zipper (LZ, exon 8), proline-rich activation domain ( ProAD, exon 9), Ser-rich stretch (Ser)
Expression
Wide in fetal and adult tissues, although the various TFEB transcript variants are expressed in a tissue-restricted manner: TFEB-A is enriched in placenta, TFEB-F in spleen, and TFEB-E and TFEB-G in brain.
Localisation
Nucleus
Function
Transcription factor; member of the basic-helix-loop-helix leucine-zipper transcription factor MiTF/TFE family (also known as the MiT family), which also contains MiTF, TFEC, and TFE3. The four members form homo- and/or heterodimers to bind the Ebox core sequence CAYGTG; the helix-loop-helix - leucine zipper region is implicated in DNA binding and dimerization (homo and heterodimerizations); mice which lack TFEB die due to defects in placental vascularization.
Homology
High homology to the other MiTF/TFE members TFE3, TFEC and MiTF, homologous to myc family of bHLH transcription factors.
Implicated in
Entity name
Renal cell carcinoma with t(6;11)(p21;q13) -> Alpha/TFEB gene fusion
Disease
Clear cell renal cell carcinomas
Prognosis
Limited follow-up available, prognosis appears to be good; no reports of developed metastases
Cytogenetics
t(6;11)(p21;q13), usually as the sole cytogenetic anomaly.
Hybrid gene
Alpha/TFEB, both fusion genes are expressed; 5-Alpha-TFEB-3 fusion transcript contains the entire open reading frame of TFEB.
Fusion protein
No fusion protein, the Alpha gene is a non-protein-encoding transcript.
Oncogenesis
Highly induced expression of full-length TFEB protein due to promoter substitution in the Alpha-TFEB fusion gene.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 11395386 | 2001 | A distinctive pediatric renal neoplasm characterized by epithelioid morphology, basement membrane production, focal HMB45 immunoreactivity, and t(6;11)(p21.1;q12) chromosome translocation. | Argani P et al |
| 14660099 | 2003 | Distinctive neoplasms characterised by specific chromosomal translocations comprise a significant proportion of paediatric renal cell carcinomas. | Argani P et al |
| 2115126 | 1990 | A helix-loop-helix protein related to the immunoglobulin E box-binding proteins. | Carr CS et al |
| 12719541 | 2003 | Cloning of an Alpha-TFEB fusion in renal tumors harboring the t(6;11)(p21;q13) chromosome translocation. | Davis IJ et al |
| 1748288 | 1991 | TFEB has DNA-binding and oligomerization properties of a unique helix-loop-helix/leucine-zipper family. | Fisher DE et al |
| 7958932 | 1994 | microphthalmia, a critical factor in melanocyte development, defines a discrete transcription factor family. | Hemesath TJ et al |
| 12837690 | 2003 | Upregulation of the transcription factor TFEB in t(6;11)(p21;q13)-positive renal cell carcinomas due to promoter substitution. | Kuiper RP et al |
| 9806910 | 1998 | The bHLH-Zip transcription factor Tfeb is essential for placental vascularization. | Steingrímsson E et al |
Other Information
Locus ID:
NCBI: 7942
MIM: 600744
HGNC: 11753
Ensembl: ENSG00000112561
Variants:
dbSNP: 7942
ClinVar: 7942
TCGA: ENSG00000112561
COSMIC: TFEB
RNA/Proteins
Expression (GTEx)
Pathways
| Pathway | Source | External ID |
|---|---|---|
| Mitophagy - animal | KEGG | ko04137 |
| Mitophagy - animal | KEGG | hsa04137 |
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37540409 | 2024 | LncRNA XXYLT1-AS2 promotes tumor progression via autophagy inhibition through ubiquitinated degradation of TFEB in hepatocellular carcinoma. | 1 |
| 38181789 | 2024 | ABCG2 is an itaconate exporter that limits antibacterial innate immunity by alleviating TFEB-dependent lysosomal biogenesis. | 2 |
| 38309196 | 2024 | TFEB regulates the odontoblastic differentiation of dental pulp stem cells by promoting a positive feedback loop between mitophagy and glycolysis. | 0 |
| 38358580 | 2024 | Transcription factor EB-mediated autophagy affects cell migration and inhibits apoptosis to promote endometriosis. | 0 |
| 38374070 | 2024 | A SPLICS reporter reveals [Formula: see text]-synuclein regulation of lysosome-mitochondria contacts which affects TFEB nuclear translocation. | 0 |
| 38481802 | 2024 | Impaired TFEB-mediated autophagy-lysosome fusion promotes tubular cell cycle G2/M arrest and renal fibrosis by suppressing ATP6V0C expression and interacting with SNAREs. | 1 |
| 38581586 | 2024 | Altered TFEB subcellular localization in nigral neurons of subjects with incidental, sporadic and GBA-related Lewy body diseases. | 0 |
| 38664707 | 2024 | TFEB regulates dendritic cell antigen presentation to modulate immune balance in asthma. | 0 |
| 38838134 | 2024 | Muscle-bone cross-talk through the FNIP1-TFEB-IGF2 axis is associated with bone metabolism in human and mouse. | 0 |
| 37540409 | 2024 | LncRNA XXYLT1-AS2 promotes tumor progression via autophagy inhibition through ubiquitinated degradation of TFEB in hepatocellular carcinoma. | 1 |
| 38181789 | 2024 | ABCG2 is an itaconate exporter that limits antibacterial innate immunity by alleviating TFEB-dependent lysosomal biogenesis. | 2 |
| 38309196 | 2024 | TFEB regulates the odontoblastic differentiation of dental pulp stem cells by promoting a positive feedback loop between mitophagy and glycolysis. | 0 |
| 38358580 | 2024 | Transcription factor EB-mediated autophagy affects cell migration and inhibits apoptosis to promote endometriosis. | 0 |
| 38374070 | 2024 | A SPLICS reporter reveals [Formula: see text]-synuclein regulation of lysosome-mitochondria contacts which affects TFEB nuclear translocation. | 0 |
| 38481802 | 2024 | Impaired TFEB-mediated autophagy-lysosome fusion promotes tubular cell cycle G2/M arrest and renal fibrosis by suppressing ATP6V0C expression and interacting with SNAREs. | 1 |
Citation
Roland P Kuiper
TFEB (transcription factor EB)
Atlas Genet Cytogenet Oncol Haematol. 2004-05-01
Online version: http://atlasgeneticsoncology.org/gene/531/tfeb
