TFE3 (transcription factor E3)

2004-05-01 Roland P Kuiper Affiliation

Identity

HGNC

TFE3

LOCATION

Xp11.23

LOCUSID

7030

FUSION GENES

Show Gene Fusions

DNA/RNA

Description

8 exons

Transcription

differential splicing removing exon 3 (with dominant negative activity of the resulting protein)

Proteins

Description

743 amino acids; 80 kDa; N-term acidic transcriptional activation domain (domain 260-271, exon 3), helix-loop-helix (344 -400), leucine zipper (409-430), and a proline/arginine rich sequence (575-743) C-term

Expression

wide; in fetal and adult tissues

Localisation

nucleus

Function

transcription factor; member of the basic helix-loop-helix family (b-HLH) of transcription factors primarily found to bind to the immunoglobulin enchancer muE3 motif, Ig K enhancers and Ig H variable regions promotors; the helix-loop-helix - leucine zipper region is implicated in DNA binding and dimerization (homo and heterodimerizations); mice which lack TFE3 in their B and T lymphocytes reconstitute the B- and T-cell compartments, but IgM levels are reduced

Homology

to other members of the myc family of helix-loop-helix transcription factors

Implicated in

Entity name

t(X;1)(p11.2;q21.2) in renal cell carcinoma --> PRCC/TTFE3

Prognosis

overall 5-yr survival rate around 85%

Hybrid gene

5 PRCC- 3 TFE3; variable breakpoint in PRCC; breakpoint in the 1st intron of TFE3

Fusion protein

N-term PRCC with the proline rich sequence fused to most of TFE3, including the acidic transcriptional activation domain, the helix-loop-helix, and the leucine zipper; the reciprocal TFE3-PRCC is expressed; it is to be noted that the normal TFE3 transcript is lost in female patients

Oncogenesis

PRCCTFE3 appears to be the fusion product that is most critical for the development of papillary renal cell carcinomas; it is a three-fold better transactivator than wild-type TFE3 and shows the characteristics associated with malignant trannsformation

Entity name

t(X;1)(p11.2;p34) in renal cell carcinoma --> PSF/TFE3

Disease

t(X;1)(p11.2;p34) has only been found in a handfull cases of papillary renal cell carcinoma

Hybrid gene

5 PSF- 3 TFE3

Fusion protein

N-term PSF and most of it fused to the DNA binding domains of TFE3 (excluding the acidic transcriptional activation domain, including the C-term helix-loop-helix, and the leucine zipper); no TFE3-PSF reciprocal transcript, as the der(X) t(X;1) is missing; the normal TFE3 transcript is found

Entity name

inv(X)(p11.2q12) in renal cell carcinoma --> NONO/TFE3

Disease

only one case of papillary renal cell carcinoma

Hybrid gene

5 NONO- 3 TFE3

Fusion protein

N-term NONO and most of it except the C-term proline rich sequence fused to the DNA binding domains of TFE3 (excluding the acidic transcriptional activation domain, including the C-term helix-loop-helix, and the leucine zipper); the reciprocal transcript is found

Entity name

Alveolar soft part sarcoma with ASPSCR1 -TFE3 fusion

Cytogenetics

der(X)t(X;17)(p11;q25) is consistently involved; it implicates: 1- the formation of a hybrid gene at the breakpoint, and also, 2- gain in Xp11-pter sequences, and loss of heterozygocity in 11q25-qter, with possible implications

Hybrid gene

5 ASPSCR1-3 TFE3; the reciprocal 5 TFE3 - 3 ASPSCR1 is most often absent. ASPSCR1 is fused in frame to TFE3 exon 3 or 4

Fusion protein

NH2 term ASPSCR1, fused to the C term of TFE3

Oncogenesis

might combine the effect of a fusion protein to that of gene(s) dosage

Entity name

primary renal ASPSCR1-TFE3 tumour

Disease

a subset of renal cell carcinoma, which presents with a combination of alveolar soft part sarcoma-like features and epithelial features is found to carry this anomaly

Cytogenetics

balanced t(X;17)(p11.2;q25), in contrast with what is found in the alveolar soft part sarcoma (see above)

Hybrid gene

5 ASPSCR1-3 TFE3

Fusion protein

NH2 term ASPSCR1, fused to the C term of TFE3

Entity name

other Xp11 involvements in renal cell carcinoma (t(X;10)(p11;q23), etc ...) are likely to implicate TFE3

Breakpoints

Article Bibliography

Pubmed ID	Last Year	Title	Authors

Other Information

Locus ID:

NCBI: 7030
MIM: 314310
HGNC: 11752
Ensembl: ENSG00000068323

Variants:

dbSNP: 7030
ClinVar: 7030
TCGA: ENSG00000068323
COSMIC: TFE3

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000068323	ENST00000315869	P19532
ENSG00000068323	ENST00000315869	A0A024QZ23
ENSG00000068323	ENST00000493583	P19532

Expression (GTEx)

100

150

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Transcriptional misregulation in cancer	KEGG	ko05202
Transcriptional misregulation in cancer	KEGG	hsa05202
Mitophagy - animal	KEGG	ko04137
Mitophagy - animal	KEGG	hsa04137

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
37936565	2024	PEComa with ASPSCR1::TFE3 fusion: expanding the molecular genetic spectrum of TFE3-rearranged PEComa with an emphasis on overlap with alveolar soft part sarcoma.	2
38073015	2024	Aberrant expression of TFE3 in granular cell tumor: Four cases in pediatrics.	0
37936565	2024	PEComa with ASPSCR1::TFE3 fusion: expanding the molecular genetic spectrum of TFE3-rearranged PEComa with an emphasis on overlap with alveolar soft part sarcoma.	2
38073015	2024	Aberrant expression of TFE3 in granular cell tumor: Four cases in pediatrics.	0
35912477	2023	TFE3 Rearrangement and Expression in Renal Cell Carcinoma.	2
36476598	2023	Application of TFE3 Immunophenotypic and TFE3 mRNA Expressions in Diagnosis and Prognostication of Adrenal Cortical Neoplasms and Distinction From Kidney Tumors.	0
36656224	2023	A case of TFE3 translocation renal cell carcinoma with rare morphological features and literature review.	0
36695651	2023	A novel VCP::TFE3 gene fusion resulting from t(X;9)(p11.23;p13.3) chromosome translocation in TFE3 rearranged renal cancer cell carcinoma.	0
36705569	2023	PKM2 controls the translation of TFE3 to maintain the integrity of the Golgi apparatus for the survival of HeLa and ME-180 cervical cancer cells.	0
36740682	2023	p53 aberration and TFE3 gene amplification may be predictors of adverse prognosis in epithelioid angiomyolipoma of the kidney.	1
36802993	2023	Expression of TFE3 in Cellular and Myxoid Type of Neurothekeoma: Four Cases in Young Children and Adolescents.	0
36987696	2023	TFEB and TFE3 drive kidney cystogenesis and tumorigenesis.	8
36997032	2023	Cystic MED15::TFE3 translocation renal cell carcinoma: histologic mimicker of multilocular cystic renal neoplasm of low malignant potential with review of the literature.	1
37188688	2023	RagD auto-activating mutations impair MiT/TFE activity in kidney tubulopathy and cardiomyopathy syndrome.	3
38619513	2023	[Expression of SCD1 in TFE3-rRCC and its effect on proliferation and migration].	0

Citation

Roland P Kuiper

TFE3 (transcription factor E3)

Atlas Genet Cytogenet Oncol Haematol. 2004-05-01

Online version: http://atlasgeneticsoncology.org/gene/86/js/lib/haematological-explorer/css/template-nav.css

Historical Card

2001-08-01 TFE3 (transcription factor E3) by Jean-Loup Huret Affiliation

Dept of Human Genetics-417, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands

1999-01-01 TFE3 (transcription factor E3) by Jean-Loup Huret,François Desangles Affiliation

Dept of Human Genetics-417, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands