ERG Gene: Function, Mutations, and Role in Cancer | NCBI, UniProt, ClinVar

ERG (ETS-related gene) encodes a member of the ETS family of transcription factors. It is involved in embryonic development, cell proliferation, differentiation, and angiogenesis. ERG is a critical regulator of hematopoiesis and vascular integrity. Chromosomal rearrangements involving ERG, most notably TMPRSS2-ERG fusion, are common in prostate cancer. ERG fusions are also characteristic of Ewing sarcoma and acute myeloid leukemia. Overexpression and mutations contribute to oncogenesis.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Androgen receptor signaling pathway (TMPRSS2-ERG fusion)

• ETS transcription factor pathway

• MAPK signaling pathway (via ERG target genes)

• PI3K/AKT signaling (ERG-mediated)

ERG is a 486-amino acid nuclear transcription factor belonging to the ETS family. It contains a conserved ETS DNA-binding domain that recognizes the core sequence GGAA/T. ERG regulates genes involved in hematopoiesis, vascular development, and cell adhesion. The protein is expressed in endothelial cells, hematopoietic stem cells, and certain epithelial tissues. Post-translational modifications include phosphorylation and sumoylation, which modulate its activity. In cancer, ERG fusions result in truncated or chimeric proteins that retain the ETS domain but lose regulatory regions, leading to aberrant transcriptional programs.