ID2 Gene: Function, Expression, and Role in Disease | NCBI, UniProt, OMIM

ID2 (Inhibitor of DNA Binding 2) encodes a member of the inhibitor of DNA binding (ID) family of helix-loop-helix (HLH) proteins. ID2 lacks a basic DNA-binding domain and functions as a dominant-negative regulator of basic HLH transcription factors by forming heterodimers, thereby inhibiting their DNA binding and transcriptional activity. It plays critical roles in cell growth, differentiation, and apoptosis, particularly in neurogenesis, hematopoiesis, and immune cell development. Dysregulation of ID2 is implicated in various cancers, including neuroblastoma, breast cancer, and leukemia.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• hsa:04350 - TGF-beta signaling pathway

• hsa:04110 - Cell cycle

• hsa:05200 - Pathways in cancer

• hsa:04650 - Natural killer cell mediated cytotoxicity

• hsa:04630 - JAK-STAT signaling pathway

ID2 is a 134-amino acid HLH protein (UniProt Q02363) that lacks a basic DNA-binding domain. It functions by forming heterodimers with E-proteins (e.g., TCF3, TCF4, TCF12), preventing their binding to E-box sequences and thereby repressing transcription of genes involved in differentiation. ID2 is predominantly nuclear but can shuttle to the cytoplasm. It is highly expressed in developing neural tissues, hematopoietic cells, and certain cancers. Post-translational modifications include phosphorylation, which modulates its stability and interaction partners.