IGF2 Gene: Insulin Like Growth Factor 2 – Function, Mutations, and Disease

IGF2 (Insulin Like Growth Factor 2) is a maternally imprinted gene located on chromosome 11p15.5. It encodes a growth factor that is structurally similar to insulin and plays a critical role in fetal and placental development, as well as postnatal growth regulation. IGF2 exerts its effects primarily through the IGF1 receptor (IGF1R) and the insulin receptor isoform A (IR-A). Loss of imprinting (LOI) leading to biallelic expression is frequently observed in various cancers and in Beckwith-Wiedemann syndrome (BWS).

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• PI3K-Akt signaling pathway (KEGG: hsa04151)

• MAPK signaling pathway (KEGG: hsa04010)

• Insulin signaling pathway (KEGG: hsa04910)

• Proteoglycans in cancer (KEGG: hsa05205)

• EGFR tyrosine kinase inhibitor resistance (KEGG: hsa01521)

IGF2 is a 180-amino-acid secreted protein (precursor) that is processed to a mature 67-amino-acid peptide. It shares structural homology with insulin and IGF1. IGF2 binds with high affinity to the IGF1 receptor (IGF1R) and the insulin receptor isoform A (IR-A), activating downstream signaling pathways such as PI3K/Akt and MAPK/ERK. The protein is highly expressed during fetal development and in certain adult tissues, particularly the liver and placenta. Dysregulation of IGF2 expression, often through loss of imprinting, is a common feature of many cancers and overgrowth syndromes.