IL1A Gene – Interleukin 1 Alpha: Function, Expression, Mutations & Disease Associations

IL1A encodes interleukin-1 alpha (IL-1α), a potent pro-inflammatory cytokine produced mainly by activated macrophages, epithelial cells, and fibroblasts. IL-1α is synthesized as a precursor (pro-IL-1α) that can be cleaved by calpain to release the mature, active form. It binds to the IL-1 receptor (IL-1R1) and recruits the IL-1 receptor accessory protein (IL-1RAcP), triggering NF-κB and MAPK signaling pathways. IL-1α plays a central role in acute and chronic inflammation, fever, hematopoiesis, and immune responses. Dysregulation of IL1A is implicated in autoinflammatory diseases, cancer, and metabolic disorders.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Interleukin-1 signaling (Reactome R-HSA-446652)

• NF-κB activation (Reactome R-HSA-975138)

• IL-1 family signaling (KEGG hsa04060)

• Cytokine-cytokine receptor interaction (KEGG hsa04060)

IL-1α is a 271-amino-acid precursor protein (31 kDa) that is cleaved by calpain to generate the mature 17.5 kDa form. The precursor contains an N-terminal propiece that can translocate to the nucleus and regulate transcription. The mature cytokine adopts a β-trefoil fold and binds IL-1R1 with high affinity. IL-1α is stored intracellularly and released upon cell damage or activation, acting as an alarmin. It is a key mediator of sterile inflammation and is targeted therapeutically by anakinra (IL-1R antagonist) and canakinumab (anti-IL-1β antibody, though IL-1α is not directly neutralized).