LIFR Gene: LIF Receptor Subunit Alpha - Function, Mutations, and Disease Associations

The LIFR gene encodes the leukemia inhibitory factor receptor subunit alpha (LIFR), a transmembrane glycoprotein that forms a heterodimeric receptor complex with the shared signaling subunit gp130. This receptor mediates the biological effects of LIF and other IL-6 family cytokines, including oncostatin M (OSM), cardiotrophin-1 (CT-1), and ciliary neurotrophic factor (CNTF). LIFR signaling is critical for embryonic implantation, placental development, neural stem cell maintenance, and bone remodeling. Loss-of-function mutations in LIFR cause Stüve-Wiedemann syndrome, a rare autosomal recessive disorder characterized by skeletal dysplasia, dysautonomia, and respiratory distress.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• IL-6 family signaling (Reactome: R-HSA-6783589)

• JAK-STAT signaling pathway (KEGG: hsa04630)

• Oncostatin M signaling (Reactome: R-HSA-8849474)

The LIFR protein (UniProt P42702) is a 1097-amino-acid type I transmembrane glycoprotein with an extracellular region containing cytokine-binding domains and fibronectin type III repeats, a single transmembrane helix, and a cytoplasmic tail with conserved Box 1 and Box 2 motifs required for JAK/STAT signaling. It functions as the specific ligand-binding subunit for LIF and OSM, forming a high-affinity receptor complex with gp130. LIFR is expressed in various tissues, including bone marrow, placenta, and brain, and plays essential roles in development, stem cell maintenance, and inflammation.