SEMA3F Gene: Function, Expression, and Role in Disease

SEMA3F (Semaphorin 3F) is a protein-coding gene that belongs to the class 3 semaphorin family. It encodes a secreted glycoprotein that functions as a chemorepellent for axons and as an inhibitor of angiogenesis and tumor growth. SEMA3F signals through neuropilin-1 and neuropilin-2 receptors and plays a critical role in neural development, immune regulation, and cancer suppression. Loss of SEMA3F expression is frequently observed in various cancers, contributing to tumor progression and metastasis.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Semaphorin interactions (Reactome: R-HSA-373755)

• Neuropilin signaling (KEGG: hsa04360)

• Axon guidance (KEGG: hsa04360)

• VEGF signaling pathway (KEGG: hsa04370)

SEMA3F encodes a 785-amino-acid secreted semaphorin with a conserved Sema domain, a PSI domain, and an immunoglobulin-like domain. The protein forms homodimers and binds to neuropilin-2 (NRP2) with high affinity, and to neuropilin-1 (NRP1) with lower affinity. SEMA3F signaling through plexin co-receptors induces cytoskeletal collapse and growth cone repulsion in neurons. In non-neuronal tissues, SEMA3F inhibits integrin-mediated adhesion and suppresses tumor angiogenesis by competing with VEGF for neuropilin binding. The protein is post-translationally modified by glycosylation and proteolytic cleavage.