Semaphorin-4G is a protein in humans encoded by the SEMA4G gene.

Semaphorins are a large family of conserved, secreted and membrane associated proteins which possess a semaphoring (Sema) domain and a PSI domain (found in plexins, semaphorins and integrins) in the N-terminal extracellular portion. Semaphorins maintain cell motility and attachment in axon guidance, immune cell maintenance, vascular growth and tumour movement.

Based on sequence and structural similarities, semaphorins are put into eight classes: invertebrates contain classes 1 and 2, viruses have class V, and vertebrates contain classes 3-7. Semaphorins serve as axon guidance ligands via multimeric receptor complexes, some (if not all) containing plexin proteins. This gene encodes a class 4 semaphorin. This gene and the gene for mitochondrial ribosomal protein L43 overlap at map location 10q24.31 and are transcribed in opposite directions.