Target intelligence / Profile preview

Semaphorin-3D (SEMA3D)

Target: SEMA3D
Molecular classification: Guidance molecule, Secreted protein, Semaphorin family (Class III), Receptor ligand, Contains sema domain, immunoglobulin domain (Ig), short basic domain

Overview

Semaphorin-3D (SEMA3D) is a secreted class III semaphorin involved in guiding neuronal and endothelial cell migration during embryonic development. It functions as a repulsive and/or attractive cue depending on tissue context, crucial for proper cardiovascular morphogenesis and axon guidance. SEMA3D signals primarily through PlexinD1 and Neuropilin-1 receptors, activating pathways that regulate actin cytoskeleton organization and cell–cell contacts. Genetic defects in SEMA3D are associated with congenital heart defects and anomalous vascular connections in both humans and experimental models. SEMA3D's role as a guidance molecule makes it a potential therapeutic target and biomarker in developmental disorders, although currently there are no approved drugs that target it directly.

Other names: Semaphorin-3DSEMA3DUNQ760/PRO1491coll-2Sema-Z2collapsin 2sema domain, immunoglobulin domain (Ig), short basic domain, secreted semaphorin 3Dsemaphorin-3D

Biological functions

Regulation of collective and directional cell migration (including endothelial and neuronal cells)Repulsive and attractive guidance cues for axon and cell movementCardiovascular morphogenesis (role in vascular development, pulmonary vein connection, and congenital heart defects)Regulation of actin network organization and cell–cell contact formation

Disease associations

Congenital heart defects and cardiovascular malformations (linked to SEMA3D gene disruptions in humans)Potential roles in neurodevelopmental disorders (due to effects on axon guidance and neuronal migration)Unclear, more research is needed

Safety considerations

Interference with normal cardiovascular and neuronal development due to broad involvement in cell migrationPossible off-target effects on vascular stability and actin organization

Biomarkers

SEMA3D expression patterns or genetic disruption are potential biomarkers for cardiovascular developmental defectsQuantification may help patient selection in congenital heart diseaseNo routine clinical biomarkers are established

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