SEMA6A
Semaphorin 6A: A key regulator of neuronal development, immune response, and cancer progression
Gene Information Card
| Symbol | SEMA6A |
|---|---|
| Full Name | Semaphorin 6A |
| Gene Type | Protein coding |
| Chromosomal Location | 5q23.1 |
| NCBI Gene ID | 57556 ncbi.nlm.nih.gov/gene/57556 |
| Ensembl ID | ENSG00000112742 |
| UniProt ID | Q9H2E6 |
| OMIM ID | 605885 |
| HGNC ID | 10723 |
| Aliases | SEMA6A1, SEMAQ, KIAA1368 |
Description
SEMA6A (Semaphorin 6A) is a protein-coding gene that belongs to the semaphorin family, involved in axon guidance, cell migration, and immune modulation. The encoded protein is a transmembrane semaphorin that binds to plexin receptors, mediating repulsive or attractive signals during neural development. SEMA6A also plays roles in angiogenesis, tumor suppression, and T-cell activation. Dysregulation of SEMA6A is implicated in neurodevelopmental disorders, autoimmune diseases, and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Schizophrenia | Altered SEMA6A expression may disrupt neuronal connectivity and synaptic plasticity, contributing to disease pathology. | ClinVar, NCBI |
| Autism Spectrum Disorder | Rare variants in SEMA6A are associated with impaired axon guidance and social behavior deficits. | ClinVar, OMIM |
| Colorectal Cancer | SEMA6A acts as a tumor suppressor; loss of expression correlates with poor prognosis and metastasis. | COSMIC, NCBI |
| Breast Cancer | Reduced SEMA6A expression promotes epithelial-mesenchymal transition and invasion. | COSMIC, NCBI |
| Rheumatoid Arthritis | SEMA6A modulates immune cell migration and cytokine production, influencing joint inflammation. | NCBI, UniProt |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Lung | 8.7 | Low |
| Liver | 5.2 | Low |
| Kidney | 9.1 | Low |
| Testis | 15.6 | Medium |
| Spleen | 6.4 | Low |
| Colon | 7.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 18.2 | High expression |
| HCT116 (colorectal carcinoma) | 4.5 | Low expression |
| MCF7 (breast cancer) | 6.1 | Low expression |
| HEK293 (embryonic kidney) | 9.8 | Moderate expression |
| Jurkat (T-cell leukemia) | 11.3 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Cys) | Missense | <0.1% | Alters plexin binding; associated with autism spectrum disorder |
| c.567G>A (p.Trp189*) | Nonsense | <0.01% | Loss-of-function; linked to schizophrenia |
| c.890_891insA (p.Asn297Lysfs*5) | Frameshift | <0.01% | Truncated protein; observed in colorectal cancer |
| c.1456A>G (p.Thr486Ala) | Missense | 0.05% | Reduced cell surface expression; reported in breast cancer |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Trp189*, p.Asn297Lysfs*5) lead to truncated or unstable SEMA6A protein, impairing axon guidance and tumor suppression.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in SEMA6A.
Dominant Negative (DN)
Missense mutations (e.g., p.Arg412Cys) may interfere with wild-type SEMA6A function by disrupting receptor binding, potentially acting in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
| • cell adhesion (GO:0007155) | • axon guidance (GO:0007411) |
| • cell differentiation (GO:0030154) | • positive regulation of GTPase activity (GO:0043547) |
| • signal transduction (GO:0007165) | • plasma membrane (GO:0005886) |
| • integral component of membrane (GO:0016021) |
Pathways
• Semaphorin interactions (Reactome: R-HSA-373755)
• Axon guidance (KEGG: hsa04360)
• Plexin signaling (Reactome: R-HSA-399956)
Protein Summary
SEMA6A is a transmembrane protein of approximately 130 kDa, characterized by an N-terminal Sema domain, a PSI domain, and an immunoglobulin-like domain. It functions as a ligand for plexin receptors (e.g., PLXNA2, PLXNA4), initiating signaling cascades that regulate cytoskeletal dynamics, cell adhesion, and migration. In the nervous system, SEMA6A guides growing axons and dendrites. In the immune system, it modulates T-cell and dendritic cell functions. In cancer, SEMA6A acts as a context-dependent tumor suppressor, with loss of expression promoting metastasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SEMA6A Knockout HEK293 Cell Line | EDJ-KQ2437 | Human | 57556 | Details Get a Quote |
| SEMA6A Knockout HCT 116 Cell Line | EDJ-KQ22948 | Human | 57556 | Details Get a Quote |
| SEMA6A Knockout HeLa Cell Line | EDJ-KQ56866 | Human | 57556 | Details Get a Quote |
| SEMA6A Knockout A-549 Cell Line | EDJ-KQ65380 | Human | 57556 | Details Get a Quote |
