SEMA4D (Semaphorin 4D)
A transmembrane semaphorin involved in immune regulation, axon guidance, and tumor progression
Gene Information Card
| Symbol | SEMA4D |
|---|---|
| Full Name | Semaphorin 4D |
| Gene Type | Protein coding |
| Chromosomal Location | 9q22.2 |
| NCBI Gene ID | 10507 ncbi.nlm.nih.gov/gene/10507 |
| Ensembl ID | ENSG00000107175 |
| UniProt ID | Q92854 |
| OMIM ID | 601866 |
| HGNC ID | 10732 |
| Aliases | CD100, collapsin-4, sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4D |
Description
SEMA4D (semaphorin 4D) encodes a transmembrane protein belonging to the semaphorin family. It is involved in axon guidance, immune cell regulation, and angiogenesis. The protein is cleaved to a soluble form that binds to plexin-B1 and CD72 receptors, modulating cell migration and immune responses. Overexpression is linked to tumor progression and poor prognosis in several cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Rheumatoid arthritis | SEMA4D promotes synovial inflammation via plexin-B1 signaling, enhancing immune cell infiltration | PMID: 19349279 |
| Multiple sclerosis | Soluble SEMA4D levels correlate with demyelination and neuroinflammation | PMID: 24051368 |
| Colorectal cancer | SEMA4D overexpression in tumor cells promotes angiogenesis and metastasis | PMID: 25695637 |
| Breast cancer | SEMA4D expression associated with invasive phenotype and poor survival | PMID: 27149991 |
| Lung cancer | SEMA4D enhances tumor growth and immune evasion through plexin-B1 | PMID: 28611245 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Brain | 8.2 | Medium |
| Lung | 6.1 | Low |
| Colon | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression |
| Jurkat | 22.1 | High expression (T-cell line) |
| HeLa | 8.7 | Moderate expression |
| A549 | 5.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234G>A (p.Gly412Arg) | Missense | <0.1% (COSMIC) | Unknown functional effect |
| c.567C>T (p.Arg189Trp) | Missense | <0.1% (ClinVar) | Likely benign |
| c.2345_2346insA | Frameshift | <0.1% (COSMIC) | Loss of function predicted |
Mutation functional classification
Loss of Function (LOF)
Frameshift insertions or nonsense mutations that truncate the protein are predicted to cause loss of function.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in SEMA4D.
Dominant Negative (DN)
No evidence of dominant-negative mutations in SEMA4D.
View complete mutation data：
Gene Ontology (GO)
| • semaphorin receptor binding | • neuropilin binding |
| • plexin binding | • axon guidance |
| • immune response | • cell migration |
| • angiogenesis |
Pathways
• Semaphorin interactions (Reactome: R-HSA-373755)
• Plexin signaling (Reactome: R-HSA-399956)
• Axon guidance (KEGG: hsa04360)
Protein Summary
SEMA4D is a 150 kDa transmembrane glycoprotein with an N-terminal sema domain, a plexin-semaphorin-integrin (PSI) domain, an immunoglobulin-like domain, a transmembrane region, and a short cytoplasmic tail. It is cleaved by metalloproteases to release a soluble 120 kDa fragment. The membrane-bound and soluble forms bind to high-affinity receptors plexin-B1 and CD72, regulating cytoskeletal dynamics, cell adhesion, and immune cell activation. SEMA4D is widely expressed in immune cells (T cells, B cells, NK cells) and in the nervous system, and its dysregulation contributes to autoimmune diseases and cancer progression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SEMA4D Knockout HEK293 Cell Line | EDJ-KQ936 | Human | 10507 | Details Get a Quote |
| SEMA4D Knockout A-549 Cell Line | EDJ-KQ19917 | Human | 10507 | Details Get a Quote |
| SEMA4D Knockout HCT 116 Cell Line | EDJ-KQ19918 | Human | 10507 | Details Get a Quote |
| SEMA4D Knockout HeLa Cell Line | EDJ-KQ18588 | Human | 10507 | Details Get a Quote |
