EPHB6
Ephrin Type-B Receptor 6: A Kinase-Deficient Receptor with Roles in Cancer and Immune Regulation
Gene Information Card
| Symbol | EPHB6 |
|---|---|
| Full Name | EPH receptor B6 |
| Gene Type | protein-coding |
| Chromosomal Location | 7q34 |
| NCBI Gene ID | 2051 ncbi.nlm.nih.gov/gene/2051 |
| Ensembl ID | ENSG00000106123 |
| UniProt ID | O15197 |
| OMIM ID | 602757 |
| HGNC ID | 3396 |
| Aliases | HEP, MGC129910, MGC129911 |
Description
EPHB6 (EPH receptor B6) is a member of the ephrin receptor subfamily of receptor tyrosine kinases. Unlike most family members, EPHB6 lacks intrinsic tyrosine kinase activity due to critical amino acid substitutions in the kinase domain. It is predominantly expressed in the brain, thymus, and certain immune cells. EPHB6 plays roles in cell adhesion, migration, and immune regulation. Altered expression and mutations have been implicated in various cancers, including melanoma, breast, and lung cancer, often correlating with prognosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Melanoma | Reduced EPHB6 expression correlates with increased metastasis and poor prognosis; may regulate cell adhesion and migration. | PMID: 15607980, 16959974 |
| Breast Cancer | EPHB6 loss promotes tumor progression and metastasis; re-expression suppresses invasive phenotype. | PMID: 20010870, 21502517 |
| Non-Small Cell Lung Cancer | Low EPHB6 expression associated with lymph node metastasis and shorter survival. | PMID: 22492982 |
| Colorectal Cancer | EPHB6 downregulation linked to advanced stage and poor outcome; potential tumor suppressor. | PMID: 23285172 |
| Immune Regulation | EPHB6 modulates T-cell receptor signaling and thymocyte development. | PMID: 10623592, 15294941 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Thymus | 8.3 | Medium |
| Lung | 2.1 | Low |
| Breast | 1.5 | Low |
| Skin | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 0.5 | Low expression |
| Jurkat (T-cell) | 6.2 | Moderate expression |
| MCF7 (breast cancer) | 1.1 | Low expression |
| A549 (lung cancer) | 0.9 | Low expression |
| SK-MEL-28 (melanoma) | 0.3 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.215G>A (p.Arg72His) | Missense | <0.1% (COSMIC) | Unknown functional effect |
| c.1045C>T (p.Arg349Trp) | Missense | <0.1% (COSMIC) | Unknown functional effect |
| c.1720G>A (p.Glu574Lys) | Missense | <0.1% (COSMIC) | Unknown functional effect |
Mutation functional classification
Loss of Function (LOF)
Reduced expression or loss of EPHB6 is associated with increased metastatic potential in several cancers, suggesting a tumor suppressor role.
Gain of Function (GOF)
No activating mutations have been reported; the kinase-dead receptor may signal through alternative mechanisms.
Dominant Negative (DN)
Not established; truncated or misfolded forms could potentially interfere with wild-type receptor function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ephrin signaling (Reactome: R-HSA-3928662)
• Ephrin B reverse signaling (Reactome: R-HSA-3928665)
Protein Summary
EPHB6 is a 998-amino acid transmembrane receptor with an extracellular ephrin-binding domain, a single transmembrane helix, and an intracellular region containing a juxtamembrane domain and a pseudokinase domain. Due to substitutions in the catalytic loop (e.g., Lys to Arg at position 660), it lacks kinase activity. It can still signal through interactions with other receptors and adaptor proteins. EPHB6 is glycosylated and localizes to the plasma membrane.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| EPHB6 Knockout HEK293 Cell Line | EDJ-KQ4548 | Human | 2051 | Details Get a Quote |
| EPHB6 Knockout HCT 116 Cell Line | EDJ-KQ27179 | Human | 2051 | Details Get a Quote |
| EPHB6 Knockout HeLa Cell Line | EDJ-KQ53168 | Human | 2051 | Details Get a Quote |
| EPHB6 Knockout A-549 Cell Line | EDJ-KQ61647 | Human | 2051 | Details Get a Quote |
