TNFRSF17 (BCMA): A Key Regulator of Plasma Cell Survival and Therapeutic Target in Multiple Myeloma
Explore the genomic, functional, and clinical significance of TNFRSF17, including its role in B-cell maturation, antibody production, and targeted therapy for multiple myeloma.
Gene Information Card
| Symbol | TNFRSF17 |
|---|---|
| Full Name | TNF receptor superfamily member 17 |
| Gene Type | protein-coding |
| Chromosomal Location | 16p13.13 |
| NCBI Gene ID | 608 ncbi.nlm.nih.gov/gene/608 |
| Ensembl ID | ENSG00000048462 |
| UniProt ID | Q02223 |
| OMIM ID | 109545 |
| HGNC ID | 11913 |
| Aliases | BCM, BCMA, CD269, TNFRSF13A |
Description
TNFRSF17 encodes B-cell maturation antigen (BCMA), a type III membrane protein belonging to the tumor necrosis factor receptor superfamily. BCMA is predominantly expressed on plasma cells and plasmablasts, where it binds to BAFF (B-cell activating factor) and APRIL (a proliferation-inducing ligand) to promote cell survival, proliferation, and antibody secretion. It is a critical regulator of humoral immunity and a well-established therapeutic target in multiple myeloma, with several approved CAR-T cell therapies and bispecific antibodies targeting BCMA.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Multiple Myeloma | Overexpression of BCMA on malignant plasma cells promotes survival via BAFF/APRIL signaling; used as a target for CAR-T and antibody-drug conjugates. | High expression in myeloma cells; clinical efficacy of anti-BCMA therapies (e.g., idecabtagene vicleucel) demonstrated in trials. |
| Immunodeficiency, Common Variable, 2 | Mutations in TNFRSF17 can impair B-cell maturation and antibody production, leading to hypogammaglobulinemia. | Rare familial cases reported; functional studies show reduced BCMA signaling. |
| Lymphoma (e.g., diffuse large B-cell lymphoma) | BCMA expression on some lymphoma subtypes may contribute to survival signals. | Expression detected in a subset of DLBCL; limited functional evidence. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 12.5 | Medium |
| Bone Marrow | 8.3 | Low |
| Lymph Node | 7.1 | Low |
| Blood | 3.2 | Low |
| Other tissues | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| RPMI-8226 (myeloma) | 45.2 | High expression; used in research |
| U266 (myeloma) | 38.7 | High expression |
| MM.1S (myeloma) | 52.1 | High expression |
| Jurkat (T-cell leukemia) | 0.5 | Negative control |
| HeLa (cervical cancer) | 0.2 | Negative control |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.310T>C (p.Cys104Arg) | Missense | Rare | Impairs ligand binding and signaling; associated with CVID. |
| c.311G>A (p.Cys104Tyr) | Missense | Rare | Disrupts disulfide bond; reduced surface expression. |
| c.313A>G (p.Thr105Ala) | Missense | Rare | Alters protein stability; potential loss-of-function. |
| c.314C>T (p.Pro105Leu) | Missense | Rare | Affects transmembrane domain; may affect signaling. |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair BCMA ligand binding or surface expression reduce plasma cell survival and antibody production, leading to immunodeficiency.
Gain of Function (GOF)
No clear gain-of-function mutations reported; overexpression in myeloma is due to transcriptional upregulation, not mutation.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by forming non-functional oligomers with wild-type BCMA.
View complete mutation data：
Gene Ontology (GO)
| • receptor activity | • tumor necrosis factor-activated receptor activity |
| • signal transduction | • positive regulation of cell population proliferation |
| • positive regulation of NF-kappaB transcription factor activity | • plasma cell differentiation |
| • humoral immune response | • cell surface receptor signaling pathway |
Pathways
• BAFF/APRIL signaling pathway
• NF-kappaB signaling pathway
• PI3K-Akt signaling pathway
• MAPK signaling pathway
• Regulation of B-cell survival and differentiation
Protein Summary
The BCMA protein is a 184-amino acid type III membrane protein with an extracellular domain containing cysteine-rich repeats, a single transmembrane domain, and a cytoplasmic tail with a TRAF-binding motif. It is synthesized as a precursor and cleaved by gamma-secretase to release a soluble form (sBCMA) that can be detected in serum. BCMA interacts with TRAF1, TRAF2, and TRAF5 to activate NF-kappaB and other survival pathways. Its expression is restricted to the B-cell lineage, with highest levels on plasma cells, making it an ideal target for immunotherapy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TNFRSF17 Knockout HEK293 Cell Line | EDJ-KQ4130 | Human | 608 | Details Get a Quote |
| Tnfrsf17(BCMA) Knockout MC-38 Cell Line | EDJ-KQ18083 | Mouse | 21935 | Details Get a Quote |
| Tnfrsf17 (BCMA) Knockout MC-38 Cell Line | EDJ-KZ517 | Mouse | Details Get a Quote | |
| TNFRSF17 Knockout HeLa Cell Line | EDJ-KQ52712 | Human | 608 | Details Get a Quote |
| TNFRSF17 Knockout A-549 Cell Line | EDJ-KQ61183 | Human | 608 | Details Get a Quote |
| TNFRSF17 Knockout HCT 116 Cell Line | EDJ-KQ69674 | Human | 608 | Details Get a Quote |
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