B-cell maturation antigen

B-cell maturation antigen (BCMA or BCM), also known as tumor necrosis factor receptor superfamily member 17 (TNFRSF17), is a protein that in humans is encoded by the TNFRSF17 gene.

TNFRSF17
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1OQD, 1XU2, 2KN1, 4ZFO
Identifiers
Aliases	TNFRSF17, BCM, BCMA, CD269, TNFRSF13A, tumor necrosis factor receptor superfamily member 17, TNF receptor superfamily member 17
External IDs	OMIM: 109545; MGI: 1343050; HomoloGene: 920; GeneCards: TNFRSF17; OMA:TNFRSF17 - orthologs
Gene location (Human) Chr. Chromosome 16 (human)[1] Band 16p13.13 Start 11,965,210 bp[1] End 11,968,068 bp[1]
Gene location (Mouse) Chr. Chromosome 16 (mouse)[2] Band 16|16 A1 Start 11,131,676 bp[2] End 11,137,938 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in rectum mucosa of transverse colon jejunal mucosa mucosa of sigmoid colon testicle lymph node epithelium of nasopharynx appendix spleen duodenum Top expressed in blastocyst morula duodenum jejunum spleen lip thymus secondary oocyte colon ileum More reference expression data BioGPS More reference expression data
Gene ontology Molecular function signaling receptor activity Cellular component endomembrane system plasma membrane membrane integral component of membrane Biological process multicellular organism development tumor necrosis factor-mediated signaling pathway lymphocyte homeostasis cell population proliferation immune system process adaptive immune response signal transduction Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 608 21935 Ensembl ENSG00000048462 ENSMUSG00000022496 UniProt Q02223 O88472 RefSeq (mRNA) NM_001192 NM_011608 RefSeq (protein) NP_001183 NP_035738 Location (UCSC) Chr 16: 11.97 – 11.97 Mb Chr 16: 11.13 – 11.14 Mb PubMed search [3] [4]
Wikidata
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BCMA TALL-1 binding domain
crystal structure of stall-1 and bcma
Identifiers
Symbol	BCMA-Tall_bind
Pfam	PF09257
InterPro	IPR015337
SCOP2	1oqd / SCOPe / SUPFAM
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

TNFRSF17 is a cell surface receptor of the TNF receptor superfamily which recognizes B-cell activating factor (BAFF).^[5][6][7]

Serum B-cell maturation antigen (sBCMA) is the cleaved form of BCMA, found at low levels in the serum of normal patients and generally elevated in patients with multiple myeloma (MM).^[8]

Function

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is preferentially expressed in mature B lymphocytes, and may be important for B cell development and autoimmune response. This receptor has been shown to specifically bind to the tumor necrosis factor (ligand) superfamily, member 13b (TNFSF13B/TALL-1/BAFF), and to lead to NF-kappaB and MAPK8/JNK activation. This receptor also binds to various TRAF family members, and thus may transduce signals for cell survival and proliferation.^[7]

Interactions

TNFRSF17 has been shown to interact with the B-cell activating factor TNFSF13B.^[9][10] A conserved domain at the N-terminus, BCMA TALL-1 binding domain, is required for binding to the TNFSF13B.^[9]

Clinical significance

TNFRSF17 is implicated in leukemia, lymphomas, and multiple myeloma^[11] (see the "Mitelman Database" ^[12] and the Atlas of Genetics and Cytogenetics in Oncology and Haematology,^[13]).

As a drug target

An antibody-drug conjugate Belantamab mafodotin (GSK2857916) has been evaluated in patients with relapsed/refractory multiple myeloma.^[14] Belantamab mafodotin was approved in the United States in August 2020 for the treatment of patients with relapsed or refractory multiple myeloma who have received at least four prior therapies.^[15]

Chimeric antigen receptor (CAR) T cells have emerged as an important therapy for multiple myeloma after first reports in preclinical and phase I clinical studies.^[16][17] A Phase 1b/2 study of JNJ-4528, a CAR-T cell therapy directed against BCMA in myeloma patients refractory to a proteasome inhibitor or immunomodulatory drug, and who had received an anti-CD38 antibody has been completed.^[18]

ALLO-715 is a CAR-T therapy by Allogene Therapeutics that targets B-cell maturation antigen (BCMA).^[19] As of June 2021^[update], it is undergoing clinical trials for the treatment of multiple myeloma.^[20] On 21 April 2021, the FDA granted Regenerative Medicine Advanced Therapy status to ALLO-715.^[21] ALLO-715 is being investigated at Memorial Sloan Kettering Cancer Center and the Mayo Clinic^[22] as part of the UNIVERSAL trial for multiple myeloma, on its own and in conjunction with the selective gamma secretase inhibitor nirogacestat.^[20][23]