{{Short description|Protein-coding gene in the species Homo sapiens}} {{Infobox_gene}} {{Infobox protein family | Symbol = BCMA-Tall_bind | Name = BCMA TALL-1 binding domain | image = PDB 1oqd EBI.jpg | width = | caption = crystal structure of stall-1 and bcma | Pfam = PF09257 | Pfam_clan = | InterPro = IPR015337 | SMART = | PROSITE = | MEROPS = | SCOP = 1oqd | TCDB = | OPM family = | OPM protein = | CAZy = | CDD = }} '''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 is a cell surface receptor of the TNF receptor superfamily which recognizes B-cell activating factor (BAFF).<ref name="pmid1396583">{{cite journal | vauthors = Laâbi Y, Gras MP, Carbonnel F, Brouet JC, Berger R, Larsen CJ, Tsapis A | title = A new gene, BCM, on chromosome 16 is fused to the interleukin 2 gene by a t(4;16)(q26;p13) translocation in a malignant T cell lymphoma | journal = The EMBO Journal | volume = 11 | issue = 11 | pages = 3897–3904 | date = November 1992 | pmid = 1396583 | pmc = 556899 | doi = 10.1002/j.1460-2075.1992.tb05482.x }}</ref><ref name="pmid8165126">{{cite journal | vauthors = Laabi Y, Gras MP, Brouet JC, Berger R, Larsen CJ, Tsapis A | title = The BCMA gene, preferentially expressed during B lymphoid maturation, is bidirectionally transcribed | journal = Nucleic Acids Research | volume = 22 | issue = 7 | pages = 1147–1154 | date = April 1994 | pmid = 8165126 | pmc = 523635 | doi = 10.1093/nar/22.7.1147 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: TNFRSF17 tumor necrosis factor receptor superfamily, member 17| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=608}}</ref>

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).<ref>{{cite journal | vauthors = Maglione PJ, Ko HM, Tokuyama M, Gyimesi G, Soof C, Li M, Sanchez E, Chen H, Radigan L, Berenson J, Cunningham-Rundles C | display-authors = 6 | title = Serum B-Cell Maturation Antigen (BCMA) Levels Differentiate Primary Antibody Deficiencies | journal = The Journal of Allergy and Clinical Immunology. In Practice | volume = 8 | issue = 1 | pages = 283–291.e1 | date = January 2020 | pmid = 31430592 | pmc = 6980522 | doi = 10.1016/j.jaip.2019.08.012 }}</ref>

== 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.<ref name="entrez" />

== Interactions ==

TNFRSF17 has been shown to interact with the B-cell activating factor TNFSF13B.<ref name=pmid12721620>{{cite journal | vauthors = Liu Y, Hong X, Kappler J, Jiang L, Zhang R, Xu L, Pan CH, Martin WE, Murphy RC, Shu HB, Dai S, Zhang G | display-authors = 6 | title = Ligand-receptor binding revealed by the TNF family member TALL-1 | journal = Nature | volume = 423 | issue = 6935 | pages = 49–56 | date = May 2003 | pmid = 12721620 | doi = 10.1038/nature01543 | s2cid = 4373708 | doi-access = free | bibcode = 2003Natur.423...49L }}</ref><ref name=pmid10908663>{{cite journal | vauthors = Shu HB, Johnson H | title = B cell maturation protein is a receptor for the tumor necrosis factor family member TALL-1 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 16 | pages = 9156–9161 | date = August 2000 | pmid = 10908663 | pmc = 16838 | doi = 10.1073/pnas.160213497 | doi-access = free | bibcode = 2000PNAS...97.9156S }}</ref> A conserved domain at the N-terminus, BCMA TALL-1 binding domain, is required for binding to the TNFSF13B.<ref name="pmid12721620" />

== Clinical significance ==

TNFRSF17 is implicated in leukemia, lymphomas, and multiple myeloma<ref>{{cite web|url=http://atlasgeneticsoncology.org/Genes/TNFRSF17ID42616ch16p13.html|title=TNFRSF17 (tumor necrosis factor receptor superfamily, member 17)|website=atlasgeneticsoncology.org}}</ref> (see the "Mitelman Database" <ref>{{cite web|url=http://cgap.nci.nih.gov/Chromosomes/Mitelman|title=Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer|access-date=2015-01-29|archive-date=2016-05-25|archive-url=https://web.archive.org/web/20160525153807/http://cgap.nci.nih.gov/Chromosomes/Mitelman|url-status=dead}}</ref> and the Atlas of Genetics and Cytogenetics in Oncology and Haematology,<ref>{{cite web|url=http://Atlasgeneticsoncology.org|title=Atlas of Genetics and Cytogenetics in Oncology and Haematology|work=atlasgeneticsoncology.org}}</ref>).

== As a drug target == An antibody-drug conjugate Belantamab mafodotin (GSK2857916) has been evaluated in patients with relapsed/refractory multiple myeloma.<ref>{{cite journal | vauthors = Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, Chari A, Abdallah AO, Callander N, Lendvai N, Sborov D, Suvannasankha A, Weisel K, Karlin L, Libby E, Arnulf B, Facon T, Hulin C, Kortüm KM, Rodríguez-Otero P, Usmani SZ, Hari P, Baz R, Quach H, Moreau P, Voorhees PM, Gupta I, Hoos A, Zhi E, Baron J, Piontek T, Lewis E, Jewell RC, Dettman EJ, Popat R, Esposti SD, Opalinska J, Richardson P, Cohen AD | display-authors = 6 | title = Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study | journal = The Lancet. Oncology | volume = 21 | issue = 2 | pages = 207–221 | date = February 2020 | pmid = 31859245 | doi = 10.1016/s1470-2045(19)30788-0 | s2cid = 209425201 }}</ref> 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.<ref name="pmid35736811">{{cite journal | vauthors = Baines AC, Ershler R, Kanapuru B, Xu Q, Shen G, Li L, Ma L, Okusanya OO, Simpson NE, Nguyen W, Theoret MR, Pazdur R, Gormley NJ | display-authors = 6 | title = FDA Approval Summary: Belantamab Mafodotin for Patients with Relapsed or Refractory Multiple Myeloma | journal = Clinical Cancer Research | volume = 28 | issue = 21 | pages = 4629–4633 | date = November 2022 | pmid = 35736811 | pmc = 9633344 | doi = 10.1158/1078-0432.CCR-22-0618 }}</ref>

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.<ref>{{cite journal | vauthors = Carpenter RO, Evbuomwan MO, Pittaluga S, Rose JJ, Raffeld M, Yang S, Gress RE, Hakim FT, Kochenderfer JN | display-authors = 6 | title = B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma | journal = Clinical Cancer Research | volume = 19 | issue = 8 | pages = 2048–2060 | date = April 2013 | pmid = 23344265 | doi = 10.1158/1078-0432.CCR-12-2422 | pmc = 3630268 }}</ref><ref>{{cite journal | vauthors = Ali SA, Shi V, Maric I, Wang M, Stroncek DF, Rose JJ, Brudno JN, Stetler-Stevenson M, Feldman SA, Hansen BG, Fellowes VS, Hakim FT, Gress RE, Kochenderfer JN | display-authors = 6 | title = T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma | journal = Blood | volume = 128 | issue = 13 | pages = 1688–1700 | date = September 2016 | pmid = 27412889 | doi = 10.1182/blood-2016-04-711903 | pmc = 5043125 }}</ref> 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.<ref>{{Cite journal| vauthors = Madduri D, Usmani SZ, Jagannath S, Singh I, Zudaire E, Yeh TM, Allred AJ, Banerjee A, Goldberg JD, Schecter JM, Zhuang S | display-authors = 6 |date=2019-11-13|title=Results from CARTITUDE-1: A Phase 1b/2 Study of JNJ-4528, a CAR-T Cell Therapy Directed Against B-Cell Maturation Antigen (BCMA), in Patients with Relapsed and/or Refractory Multiple Myeloma (R/R MM) |journal=Blood |language=en |volume=134 |issue=Supplement_1 |pages=577 |doi=10.1182/blood-2019-121731 | s2cid = 209265279 |issn=0006-4971 |doi-access=free}}</ref>

ALLO-715 is a CAR-T therapy by Allogene Therapeutics that targets B-cell maturation antigen (BCMA).<ref>{{Cite journal| vauthors = Sommer C, Boldajipour B, Valton J, Galetto R, Bentley T, Sutton J, Ni Y, Leonard M, Van Blarcom T, Smith J, Chaparro-Riggers J |date=2018-11-29|title=ALLO-715, an Allogeneic BCMA CAR T Therapy Possessing an Off-Switch for the Treatment of Multiple Myeloma|journal=Blood|volume=132|issue=Supplement 1|pages=591|doi=10.1182/blood-2018-99-119227|issn=0006-4971|doi-access=free}}</ref> {{as of|2021|6}}, it is undergoing clinical trials for the treatment of multiple myeloma.<ref name="universal-trial">{{ClinicalTrialsGov|NCT04093596|Allogene Therapeutics|date=2021-06-23|title=A Single-Arm, Open-Label, Phase 1 Study of the Safety, Efficacy, and Cellular Kinetics/Pharmacodynamics of ALLO-715 to Evaluate an Anti-BCMA Allogeneic CAR T Cell Therapy With or Without Nirogacestat in Subjects With Relapsed/Refractory Multiple Myeloma}}</ref> On 21 April 2021, the FDA granted Regenerative Medicine Advanced Therapy status to ALLO-715.<ref>{{Cite web |title=FDA Grants RMAT Designation to ALLO-715 for Relapsed/Refractory Multiple Myeloma |url=https://www.onclive.com/view/fda-grants-rmat-designation-to-allo-715-for-relapsed-refractory-multiple-myeloma |access-date=2022-05-10 |website=OncLive |date=21 April 2021 |language=en}}</ref> ALLO-715 is being investigated at Memorial Sloan Kettering Cancer Center and the Mayo Clinic<ref>{{Cite web |title=Safety and Efficacy of ALLO-715 and ALLO-647 BCMA Allogenic CAR T Cells in Adults With Relapsed or Refractory Multiple Myeloma (UNIVERSAL) |url=https://www.mayo.edu/research/clinical-trials/cls-20484366 |access-date=2022-05-10 |website=Mayo Clinic |language=en}}</ref> as part of the UNIVERSAL trial for multiple myeloma, on its own and in conjunction with the selective gamma secretase inhibitor nirogacestat.<ref name="universal-trial" /><ref>{{Cite web | vauthors = Taylor NP |date=2020-12-07 |title=ASH: Allogene's off-the-shelf CAR-T posts 60% response rate in fiercely competitive BCMA field |url=https://www.fiercebiotech.com/biotech/ash-allogene-s-off-shelf-car-t-posts-60-response-rate-fiercely-competitive-bcma-field |access-date=2022-05-10 |website=Fierce Biotech |language=en}}</ref>

== References == {{reflist}}

== External links == * {{UCSC gene info|TNFRSF17}}

== Further reading == {{refbegin | 2}} * {{cite journal | vauthors = Treml LS, Crowley JE, Cancro MP | title = BLyS receptor signatures resolve homeostatically independent compartments among naïve and antigen-experienced B cells | journal = Seminars in Immunology | volume = 18 | issue = 5 | pages = 297–304 | date = October 2006 | pmid = 16919470 | doi = 10.1016/j.smim.2006.07.001 }} * {{cite journal | vauthors = Mackay F, Leung H | title = The role of the BAFF/APRIL system on T cell function | journal = Seminars in Immunology | volume = 18 | issue = 5 | pages = 284–289 | date = October 2006 | pmid = 16931039 | doi = 10.1016/j.smim.2006.04.005 }} * {{cite journal | vauthors = Gras MP, Laâbi Y, Linares-Cruz G, Blondel MO, Rigaut JP, Brouet JC, Leca G, Haguenauer-Tsapis R, Tsapis A | display-authors = 6 | title = BCMAp: an integral membrane protein in the Golgi apparatus of human mature B lymphocytes | journal = International Immunology | volume = 7 | issue = 7 | pages = 1093–1106 | date = July 1995 | pmid = 8527407 | doi = 10.1093/intimm/7.7.1093 }} * {{cite journal | vauthors = Loftus BJ, Kim UJ, Sneddon VP, Kalush F, Brandon R, Fuhrmann J, Mason T, Crosby ML, Barnstead M, Cronin L, Deslattes Mays A, Cao Y, Xu RX, Kang HL, Mitchell S, Eichler EE, Harris PC, Venter JC, Adams MD | display-authors = 6 | title = Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q | journal = Genomics | volume = 60 | issue = 3 | pages = 295–308 | date = September 1999 | pmid = 10493829 | doi = 10.1006/geno.1999.5927 }} * {{cite journal | vauthors = Gross JA, Johnston J, Mudri S, Enselman R, Dillon SR, Madden K, Xu W, Parrish-Novak J, Foster D, Lofton-Day C, Moore M, Littau A, Grossman A, Haugen H, Foley K, Blumberg H, Harrison K, Kindsvogel W, Clegg CH | display-authors = 6 | title = TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease | journal = Nature | volume = 404 | issue = 6781 | pages = 995–999 | date = April 2000 | pmid = 10801128 | doi = 10.1038/35010115 | s2cid = 4323357 | bibcode = 2000Natur.404..995G }} * {{cite journal | vauthors = Hatzoglou A, Roussel J, Bourgeade MF, Rogier E, Madry C, Inoue J, Devergne O, Tsapis A | display-authors = 6 | title = TNF receptor family member BCMA (B cell maturation) associates with TNF receptor-associated factor (TRAF) 1, TRAF2, and TRAF3 and activates NF-kappa B, elk-1, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase | journal = Journal of Immunology | volume = 165 | issue = 3 | pages = 1322–1330 | date = August 2000 | pmid = 10903733 | doi = 10.4049/jimmunol.165.3.1322 | doi-access = free }} * {{cite journal | vauthors = Shu HB, Johnson H | title = B cell maturation protein is a receptor for the tumor necrosis factor family member TALL-1 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 16 | pages = 9156–9161 | date = August 2000 | pmid = 10908663 | pmc = 16838 | doi = 10.1073/pnas.160213497 | doi-access = free | bibcode = 2000PNAS...97.9156S }} * {{cite journal | vauthors = Yu G, Boone T, Delaney J, Hawkins N, Kelley M, Ramakrishnan M, McCabe S, Qiu WR, Kornuc M, Xia XZ, Guo J, Stolina M, Boyle WJ, Sarosi I, Hsu H, Senaldi G, Theill LE | display-authors = 6 | title = APRIL and TALL-I and receptors BCMA and TACI: system for regulating humoral immunity | journal = Nature Immunology | volume = 1 | issue = 3 | pages = 252–256 | date = September 2000 | pmid = 10973284 | doi = 10.1038/79802 | s2cid = 6799584 }} * {{cite journal | vauthors = Kawasaki A, Tsuchiya N, Fukazawa T, Hashimoto H, Tokunaga K | title = Presence of four major haplotypes in human BCMA gene: lack of association with systemic lupus erythematosus and rheumatoid arthritis | journal = Genes and Immunity | volume = 2 | issue = 5 | pages = 276–279 | date = August 2001 | pmid = 11528522 | doi = 10.1038/sj.gene.6363770 | s2cid = 12315457 | doi-access = }} * {{cite journal | vauthors = Novak AJ, Darce JR, Arendt BK, Harder B, Henderson K, Kindsvogel W, Gross JA, Greipp PR, Jelinek DF | display-authors = 6 | title = Expression of BCMA, TACI, and BAFF-R in multiple myeloma: a mechanism for growth and survival | journal = Blood | volume = 103 | issue = 2 | pages = 689–694 | date = January 2004 | pmid = 14512299 | doi = 10.1182/blood-2003-06-2043 | doi-access = free }} * {{cite journal | vauthors = Hymowitz SG, Patel DR, Wallweber HJ, Runyon S, Yan M, Yin J, Shriver SK, Gordon NC, Pan B, Skelton NJ, Kelley RF, Starovasnik MA | display-authors = 6 | title = Structures of APRIL-receptor complexes: like BCMA, TACI employs only a single cysteine-rich domain for high affinity ligand binding | journal = The Journal of Biological Chemistry | volume = 280 | issue = 8 | pages = 7218–7227 | date = February 2005 | pmid = 15542592 | doi = 10.1074/jbc.M411714200 | doi-access = free }} * {{cite journal | vauthors = Bellucci R, Alyea EP, Chiaretti S, Wu CJ, Zorn E, Weller E, Wu B, Canning C, Schlossman R, Munshi NC, Anderson KC, Ritz J | display-authors = 6 | title = Graft-versus-tumor response in patients with multiple myeloma is associated with antibody response to BCMA, a plasma-cell membrane receptor | journal = Blood | volume = 105 | issue = 10 | pages = 3945–3950 | date = May 2005 | pmid = 15692072 | pmc = 1895080 | doi = 10.1182/blood-2004-11-4463 }} * {{cite journal | vauthors = Hendriks J, Planelles L, de Jong-Odding J, Hardenberg G, Pals ST, Hahne M, Spaargaren M, Medema JP | display-authors = 6 | title = Heparan sulfate proteoglycan binding promotes APRIL-induced tumor cell proliferation | journal = Cell Death and Differentiation | volume = 12 | issue = 6 | pages = 637–648 | date = June 2005 | pmid = 15846369 | doi = 10.1038/sj.cdd.4401647 | doi-access = free }} * {{cite journal | vauthors = Chiu A, Xu W, He B, Dillon SR, Gross JA, Sievers E, Qiao X, Santini P, Hyjek E, Lee JW, Cesarman E, Chadburn A, Knowles DM, Cerutti A | display-authors = 6 | title = Hodgkin lymphoma cells express TACI and BCMA receptors and generate survival and proliferation signals in response to BAFF and APRIL | journal = Blood | volume = 109 | issue = 2 | pages = 729–739 | date = January 2007 | pmid = 16960154 | pmc = 1785096 | doi = 10.1182/blood-2006-04-015958 }} * {{cite journal | vauthors = Smirnova AS, Andrade-Oliveira V, Gerbase-DeLima M | title = Identification of new splice variants of the genes BAFF and BCMA | journal = Molecular Immunology | volume = 45 | issue = 4 | pages = 1179–1183 | date = February 2008 | pmid = 17825416 | doi = 10.1016/j.molimm.2007.07.028 }} {{refend}}

{{NLM content}} {{PDB Gallery|geneid=608}} {{Clusters of differentiation}} {{Tumor necrosis factor receptor superfamily}} {{Cytokine receptor modulators}} {{InterPro content|IPR015337}}

Category:Protein domains Category:Clusters of differentiation Category:TNF receptor family