TNFRSF17 (tumor necrosis factor receptor superfamily, member 17)

2014-10-01   Abigail Gillespie , Eric Sanchez , George Tang , Haiming Chen , James Berenson 

Institute for Myeloma & Bone Cancer Research, 9201 W. Sunset Blvd., Ste. 300, West Hollywood, CA 90069, USA

Identity

HGNC
LOCATION
16p13.13
LOCUSID
ALIAS
BCM,BCMA,CD269,TNFRSF13A
FUSION GENES

Abstract

B Cell Maturation Antigen (BCMA) is a transmembrane signaling protein preferentially expressed on plasma cells. Its ligands include B-Cell Activating Factor (BAFF) and A Proliferation Inducing Ligand (APRIL). BCMA is involved in JNK and NF-kB activation pathways that induce B-cell development and autoimmune responses. BCMA has been implicated in autoimmune disorders as well as B-lymphocyte malignancies.

DNA/RNA

Description

Spans 3.8 kb; 3 exons, 2 introns.

Transcription

961 nt mRNA.

Proteins

Description

184 aa; a glycoprotein with a single transmembrane domain; N-terminally glycosylated at asparagine 42 regulates its function (Huang et al., 2013). BCMA is a signaling protein that activates the NF-kB. BCMA contains one cysteine rich domain and a DXL motif, comprised of (Phe/Tyr/Trp)-Asp-Xaa-Leu-(Val/Thr)-(Arg/Gly), to facilitate ligand binding with BAFF or APRIL (Hymowitz et al., 2005).

Expression

Preferentially expressed in lymph node tissue, B lymphoblast, NK cells, and dendritic cells.

Localisation

Plasma membrane.

Function

BCMA mediates the development and survival of B cell lymphocytes that maintain humoral immunity.

Homology

TNFRSF17 is conserved in P. Troglodytes, M. mulatta, C. lupus, B. taurus, M. musculus, and R. norvegicus.

Mutations

Note

22 single nucleotide polymorphisms (SNP) have been reported.

Implicated in

Entity name
Disease
Multiple myeloma is a fatal malignancy that involves the abnormal proliferation and accumulation of plasma cells characterized by their resistance to apoptosis. Sanchez et al. not only showed increased expression of BCMA in patients plasma cells, but that patients with multiple myeloma have a high concentration of BCMA protein circulating in their blood. Furthermore, the group found that higher levels of circulating BCMA are associated with a worse prognosis.
Prognosis
Poor.
Entity name
Acute myelomonocytic leukemia (AMML) with eosinophilia
Disease
AMML is a malignancy involving myeloid precursors of the bone marrow. Although this condition is rare, it is a common type of pediatric acute myeloid leukemia. In about 50% of the cases of AMML, increased numbers of abnormal eosinophils are observed in the bone marrow (eosinophilia). AMML patients with eosinophilia who carry a pericentric inversion at 16(p13q22) tend to have a better prognosis.
Prognosis
61% 5 year survival rate; AMML patients who carry the pericentric inversion have a higher rate of complete remission than those without the inversion (Chang et al., 2006).
Cytogenetics
Pericentric inversion at 16(p13q22) in 3-5% of AMML cases.
Entity name
T cell lymphoma
Note
(4;16)(q26;p13.1) chromosome translocation, which led to the discovery of BCMA, was noted by Laâbi et al. in a single case of T cell lymphoma. This translocation resulted in a IL-2/BCMA composite gene.
Atlas Image
Partial R-Banded karyotype. The karyotype shows a (4;16) (q26;p13.1) chromosomal translocation that led to the identification of BCMA by Laâbi et al. (Laâbi et al., 1992).
Entity name
Acute monocytic leukemia
Note
t(8;16)(p11;p13) translocation has been noted in cases of acute monocytic leukemia (Laâbi et al., 1992).
Note
Translocation (16;18)(p13;q21.3) has been reported in follicular lymphoma (Mahmoodi et al., 2004).

Bibliography

Pubmed IDLast YearTitleAuthors
172144002006Acute myelomonocytic leukemia with abnormal eosinophils: a case report with multi-modality diagnostic work-up.Chang ST et al
237762382013B-cell maturation antigen is modified by a single N-glycan chain that modulates ligand binding and surface retention.Huang HW et al
155425922005Structures of APRIL-receptor complexes: like BCMA, TACI employs only a single cysteine-rich domain for high affinity ligand binding.Hymowitz SG et al
13965831992A 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.Laâbi Y et al
154741532004Translocation (16;18)(p13;q21.3) in follicular lymphoma.Mahmoodi M et al

Other Information

Locus ID:

NCBI: 608
MIM: 109545
HGNC: 11913
Ensembl: ENSG00000048462

Variants:

dbSNP: 608
ClinVar: 608
TCGA: ENSG00000048462
COSMIC: TNFRSF17

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000048462ENST00000053243Q02223
ENSG00000048462ENST00000396495Q02223
ENSG00000048462ENST00000562385H3BMB5

Expression (GTEx)

0
50
100
150

Pathways

PathwaySourceExternal ID
Cytokine-cytokine receptor interactionKEGGko04060
Cytokine-cytokine receptor interactionKEGGhsa04060
Intestinal immune network for IgA productionKEGGko04672
Intestinal immune network for IgA productionKEGGhsa04672
Immune SystemREACTOMER-HSA-168256
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
TNFR2 non-canonical NF-kB pathwayREACTOMER-HSA-5668541
TNFs bind their physiological receptorsREACTOMER-HSA-5669034

References

Pubmed IDYearTitleCitations
233442652013B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma.145
145122992004Expression of BCMA, TACI, and BAFF-R in multiple myeloma: a mechanism for growth and survival.112
180251702007Regulated expression of BAFF-binding receptors during human B cell differentiation.71
169601542007Hodgkin lymphoma cells express TACI and BCMA receptors and generate survival and proliferation signals in response to BAFF and APRIL.55
271273032016APRIL and BCMA promote human multiple myeloma growth and immunosuppression in the bone marrow microenvironment.52
260658932015γ-Secretase directly sheds the survival receptor BCMA from plasma cells.50
155425922005Structures of APRIL-receptor complexes: like BCMA, TACI employs only a single cysteine-rich domain for high affinity ligand binding.45
228046692012Serum B-cell maturation antigen is elevated in multiple myeloma and correlates with disease status and survival.45
169310392006The role of the BAFF/APRIL system on T cell function.41
156920722005Graft-versus-tumor response in patients with multiple myeloma is associated with antibody response to BCMA, a plasma-cell membrane receptor.38

Citation

Abigail Gillespie ; Eric Sanchez ; George Tang ; Haiming Chen ; James Berenson

TNFRSF17 (tumor necrosis factor receptor superfamily, member 17)

Atlas Genet Cytogenet Oncol Haematol. 2014-10-01

Online version: http://atlasgeneticsoncology.org/gene/42616/tnfrsf17