TNFSF13B

Summary

TNFSF13B (TNF superfamily member 13b, HGNC:11929) is a protein-coding gene on chromosome 13q33.3, encoding Tumor necrosis factor ligand superfamily member 13B (Q9Y275). Cytokine that binds to TNFRSF13B/TACI and TNFRSF17/BCMA.

The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This cytokine is a ligand for receptors TNFRSF13B/TACI, TNFRSF17/BCMA, and TNFRSF13C/BAFFR. This cytokine is expressed in B cell lineage cells, and acts as a potent B cell activator. It has been also shown to play an important role in the proliferation and differentiation of B cells. Alternatively spliced transcript variants encoding distinct isoforms have been identified.

Source: NCBI Gene 10673 — RefSeq curated summary.

At a glance

• GWAS associations: 22
• Clinical variants (ClinVar): 15 total
• Druggable target: yes
• MANE Select transcript: NM_006573

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11929
Approved symbol	TNFSF13B
Name	TNF superfamily member 13b
Location	13q33.3
Locus type	gene with protein product
Status	Approved
Aliases	BAFF, THANK, BLYS, TALL-1, TALL1, CD257
Ensembl gene	ENSG00000102524
Ensembl biotype	protein_coding
OMIM	603969
Entrez	10673

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000375887, ENST00000430559, ENST00000479435, ENST00000486502, ENST00000493765, ENST00000542136

RefSeq mRNA: 2 — MANE Select: NM_006573 NM_001145645, NM_006573

CCDS: CCDS45067, CCDS9509

Canonical transcript exons

ENST00000375887 — 6 exons

Exon	Start	End
ENSE00000686291	108270340	108270424
ENSE00001811977	108269718	108270234
ENSE00003539446	108303454	108303604
ENSE00003592544	108286803	108286859
ENSE00003687225	108303253	108303365
ENSE00003915320	108306826	108308478

Expression profiles

Bgee: expression breadth ubiquitous, 226 present calls, max score 98.06.

FANTOM5 (CAGE): breadth broad, TPM avg 26.7517 / max 1553.1655, expressed in 567 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
135975	20.2612	419
135977	1.1974	220
135972	1.1855	296
135973	1.0505	252
135974	0.9995	202
135979	0.9959	236
135976	0.6846	170
135980	0.2222	109
135978	0.1549	89

Top tissues by expression

247 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.06	gold quality
leukocyte	CL:0000738	97.75	gold quality
blood	UBERON:0000178	95.90	gold quality
trabecular bone tissue	UBERON:0002483	94.73	gold quality
buccal mucosa cell	CL:0002336	94.05	silver quality
bone marrow	UBERON:0002371	91.61	gold quality
vermiform appendix	UBERON:0001154	91.35	gold quality
germinal epithelium of ovary	UBERON:0001304	91.12	gold quality
epithelial cell of pancreas	CL:0000083	91.09	gold quality
granulocyte	CL:0000094	90.42	gold quality
decidua	UBERON:0002450	88.88	gold quality
ileal mucosa	UBERON:0000331	88.69	gold quality
lymph node	UBERON:0000029	88.16	gold quality
parietal pleura	UBERON:0002400	87.92	gold quality
visceral pleura	UBERON:0002401	87.52	gold quality
bone marrow cell	CL:0002092	87.12	gold quality
cardiac muscle of right atrium	UBERON:0003379	86.30	silver quality
caecum	UBERON:0001153	85.99	gold quality
pancreatic ductal cell	CL:0002079	85.11	silver quality
gall bladder	UBERON:0002110	84.20	gold quality
duodenum	UBERON:0002114	83.34	gold quality
left ventricle myocardium	UBERON:0006566	82.69	silver quality
pericardium	UBERON:0002407	82.52	gold quality
palpebral conjunctiva	UBERON:0001812	82.07	gold quality
spleen	UBERON:0002106	81.81	gold quality
superficial temporal artery	UBERON:0001614	81.80	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.04	gold quality
right lung	UBERON:0002167	80.95	gold quality
rectum	UBERON:0001052	80.93	gold quality
jejunal mucosa	UBERON:0000399	79.77	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-CURD-95	yes	287.03
E-CURD-122	yes	67.78
E-HCAD-6	yes	41.26
E-MTAB-10553	yes	35.19
E-MTAB-6701	yes	31.66
E-MTAB-10287	yes	24.77
E-CURD-112	yes	23.53
E-CURD-88	yes	18.49
E-HCAD-13	yes	14.00
E-CURD-46	yes	13.66
E-ANND-3	yes	10.38
E-MTAB-9067	yes	9.98
E-HCAD-1	yes	9.27
E-MTAB-9801	yes	7.02

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, CREB1, FOS, HIF1A, IRF1, IRF8, NFATC1, NFATC2, NFKB1, NFKB2, NFKB, REL, RELA, RELB, SMAD3, SMAD4, SMAD7, STAT1, TCF3

miRNA regulators (miRDB)

122 targeting TNFSF13B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-374A-5P	99.90	71.34	2923

Literature-anchored findings (GeneRIF, showing 40)

• interacts with newly identified receptor BAFF-R, which appears to be the principal receptor for BAFF-mediated mature B cell survival (PMID:11509692)
• BAFF may play a role in the development of T cell responses, in addition to its role in B cell homeostasis. (PMID:11714784)
• Levels of BLyS protein were, on average, threefold higher in patients with follicular lymphoma compared to normal donors (PMID:11823048)
• crystal structure of the TNF-homologous domain (PMID:11827482)
• determined the three-dimensional crystal structure of BLyS to 2.0 A resolution and identified receptor recognition segments using limited proteolysis coupled with mass spectrometry (PMID:11862220)
• BAFF is a survival and maturation factor for mouse B cells (PMID:12115621)
• 10 genes, including interleukin (IL)-10, lymphocyte activation gene-1 (LAG-1), GCP-2, PBEF, ferritin, PIM-2, TFG, CD27 ligand, DUSP5, and archain, were up-regulated at the mRNA level by TALL-1 stimulation in B lymphoma cells and/or primary B lymphocytes. (PMID:12149433)
• aberrantly expressed by B chronic lymphocytic leukemia cells (PMID:12351410)
• When coexpressed with APRIL, BLYS forms active heterotrimeric molecules that circulate in the serum of patients with systemic immune-based rheumatic diseases. (PMID:12370363)
• REVIEW: role in regulating the peripheral B cell compartment and humoral immunity, and the contribution of altered BLyS expression to B lymphocyte diseases (PMID:12389615)
• Review. BLyS is one of the most important cytokines of the TNF superfamily. It supports normal B-cell function & promotes B-cell autoimmunity. (PMID:12408045)
• macrophage- and DC-derived BAFF is a key molecule by which macrophages and DCs directly regulate human B-cell proliferative responses to T-cell-independent stimuli. (PMID:12531790)
• crystal structure and interactions with BAFF receptor (PMID:12715002)
• BAFF/BLyS receptor 3 comprises a minimal TNF receptor-like module that encodes a highly focused ligand-binding site. (PMID:12755599)
• BAFF may enhance humoral immunity in vivo by promoting survival of Ig-secreting cells via a B cell maturation antigen-dependent mechanism (PMID:12865416)
• alternative splicing of the BAFF gene regulates receptor binding and biopresentation of the B cell survival cytokine, BAFF (PMID:12867412)
• B-CLL cells can be rescued from apoptosis through an autocrine process involving BAFF, APRIL, and their receptors. (PMID:14504101)
• BAFF up-regulates activation-induced cytidine deaminase and enhances class-switch DNA recombination in Epstein-Barr virus-infected B cells. (PMID:14607922)
• BAFF may play an important role in FDC-B-cell interactions through the B-cell coreceptor complex and a possibly sequential link between the T cell-independent and -dependent B-cell responses in the germinal centers. (PMID:14630796)
• Dysregulation of BLyS over extended periods of time is common in patients with systemic lupus erythematosus (PMID:14673998)
• Exposure of non-Hodgkin’s lymphoma B cells to recombinant or myeloid cell-derived BAFF attenuates apoptosis, increases NF-kappa B activation, up-regulates Bcl-2 and Bcl-xL, and down-regulates Bax. (PMID:14978135)
• serum levels of BAFF and APRIL were increased about 5-fold in patients with multiple myeloma as compared with healthy donors (PMID:15070697)
• Antagonissts may provide treatment for systsemic lupus erythematosus (REVIEW) (PMID:15230285)
• BLyS and its receptors represent a potentially important therapeutic target in B-cell lymphoma (PMID:15251985)
• novel mechanism that might dramatically exacerbate the release of BLyS by neutrophils during pathologic inflammatory responses. (PMID:15358625)
• Review. BLyS plasma levels in systemic lupus erythematosus, Sjogren’s syndrome & rheumatoid arthritis are higher in patients than controls. BLyS may have a role in the interaction between the monocyte & the B lymphocyte in some autoimmune disease. (PMID:15470519)
• another form of TACI exists wherein the N-terminal cysteine-rich domain (CRD) is removed by alternative splicing and is capable of ligand-induced cell signaling and that the second CRD alone (TACI_d2) contains full affinity for both APRIL and BAFF (PMID:15542592)
• The induced expression of BAFF on fibroblast-like synoviocytes by proinflammatory cytokines in vitro may enhance the capacity of such cells to protect B cells from apoptosis in inflammatory microenvironments in vivo. (PMID:15634908)
• Macrophages promote Burkitt’s lymphoma cell survival through a B-cell survival factor (BAFF)-dependent mechanism. (PMID:15728515)
• show that the main site of production for BAFF and APRIL is the bone marrow (BM) environment, and that production is mainly by monocytes and neutrophils. In addition, osteoclasts produce very high levels of APRIL, unlike BM stromal cells (PMID:15827134)
• BAFF transgene overexpression in vivo promotes delayed-type hypersensitivity, which is a classical type 1 T-helper (Th1) cell response, and suppresses Th2-dependent allergic airway responses. (PMID:15843552)
• conclude that BAFF and APRIL from NLCs can function in a paracrine manner to support leukemia cell survival via mechanisms that are distinct from those of SDF-1alpha (PMID:15860672)
• Serum levels of sBAFF and sAPRIL were increased in Sjogren’s syndrome, especially in anti-Ro/La+ patients (PMID:15981083)
• The known effect of B cells in periodontitis would be partly mediated by salivary BAFF in patients with primary Sjogren’s syndrome. (PMID:16052575)
• BLyS regulates B cell as well as T cell function and has pro- and antiinflammatory activities in rheumatoid arthritis. (PMID:16239971)
• In Wagener’s granulomatosis (WG) patients, serum levels of BAFF are significantly increased, therefore BAFF is proposed to be a possible pathogenic factor in WG. (PMID:16242914)
• B cell homeostasis is maintained by BAFF-mediated regulation of Bcl-2-binding protein, BIM. (PMID:16301744)
• BLyS was found to increase the viability and proliferation of malignant B cells from Waldenstrom macroglobulinemia patients. (PMID:16304043)
• Full-length BLyS and DeltaBLyS mRNA levels are elevated in systemic lupus erythematosis and are more closely associated with disease activity than are BLyS protein levels. (PMID:16356193)
• Ala134-BAFF is more efficacious than myc-Gln136-BAFF in inducing B cell proliferation. Formation of the 60-mer in solution by BAFF extracellular domain is an intrinsic property of the protein. This more active form of BAFF may be physiologically relevant. (PMID:16475789)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tnfsf13b	ENSDARG00000012945
mus_musculus	Tnfsf13b	ENSMUSG00000031497
rattus_norvegicus	Tnfsf13b	ENSRNOG00000014464

Paralogs (2): TNFSF13 (ENSG00000161955), TNFSF12 (ENSG00000239697)

Protein

Protein identifiers

Tumor necrosis factor ligand superfamily member 13B — Q9Y275 (reviewed: Q9Y275)

Alternative names: B lymphocyte stimulator, B-cell-activating factor, BAFF, Dendritic cell-derived TNF-like molecule, TNF- and APOL-related leukocyte expressed ligand 1

All UniProt accessions (2): Q9Y275, A0A0U5J7Q1

UniProt curated annotations — full annotation on UniProt →

Function. Cytokine that binds to TNFRSF13B/TACI and TNFRSF17/BCMA. TNFSF13/APRIL binds to the same 2 receptors. Together, they form a 2 ligands -2 receptors pathway involved in the stimulation of B- and T-cell function and the regulation of humoral immunity. A third B-cell specific BAFF-receptor (BAFFR/BR3) promotes the survival of mature B-cells and the B-cell response. Isoform 2 seems to inhibit isoform 1 secretion and bioactivity. Acts as a transcription factor for its own parent gene, in association with NF-kappa-B p50 subunit, at least in autoimmune and proliferative B-cell diseases. The presence of Delta4BAFF is essential for soluble BAFF release by IFNG/IFN-gamma-stimulated monocytes and for B-cell survival. It can directly or indirectly regulate the differential expression of a large number of genes involved in the innate immune response and the regulation of apoptosis.

Subunit / interactions. Homotrimer. Isoform 2 heteromultimerizes with isoform 1, probably limiting the amount of functional isoform 1 on the cell surface. Isoform 3 is unlikely form trimers or bind to BAFF receptors.

Subcellular location. Cell membrane Secreted.

Tissue specificity. Abundantly expressed in peripheral blood Leukocytes and is specifically expressed in monocytes and macrophages. Also found in the spleen, lymph node, bone marrow, T-cells and dendritic cells. A lower expression seen in placenta, heart, lung, fetal liver, thymus, and pancreas. Isoform 2 is expressed in many myeloid cell lines.

Post-translational modifications. The soluble form derives from the membrane form by proteolytic processing. Isoform 2 is not efficiently shed from the membrane unlike isoform 1. N-glycosylated.

Induction. Up-regulated by exposure to IFNG/IFN-gamma. Down-regulated by phorbol myristate acetate/ionomycin treatment.

Similarity. Belongs to the tumor necrosis factor family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y275-1	1	yes
Q9Y275-2	2, DeltaBAFF
Q9Y275-3	3, Delta4BAFF

RefSeq proteins (2): NP_001139117, NP_006564* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006052	TNF_dom	Domain
IPR008983	Tumour_necrosis_fac-like_dom	Homologous_superfamily
IPR051748	TNF_Ligand_Superfamily	Family

Pfam: PF00229

UniProt features (29 total): strand 12, splice variant 3, chain 2, topological domain 2, turn 2, glycosylation site 2, disulfide bond 1, sequence variant 1, transmembrane region 1, domain 1, region of interest 1, site 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
1KXG	X-RAY DIFFRACTION	2
5Y9J	X-RAY DIFFRACTION	2.05
4ZCH	X-RAY DIFFRACTION	2.43
1OQE	X-RAY DIFFRACTION	2.5
8ZUJ	ELECTRON MICROSCOPY	2.58
1OQD	X-RAY DIFFRACTION	2.6
1KD7	X-RAY DIFFRACTION	2.8
6FXN	X-RAY DIFFRACTION	2.9
1JH5	X-RAY DIFFRACTION	3
1OSG	X-RAY DIFFRACTION	3
3V56	X-RAY DIFFRACTION	3
4V46	X-RAY DIFFRACTION	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y275-F1	78.94	0.63

Antibody-complex structures (SAbDab): 2 — 5Y9J, 6FXN

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 133–134 (cleavage)

Disulfide bonds (1): 232–245

Glycosylation sites (2): 124, 242

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5668541	TNFR2 non-canonical NF-kB pathway
R-HSA-5669034	TNFs bind their physiological receptors
R-HSA-5676594	TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway

MSigDB gene sets: 287 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_B_CELL_HOMEOSTASIS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_B_CELL_ACTIVATION, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_LYMPHOCYTE_HOMEOSTASIS, GOBP_LYMPHOCYTE_COSTIMULATION, GOBP_B_CELL_PROLIFERATION, LHX3_01, GOBP_POSITIVE_REGULATION_OF_B_CELL_PROLIFERATION, CEBPB_01

GO Biological Process (20): B cell homeostasis (GO:0001782), lymphocyte homeostasis (GO:0002260), transitional one stage B cell differentiation (GO:0002333), germinal center formation (GO:0002467), positive regulation of germinal center formation (GO:0002636), immune response (GO:0006955), signal transduction (GO:0007165), positive regulation of B cell proliferation (GO:0030890), T cell costimulation (GO:0031295), B cell costimulation (GO:0031296), tumor necrosis factor-mediated signaling pathway (GO:0033209), T cell proliferation (GO:0042098), B cell proliferation (GO:0042100), positive regulation of T cell proliferation (GO:0042102), skin development (GO:0043588), immune system process (GO:0002376), cell communication (GO:0007154), signaling (GO:0023052), B cell differentiation (GO:0030183), regulation of immune response (GO:0050776)

GO Molecular Function (4): signaling receptor binding (GO:0005102), cytokine activity (GO:0005125), tumor necrosis factor receptor binding (GO:0005164), protein binding (GO:0005515)

GO Cellular Component (7): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), plasma membrane (GO:0005886), focal adhesion (GO:0005925), membrane (GO:0016020), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
TNFR2 non-canonical NF-kB pathway	2
Cytokine Signaling in Immune system	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cellular process	2
positive regulation of lymphocyte proliferation	2
positive regulation of B cell activation	2
lymphocyte costimulation	2
positive regulation of T cell activation	2
lymphocyte proliferation	2
B cell activation	2
lymphocyte homeostasis	1
leukocyte homeostasis	1
transitional stage B cell differentiation	1
adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	1
anatomical structure formation involved in morphogenesis	1
germinal center formation	1
regulation of germinal center formation	1
positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	1
positive regulation of developmental process	1
immune system process	1
response to stimulus	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of B cell proliferation	1
B cell proliferation	1
cytokine-mediated signaling pathway	1
cellular response to tumor necrosis factor	1
T cell activation	1
T cell proliferation	1
regulation of T cell proliferation	1
animal organ development	1
biological_process	1
regulation of biological process	1
lymphocyte differentiation	1
regulation of immune system process	1
immune response	1
regulation of response to stimulus	1
protein binding	1
receptor ligand activity	1
tumor necrosis factor receptor superfamily binding	1

Protein interactions and networks

STRING

3008 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TNFSF13B	TNFRSF17	Q02223	999
TNFSF13B	TNFRSF13B	O14836	999
TNFSF13B	TNFRSF13C	Q96RJ3	999
TNFSF13B	CD40LG	P29965	920
TNFSF13B	CD40	P25942	915
TNFSF13B	ICOSLG	O75144	874
TNFSF13B	ICOS	Q9Y6W8	859
TNFSF13B	TNFRSF1A	P19438	852
TNFSF13B	TNFSF12	O43508	835
TNFSF13B	LTBR	P36941	819
TNFSF13B	CXCL13	O43927	817
TNFSF13B	NFKB2	Q00653	797
TNFSF13B	CAMLG	P49069	792
TNFSF13B	CR2	P20023	780
TNFSF13B	TNF	P01375	770

IntAct

17 interactions, top by confidence:

A	B	Type	Score
TNFSF13B	TNFRSF13B	psi-mi:“MI:0915”(physical association)	0.840
TNFRSF13B	TNFSF13B	psi-mi:“MI:0915”(physical association)	0.840
TNFSF13B	TNFRSF13B	psi-mi:“MI:0407”(direct interaction)	0.840
TNFRSF13B	TNFSF13B	psi-mi:“MI:0407”(direct interaction)	0.840
TNFSF13B	IPO8	psi-mi:“MI:0914”(association)	0.640
TNFSF13B	TNFRSF17	psi-mi:“MI:0915”(physical association)	0.610
TNFSF13B	TNFRSF17	psi-mi:“MI:0407”(direct interaction)	0.610
CSE1L	TNFSF13B	psi-mi:“MI:0915”(physical association)	0.500
KPNB1	TNFSF13B	psi-mi:“MI:0915”(physical association)	0.500
TNFSF13B	TNFRSF13C	psi-mi:“MI:0407”(direct interaction)	0.440
IL1R2	TNFSF13B	psi-mi:“MI:0915”(physical association)	0.400
TNFSF13B	HEATR1	psi-mi:“MI:0914”(association)	0.350
TNFSF13B	TNPO2	psi-mi:“MI:0914”(association)	0.350

BioGRID (209): CAND2 (Affinity Capture-MS), IPO7 (Affinity Capture-MS), PDSS1 (Affinity Capture-MS), MON2 (Affinity Capture-MS), FANCD2 (Affinity Capture-MS), RANBP6 (Affinity Capture-MS), MFAP3 (Affinity Capture-MS), FAM160B1 (Affinity Capture-MS), IMPAD1 (Affinity Capture-MS), HOOK2 (Affinity Capture-MS), TTC17 (Affinity Capture-MS), HOOK1 (Affinity Capture-MS), BRAT1 (Affinity Capture-MS), NUP85 (Affinity Capture-MS), LRIG3 (Affinity Capture-MS)

ESM2 similar proteins: A1A5X5, A4IH36, D4AB34, O93449, O95150, O97605, O97626, P04088, P04924, P09529, P10600, P15203, P16047, P17125, P17491, P27093, P36939, P36940, P41047, P42917, P48023, P50591, P50592, P59694, P59695, P63306, P63307, P63308, Q04999, Q07258, Q5UBV8, Q5XIG2, Q6PGN1, Q80WL1, Q861W5, Q8BGU2, Q8BMF8, Q8IUK8, Q8K3Y7, Q8R2Z0

Diamond homologs: O75888, Q92838, Q9BEG5, Q9D777, Q9WU72, Q9Y275

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
TNFSF13B	“up-regulates activity”	TNFRSF13C	binding
TNFSF13B	up-regulates	TNFRSF13B	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

15 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	5
Likely benign	2
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

916 predictions. Top by Δscore:

Variant	Effect	Δscore
13:108270205:G:GT	donor_gain	1.0000
13:108270231:GAAA:G	donor_gain	1.0000
13:108270233:AAG:A	donor_loss	1.0000
13:108270234:AGT:A	donor_loss	1.0000
13:108270235:G:GG	donor_gain	1.0000
13:108270236:TGAG:T	donor_loss	1.0000
13:108270237:GAGT:G	donor_loss	1.0000
13:108270423:AGGTA:A	donor_loss	1.0000
13:108270425:G:GC	donor_loss	1.0000
13:108270426:T:G	donor_loss	1.0000
13:108286801:A:AG	acceptor_gain	1.0000
13:108286802:G:GA	acceptor_gain	1.0000
13:108302880:G:GT	donor_gain	1.0000
13:108302881:A:T	donor_gain	1.0000
13:108302894:G:GG	donor_gain	1.0000
13:108303448:TCTTA:T	acceptor_loss	1.0000
13:108303451:TAG:T	acceptor_loss	1.0000
13:108303452:A:AC	acceptor_loss	1.0000
13:108303453:G:GT	acceptor_loss	1.0000
13:108303601:GCTG:G	donor_gain	1.0000
13:108270232:A:T	donor_gain	0.9900
13:108270232:AAA:A	donor_gain	0.9900
13:108270233:AA:A	donor_gain	0.9900
13:108270238:A:AC	donor_loss	0.9900
13:108270239:G:T	donor_loss	0.9900
13:108286802:GTC:G	acceptor_gain	0.9900
13:108286802:GTCA:G	acceptor_gain	0.9900
13:108287089:G:GT	donor_gain	0.9900
13:108302853:A:G	donor_gain	0.9900
13:108303452:A:AG	acceptor_gain	0.9900

AlphaMissense

1832 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:108286824:T:C	L149P	0.999
13:108303268:T:A	V166D	0.999
13:108303273:T:A	W168R	0.999
13:108303273:T:C	W168R	0.999
13:108303355:T:A	I195K	0.999
13:108303553:T:A	C232S	0.999
13:108303553:T:C	C232R	0.999
13:108303554:G:A	C232Y	0.999
13:108303554:G:C	C232S	0.999
13:108303555:T:G	C232W	0.999
13:108303593:G:A	C245Y	0.999
13:108303594:C:G	C245W	0.999
13:108306856:T:A	L259H	0.999
13:108303275:G:C	W168C	0.998
13:108303275:G:T	W168C	0.998
13:108303325:T:A	I185K	0.998
13:108303325:T:C	I185T	0.998
13:108303331:T:A	V187D	0.998
13:108303491:T:C	L211P	0.998
13:108303501:G:C	R214S	0.998
13:108303501:G:T	R214S	0.998
13:108303554:G:T	C232F	0.998
13:108303592:T:A	C245S	0.998
13:108303592:T:C	C245R	0.998
13:108303593:G:C	C245S	0.998
13:108306838:T:C	L253P	0.998
13:108306849:G:C	D257H	0.998
13:108306850:A:T	D257V	0.998
13:108306856:T:C	L259P	0.998
13:108306868:T:A	I263K	0.998

dbSNP variants (sampled 300 via entrez): RS1000062731 (13:108289178 G>A,T), RS1000178672 (13:108289516 A>C), RS1000247931 (13:108283264 T>C), RS1000321040 (13:108278482 A>G), RS1000339265 (13:108276269 C>T), RS1000339960 (13:108295277 C>A,G,T), RS1000589508 (13:108276421 G>A), RS1000641980 (13:108276701 A>G,T), RS1000831047 (13:108271542 A>G), RS1000946964 (13:108293904 T>C), RS1000952515 (13:108289427 A>C,G), RS1000991403 (13:108300789 A>T), RS1001067408 (13:108287708 C>G,T), RS1001134599 (13:108294472 G>T), RS1001160882 (13:108283243 C>T)

Disease associations

OMIM: gene MIM:603969 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

22 associations (top):

Study	Trait	p-value
GCST003995_5	Tonsillectomy	1.000000e-17
GCST004068_71	Venous thromboembolism adjusted for sickle cell variant rs77121243-T	5.000000e-06
GCST004603_130	Platelet count	1.000000e-09
GCST004607_93	Plateletcrit	2.000000e-12
GCST004610_136	White blood cell count	9.000000e-11
GCST004616_51	Platelet distribution width	2.000000e-10
GCST004626_125	Myeloid white cell count	1.000000e-10
GCST005014_122	Tonsillectomy	1.000000e-17
GCST005990_17	Non-albumin protein levels	1.000000e-09
GCST006585_2654	Blood protein levels	3.000000e-07
GCST008576_7	IgG levels	5.000000e-08
GCST009391_1641	Metabolite levels	6.000000e-06
GCST010241_216	Apolipoprotein A1 levels	1.000000e-09
GCST010242_176	HDL cholesterol levels	2.000000e-11
GCST012490_262	Femur bone mineral density x serum urate levels interaction	1.000000e-08
GCST90002393_299	Monocyte count	3.000000e-14
GCST90002393_300	Monocyte count	5.000000e-37
GCST90002394_397	Monocyte percentage of white cells	4.000000e-24
GCST90002400_124	Plateletcrit	9.000000e-17
GCST90002401_62	Platelet distribution width	3.000000e-14
GCST90002402_219	Platelet count	4.000000e-09
GCST90016667_1	Spleen volume	7.000000e-14

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0007924	tonsillectomy risk measurement
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0007984	platelet component distribution width
EFO:0007787	plasma betaine measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004531	urate measurement
EFO:0005091	monocyte count
EFO:0007989	monocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2364158 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3759467	TNFSF13B	3	2.50	1	rituximab
rs9514827	TNFSF13B		0.00	0

CTD chemical–gene interactions

48 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	increases expression, decreases expression	3
Valproic Acid	decreases expression	3
bisphenol A	decreases expression, decreases methylation	2
Lipopolysaccharides	affects cotreatment, affects expression, increases expression, decreases reaction	2
aristolochic acid I	increases expression	1
bisphenol F	decreases methylation	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
trichostatin A	increases expression	1
3,4-dichloroaniline	increases expression	1
arsenite	affects binding, increases activity, increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
diphenylarsinic acid	increases secretion	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
pyrachlostrobin	increases expression	1
picoxystrobin	increases expression	1
(+)-JQ1 compound	decreases expression	1
Arsenic Trioxide	affects expression	1
Acetaminophen	affects cotreatment, affects expression, decreases expression	1
Air Pollutants, Occupational	decreases expression	1
Antimycin A	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Demecolcine	increases expression	1
Succimer	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.