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25 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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TNFSF13
TNF superfamily member 13
Chromosome 17 · 17p13.1
NCBI Gene: 8741Ensembl: ENSG00000161955.17HGNC: HGNC:11928UniProt: O75888
219PubMed Papers
20Diseases
2Drugs
0Pathogenic Variants
RESEARCH IMPACT
Trending
CLINICAL
Clinical Trials
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingpositive regulation of isotype switching to IgA isotypescytoplasmextracellular exosomeIGA glomerulonephritisSnoringmyeloproliferative disorderhypertension
✦AI Summary

TNFSF13, also known as A Proliferation-Inducing Ligand (APRIL), is a TNF superfamily cytokine that serves as a crucial regulator of B cell biology and humoral immunity 1. The protein binds to receptors TNFRSF13B/TACI and TNFRSF17/BCMA, playing essential roles in B cell survival, proliferation, and immunoglobulin class switching 2. APRIL promotes plasma cell generation and survival, making it fundamental for antibody production 3. However, dysregulated APRIL signaling contributes to autoimmune pathogenesis, particularly in IgA nephropathy where it mediates production of galactose-deficient IgA1 and pathogenic immune complexes that deposit in glomeruli 43. The protein also activates NF-κB signaling pathways through interaction with HSPG2, promoting fibroblast proliferation and inflammatory responses in fibrotic diseases 5. Therapeutically, APRIL represents an attractive target for treating B cell-mediated autoimmune diseases. Multiple APRIL-targeting therapies including sibeprenlimab, telitacicept, and povetacicept have shown clinical efficacy in reducing proteinuria and pathogenic antibody levels in conditions like IgA nephropathy and systemic lupus erythematosus 678, offering advantages over B cell depletion strategies by preserving memory B cell function.

Sources cited
1
APRIL is a TNF family member that serves as a fundamental survival factor for B cells
PMID: 12427767
2
APRIL plays central roles in B-cell survival, proliferation, and Ig class switching
PMID: 39182759
3
APRIL is crucial for plasma cell generation and survival, and mediates production of galactose-deficient IgA1 in IgA nephropathy
PMID: 39408691
4
APRIL has pathogenic role in IgA nephropathy involving aberrant IgA1 production and immune complex deposition
PMID: 31027890
5
TNFSF13 activates NF-κB signaling through HSPG2 interaction, promoting fibroblast proliferation and inflammation
PMID: 38046235
6
Sibeprenlimab (APRIL inhibitor) significantly reduced proteinuria in IgA nephropathy patients
PMID: 37916620
7
Telitacicept (APRIL/BAFF inhibitor) received approval for systemic lupus erythematosus treatment
PMID: 34463932
8
Povetacicept showed enhanced APRIL/BAFF inhibition and efficacy in autoimmune disease models
PMID: 36705554
Disease Associationsⓘ20
IGA glomerulonephritisOpen Targets
0.58Moderate
SnoringOpen Targets
0.40Weak
myeloproliferative disorderOpen Targets
0.34Weak
hypertensionOpen Targets
0.34Weak
glioblastoma multiformeOpen Targets
0.32Weak
Abnormality of the skeletal systemOpen Targets
0.31Weak
metabolic syndromeOpen Targets
0.31Weak
lupus nephritisOpen Targets
0.29Weak
central nervous system cancerOpen Targets
0.29Weak
neuroblastomaOpen Targets
0.27Weak
lymphomaOpen Targets
0.26Weak
systemic lupus erythematosusOpen Targets
0.25Weak
female infertilityOpen Targets
0.13Weak
anovulationOpen Targets
0.13Weak
rheumatoid arthritisOpen Targets
0.13Weak
chronic lymphocytic leukemiaOpen Targets
0.11Weak
neoplasmOpen Targets
0.10Weak
non-small cell lung carcinomaOpen Targets
0.10Weak
multiple sclerosisOpen Targets
0.10Weak
memory impairmentOpen Targets
0.10Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets2
ATACICEPTPhase III
Tumor necrosis factor ligand superfamily member 13B inhibitor
lymphoma
SIBEPRENLIMABPhase III
Tumor necrosis factor ligand superfamily member 13 inhibitor
IGA glomerulonephritis
Related Genes
TNFRSF17Protein interaction100%TNFRSF13BProtein interaction98%TNFRSF13CProtein interaction94%TNFSF12Protein interaction85%SETProtein interaction80%ANP32AProtein interaction80%
Tissue Expression6 tissues
Lung
100%
Bone Marrow
93%
Ovary
65%
Liver
34%
Heart
32%
Brain
29%
Gene Interaction Network
Click a node to explore
TNFSF13TNFRSF17TNFRSF13BTNFRSF13CTNFSF12SETANP32A
PROTEIN STRUCTURE
Preparing viewer…
PDB4ZCH · 2.43 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.85LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.57 [0.40–0.85]
RankingsWhere TNFSF13 stands among ~20K protein-coding genes
  • #1,891of 20,598
    Most Researched219 · top 10%
  • #7,399of 17,882
    Most Constrained (LOEUF)0.85
Genes detectedTNFSF13
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
A Phase 2 Trial of Sibeprenlimab in Patients with IgA Nephropathy.
PMID: 37916620
N Engl J Med · 2024
1.00
2
Telitacicept: First Approval.
PMID: 34463932
Drugs · 2021
0.90
3
Povetacicept, an Enhanced Dual APRIL/BAFF Antagonist That Modulates B Lymphocytes and Pathogenic Autoantibodies for the Treatment of Lupus and Other B Cell-Related Autoimmune Diseases.
PMID: 36705554
Arthritis Rheumatol · 2023
0.80
4
Exosome Derived from Mesenchymal Stem Cells Alleviates Hypertrophic Scar by Inhibiting the Fibroblasts via TNFSF-13/HSPG2 Signaling Pathway.
PMID: 38046235
Int J Nanomedicine · 2023
0.70
5
Zigakibart demonstrates clinical safety and efficacy in a Phase 1/2 trial of healthy volunteers and patients with IgA nephropathy.
PMID: 40482854
Kidney Int · 2025
0.64