TNFSF13

Chr 17

TNF superfamily member 13

Also known as: APRIL, CD256, TALL-2, TALL2, TNLG7B, TRDL-1, UNQ383/PRO715, ZTNF2

NCBI Gene: 8741ENSG00000161955UniProt: O75888

The protein encoded by this gene is a member of the tumor necrosis factor (TNF) ligand family. This protein is a ligand for TNFRSF17/BCMA, a member of the TNF receptor family. This protein and its receptor are both found to be important for B cell development. In vitro experiments suggested that this protein may be able to induce apoptosis through its interaction with other TNF receptor family proteins such as TNFRSF6/FAS and TNFRSF14/HVEM. Alternative splicing results in multiple transcript variants. Some transcripts that skip the last exon of the upstream gene (TNFSF12) and continue into the second exon of this gene have been identified; such read-through transcripts are contained in GeneID 407977, TNFSF12-TNFSF13. [provided by RefSeq, Oct 2010]

51
ClinVar variants
22
Pathogenic / LP
0.82
pLI score
1
Active trials
Clinical Summary— TNFSF13
🧬
Gene-Disease Validity (ClinGen)
common variable immunodeficiency · ARLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.82) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 21 VUS of 51 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.44LOEUF
pLI 0.817
Z-score 3.02
OE 0.14 (0.06–0.44)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.53Z-score
OE missense 0.87 (0.75–1.02)
121 obs / 138.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.14 (0.06–0.44)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.75–1.02)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03
0≤1.21.6
LoF obs/exp: 2 / 14.4Missense obs/exp: 121 / 138.4Syn Z: -0.20

ClinVar Variant Classifications

51 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic2
VUS21
Likely Benign3
Benign5
20
Pathogenic
2
Likely Pathogenic
21
VUS
3
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
20
0
20
Likely Pathogenic
1
0
1
0
2
VUS
0
10
10
1
21
Likely Benign
0
1
1
1
3
Benign
0
1
3
1
5
Total11235351

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TNFSF13 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Zigakibart demonstrates clinical safety and efficacy in a Phase 1/2 trial of healthy volunteers and patients with IgA nephropathy.
Kooienga L et al.·Kidney Int
2025Clinical trial
Association between CCDC132, FDX1 and TNFSF13 gene polymorphisms and the risk of IgA nephropathy.
Niu D et al.·Nephrology (Carlton)
2015
Mendelian randomization and colocalization analysis reveal novel drug targets for myasthenia gravis.
Ouyang Y et al.·Hum Genomics
2024
Association of TNFSF13 polymorphisms with IgA nephropathy in a Chinese Han population.
Zhong Z et al.·J Gene Med
2017
Potential Role of PARVB in Macrophage-Mediated Immunosuppression and Cervical Cancer Progression.
Guo A et al.·Lab Invest
2025
Protein and functional isoform levels and genetic variants of the BAFF and APRIL pathway components in systemic lupus erythematosus.
Ortiz-Aljaro P et al.·Sci Rep
2022Functional
There is no gene for CVID - novel monogenetic causes for primary antibody deficiency.
Ramirez NJ et al.·Curr Opin Immunol
2021Review
Genetic Determinants of Colonic Diverticulosis-A Systematic Review.
Nehring P et al.·Genes (Basel)
2025Review
Exploring the role of APRIL in autoimmunity: implications for therapeutic targeting in systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome.
Poznyak AV et al.·Front Immunol
2025Review
The role of senescence-related genes in major depressive disorder: insights from machine learning and single cell analysis.
Lian K et al.·BMC Psychiatry
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
M2 macrophage-derived paracrine factor TNFSF13 affects the fibrogenic alterations in endothelial cells and cardiac fibroblasts by mediating the NF-κB and Akt pathway.
Tan X et al.·J Biochem Mol Toxicol
2024
A Retrospective Exploratory Analysis for Serum Extracellular Vesicles Reveals APRIL (TNFSF13), CXCL13, and VEGF-A as Prognostic Biomarkers for Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.
Jung HH et al.·Int J Mol Sci
2023🔓 Open Access
TNFSF13 Is a Novel Onco-Inflammatory Marker and Correlates With Immune Infiltration in Gliomas.
Chen R et al.·Front Immunol
2021🔓 Open Access
Association of Common Variants of TNFSF13 and TNFRSF13B Genes with CLL Risk and Clinical Picture, as Well as Expression of Their Products-APRIL and TACI Molecules.
Jasek M et al.·Cancers (Basel)
2020🔓 Open Access
TNFSF13 upregulation confers chemotherapeutic resistance via triggering autophagy initiation in triple-negative breast cancer.
Lin HY et al.·J Mol Med (Berl)
2020
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Cardiovascular DiseaseFrailty

Investigating the Combined Effects of Protein, Blueberries, and Exercise on Cardiovascular Health and Frailty in Older Nova Scotians

NOT YET RECRUITING
NCT06693271Phase NANova Scotia Health AuthorityStarted 2025-01-01
intervention of protein, blueberriesExercise training

External Resources

Links to major genomics databases and tools