TNFSF13

Chr 17

TNF superfamily member 13

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

The encoded protein is a TNF ligand family cytokine that binds to TNFRSF13B/TACI and TNFRSF17/BCMA receptors and regulates B cell development and tumor cell growth. Mutations cause autosomal recessive immunodeficiency affecting B cell function and antibody production. The gene is highly constrained against loss-of-function variants (LOEUF 0.44), indicating that complete protein loss is likely not tolerated.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.44
Clinical SummaryTNFSF13
🧬
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 unique 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

Moderate LoF intolerance
LoF Constraint
0.44LOEUF
pLI 0.817
Z-score 3.02
OE 0.14 (0.060.44)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.53Z-score
OE missense 0.87 (0.751.02)
121 obs / 138.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.14 (0.060.44)
00.351.4
Missense OE0.87 (0.751.02)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 2 / 14.4Missense obs/exp: 121 / 138.4Syn Z: -0.20

ClinVar Variant Classifications

51 submitted variants in 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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →