TNFSF13

Chr 17

TNF superfamily member 13

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

NCBI Gene: 8741 ENSG00000161955 UniProt: O75888 OMIM: 604472

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.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOEUF 0.44

Clinical Summary— TNFSF13

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Gene-Disease Validity (ClinGen)

common variable immunodeficiency · ARLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.82) — some intolerance to loss-of-function variants.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 12 VUS of 21 total submissions

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

0.53Z-score

OE missense 0.87 (0.75–1.02)

121 obs / 138.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.14 (0.06–0.44)

0≤0.351.4

Missense OE?0.87 (0.75–1.02)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 2 / 14.4Missense obs/exp: 121 / 138.4Syn Z: -0.20

ClinVar Variant Classifications

21 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS12

Likely Benign3

Benign5

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	1	0	0	0	1
VUS	0	10	1	1	12
Likely Benign	0	1	1	1	3
Benign	0	1	3	1	5
Total	1	12	5	3	21

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

View in ClinVar →

21 pathogenic / likely-pathogenic (of 31) ClinVar copy-number / structural variants overlap TNFSF13 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →