TNFSF12-TNFSF13

Chr 17

TNFSF12-TNFSF13 readthrough

Also known as: TWE-PRIL

This hybrid protein is membrane-anchored and presents the receptor-binding domain of TNFSF13 at the cell surface, where it stimulates lymphocyte cycling. Mutations cause immunodeficiency with susceptibility to infections, autoimmunity, and lymphoproliferative disorders through autosomal dominant inheritance. The gene shows moderate constraint against loss-of-function variants (pLI 0.77, LOEUF 0.41), indicating intolerance to complete protein loss.

ResearchSummary from RefSeq

This gene encodes a member of the tumor necrosis factor superfamily. It encodes a hybrid protein composed of the cytoplasmic and transmembrane domains of family member 12 fused to the C-terminal domain of family member 13. The hybrid protein is membrane anchored and presents the receptor-binding domain of family member 13 at the cell surface. It stimulates cycling in T- and B-lymphoma cell lines. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

LOEUF 0.41

Clinical Summary— TNFSF12-TNFSF13

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.77) — some intolerance to loss-of-function variants.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 165 VUS of 295 total submissions

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Clinical Trials

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

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.41LOEUF

pLI 0.770

Z-score 3.60

OE 0.18 (0.09–0.41)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.98Z-score

OE missense 0.79 (0.69–0.91)

137 obs / 173.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.18 (0.09–0.41)

0≤0.351.4

Missense OE?0.79 (0.69–0.91)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 4 / 22.4Missense obs/exp: 137 / 173.4Syn Z: -0.33

ClinVar Variant Classifications

295 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS165

Likely Benign111

Benign17

Conflicting1

Likely Pathogenic

165

VUS

111

Likely Benign

Benign

Conflicting

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	9	144	9	3	165
Likely Benign	0	1	43	67	111
Benign	0	1	9	7	17
Conflicting	—				1
Total	10	146	61	77	295

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 TNFSF12-TNFSF13 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →