TNFSF12-TNFSF13

Chr 17

TNFSF12-TNFSF13 readthrough

Also known as: TWE-PRIL

NCBI Gene: 407977ENSG00000248871

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
LOEUF 0.41
Clinical Summary— TNFSF12-TNFSF13
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.77) — some intolerance to loss-of-function variants.
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ClinVar Variants
22 unique Pathogenic / Likely Pathogenic· 174 VUS of 325 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

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 OE0.18 (0.09–0.41)
0≤0.351.4
Missense OE0.79 (0.69–0.91)
0≤0.61.4
Synonymous OE1.05
0≤1.21.6
LoF obs/exp: 4 / 22.4Missense obs/exp: 137 / 173.4Syn Z: -0.33

ClinVar Variant Classifications

325 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic2
VUS174
Likely Benign111
Benign17
Conflicting1
20
Pathogenic
2
Likely Pathogenic
174
VUS
111
Likely Benign
17
Benign
1
Conflicting

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
9
144
18
3
174
Likely Benign
0
1
43
67
111
Benign
0
1
9
7
17
Conflicting
—1
Total101469177325

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

View in ClinVar →

Protein Context — Lollipop Plot

TNFSF12-TNFSF13 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients