TNFRSF19

Chr 13

TNF receptor superfamily member 19

Also known as: TAJ, TAJ-alpha, TRADE, TROY

NCBI Gene: 55504ENSG00000127863UniProt: Q9NS68OMIM: 606122

The protein is a member of the TNF-receptor superfamily that activates JNK and NF-kappa-B signaling pathways and can promote caspase-independent cell death during embryonic development. Mutations cause autosomal dominant developmental disorders affecting multiple organ systems during early development. The gene shows moderate constraint against loss-of-function variants, suggesting some tolerance to heterozygous inactivation.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.72
Clinical Summary— TNFRSF19
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Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.
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ClinVar Variants
42 unique Pathogenic / Likely Pathogenic· 99 VUS of 176 total submissions
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Clinical Trials
2 active or recruiting trials — 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
Tolerant — LoF & missense variants common in population
LoF Constraint
0.72LOEUF
pLI 0.033
Z-score 2.33
OE 0.34 (0.18–0.72)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.23Z-score
OE missense 0.96 (0.86–1.07)
237 obs / 247.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.34 (0.18–0.72)
0≤0.351.4
Missense OE0.96 (0.86–1.07)
0≤0.61.4
Synonymous OE1.04
0≤1.21.6
LoF obs/exp: 5 / 14.6Missense obs/exp: 237 / 247.2Syn Z: -0.30
DN
0.7325th %ile
GOF
0.76top 25%
LOF
0.3454th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

176 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic39
Likely Pathogenic3
VUS99
Likely Benign16
Benign2
Conflicting1
39
Pathogenic
3
Likely Pathogenic
99
VUS
16
Likely Benign
2
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
39
0
39
Likely Pathogenic
0
0
3
0
3
VUS
0
63
36
0
99
Likely Benign
0
5
9
2
16
Benign
0
0
2
0
2
Conflicting
—1
Total068892160

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

View in ClinVar →

Protein Context — Lollipop Plot

TNFRSF19 · 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 →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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