TNF receptor-associated periodic fever syndrome (TRAPS): genes and variants
TNF receptor-associated periodic fever syndrome (TRAPS) is linked to 1 analyzed protein (TNFRSF1A). 21 DNA variants are known to cause it; 168 more are uncertain, and 2 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to TNF receptor-associated periodic fever syndrome (TRAPS)
TNFRSF1A: Tumor necrosis factor receptor superfamily member 1A
It mediates many inflammatory and cell-death responses to TNF through NF-kappaB, MAPK, and death-domain signaling. Dominant pathogenic variants that alter receptor handling cause TNF receptor-associated periodic syndrome, an inherited autoinflammatory disease.
21 disease-causing and 168 uncertain variants in TNFRSF1A are linked to TNF receptor-associated periodic fever syndrome (TRAPS).
Where TNF receptor-associated periodic fever syndrome (TRAPS) variants cluster
- TNFRSF1A Extracellular (positions 30–211): 21 of 21 disease-causing changes, 2.5× more than its size predicts.
Known disease-causing variants in TNF receptor-associated periodic fever syndrome (TRAPS)
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| TNFRSF1A C59S | 59 | TNFR-Cys 1 | Disease-causing (★★) |
| TNFRSF1A C102Y | 102 | TNFR-Cys 2 | Disease-causing (★★) |
| TNFRSF1A C59R | 59 | TNFR-Cys 1 | Disease-causing (★★) |
| TNFRSF1A C59Y | 59 | TNFR-Cys 1 | Disease-causing (★★) |
| TNFRSF1A C99R | 99 | TNFR-Cys 2 | Disease-causing (★★) |
| TNFRSF1A C84Y | 84 | TNFR-Cys 2 | Disease-causing (★★) |
| TNFRSF1A T79M | 79 | TNFR-Cys 1 | Disease-causing (★★) |
| TNFRSF1A R121W | 121 | TNFR-Cys 2 | Disease-causing (★★) |
| TNFRSF1A I199N | 199 | Extracellular | Disease-causing (★★) |
| TNFRSF1A C58F | 58 | TNFR-Cys 1 | Disease-causing (★) |
| TNFRSF1A C102F | 102 | TNFR-Cys 2 | Disease-causing (★) |
| TNFRSF1A C58G | 58 | TNFR-Cys 1 | Disease-causing (★) |
| TNFRSF1A C102W | 102 | TNFR-Cys 2 | Disease-causing (★) |
| TNFRSF1A C117G | 117 | TNFR-Cys 2 | Disease-causing (★) |
| TNFRSF1A C81R | 81 | TNFR-Cys 1 | Disease-causing (★) |
| TNFRSF1A C72Y | 72 | TNFR-Cys 1 | Disease-causing (★) |
| TNFRSF1A C127Y | 127 | TNFR-Cys 3 | Disease-causing (★) |
| TNFRSF1A C99S | 99 | TNFR-Cys 2 | Disease-causing |
| TNFRSF1A C117R | 117 | TNFR-Cys 2 | Disease-causing |
| TNFRSF1A C117Y | 117 | TNFR-Cys 2 | Disease-causing |
| TNFRSF1A C62Y | 62 | TNFR-Cys 1 | Disease-causing |
Uncertain variants in TNF receptor-associated periodic fever syndrome (TRAPS) that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| TNFRSF1A C81W | 81 | TNFR-Cys 1 | Uncertain (★) | +6: 3 other pathogenic changes within 3 positions; C81R at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 0.99 |
| TNFRSF1A C81G | 81 | TNFR-Cys 1 | Uncertain (★) | +6: 3 other pathogenic changes within 3 positions; C81R at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 0.99 |
Which prediction tools work for TNF receptor-associated periodic fever syndrome (TRAPS)
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- CADD: 100 out of 100
- CATVariant: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- REVEL: 97 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- phyloP: 96 out of 100
- SIFT: 96 out of 100
- PolyPhen-2: 95 out of 100 (learned from overlapping clinical labels, so this is optimistic)
Diseases related to TNF receptor-associated periodic fever syndrome (TRAPS)
- Autoinflammatory syndrome, also linked to TNFRSF1A
- Behcet disease, also linked to TNFRSF1A
Frequently asked questions
Which genes are linked to TNF receptor-associated periodic fever syndrome (TRAPS)?
In CATVariant, TNF receptor-associated periodic fever syndrome (TRAPS) is linked to 1 analyzed protein: TNFRSF1A (Tumor necrosis factor receptor superfamily member 1A).
How many genetic variants are linked to TNF receptor-associated periodic fever syndrome (TRAPS)?
224 variants: 21 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 168 are of uncertain significance or have conflicting reports.
Which uncertain variants in TNF receptor-associated periodic fever syndrome (TRAPS) look disease-causing?
2 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example TNFRSF1A C81W and TNFRSF1A C81G. These are leads for expert review, not diagnoses.
Which variant effect predictor works best for TNF receptor-associated periodic fever syndrome (TRAPS)?
Among tools not trained on clinical labels, CADD separates this disease's known disease-causing variants from harmless ones best (AUROC 1.00, based on 8 disease-causing and 12 harmless variants).
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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