Carpal tunnel syndrome: genes and variants
Carpal tunnel syndrome is linked to 2 analyzed proteins (TTR and SERPINA1). 8 DNA variants are known to cause it; 21 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: carpal tunnel syndrome 1
Genes linked to Carpal tunnel syndrome
TTR: Transthyretin
Its tetramer transports thyroxine and retinol-binding protein, but destabilization can expose aggregation-prone monomers. Pathogenic variants cause hereditary transthyretin amyloidosis affecting peripheral nerves and heart, while wild-type protein can also form cardiac amyloid with aging.
8 disease-causing and 21 uncertain variants in TTR are linked to Carpal tunnel syndrome.
SERPINA1: Alpha-1-antitrypsin
Its circulating alpha-1-antitrypsin activity protects lung tissue by neutralizing neutrophil elastase and related proteases. Severe deficiency predisposes to early emphysema, while accumulation of misfolded protein in hepatocytes can cause chronic liver disease.
0 disease-causing and 0 uncertain variants in SERPINA1 are linked to Carpal tunnel syndrome.
Known disease-causing variants in Carpal tunnel syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| TTR A117S | 117 | Disease-causing (★★) | |
| TTR S97Y | 97 | Disease-causing (★★) | |
| TTR F84L | 84 | Disease-causing (★★) | |
| TTR A117G | 117 | Disease-causing (★★) | |
| TTR V50M | 50 | Disease-causing (★★) | |
| TTR I88L | 88 | Disease-causing (★★) | |
| TTR I127V | 127 | Disease-causing (★★) | |
| TTR Y134H | 134 | Disease-causing |
Which prediction tools work for Carpal tunnel syndrome
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- CATVariant: 88 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- MetaLR: 86 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- PolyPhen-2: 65 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 59 out of 100
Same protein, different disease
- Amyloidosis, hereditary systemic 1 is also caused by TTR variants; they fall mostly in different places as the Carpal tunnel syndrome variants (101 disease-causing).
Diseases related to Carpal tunnel syndrome
- Charcot-Marie-Tooth disease, also linked to TTR
- Amyloidosis, hereditary systemic 1, also linked to TTR
- Alpha-1-antitrypsin deficiency, also linked to SERPINA1
- Hyperthyroxinemia, dystransthyretinemic, also linked to TTR
Frequently asked questions
Which genes are linked to Carpal tunnel syndrome?
In CATVariant, Carpal tunnel syndrome is linked to 2 analyzed proteins: TTR (Transthyretin) and SERPINA1 (Alpha-1-antitrypsin).
How many genetic variants are linked to Carpal tunnel syndrome?
32 variants: 8 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 21 are of uncertain significance or have conflicting reports.
Which uncertain variants in Carpal tunnel syndrome look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
Which variant effect predictor works best for Carpal tunnel syndrome?
Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.59, based on 8 disease-causing and 48 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.
Download every variant as CSV · Browse all diseases · Methods · About the Center