Primary erythromelalgia: genes and variants
Primary erythromelalgia is linked to 1 analyzed protein (SCN9A). 6 DNA variants are known to cause it; 35 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Primary erythromelalgia
SCN9A: Sodium channel protein type 9 subunit alpha
The protein forms Nav1.7, a voltage-gated sodium channel that amplifies electrical signals in peripheral sensory neurons. Changes in Nav1.7 activity can produce either excessive pain or congenital insensitivity to pain, making SCN9A central to pain biology.
6 disease-causing and 35 uncertain variants in SCN9A are linked to Primary erythromelalgia.
Where Primary erythromelalgia variants cluster
- SCN9A S5 of repeat II (positions 866–888): 3 of 6 disease-causing changes, 43.2× more than its size predicts.
Known disease-causing variants in Primary erythromelalgia
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| SCN9A L869H | 869 | II | Disease-causing (★★) |
| SCN9A L834R | 834 | II | Disease-causing (★) |
| SCN9A Q886E | 886 | II | Disease-causing (★) |
| SCN9A L869F | 869 | II | Disease-causing |
| SCN9A F1460V | 1460 | III | Disease-causing |
| SCN9A F216S | 216 | I | Disease-causing |
Same protein, different disease
- Generalized epilepsy with febrile seizures plus is also caused by SCN9A variants; they fall mostly in different places as the Primary erythromelalgia variants (14 disease-causing).
- Neuropathy, hereditary sensory and autonomic, type 2A is also caused by SCN9A variants; they fall mostly in different places as the Primary erythromelalgia variants (14 disease-causing).
- Paroxysmal extreme pain disorder is also caused by SCN9A variants; they fall mostly in different places as the Primary erythromelalgia variants (4 disease-causing).
- Channelopathy-associated congenital insensitivity to pain is also caused by SCN9A variants; they fall mostly in different places as the Primary erythromelalgia variants (3 disease-causing).
Diseases related to Primary erythromelalgia
- Amyotrophic lateral sclerosis, also linked to SCN9A
- Generalized epilepsy with febrile seizures plus, also linked to SCN9A
- Cardiac arrhythmia, also linked to SCN9A
- Epilepsy, also linked to SCN9A
- Neuropathy, hereditary sensory and autonomic, type 2A, also linked to SCN9A
- Paroxysmal extreme pain disorder, also linked to SCN9A
- Focal epilepsy, also linked to SCN9A
- Channelopathy-associated congenital insensitivity to pain, also linked to SCN9A
- Lennox-Gastaut syndrome, also linked to SCN9A
Frequently asked questions
Which genes are linked to Primary erythromelalgia?
In CATVariant, Primary erythromelalgia is linked to 1 analyzed protein: SCN9A (Sodium channel protein type 9 subunit alpha).
How many genetic variants are linked to Primary erythromelalgia?
48 variants: 6 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 35 are of uncertain significance or have conflicting reports.
Which uncertain variants in Primary erythromelalgia look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
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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