King Denborough syndrome: genes and variants
King Denborough syndrome is linked to 1 analyzed protein (RYR1). 4 DNA variants are known to cause it; 7 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: King-Denborough syndrome
Genes linked to King Denborough syndrome
RYR1: Ryanodine receptor 1
It releases calcium from the skeletal-muscle sarcoplasmic reticulum when Cav1.1 senses membrane depolarization, directly coupling excitation to contraction. Pathogenic variants cause malignant-hyperthermia susceptibility and a broad spectrum of congenital RYR1-related myopathies.
4 disease-causing and 7 uncertain variants in RYR1 are linked to King Denborough syndrome.
Known disease-causing variants in King Denborough syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| RYR1 R4893L | 4893 | Pore-forming | Disease-causing (★★) |
| RYR1 G4935D | 4935 | Transmembrane | Disease-causing (★) |
| RYR1 I2167S | 2167 | 6 X approximate repeats | Disease-causing (★) |
| RYR1 R2234S | 2234 | 6 X approximate repeats | Disease-causing (★) |
Same protein, different disease
- Central core myopathy is also caused by RYR1 variants; they fall mostly in different places as the King Denborough syndrome variants (8 disease-causing).
- RYR1-related myopathy is also caused by RYR1 variants; they fall mostly in different places as the King Denborough syndrome variants (3 disease-causing).
- Centronuclear myopathy is also caused by RYR1 variants; they fall mostly in different places as the King Denborough syndrome variants (3 disease-causing).
Diseases related to King Denborough syndrome
- Central core myopathy, also linked to RYR1
- Fetal akinesia deformation sequence, also linked to RYR1
- Myopathy, also linked to RYR1
- Centronuclear myopathy, also linked to RYR1
- RYR1-related myopathy, also linked to RYR1
- Arthrogryposis multiplex congenita, also linked to RYR1
- Congenital multicore myopathy with external ophthalmoplegia, also linked to RYR1
Frequently asked questions
Which genes are linked to King Denborough syndrome?
In CATVariant, King Denborough syndrome is linked to 1 analyzed protein: RYR1 (Ryanodine receptor 1).
How many genetic variants are linked to King Denborough syndrome?
20 variants: 4 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 7 are of uncertain significance or have conflicting reports.
Which uncertain variants in King Denborough syndrome 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.
Download every variant as CSV · Browse all diseases · Methods · About the Center