Centronuclear myopathy: genes and variants

Genes linked to Centronuclear myopathy

• 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.

  3 disease-causing and 2 uncertain variants in RYR1 are linked to Centronuclear myopathy.

• FHL1: Four and a half LIM domains protein 1

  It organizes protein complexes in striated muscle and participates in mechanosensing, sarcomere structure, and transcriptional responses. X-linked pathogenic variants cause a spectrum including reducing-body myopathy, Emery-Dreifuss muscular dystrophy, scapuloperoneal myopathy, and cardiomyopathy.

  1 disease-causing and 0 uncertain variants in FHL1 are linked to Centronuclear myopathy.

Weakly linked (only a few uncertain records): OPA1.

Known disease-causing variants in Centronuclear myopathy

Same protein, different disease

• Central core myopathy is also caused by RYR1 variants; they fall mostly in different places as the Centronuclear myopathy variants (8 disease-causing).
• King Denborough syndrome is also caused by RYR1 variants; they fall mostly in different places as the Centronuclear myopathy variants (4 disease-causing).
• RYR1-related myopathy is also caused by RYR1 variants; they fall mostly in different places as the Centronuclear myopathy variants (3 disease-causing).
• X-linked myopathy with postural muscle atrophy is also caused by FHL1 variants; they fall mostly in different places as the Centronuclear myopathy variants (17 disease-causing).
• Myopathy, reducing body, X-linked, early-onset, severe is also caused by FHL1 variants; they fall mostly in different places as the Centronuclear myopathy variants (5 disease-causing).
• Myopathy, reducing body, X-linked, childhood-onset is also caused by FHL1 variants; they fall mostly in different places as the Centronuclear myopathy variants (3 disease-causing).

Diseases related to Centronuclear myopathy

• Myopathy, also linked to FHL1 and RYR1
• X-linked myopathy with postural muscle atrophy, also linked to FHL1
• Emery-Dreifuss muscular dystrophy, also linked to FHL1
• Central core myopathy, also linked to RYR1
• Fetal akinesia deformation sequence, also linked to RYR1
• Myopathy, reducing body, X-linked, early-onset, severe, also linked to FHL1
• King Denborough syndrome, also linked to RYR1
• Myopathy, reducing body, X-linked, childhood-onset, also linked to FHL1
• RYR1-related myopathy, also linked to RYR1
• Arthrogryposis multiplex congenita, also linked to RYR1
• Congenital multicore myopathy with external ophthalmoplegia, also linked to RYR1
• Uruguay Faciocardiomusculoskeletal syndrome, also linked to FHL1

Frequently asked questions

Which genes are linked to Centronuclear myopathy?

In CATVariant, Centronuclear myopathy is linked to 2 analyzed proteins: RYR1 (Ryanodine receptor 1) and FHL1 (Four and a half LIM domains protein 1).

How many genetic variants are linked to Centronuclear myopathy?

8 variants: 4 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 2 are of uncertain significance or have conflicting reports.

Which uncertain variants in Centronuclear myopathy 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