Limb-girdle muscular dystrophy: genes and variants
Limb-girdle muscular dystrophy is linked to 3 analyzed proteins (DES, HMGCR and LMNA). 3 DNA variants are known to cause it; 14 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 Limb-girdle muscular dystrophy
DES: Desmin
Its desmin filaments mechanically integrate sarcomeres with the nucleus, mitochondria, and cell junctions in striated muscle. Pathogenic variants cause desmin-related myopathy and can produce cardiomyopathy, conduction disease, and skeletal-muscle weakness.
1 disease-causing and 1 uncertain variants in DES are linked to Limb-girdle muscular dystrophy.
HMGCR: 3-hydroxy-3-methylglutaryl-coenzyme A reductase
It controls the rate-limiting step of the mevalonate pathway and therefore strongly regulates endogenous cholesterol production. Statins lower LDL cholesterol by inhibiting this activity, causing the liver to increase LDL-receptor-mediated clearance from blood.
1 disease-causing and 0 uncertain variants in HMGCR are linked to Limb-girdle muscular dystrophy.
LMNA: Prelamin-A/C
The gene product produces lamins A and C, structural proteins that form the nuclear lamina beneath the inner nuclear membrane. Lamins help maintain nuclear shape and organize chromatin, and LMNA variants are associated with muscular dystrophy, cardiomyopathy, lipodystrophy, and premature-aging syndromes.
1 disease-causing and 0 uncertain variants in LMNA are linked to Limb-girdle muscular dystrophy.
Weakly linked (only a few uncertain records): COL6A3, FKRP, LAMA2, COL6A2, FLNC, NEB, POLG, RYR1 and 3 more.
Known disease-causing variants in Limb-girdle muscular dystrophy
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| LMNA Y376H | 376 | IF rod | Disease-causing (★★) |
| DES L385P | 385 | IF rod | Disease-causing (★) |
| HMGCR G822D | 822 | Cytoplasmic | Disease-causing (★) |
Same protein, different disease
- Desmin-related myofibrillar myopathy is also caused by DES variants; they fall mostly in different places as the Limb-girdle muscular dystrophy variants (37 disease-causing).
- Dilated cardiomyopathy is also caused by DES variants; they fall mostly in different places as the Limb-girdle muscular dystrophy variants (5 disease-causing).
- Primary dilated cardiomyopathy is also caused by DES variants; they fall mostly in different places as the Limb-girdle muscular dystrophy variants (3 disease-causing).
- Neurogenic scapuloperoneal syndrome, Kaeser type is also caused by DES variants; they fall mostly in different places as the Limb-girdle muscular dystrophy variants (3 disease-causing).
- Charcot-Marie-Tooth disease is also caused by LMNA variants; they fall mostly in different places as the Limb-girdle muscular dystrophy variants (130 disease-causing).
- Dilated cardiomyopathy is also caused by LMNA variants; they fall mostly in different places as the Limb-girdle muscular dystrophy variants (21 disease-causing).
- Familial partial lipodystrophy, Dunnigan type is also caused by LMNA variants; they fall mostly in different places as the Limb-girdle muscular dystrophy variants (13 disease-causing).
- Emery-Dreifuss muscular dystrophy is also caused by LMNA variants; they fall mostly in different places as the Limb-girdle muscular dystrophy variants (12 disease-causing).
- Congenital muscular dystrophy due to LMNA mutation is also caused by LMNA variants; they fall mostly in different places as the Limb-girdle muscular dystrophy variants (11 disease-causing).
Diseases related to Limb-girdle muscular dystrophy
- Dilated cardiomyopathy, also linked to DES and LMNA
- Primary dilated cardiomyopathy, also linked to DES and LMNA
- Primary familial dilated cardiomyopathy, also linked to DES and LMNA
- Charcot-Marie-Tooth disease, also linked to LMNA
- Familial hypercholesterolemia, also linked to HMGCR
- Alzheimer disease, also linked to HMGCR
- Bethlem myopathy, also linked to LMNA
- Type 2 diabetes mellitus, also linked to HMGCR
- Hyperlipoproteinemia, also linked to HMGCR
- Desmin-related myofibrillar myopathy, also linked to DES
- Arrhythmogenic right ventricular dysplasia, also linked to LMNA
- Myofibrillar myopathy, also linked to DES
Frequently asked questions
Which genes are linked to Limb-girdle muscular dystrophy?
In CATVariant, Limb-girdle muscular dystrophy is linked to 3 analyzed proteins: DES (Desmin), HMGCR (3-hydroxy-3-methylglutaryl-coenzyme A reductase) and LMNA (Prelamin-A/C).
How many genetic variants are linked to Limb-girdle muscular dystrophy?
20 variants: 3 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 14 are of uncertain significance or have conflicting reports.
Which uncertain variants in Limb-girdle muscular dystrophy 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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