Autosomal recessive limb-girdle muscular dystrophy: genes and variants

Genes linked to Autosomal recessive limb-girdle muscular dystrophy

• SGCA: Alpha-sarcoglycan

  It is part of the sarcoglycan complex that stabilizes the muscle-cell membrane during contraction by linking dystrophin-associated structures to extracellular matrix. Biallelic loss-of-function variants cause limb-girdle muscular dystrophy R3 with progressive proximal weakness and possible cardiomyopathy.

  61 disease-causing and 156 uncertain variants in SGCA are linked to Autosomal recessive limb-girdle muscular dystrophy.

• FKRP: Ribitol 5-phosphate transferase FKRP

  It is required for proper glycosylation of alpha-dystroglycan, enabling muscle fibers and other cells to attach effectively to extracellular matrix. Biallelic pathogenic variants cause dystroglycanopathies ranging from limb-girdle muscular dystrophy to severe congenital muscular dystrophy with brain or eye involvement.

  20 disease-causing and 38 uncertain variants in FKRP are linked to Autosomal recessive limb-girdle muscular dystrophy.

• TUBA1A: Tubulin alpha-1A chain

  An alpha-tubulin chain that pairs with beta-tubulin to build microtubules. Microtubules provide tracks for transport and help shape dividing and migrating cells, making TUBA1A especially important for fetal brain development.

  1 disease-causing and 0 uncertain variants in TUBA1A are linked to Autosomal recessive limb-girdle muscular dystrophy.

• DYSF: Dysferlin

  It is required for calcium-dependent membrane repair in skeletal muscle and contributes to vesicle fusion after sarcolemmal injury. Biallelic loss-of-function variants cause dysferlinopathies, including limb-girdle muscular dystrophy R2 and Miyoshi distal myopathy.

  0 disease-causing and 0 uncertain variants in DYSF are linked to Autosomal recessive limb-girdle muscular dystrophy.

• TTN: Titin

  Its enormous titin polypeptide spans much of the sarcomere and provides passive elasticity, structural alignment, and mechanosensing in striated muscle. Truncating variants are among the most common genetic causes of dilated cardiomyopathy, while other variants cause diverse skeletal and cardiac myopathies.

  0 disease-causing and 5 uncertain variants in TTN are linked to Autosomal recessive limb-girdle muscular dystrophy.

Where Autosomal recessive limb-girdle muscular dystrophy variants cluster

• FKRP Zinc finger loop (positions 289–318): 3 of 20 disease-causing changes, 2.5× more than its size predicts.

Known disease-causing variants in Autosomal recessive limb-girdle muscular dystrophy

Showing 60 of 82.

Uncertain variants in Autosomal recessive limb-girdle muscular dystrophy that look disease-causing

Same protein, different disease

• Walker-Warburg congenital muscular dystrophy is also caused by FKRP variants; they fall partly in the same places as the Autosomal recessive limb-girdle muscular dystrophy variants (44 disease-causing).
• Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5 is also caused by FKRP variants; they fall mostly in different places as the Autosomal recessive limb-girdle muscular dystrophy variants (13 disease-causing).
• Muscular dystrophy-dystroglycanopathy type B5 is also caused by FKRP variants; they fall mostly in different places as the Autosomal recessive limb-girdle muscular dystrophy variants (6 disease-causing).
• Tubulinopathy is also caused by TUBA1A variants; they fall mostly in different places as the Autosomal recessive limb-girdle muscular dystrophy variants (101 disease-causing).
• Lissencephaly due to TUBA1A mutation is also caused by TUBA1A variants; they fall mostly in different places as the Autosomal recessive limb-girdle muscular dystrophy variants (62 disease-causing).
• Tubulinopathy-associated dysgyria is also caused by TUBA1A variants; they fall mostly in different places as the Autosomal recessive limb-girdle muscular dystrophy variants (6 disease-causing).
• TUBA1A-associated tubulinopathy is also caused by TUBA1A variants; they fall mostly in different places as the Autosomal recessive limb-girdle muscular dystrophy variants (3 disease-causing).

Diseases related to Autosomal recessive limb-girdle muscular dystrophy

• Hypertrophic cardiomyopathy, also linked to TTN
• Dilated cardiomyopathy, also linked to TTN
• Tubulinopathy, also linked to TUBA1A
• Cardiac arrhythmia, also linked to TTN
• Lissencephaly due to TUBA1A mutation, also linked to TUBA1A
• Walker-Warburg congenital muscular dystrophy, also linked to FKRP
• Gastric cancer, also linked to TUBA1A
• Non-small cell lung carcinoma, also linked to TUBA1A
• West syndrome, also linked to TUBA1A
• Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5, also linked to FKRP
• Muscular dystrophy, also linked to FKRP
• Multiple myeloma, also linked to TUBA1A

Frequently asked questions

Which genes are linked to Autosomal recessive limb-girdle muscular dystrophy?

In CATVariant, Autosomal recessive limb-girdle muscular dystrophy is linked to 5 analyzed proteins: SGCA (Alpha-sarcoglycan), FKRP (Ribitol 5-phosphate transferase FKRP), TUBA1A (Tubulin alpha-1A chain), DYSF (Dysferlin) and TTN (Titin).

How many genetic variants are linked to Autosomal recessive limb-girdle muscular dystrophy?

424 variants: 82 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 199 are of uncertain significance or have conflicting reports.

Which uncertain variants in Autosomal recessive limb-girdle muscular dystrophy look disease-causing?

9 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example SGCA P73L, SGCA P70S, SGCA G68R, SGCA C232W and SGCA G91C. These are leads for expert review, not diagnoses.

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