On this page
SGCA
sarcoglycan alpha
The SGCA gene provides instructions for the alpha-sarcoglycan protein, a key component of the sarcoglycan complex essential for maintaining muscle cell integrity and function. The SGCA gene plays a crucial role in muscle health by encoding a protein that is part of a larger complex.
SGCA is located on the long (q) arm of chromosome 17, at band 17q21.33. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 17 in the library →Available at Jeen Health
Clinical tests that include this
Overview
The SGCA gene, also known as sarcoglycan alpha, produces a protein that is integral to the structural integrity of muscle cells. This protein is a component of the sarcoglycan complex, which is found in the membrane surrounding muscle fibres. The complex works to link the internal structure of muscle cells to the surrounding extracellular matrix, providing stability and protecting muscles from injury during activity.
What the gene does
The SGCA gene instructs cells to create the alpha-sarcoglycan protein, which is a subunit of the sarcoglycan protein complex. This complex is embedded within the muscle cell membrane and plays a critical role in maintaining the structural architecture of muscle tissue. It functions by binding to and stabilising the dystrophin complex, a larger protein assembly that reinforces muscle fibres and shields them from damage during the cycles of muscle contraction and relaxation. Essentially, the sarcoglycan complex, via its connection to the dystrophin complex, acts as an anchor, connecting the muscle cell's internal structural framework (cytoskeleton) with the network of proteins and molecules outside the cell (extracellular matrix).
Video: Genetics 101
Chromosome location
The SGCA gene is located on the long arm of chromosome 17 at position 21.33, which is written as 17q21.33. This gene spans a specific region of the human genome, contributing to the genetic blueprint for muscle function.
Protein structure
The SGCA gene encodes a protein composed of 387 amino acids. Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Genetic variants in the SGCA gene can alter the structure or function of the alpha-sarcoglycan protein. These changes may disrupt the integrity of the sarcoglycan complex and its ability to stabilise muscle cells. Such variants are typically inherited in an autosomal recessive pattern.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.269A>G | p.Tyr90Cys | Pathogenic | ★★★☆ | Autosomal recessive limb-girdle muscular dystrophy |
c.292C>T | p.Arg98Cys | Pathogenic | ★★★☆ | Autosomal recessive limb-girdle muscular dystrophy |
c.307A>G | p.Ile103Val | Pathogenic | ★★★☆ | Autosomal recessive limb-girdle muscular dystrophy |
c.37+6T>C | - | Pathogenic | ★★★☆ | Autosomal recessive limb-girdle muscular dystrophy |
c.402C>G | p.Tyr134Ter | Pathogenic | ★★★☆ | Autosomal recessive limb-girdle muscular dystrophy |
c.585-1G>A | - | Pathogenic | ★★★☆ | Autosomal recessive limb-girdle muscular dystrophy |
c.613C>T | p.Pro205Ser | Pathogenic | ★★★☆ | Autosomal recessive limb-girdle muscular dystrophy |
c.724G>T | p.Val242Phe | Pathogenic | ★★★☆ | Autosomal recessive limb-girdle muscular dystrophy |
c.739G>A | p.Val247Met | Pathogenic | ★★★☆ | Autosomal recessive limb-girdle muscular dystrophy |
c.92T>C | p.Leu31Pro | Pathogenic | ★★★☆ | Autosomal recessive limb-girdle muscular dystrophy |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Variants in the SGCA gene are associated with limb-girdle muscular dystrophy. This condition is characterised by progressive weakness and wasting of muscles, primarily affecting those around the hips and shoulders. The severity and age of onset can vary among affected individuals.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic SGCA variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
The SGCA gene is included on several NHS Genomic Medicine Service national test panels. It is listed with a 'green' status for Acute rhabdomyolysis (R419), Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies (R82), and Rhabdomyolysis and metabolic muscle disorders. This indicates that there is strong evidence supporting its association with these conditions in a clinical diagnostic context.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the function of the SGCA gene?
The SGCA gene provides instructions for making the alpha-sarcoglycan protein, a crucial component of the sarcoglycan complex. This complex helps to stabilise muscle cell membranes and protect muscle fibres from damage during contraction and relaxation by linking them to the surrounding connective tissue.
What conditions are associated with variants in the SGCA gene?
Variants in the SGCA gene are associated with limb-girdle muscular dystrophy. This is a group of genetic conditions characterised by progressive muscle weakness, particularly affecting the muscles around the shoulders and hips.
How are SGCA gene variants inherited?
Variants in the SGCA gene are typically inherited in an autosomal recessive pattern. This means that an individual must inherit two copies of the altered gene, one from each parent, to develop a related condition.
References
- Broglio L, Tentorio M, Cotelli MS. Limb-girdle muscular dystrophy-associated protein diseases. The neurologist. 2010. PMID: 21150381
- Sandonà D, Betto R. Sarcoglycanopathies: molecular pathogenesis and therapeutic prospects. Expert reviews in molecular medicine. 2009. PMID: 19781108
- Trabelsi M, Kavian N, Daoud F. Revised spectrum of mutations in sarcoglycanopathies. European journal of human genetics : EJHG. 2008. PMID: 18285821
- Guglieri M, Straub V, Bushby K. Limb-girdle muscular dystrophies. Current opinion in neurology. 2008. PMID: 18769252
- Meena AK, Sreenivas D, Sundaram C. Sarcoglycanopathies: a clinico-pathological study. Neurology India. 2007. PMID: 17558114
- Straub V, Bushby K. The childhood limb-girdle muscular dystrophies. Seminars in pediatric neurology. 2006. PMID: 17027860
- Ozawa E, Mizuno Y, Hagiwara Y. Molecular and cell biology of the sarcoglycan complex. Muscle & nerve. 2005. PMID: 15937871
- Guglieri M, Magri F, Comi GP. Molecular etiopathogenesis of limb girdle muscular and congenital muscular dystrophies: boundaries and contiguities. Clinica chimica acta; international journal of clinical chemistry. 2005. PMID: 16002060
- Laval SH, Bushby KM. Limb-girdle muscular dystrophies--from genetics to molecular pathology. Neuropathology and applied neurobiology. 2004. PMID: 15043707
- Hack AA, Groh ME, McNally EM. Sarcoglycans in muscular dystrophy. Microscopy research and technique. 2000. PMID: 10679964