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SGCG
sarcoglycan gamma
The SGCG gene provides instructions for a protein called gamma-sarcoglycan, which is crucial for maintaining the structural integrity of muscle cells. The SGCG gene produces a component of the sarcoglycan protein complex, located in the membrane surrounding muscle cells.
SGCG is located on the long (q) arm of chromosome 13, at band 13q12.12. Arm ratio per GRCh38 - banding schematic.
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Overview
The SGCG gene, also known as sarcoglycan gamma, is responsible for producing the gamma-sarcoglycan protein. This protein is a key part of the sarcoglycan complex, a group of proteins found within the membrane of muscle cells. The proper functioning of SGCG is essential for maintaining the structure and strength of muscle tissue, particularly during the repeated movements of muscle contraction and relaxation.
What the gene does
The SGCG gene directs the synthesis of the gamma component of the sarcoglycan protein complex. This complex is situated within the membrane that encloses muscle cells. Its primary role involves connecting to and stabilising the dystrophin complex, a larger assembly of proteins including dystrophins and dystroglycans. This connection is critical for strengthening muscle fibres and shielding them from injury that can occur as muscles contract and relax. Essentially, the sarcoglycan and dystrophin complexes act as an anchoring system, linking the internal structural framework (cytoskeleton) of each muscle cell to the surrounding network of proteins and molecules (extracellular matrix). This comprehensive structure is vital for the mechanical stability of muscle tissue.
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Chromosome location
The SGCG gene is located on chromosome 13, specifically at position 13q12.12. This address refers to the long (q) arm of chromosome 13, within band 12.12. Understanding the chromosomal location helps in mapping genes and identifying genetic changes that may affect their function.
Protein structure
The SGCG gene codes for a protein that is 291 amino acids in length. Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Genetic variations within the SGCG gene can alter the function or production of the gamma-sarcoglycan protein. These changes, known as pathogenic variants, can disrupt the structural integrity of muscle cells. The impact of such variants depends on their specific nature and location within the gene.
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.195+4_195+7del | - | Pathogenic | ★★★☆ | Autosomal recessive limb-girdle muscular dystrophy type 2C |
c.525del | p.Phe175fs | Pathogenic | ★★★☆ | Autosomal recessive limb-girdle muscular dystrophy |
c.526G>T | p.Glu176Ter | Pathogenic | ★★★☆ | Autosomal recessive limb-girdle muscular dystrophy |
c.579-2A>G | - | Pathogenic | ★★★☆ | Autosomal recessive limb-girdle muscular dystrophy |
c.787G>A | p.Glu263Lys | Pathogenic | ★★★☆ | Autosomal recessive limb-girdle muscular dystrophy |
c.848G>A | p.Cys283Tyr | Pathogenic | ★★★☆ | Autosomal recessive limb-girdle muscular dystrophy |
c.87dup | p.Gly30fs | Pathogenic | ★★★☆ | Autosomal recessive limb-girdle muscular dystrophy |
c.216T>A | p.Cys72Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Autosomal recessive limb-girdle muscular dystrophy type 2C |
c.298-2A>G | - | Pathogenic/Likely pathogenic | ★★☆☆ | Autosomal recessive limb-girdle muscular dystrophy type 2C |
c.320C>T | p.Ser107Leu | Pathogenic/Likely pathogenic | ★★☆☆ | Autosomal recessive limb-girdle muscular dystrophy type 2C |
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
Pathogenic variants in the SGCG gene are primarily associated with a group of inherited muscle disorders. These conditions typically affect muscle strength and function, leading to progressive muscle weakness. The specific clinical presentation can vary depending on the nature of the genetic variant.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic SGCG 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 SGCG gene is included in several NHS Genomic Medicine Service national test panels. It is listed on the 'Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies' panel (R82) and the 'Paediatric or syndromic cardiomyopathy' panel (R135), both with a 'green' status, indicating strong evidence for its gene-disease association in these contexts.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does the SGCG gene do?
The SGCG gene provides instructions for making gamma-sarcoglycan, a protein that is part of a complex in muscle cell membranes. This complex helps maintain the structure of muscle tissue and protects muscle fibres from injury during contraction.
What happens if there is a change in the SGCG gene?
Changes, or pathogenic variants, in the SGCG gene can lead to problems with the structure and stability of muscle cells. This can result in conditions characterised by progressive muscle weakness and damage.
How is SGCG related to muscle function?
SGCG is vital for muscle function because its protein product helps anchor the muscle cell's internal framework to its external surroundings. This connection strengthens muscle fibres and prevents damage when muscles are used.
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
- Georgieva B, Todorova A, Tournev I. C283Y gamma-sarcoglycan gene mutation in the Bulgarian Roma (Gypsy) population: prevalence study and carrier screening in a high-risk community. Clinical genetics. 2004. PMID: 15479193
- Bönnemann CG, Wong J, Jones KJ. Primary gamma-sarcoglycanopathy (LGMD 2C): broadening of the mutational spectrum guided by the immunohistochemical profile. Neuromuscular disorders : NMD. 2002. PMID: 11801399
- Hack AA, Groh ME, McNally EM. Sarcoglycans in muscular dystrophy. Microscopy research and technique. 2000. PMID: 10679964