Details for: SGCA

Gene ID: 6442

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: SGCA

Ensembl ID: ENSG00000108823

Description: sarcoglycan alpha

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • muscle cell CL0000187
    CSI 10.74
    rCSI 22.06%
    PRS 96.71
  • microcirculation associated smooth muscle cell CL0008035
    CSI 8.02
    rCSI 23.23%
    PRS 96.27
  • tracheobronchial smooth muscle cell CL0019019
    CSI 7.69
    rCSI 13.55%
    PRS 97.82
  • skin fibroblast CL0002620
    CSI 5.4
    rCSI 4.66%
    PRS 96.7
  • perivascular cell CL4033054
    CSI 5.03
    rCSI 6.87%
    PRS 98.21
  • fibroblast of lung CL0002553
    CSI 4.82
    rCSI 4.49%
    PRS 97.69
  • lung pericyte CL0009089
    CSI 4.78
    rCSI 12.61%
    PRS 98.25
  • smooth muscle cell CL0000192
    CSI 3.53
    rCSI 8.41%
    PRS 93.9
  • regular ventricular cardiac myocyte CL0002131
    CSI 2.92
    rCSI 18.26%
    PRS 92.66
  • alveolar type 1 fibroblast cell CL4028004
    CSI 2.79
    rCSI 3.06%
    PRS 97.56
  • fast muscle cell CL0000190
    CSI 2.79
    rCSI 10.89%
    PRS 90.4
  • skeletal muscle satellite cell CL0000594
    CSI 2.64
    rCSI 7.72%
    PRS 98.36
  • vascular associated smooth muscle cell CL0000359
    CSI 2.57
    rCSI 8.34%
    PRS 96.28
  • cardiac muscle cell CL0000746
    CSI 1.79
    rCSI 2.56%
    PRS 91.92
  • blood vessel smooth muscle cell CL0019018
    CSI 1.35
    rCSI 10.94%
    PRS 96.08
  • smooth muscle cell of prostate CL1000487
    CSI 1.12
    rCSI 6.56%
    PRS 97.73
  • cell of skeletal muscle CL0000188
    CSI 1.02
    rCSI 11.11%
    PRS 93.13
  • bronchiolar smooth muscle cell CL4033017
    CSI 0.96
    rCSI 14.34%
    PRS 98.47
  • pancreatic stellate cell CL0002410
    CSI 0.77
    rCSI 4.47%
    PRS 97.11

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [SGCA](/details-gene/6442) (sarcoglycan alpha) is a protein-coding gene located on chromosome 17q21.33. It encodes alpha-sarcoglycan, an integral transmembrane component of the sarcoglycan complex. This complex is a critical sub-unit of the larger dystrophin-associated glycoprotein complex (DAGC), which links the internal cytoskeleton of muscle fibers to the extracellular matrix, thereby providing structural stability to the sarcolemma during muscle contraction. Expression data reveals that [SGCA](/details-gene/6442) is a defining marker for various types of [muscle cell](/details-cell/CL0000187)s, including skeletal, smooth, and cardiac muscle. Clinically, mutations in [SGCA](/details-gene/6442) are the primary cause of limb-girdle muscular dystrophy type 2D (LGMD2D, OMIM: [600119](https://omim.org/entry/600119)), a form of autosomal recessive muscular dystrophy characterized by progressive muscle weakness ([Link](https://doi.org/10.1016/0092-8674(94)90527-4), [Link](https://doi.org/10.1172/jci118152)). ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [SGCA](/details-gene/6442) highlights its fundamental role in the structure and function of contractile tissues. It exhibits its highest significance in [muscle cell](/details-cell/CL0000187) (CSI: 10.74), confirming its central role in muscle biology. This high expression extends across different muscle lineages, including [microcirculation associated smooth muscle cell](/details-cell/CL0008035) (CSI: 8.02), [tracheobronchial smooth muscle cell](/details-cell/CL0019019) (CSI: 7.69), [regular ventricular cardiac myocyte](/details-cell/CL0002131) (CSI: 2.92), and [fast muscle cell](/details-cell/CL0000190) (CSI: 2.79). This pattern underscores its conserved and essential function in maintaining membrane integrity across diverse muscle types. Beyond canonical muscle cells, [SGCA](/details-gene/6442) also shows significant expression in various mesenchymal and stromal cell types that possess contractile or structural properties. These include [skin fibroblast](/details-cell/CL0002620) (CSI: 5.40), [perivascular cell](/details-cell/CL4033054) (CSI: 5.03), [fibroblast of lung](/details-cell/CL0002553) (CSI: 4.82), and [lung pericyte](/details-cell/CL0009089) (CSI: 4.78). This suggests a broader function for [SGCA](/details-gene/6442) in maintaining the structural integrity and mechanosensing capabilities of connective tissues and the vasculature, likely by participating in analogous cytoskeleton-matrix connections in these non-muscle cell types. ## Pathways and Molecular Function The functional annotations for [SGCA](/details-gene/6442) are highly consistent with its expression pattern and known role in muscle pathology. Its involvement in the biological processes of [Muscle contraction](/details-cell/GO:0006936), [Muscle organ development](/details-cell/GO:0007517), and [Skeletal muscle tissue regeneration](/details-cell/GO:0043403) solidifies its identity as a key muscle-related gene. At the molecular level, its functions include [Calcium ion binding](/details-cell/GO:0005509) and general [Protein binding](/details-cell/GO:0005515). These activities are critical for the assembly and regulation of the protein complexes it belongs to. Cellular component analysis places [SGCA](/details-gene/6442) precisely at its site of action: the [Sarcolemma](/details-cell/GO:0042383) (the muscle cell membrane), where it is a core component of both the [Sarcoglycan complex](/details-cell/GO:0016012) and the overarching [Dystrophin-associated glycoprotein complex](/details-cell/GO:0016010). This complex physically links the actin [Cytoskeleton](/details-cell/GO:0005856) inside the cell to the extracellular matrix, protecting the cell from damage induced by contraction and relaxation cycles. ## Research Directions The well-established link between [SGCA](/details-gene/6442) mutations and muscular dystrophy provides a clear foundation for future research, particularly in understanding disease mechanisms and exploring its function in non-muscle cells. ### Proposed Hypotheses: 1. **Allelic heterogeneity dictates disease severity:** Research has shown that different mutations in [SGCA](/details-gene/6442) can lead to a wide spectrum of clinical severity in LGMD2D, from severe childhood onset to milder adult forms ([Link](https://doi.org/10.1038/ng0695-243)). It is hypothesized that specific classes of missense mutations, as opposed to null mutations, result in a partially functional or unstable alpha-sarcoglycan protein. This residual function may be sufficient to delay disease onset or reduce its severity by allowing for the formation of a less stable, but still partially operative, sarcoglycan complex at the sarcolemma. 2. **[SGCA](/details-gene/6442) modulates mechanotransduction in fibroblasts and pericytes:** The significant expression of [SGCA](/details-gene/6442) in [skin fibroblast](/details-cell/CL0002620)s and [lung pericyte](/details-cell/CL0009089)s suggests it plays a role beyond muscle stabilization. We hypothesize that in these cells, [SGCA](/details-gene/6442) is part of a mechanosensing complex that translates external physical forces into intracellular biochemical signals, thereby regulating processes such as extracellular matrix remodeling, fibrosis, and vascular tone. ### Key Experiment Proposal: To test the hypothesis that [SGCA](/details-gene/6442) modulates mechanotransduction in fibroblasts, the following experiment could be conducted: * **Objective:** Determine the impact of [SGCA](/details-gene/6442) loss on fibroblast mechanosensing and contractile function. * **Methodology:** Utilize CRISPR-Cas9 to generate [SGCA](/details-gene/6442) knockout (KO) and isogenic control human dermal fibroblasts. These cells would be cultured on hydrogels of varying stiffness (e.g., 1 kPa vs. 25 kPa) to mimic soft and fibrotic tissue environments. The cellular response would be quantified using traction force microscopy to measure contractile forces exerted by the cells. Simultaneously, immunofluorescence staining for key cytoskeletal (F-actin, vimentin) and mechanotransduction (YAP/TAZ nuclear localization) markers would be performed. Changes in the expression of fibrosis-related genes (e.g., *COL1A1*, *ACTA2*) would be assessed by RT-qPCR or RNA-seq. A diminished ability of KO fibroblasts to generate force and activate mechanosensitive pathways, particularly on stiff substrates, would support the hypothesis. ### Therapeutic Potential: Given that LGMD2D is a monogenic, loss-of-function disease, [SGCA](/details-gene/6442) is an ideal candidate for gene replacement therapy rather than inhibition. The primary therapeutic strategy would be to restore a functional copy of the gene in affected muscle tissues. Its high specificity to muscle is advantageous, as it allows for targeted delivery (e.g., via adeno-associated virus (AAV) vectors with muscle-specific promoters), which could minimize off-target effects. Such an approach aims to reconstitute the sarcoglycan complex, restore sarcolemmal integrity, and halt or reverse the progression of muscle degeneration, representing a promising avenue for treating this debilitating disease.

Genular Protein ID: 2519417161

Symbol: SGCA_HUMAN

Name: Alpha-sarcoglycan

UniProtKB Accession Codes:

Q16586 A6NEB8 A8K3K7 Q13710 Q13712

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CORUM 1 CTD 1 ChiTaRS 1 ComplexPortal 4 DNASU 1 DisGeNET 1 EMBL 8 Ensembl 2 ExpressionAtlas 1 GO 12 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PIR 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 RefSeq 2 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 neXtProt 1

Citations:

PubMed ID: 8069911

Title: Missense mutations in the adhalin gene linked to autosomal recessive muscular dystrophy.

PubMed ID: 8069911

DOI: 10.1016/0092-8674(94)90527-4

PubMed ID: 7937874

Title: Human adhalin is alternatively spliced and the gene is on chromosome 17q21.

PubMed ID: 7937874

DOI: 10.1073/pnas.91.21.9690

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16625196

Title: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

PubMed ID: 16625196

DOI: 10.1038/nature04689

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 8528203

Title: A common missense mutation in the adhalin gene in three unrelated Brazilian families with a relatively mild form of autosomal recessive limb-girdle muscular dystrophy.

PubMed ID: 8528203

DOI: 10.1093/hmg/4.7.1163

PubMed ID: 7657792

Title: Adhalin gene mutations in patients with autosomal recessive childhood onset muscular dystrophy with adhalin deficiency.

PubMed ID: 7657792

DOI: 10.1172/jci118152

PubMed ID: 7663524

Title: Primary adhalinopathy: a common cause of autosomal recessive muscular dystrophy of variable severity.

PubMed ID: 7663524

DOI: 10.1038/ng0695-243

PubMed ID: 9192266

Title: Mutational diversity and hot spots in the alpha-sarcoglycan gene in autosomal recessive muscular dystrophy (LGMD2D).

PubMed ID: 9192266

DOI: 10.1136/jmg.34.6.470

PubMed ID: 9032047

Title: Mutations in the sarcoglycan genes in patients with myopathy.

PubMed ID: 9032047

DOI: 10.1056/nejm199702273360904

PubMed ID: 9585331

Title: Homozygous alpha-sarcoglycan mutation in two siblings: one asymptomatic and one steroid-responsive mild limb-girdle muscular dystrophy patient.

PubMed ID: 9585331

DOI: 10.1002/(sici)1097-4598(199806)21:6<769::aid-mus9>3.0.co;2-5

PubMed ID: 30345904

Title: The impact of PYROXD1 deficiency on cellular respiration and correlations with genetic analyses of limb-girdle muscular dystrophy in Saudi Arabia and Sudan.

PubMed ID: 30345904

DOI: 10.1152/physiolgenomics.00036.2018

Sequence Information:

  • Length: 387
  • Mass: 42875
  • Checksum: 9CD0270A00BE03E6
  • Sequence:
    • MAETLFWTPL LVVLLAGLGD TEAQQTTLHP LVGRVFVHTL DHETFLSLPE HVAVPPAVHI 
TYHAHLQGHP DLPRWLRYTQ RSPHHPGFLY GSATPEDRGL QVIEVTAYNR DSFDTTRQRL 
VLEIGDPEGP LLPYQAEFLV RSHDAEEVLP STPASRFLSA LGGLWEPGEL QLLNVTSALD 
RGGRVPLPIE GRKEGVYIKV GSASPFSTCL KMVASPDSHA RCAQGQPPLL SCYDTLAPHF 
RVDWCNVTLV DKSVPEPADE VPTPGDGILE HDPFFCPPTE APDRDFLVDA LVTLLVPLLV 
ALLLTLLLAY VMCCRREGRL KRDLATSDIQ MVHHCTIHGN TEELRQMAAS REVPRPLSTL 
PMFNVHTGER LPPRVDSAQV PLILDQH

Genular Protein ID: 2855513227

Symbol: A0A0S2Z4P8_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A0S2Z4P8

Database IDs:

ARBA 6 AlphaFoldDB 1 Antibodypedia 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 4 ExpressionAtlas 1 GO 2 InterPro 4 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 Pfam 1 RefSeq 1 SAM 1 SMART 2 SUPFAM 1 VEuPathDB 1

Citations:

PubMed ID: 11181995

Title: The sequence of the human genome.

PubMed ID: 11181995

DOI: 10.1126/science.1058040

PubMed ID: 26871637

Title: Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.

PubMed ID: 26871637

DOI: 10.1016/j.cell.2016.01.029

Sequence Information:

  • Length: 263
  • Mass: 29354
  • Checksum: A5437E496658776B
  • Sequence:
    • MAETLFWTPL LVVLLAGLGD TEAQQTTLHP LVGRVFVHTL DHETFLSLPE HVAVPPAVHI 
TYHAHLQGHP DLPRWLRYTQ RSPHHPGFLY GSATPEDRGL QVIEVTAYNR DSFDTTRQRL 
VLEIGDPEGP LLPYQAEFLV RSHDAEEVLP STPASRFLSA LGGLWEPGEL QLLNVTSALD 
RGGRVPLPIE GRKEGLKRDL ATSDIQMVHH CTIHGNTEEL RQMAASREVP RPLSTLPMFN 
VHTGERLPPR VDSAQVPLIL DQH