SGCA

sarcoglycan alpha

Basic information

Region (hg38): 17:50164214-50175928

Previous symbols: [ "ADL" ]

Links

ENSG00000108823

∙ NCBI:6442 ∙ OMIM:600119 ∙ HGNC:10805 ∙ Uniprot:Q16586 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

autosomal recessive limb-girdle muscular dystrophy type 2D (Definitive), mode of inheritance: AR
autosomal recessive limb-girdle muscular dystrophy type 2D (Strong), mode of inheritance: AR
autosomal recessive limb-girdle muscular dystrophy type 2D (Definitive), mode of inheritance: AR
autosomal recessive limb-girdle muscular dystrophy type 2D (Supportive), mode of inheritance: AR
autosomal recessive limb-girdle muscular dystrophy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Muscular dystrophy, limb-girdle, autosomal recessive 3	AR	Cardiovascular	The condition can include severe cardiac manifestations, and knowledge may allow surveillance (eg, with EKG, echocardiogram, and Holter monitoring) and early medical management, which may ameliorate morbidity and mortality; Heart transplantation may be indicated in individuals with severe dilated cardiomyopathy	Cardiovascular; Musculoskeletal	8069911; 7987694; 8528203; 7663524; 9032047; 18285821; 20627570

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SGCA gene.

Autosomal_recessive_limb-girdle_muscular_dystrophy_type_2D (715 variants)
not_provided (171 variants)
not_specified (44 variants)
Inborn_genetic_diseases (38 variants)
Autosomal_recessive_limb-girdle_muscular_dystrophy (31 variants)
Sarcoglycanopathy (29 variants)
SGCA-related_disorder (16 variants)
Abnormality_of_the_musculature (7 variants)
Cardiomyopathy (2 variants)
Muscular_dystrophy (2 variants)
Qualitative_or_quantitative_defects_of_alpha-sarcoglycan (1 variants)
Hypertrophic_cardiomyopathy (1 variants)
Proximal_muscle_weakness (1 variants)
Elevated_circulating_creatine_kinase_concentration (1 variants)
See_cases (1 variants)
Limb-girdle_muscular_dystrophy (1 variants)
Arrhythmogenic_right_ventricular_cardiomyopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SGCA gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000023.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous		2 clinvar	12 clinvar	203 clinvar	1 clinvar	218
missense	11 clinvar	65 clinvar	188 clinvar	13 clinvar	2 clinvar	279
nonsense	6 clinvar	15 clinvar				21
start loss		2				2
frameshift	33 clinvar	39 clinvar	1 clinvar			73
splice donor/acceptor (+/-2bp)	6 clinvar	23 clinvar	2 clinvar			31
Total	56	146	203	216	3

Highest pathogenic variant AF is 0.00046966

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SGCA	protein_coding	protein_coding	ENST00000262018	9	11718

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00271	0.985	125721	0	27	125748	0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.676	214	244	0.878	0.0000162	2445
Missense in Polyphen		68	85.262	0.79754		880
Synonymous	0.108	99	100	0.986	0.00000648	836
Loss of Function	2.19	7	16.7	0.420	8.08e-7	181

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000217	0.000213
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000158	0.000158
Middle Eastern	0.000218	0.000217
South Asian	0.00	0.00
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.;
Pathway: Dilated cardiomyopathy (DCM) - Homo sapiens (human);Viral myocarditis - Homo sapiens (human);Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Arrhythmogenic Right Ventricular Cardiomyopathy (Consensus)

Recessive Scores

pRec: 0.103

Intolerance Scores

loftool: 0.0528
rvis_EVS: -0.71
rvis_percentile_EVS: 14.5

Haploinsufficiency Scores

pHI: 0.136
hipred: Y
hipred_score: 0.696
ghis: 0.586

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.554

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Sgca
Phenotype: homeostasis/metabolism phenotype; muscle phenotype; immune system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan);

Gene ontology

Biological process: muscle contraction;muscle organ development
Cellular component: cytoplasm;cytoskeleton;cell-cell junction;dystrophin-associated glycoprotein complex;sarcoglycan complex;integral component of membrane;sarcolemma;membrane raft
Molecular function: calcium ion binding;protein binding