SGCA

Chr 17AR

sarcoglycan alpha

Also known as: 50DAG, ADL, DAG2, DMDA2, LGMD2D, LGMDR3, SCARMD1, adhalin

NCBI Gene: 6442ENSG00000108823UniProt: Q16586OMIM: 600119

This protein is a component of the dystrophin-glycoprotein complex that stabilizes muscle fiber membranes and links the actin cytoskeleton to the extracellular matrix in striated muscle. Mutations cause autosomal recessive limb-girdle muscular dystrophy type 2D through a predicted gain-of-function mechanism. The inheritance pattern is autosomal recessive.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
GOFmechanismARLOEUF 0.791 OMIM phenotype
VCEP Guidelines: Limb Girdle Muscular DystrophyReleased
ClinGen Panel
Clinical Summary— SGCA
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Gene-Disease Validity (ClinGen)
autosomal recessive limb-girdle muscular dystrophy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
166 unique Pathogenic / Likely Pathogenic· 191 VUS of 700 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.79LOEUF
pLI 0.003
Z-score 2.19
OE 0.42 (0.24–0.79)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.68Z-score
OE missense 0.88 (0.79–0.98)
214 obs / 243.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.42 (0.24–0.79)
0≤0.351.4
Missense OE0.88 (0.79–0.98)
0≤0.61.4
Synonymous OE0.99
0≤1.21.6
LoF obs/exp: 7 / 16.7Missense obs/exp: 214 / 243.7Syn Z: 0.11
DN
0.6064th %ile
GOF
0.6638th %ile
LOF
0.3068th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

700 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic46
Likely Pathogenic120
VUS191
Likely Benign273
Benign24
Conflicting44
46
Pathogenic
120
Likely Pathogenic
191
VUS
273
Likely Benign
24
Benign
44
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
31
2
13
0
46
Likely Pathogenic
76
37
6
1
120
VUS
3
157
21
10
191
Likely Benign
0
1
124
148
273
Benign
0
0
24
0
24
Conflicting
—44
Total110197188159698

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SGCA · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients