SGCA

Chr 17AR

sarcoglycan alpha

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

NCBI Gene: 6442ENSG00000108823UniProt: Q16586

This gene encodes a component of the dystrophin-glycoprotein complex (DGC), which is critical to the stability of muscle fiber membranes and to the linking of the actin cytoskeleton to the extracellular matrix. Its expression is thought to be restricted to striated muscle. Mutations in this gene result in type 2D autosomal recessive limb-girdle muscular dystrophy. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

Primary Disease Associations & Inheritance

Muscular dystrophy, limb-girdle, autosomal recessive 3MIM #608099
AR
698
ClinVar variants
143
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SGCA
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
143 Pathogenic / Likely Pathogenic· 194 VUS of 698 total submissions
Some data sources returned errors (1)

clinvarCount: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.79LOEUF
pLI 0.003
Z-score 2.19
OE 0.42 (0.24–0.79)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.68Z-score
OE missense 0.88 (0.79–0.98)
214 obs / 243.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.42 (0.24–0.79)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.79–0.98)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 7 / 16.7Missense obs/exp: 214 / 243.7Syn Z: 0.11

ClinVar Variant Classifications

698 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic44
Likely Pathogenic99
VUS194
Likely Benign314
Benign21
Conflicting26
44
Pathogenic
99
Likely Pathogenic
194
VUS
314
Likely Benign
21
Benign
26
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
25
4
15
0
44
Likely Pathogenic
50
31
17
1
99
VUS
3
162
21
8
194
Likely Benign
0
1
128
185
314
Benign
0
0
21
0
21
Conflicting
—26
Total78198202194698

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
SARCOGLYCAN, ALPHA; SGCA
MIM #600119 · *

Muscular dystrophy, limb-girdle, autosomal recessive 3

MIM #608099

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness.
Töpf A et al.·Genet Med
2020Cohort
Sarcoglycanopathies: an update.
Vainzof M et al.·Neuromuscul Disord
2021Review
Autosomal recessive limb-girdle and Miyoshi muscular dystrophies in the Netherlands: The clinical and molecular spectrum of 244 patients.
Ten Dam L et al.·Clin Genet
2019Cohort
New genotype-phenotype correlations in a large European cohort of patients with sarcoglycanopathy.
Alonso-Pérez J et al.·Brain
2020Cohort
Exome sequencing revealed variants in SGCA and SIL1 genes underlying limb girdle muscular dystrophy and Marinesco-Sjögren syndrome patients.
Faheem A et al.·Mol Biol Rep
2024Cohort
Sarcoglycanopathies: From clinical diagnosis to new promising therapies.
Borland H et al.·J Neuromuscul Dis
2025Review
Profiling of pathogenic variants in Japanese patients with sarcoglycanopathy.
Shimazaki R et al.·Orphanet J Rare Dis
2025Cohort
Low expression of SGCA promotes lung squamous cell carcinoma malignant progression.
Chen G et al.·Sci Rep
2025
Defining clinical endpoints in limb girdle muscular dystrophy: a GRASP-LGMD study.
Doody A et al.·BMC Neurol
2024
LGMD2E is the most common type of sarcoglycanopathies in the Iranian population.
Alavi A et al.·J Neurogenet
2017
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools