SGCB

Chr 4AR

sarcoglycan beta

Also known as: A3b, LGMD2E, LGMDR4, SGC

NCBI Gene: 6443 ENSG00000163069 UniProt: Q16585 OMIM: 600900

The protein is a transmembrane component of the dystrophin-glycoprotein complex that stabilizes muscle fiber membranes and links the muscle cytoskeleton to the extracellular matrix. Mutations cause limb-girdle muscular dystrophy type 4 through autosomal recessive inheritance. Loss of functional protein disrupts the structural integrity of the sarcolemma, leading to progressive muscle weakness and degeneration.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the sarcoglycan family. Sarcoglycans are transmembrane components in the dystrophin-glycoprotein complex which help stabilize the muscle fiber membranes and link the muscle cytoskeleton to the extracellular matrix. Mutations in this gene have been associated with limb-girdle muscular dystrophy.[provided by RefSeq, Oct 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 1.471 OMIM phenotype

VCEP Guidelines: Limb Girdle Muscular DystrophyReleased

ClinGen Panel

Clinical Summary— SGCB

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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

137 unique Pathogenic / Likely Pathogenic· 235 VUS of 656 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — SGCB

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.47LOEUF

pLI 0.000

Z-score 0.42

OE 0.87 (0.53–1.47)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.00Z-score

OE missense 1.00 (0.89–1.13)

178 obs / 177.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.87 (0.53–1.47)

0≤0.351.4

Missense OE?1.00 (0.89–1.13)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 10 / 11.5Missense obs/exp: 178 / 177.8Syn Z: -0.98

This gene — mechanism propensity

0.6646th %ile

GOF

0.6151th %ile

LOF

0.4038th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

LOF74% of P/LP variants are LoF

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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

656 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic60

Likely Pathogenic77

VUS235

Likely Benign220

Benign16

Conflicting39

Pathogenic

Likely Pathogenic

235

VUS

220

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	42	10	8	0	60
Likely Pathogenic	59	15	3	0	77
VUS	4	154	71	6	235
Likely Benign	0	0	90	130	220
Benign	0	2	14	0	16
Conflicting	—				39
Total	105	181	186	136	647

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

View in ClinVar →

16 pathogenic / likely-pathogenic (of 22) ClinVar copy-number / structural variants overlap SGCB — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →