Qualitative or quantitative defects of beta-sarcoglycan

Summary

Qualitative or quantitative defects of beta-sarcoglycan (MONDO:0016142) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 85

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	qualitative or quantitative defects of beta-sarcoglycan
Mondo ID	MONDO:0016142
MeSH	C535435
Orphanet	207063
UMLS	C2930900
MedGen	418943
GARD	0020391
Is cancer (heuristic)	no

Also known as: beta-sarcoglycanopathy

Data availability: 85 ClinVar variants.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › qualitative or quantitative protein defects in neuromuscular diseases › sarcoglycanopathy › qualitative or quantitative defects of beta-sarcoglycan

Related subtypes (3): qualitative or quantitative defects of alpha-sarcoglycan, qualitative or quantitative defects of gamma-sarcoglycan, qualitative or quantitative defects of delta-sarcoglycan

Subtypes (1): autosomal recessive limb-girdle muscular dystrophy type 2E

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

85 retrieved; paginated sample, class counts are floors:

57 uncertain significance, 10 conflicting classifications of pathogenicity, 7 benign, 6 likely benign, 3 pathogenic/likely pathogenic, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
282860	NM_000232.5(SGCB):c.1_2del (p.Met1fs)	LOC129992585	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
284502	NM_000232.5(SGCB):c.31C>T (p.Gln11Ter)	SGCB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
42035	NM_000232.5(SGCB):c.341C>T (p.Ser114Phe)	SGCB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
381511	NM_000232.5(SGCB):c.-16C>G	LOC129992585	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
255606	NM_000232.5(SGCB):c.943G>A (p.Gly315Arg)	SGCB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
285961	NM_000232.5(SGCB):c.496A>G (p.Ile166Val)	SGCB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
288286	NM_000232.5(SGCB):c.495C>T (p.Asp165=)	SGCB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348882	NM_000232.5(SGCB):c.798C>A (p.Thr266=)	SGCB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348883	NM_000232.5(SGCB):c.34-9C>A	SGCB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
516368	NM_000232.5(SGCB):c.243+6T>A	SGCB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
767636	NM_000232.5(SGCB):c.939C>T (p.Pro313=)	SGCB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
900490	NM_000232.5(SGCB):c.558T>G (p.Thr186=)	SGCB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
92661	NM_000232.5(SGCB):c.368A>C (p.Tyr123Ser)	SGCB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
577280	NM_000232.5(SGCB):c.29A>G (p.Glu10Gly)	LOC129992585	Uncertain significance	criteria provided, multiple submitters, no conflicts
284821	NM_000232.5(SGCB):c.392G>A (p.Arg131Gln)	SGCB	Uncertain significance	criteria provided, multiple submitters, no conflicts
285160	NM_000232.5(SGCB):c.502A>G (p.Met168Val)	SGCB	Uncertain significance	criteria provided, multiple submitters, no conflicts
348847	NM_000232.4(SGCB):c.*3258G>C	SGCB	Uncertain significance	criteria provided, single submitter
348848	NM_000232.5(SGCB):c.*3216A>G	SGCB	Uncertain significance	criteria provided, single submitter
348849	NM_000232.5(SGCB):c.*2984G>A	SGCB	Uncertain significance	criteria provided, single submitter
348852	NM_000232.5(SGCB):c.*2811G>A	SGCB	Uncertain significance	criteria provided, single submitter
348853	NM_000232.5(SGCB):c.*2764G>A	SGCB	Uncertain significance	criteria provided, single submitter
348854	NM_000232.5(SGCB):c.*2707T>C	SGCB	Uncertain significance	criteria provided, single submitter
348855	NM_000232.5(SGCB):c.*2580C>T	SGCB	Uncertain significance	criteria provided, single submitter
348856	NM_000232.5(SGCB):c.*2351C>T	SGCB	Uncertain significance	criteria provided, single submitter
348858	NM_000232.5(SGCB):c.*2166T>C	SGCB	Uncertain significance	criteria provided, single submitter
348866	NM_000232.5(SGCB):c.*1135C>G	SGCB	Uncertain significance	criteria provided, single submitter
348867	NM_000232.5(SGCB):c.*1127A>G	SGCB	Uncertain significance	criteria provided, single submitter
348869	NM_000232.5(SGCB):c.*1118G>T	SGCB	Uncertain significance	criteria provided, single submitter
348870	NM_000232.5(SGCB):c.*1115G>T	SGCB	Uncertain significance	criteria provided, single submitter
348871	NM_000232.5(SGCB):c.*1113G>A	SGCB	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SGCB	Orphanet:119	Beta-sarcoglycan-related limb-girdle muscular dystrophy R4

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SGCB	HGNC:10806	ENSG00000163069	Q16585	Beta-sarcoglycan	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SGCB	Beta-sarcoglycan	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.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SGCB	Other/Unknown	no		Sarcoglycan, Sgcb

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
skeletal muscle tissue of biceps brachii	1
skeletal muscle tissue of rectus abdominis	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SGCB	288	ubiquitous	marker	tendon of biceps brachii, skeletal muscle tissue of rectus abdominis, skeletal muscle tissue of biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SGCB	781

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SGCB	Q16585	76.67

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of the dystrophin-glycoprotein complex (DGC)	1	308.6×	0.010	SGCB
Non-integrin membrane-ECM interactions	1	154.3×	0.010	SGCB
Extracellular matrix organization	1	63.1×	0.016	SGCB

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
glucose import in response to insulin stimulus	1	2808.7×	0.002	SGCB
vascular associated smooth muscle cell development	1	1685.2×	0.002	SGCB
cardiac muscle cell development	1	624.1×	0.004	SGCB
response to glucose	1	255.3×	0.007	SGCB
muscle organ development	1	166.8×	0.008	SGCB
glucose homeostasis	1	130.6×	0.009	SGCB
gene expression	1	79.9×	0.013	SGCB

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SGCB	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	SGCB

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SGCB	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.