autosomal recessive limb-girdle muscular dystrophy type 2E

Summary

autosomal recessive limb-girdle muscular dystrophy type 2E (MONDO:0011423) is a disease caused by SGCB (GenCC Definitive), with 1 cohort gene and 2 clinical trials.

At a glance

• Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
• Causal gene: SGCB (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 548
• Phenotypes (HPO): 13
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000	0.1	Europe	Validated
Point prevalence	<1 / 1 000 000	0.07	United Kingdom	Validated

Signs & symptoms

Clinical features (HPO)

13 HPO clinical features (Orphanet curated; top 13 by frequency):

HPO ID	Term	Frequency
HP:0000750	Delayed speech and language development	Frequent (30-79%)
HP:0002058	Myopathic facies	Frequent (30-79%)
HP:0002136	Broad-based gait	Frequent (30-79%)
HP:0002515	Waddling gait	Frequent (30-79%)
HP:0003198	Myopathy	Frequent (30-79%)
HP:0003236	Elevated circulating creatine kinase concentration	Frequent (30-79%)
HP:0003391	Gowers sign	Frequent (30-79%)
HP:0003557	Increased variability in muscle fiber diameter	Frequent (30-79%)
HP:0003749	Pelvic girdle muscle weakness	Frequent (30-79%)
HP:0008981	Calf muscle hypertrophy	Frequent (30-79%)
HP:0001288	Gait disturbance	Frequent (30-79%)
HP:0001638	Cardiomyopathy	Occasional (5-29%)
HP:0002913	Myoglobinuria	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive limb-girdle muscular dystrophy type 2E
Mondo ID	MONDO:0011423
OMIM	604286
Orphanet	119
DOID	DOID:0110279
SNOMED CT	718850008
UMLS	C1858593
MedGen	347674
GARD	0003851
Is cancer (heuristic)	no

Also known as: autosomal recessive limb-girdle muscular dystrophy caused by mutation in SGCB · autosomal recessive limb-girdle muscular dystrophy type 2E · beta-sarcoglycan limb-girdle muscular dystrophy · beta-sarcoglycan-related LGMD R4 · beta-sarcoglycan-related limb-girdle muscular dystrophy R4 · beta-sarcoglycanopathy · LGMD due to beta-sarcoglycan deficiency · LGMD type 2E · LGMD2E · LGMDR4 · limb-girdle muscular dystrophy due to beta-sarcoglycan deficiency · limb-girdle muscular dystrophy type 2E · muscular dystrophy limb-girdle with beta-sarcoglycan deficiency · muscular dystrophy, limb-girdle, autosomal recessive 4 · muscular dystrophy, limb-girdle, type 2E · SGCB autosomal recessive limb-girdle muscular dystrophy

Data availability: 548 ClinVar variants · 4 GenCC gene-disease records · 3 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › autosomal recessive limb-girdle muscular dystrophy › autosomal recessive limb-girdle muscular dystrophy type 2E

Related subtypes (31): epidermolysis bullosa simplex 5B, with muscular dystrophy, autosomal recessive limb-girdle muscular dystrophy type 2A, autosomal recessive limb-girdle muscular dystrophy type 2B, autosomal recessive limb-girdle muscular dystrophy type 2C, autosomal recessive limb-girdle muscular dystrophy type 2H, autosomal recessive limb-girdle muscular dystrophy type 2F, autosomal recessive limb-girdle muscular dystrophy type 2G, autosomal recessive limb-girdle muscular dystrophy type 2I, autosomal recessive limb-girdle muscular dystrophy type 2D, autosomal recessive limb-girdle muscular dystrophy type 2J, autosomal recessive limb-girdle muscular dystrophy type 2K, autosomal recessive limb-girdle muscular dystrophy type 2L, autosomal recessive limb-girdle muscular dystrophy type 2M, autosomal recessive limb-girdle muscular dystrophy type 2O, autosomal recessive limb-girdle muscular dystrophy type 2N, autosomal recessive limb-girdle muscular dystrophy type 2Q, autosomal recessive limb-girdle muscular dystrophy type 2P, autosomal recessive limb-girdle muscular dystrophy type 2T, autosomal recessive limb-girdle muscular dystrophy type R18, autosomal recessive limb-girdle muscular dystrophy type 2U, limb-girdle muscular dystrophy due to POMK deficiency, autosomal recessive limb-girdle muscular dystrophy type 2X, autosomal recessive limb-girdle muscular dystrophy type 2W, autosomal recessive limb-girdle muscular dystrophy type 2Y, autosomal recessive limb-girdle muscular dystrophy type 2R1, muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 8, muscular dystrophy, limb-girdle, autosomal recessive 23, muscular dystrophy, limb-girdle, autosomal recessive 26, muscular dystrophy, limb-girdle, autosomal recessive 27, muscular dystrophy, limb-girdle, autosomal recessive 28, muscular dystrophy, limb-girdle, autosomal recessive 29

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

548 retrieved; paginated sample, class counts are floors:

204 likely benign, 162 uncertain significance, 60 pathogenic, 51 likely pathogenic, 37 conflicting classifications of pathogenicity, 28 pathogenic/likely pathogenic, 6 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
663428	NC_000004.12:g.(?52023947)(52038269_?)del	LOC129992584	Pathogenic	criteria provided, single submitter
1180805	NM_000232.5(SGCB):c.1A>T (p.Met1Leu)	LOC129992585	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1391801	NM_000232.5(SGCB):c.-10_13del (p.Met1fs)	LOC129992585	Pathogenic	criteria provided, single submitter
1686638	NM_000232.5(SGCB):c.3G>T (p.Met1Ile)	LOC129992585	Pathogenic	criteria provided, single submitter
193065	NM_000232.5(SGCB):c.32dup (p.Gln12fs)	LOC129992585	Pathogenic	criteria provided, multiple submitters, no conflicts
2678687	NM_000232.5(SGCB):c.-15_8dup (p.Ala5fs)	LOC129992585	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2678689	NM_000232.5(SGCB):c.-10_16dup (p.Ala6fs)	LOC129992585	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2700315	NM_000232.5(SGCB):c.-8_8dup (p.Ala4fs)	LOC129992585	Pathogenic	criteria provided, single submitter
282860	NM_000232.5(SGCB):c.1_2del (p.Met1fs)	LOC129992585	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2852462	NM_000232.5(SGCB):c.-12_23dup (p.Ala9fs)	LOC129992585	Pathogenic	criteria provided, single submitter
2977165	NM_000232.5(SGCB):c.-10_19dup (p.Ala7fs)	LOC129992585	Pathogenic	criteria provided, single submitter
466600	NC_000004.12:g.(?52038207)(52038279_?)del	LOC129992585	Pathogenic	criteria provided, single submitter
534947	NM_000232.5(SGCB):c.28G>T (p.Glu10Ter)	LOC129992585	Pathogenic	criteria provided, multiple submitters, no conflicts
837812	NM_000232.5(SGCB):c.33+1G>C	LOC129992585	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
862654	NM_000232.5(SGCB):c.2T>C (p.Met1Thr)	LOC129992585	Pathogenic	criteria provided, multiple submitters, no conflicts
1073925	NM_000232.5(SGCB):c.82G>T (p.Glu28Ter)	SGCB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074218	NM_000232.5(SGCB):c.255dup (p.Ile86fs)	SGCB	Pathogenic	criteria provided, single submitter
1074829	NM_000232.5(SGCB):c.567dup (p.His190fs)	SGCB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076257	NM_000232.5(SGCB):c.261G>A (p.Trp87Ter)	SGCB	Pathogenic	criteria provided, single submitter
1076904	NM_000232.5(SGCB):c.325C>T (p.Arg109Ter)	SGCB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1180815	NM_000232.5(SGCB):c.185del (p.Gly62fs)	SGCB	Pathogenic	criteria provided, single submitter
1180817	NM_000232.5(SGCB):c.34-1G>A	SGCB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1215280	NM_000232.5(SGCB):c.-18_8dup (p.Ala6fs)	SGCB	Pathogenic	criteria provided, multiple submitters, no conflicts
1301699	NM_000232.5(SGCB):c.622-1G>C	SGCB	Pathogenic	criteria provided, multiple submitters, no conflicts
1323586	NM_000232.5(SGCB):c.102del (p.Glu35fs)	SGCB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1364546	NM_000232.5(SGCB):c.579dup (p.Gly194fs)	SGCB	Pathogenic	criteria provided, single submitter
1414584	NM_000232.5(SGCB):c.85dup (p.Arg29fs)	SGCB	Pathogenic	criteria provided, single submitter
1443062	NM_000232.5(SGCB):c.30del (p.Glu10fs)	SGCB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1451523	NM_000232.5(SGCB):c.539dup (p.Ser181fs)	SGCB	Pathogenic	criteria provided, single submitter
1451596	NM_000232.5(SGCB):c.735_736del (p.Asn246fs)	SGCB	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
SGCB	Definitive	Autosomal recessive	autosomal recessive limb-girdle muscular dystrophy type 2E	5

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	gencc,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: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05989620	Not specified	RECRUITING	Long-Term Development of Muscular Dystrophy Outcome Assessments
NCT04509609	Not specified	COMPLETED	Clinical Determinants of Disease Progression in Patients With Limb Girdle Muscular Distrophy Type 2E