autosomal recessive limb-girdle muscular dystrophy type 2C

Summary

autosomal recessive limb-girdle muscular dystrophy type 2C (MONDO:0009677) is a disease caused by SGCG (GenCC Definitive), with 4 cohort genes and 4 clinical trials.

At a glance

• Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
• Causal gene: SGCG (GenCC Definitive)
• Cohort genes: 4
• ClinVar variants: 521
• Phenotypes (HPO): 27
• Clinical trials: 4

Clinical features

Epidemiology

Prevalence records

3 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000	0.2	Europe	Validated
Annual incidence	1-9 / 1 000 000	0.18	Japan	Validated
Point prevalence	1-9 / 1 000 000	0.13	United Kingdom	Validated

Signs & symptoms

Clinical features (HPO)

27 HPO clinical features (Orphanet curated; top 27 by frequency):

HPO ID	Term	Frequency
HP:0000158	Macroglossia	Frequent (30-79%)
HP:0001667	Right ventricular hypertrophy	Frequent (30-79%)
HP:0002136	Broad-based gait	Frequent (30-79%)
HP:0002359	Frequent falls	Frequent (30-79%)
HP:0002515	Waddling gait	Frequent (30-79%)
HP:0002938	Lumbar hyperlordosis	Frequent (30-79%)
HP:0003236	Elevated circulating creatine kinase concentration	Frequent (30-79%)
HP:0003458	EMG: myopathic abnormalities	Frequent (30-79%)
HP:0003484	Upper limb muscle weakness	Frequent (30-79%)
HP:0003551	Difficulty climbing stairs	Frequent (30-79%)
HP:0003557	Increased variability in muscle fiber diameter	Frequent (30-79%)
HP:0003691	Scapular winging	Frequent (30-79%)
HP:0003707	Calf muscle pseudohypertrophy	Frequent (30-79%)
HP:0003730	EMG: myotonic runs	Frequent (30-79%)
HP:0004311	Abnormal macrophage morphology	Frequent (30-79%)
HP:0008981	Calf muscle hypertrophy	Frequent (30-79%)
HP:0009046	Difficulty running	Frequent (30-79%)
HP:0030007	EMG: positive sharp waves	Frequent (30-79%)
HP:0100284	EMG: myotonic discharges	Frequent (30-79%)
HP:0100297	Increased endomysial connective tissue	Frequent (30-79%)
HP:0000276	Long face	Occasional (5-29%)
HP:0001771	Achilles tendon contracture	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0003391	Gowers sign	Occasional (5-29%)
HP:0003722	Neck flexor weakness	Occasional (5-29%)
HP:0025169	Left ventricular systolic dysfunction	Occasional (5-29%)
HP:0030051	Tip-toe gait	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive limb-girdle muscular dystrophy type 2C
Mondo ID	MONDO:0009677
MeSH	C535900
OMIM	253700
Orphanet	353
DOID	DOID:0110277
UMLS	C0410173
MedGen	98045
GARD	0002429
Is cancer (heuristic)	no

Also known as: autosomal recessive limb-girdle muscular dystrophy caused by mutation in SGCG · autosomal recessive limb-girdle muscular dystrophy type 2C · DMDA1 · gamma-sarcoglycanopathy · LGMD2C · limb-girdle muscular dystrophy due to gamma-sarcoglycan deficiency · limb-girdle muscular dystrophy with gamma-sarcoglycan deficiency · limb-girdle muscular dystrophy, type 2C · Maghrebian myopathy · muscular dystrophy, limb-girdle, autosomal recessive 5 · muscular dystrophy, limb-girdle, type 2C · SCARMD · SGCG autosomal recessive limb-girdle muscular dystrophy

Data availability: 521 ClinVar variants · 1 ClinGen variant curation · 4 GenCC gene-disease records.

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 2C

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 2H, autosomal recessive limb-girdle muscular dystrophy type 2F, autosomal recessive limb-girdle muscular dystrophy type 2G, autosomal recessive limb-girdle muscular dystrophy type 2E, 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

521 retrieved; paginated sample, class counts are floors:

176 likely benign, 162 uncertain significance, 61 pathogenic, 46 likely pathogenic, 27 conflicting classifications of pathogenicity, 24 benign, 23 pathogenic/likely pathogenic, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
4072354	Multiple alleles		Pathogenic	criteria provided, single submitter
644834	NC_000013.11:g.(?23093196)(23203899_?)del	LINC00362	Pathogenic	criteria provided, single submitter
583650	NC_000013.11:g.(?23093196)(23411259_?)del	LOC130009363	Pathogenic	criteria provided, single submitter
1707558	NM_000231.3(SGCG):c.579-5729_702+1720del	LOC130009364	Pathogenic	criteria provided, single submitter
2579219	GRCh38/hg38 13q12.12(chr13:23315907-23322480)x0	LOC130009364	Pathogenic	criteria provided, single submitter
652383	NC_000013.11:g.(?23093196)(23411249_?)del	LOC130009367	Pathogenic	criteria provided, single submitter
2422612	NC_000013.10:g.(?23898487)(24463459_?)del	PCOTH	Pathogenic	criteria provided, single submitter
3244163	NC_000013.10:g.(?23894756)(24463459_?)del	PCOTH	Pathogenic	criteria provided, single submitter
3244162	NC_000013.10:g.(?23853478)(23985378_?)del	SACS	Pathogenic	criteria provided, single submitter
1067944	NM_000231.3(SGCG):c.386-2A>C	SGCG	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070855	NC_000013.10:g.(?23898497)(23898690_?)del	SGCG	Pathogenic	criteria provided, single submitter
1071940	NM_000231.3(SGCG):c.673_674insTATTCTTTTTCTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNGACGGGGTTTCACCGTGTTAGCCAGGATGGTCTCGATCTCCTGACCTCGTGATCCGCCCGTCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCC (p.Asp225delinsValPhePhePhePhePhePhePhePhePheXaaXaaXaaXaaAspGlyValSerProCysTer)	SGCG	Pathogenic	criteria provided, single submitter
1073532	NM_000231.3(SGCG):c.699_702del (p.Met234fs)	SGCG	Pathogenic	criteria provided, single submitter
1074004	NM_000231.3(SGCG):c.298-1G>A	SGCG	Pathogenic	criteria provided, multiple submitters, no conflicts
1076779	NM_000231.3(SGCG):c.511G>T (p.Glu171Ter)	SGCG	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1173091	NM_000231.3(SGCG):c.128T>A (p.Leu43Ter)	SGCG	Pathogenic	criteria provided, multiple submitters, no conflicts
1323589	NM_000231.3(SGCG):c.526G>T (p.Glu176Ter)	SGCG	Pathogenic	reviewed by expert panel
1323590	NM_000231.3(SGCG):c.177dup (p.Val60fs)	SGCG	Pathogenic	criteria provided, multiple submitters, no conflicts
1366500	NM_000231.3(SGCG):c.174_175insTTTTTTTTTTTTTTTTTTNNNNNNNNNNTTGTTAGCCAGGATGGTCTCGATCTCCTGACCTCATGATCCACCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCACAATTTGGATTCTT (p.Lys59delinsPhePhePhePhePhePheXaaXaaXaaXaaValSerGlnAspGlyLeuAspLeuLeuThrSerTer)	SGCG	Pathogenic	criteria provided, single submitter
1383126	NM_000231.3(SGCG):c.524_527del (p.Phe175fs)	SGCG	Pathogenic	criteria provided, single submitter
1391542	NM_000231.3(SGCG):c.533del (p.His177_Ser178insTer)	SGCG	Pathogenic	criteria provided, single submitter
1397202	NM_000231.3(SGCG):c.87T>A (p.Tyr29Ter)	SGCG	Pathogenic	criteria provided, single submitter
1408922	NM_000231.3(SGCG):c.824_827del (p.Ser275fs)	SGCG	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1452070	NM_000231.3(SGCG):c.648_649insC (p.Lys217fs)	SGCG	Pathogenic	criteria provided, single submitter
1452677	NM_000231.3(SGCG):c.559del (p.Asp187fs)	SGCG	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1455016	NM_000231.3(SGCG):c.775_776del (p.Gln259fs)	SGCG	Pathogenic	criteria provided, single submitter
1455914	NM_000231.3(SGCG):c.549dup (p.Val184fs)	SGCG	Pathogenic	criteria provided, multiple submitters, no conflicts
1459731	NC_000013.10:g.(?23755215)(23853627_?)del	SGCG	Pathogenic	criteria provided, single submitter
1459732	NC_000013.10:g.(?23824749)(23853637_?)del	SGCG	Pathogenic	criteria provided, single submitter
1459762	NM_000231.3(SGCG):c.105T>A (p.Cys35Ter)	SGCG	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · 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
SGCG	Definitive	Autosomal recessive	autosomal recessive limb-girdle muscular dystrophy type 2C	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SGCG	Orphanet:353	Gamma-sarcoglycan-related limb-girdle muscular dystrophy R5
SACS	Orphanet:98	Autosomal recessive spastic ataxia of Charlevoix-Saguenay

Cohort genes → proteins

4 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SGCG	HGNC:10809	ENSG00000102683	Q13326	Gamma-sarcoglycan	gencc,clinvar
SACS	HGNC:10519	ENSG00000151835	Q9NZJ4	Sacsin	clinvar
PCOTH	HGNC:39839	ENSG00000205861	Q58A44	Prostate collagen triple helix protein	clinvar
LINC00362	HGNC:42682	ENSG00000229483		long intergenic non-protein coding RNA 362	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SGCG	Gamma-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.
SACS	Sacsin	Co-chaperone which acts as a regulator of the Hsp70 chaperone machinery and may be involved in the processing of other ataxia-linked proteins.
PCOTH	Prostate collagen triple helix protein	May be involved in growth and survival of prostate cancer cells through the TAF-Ibeta pathway.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 4 · 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	4	1.8×	0.097

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SGCG	Other/Unknown	no		Sarcoglycan, Sarcoglycan_gamma/delta/zeta
SACS	Other/Unknown	no		Ubiquitin-like_dom, DnaJ_domain, HEPN_dom
PCOTH	Other/Unknown	no
LINC00362	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

3 cohort genes 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	2
gluteal muscle	1
skeletal muscle tissue of rectus abdominis	1
triceps brachii	1
Brodmann (1909) area 23	1
frontal pole	1
middle frontal gyrus	1
left testis	1
right testis	1
blood	1
primary visual cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SGCG	184	broad	marker	skeletal muscle tissue of rectus abdominis, gluteal muscle, triceps brachii
SACS	286	ubiquitous	marker	Brodmann (1909) area 23, middle frontal gyrus, frontal pole
PCOTH	170	broad	marker	right testis, left testis, male germ line stem cell (sensu Vertebrata) in testis
LINC00362	41		yes	male germ line stem cell (sensu Vertebrata) in testis, primary visual cortex, blood

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SACS	1,441
SGCG	923
PCOTH	5
LINC00362	0

Intra-cohort edges

A	B	Sources
SACS	SGCG	string_interaction

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SACS	Q9NZJ4	7

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SGCG	Q13326	80.24
PCOTH	Q58A44	78.90

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 4 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	SGCG
Non-integrin membrane-ECM interactions	1	154.3×	0.010	SGCG
Extracellular matrix organization	1	63.1×	0.016	SGCG

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of inclusion body assembly	1	842.6×	0.005	SACS
cardiac muscle tissue development	1	443.5×	0.005	SGCG
heart contraction	1	383.0×	0.005	SGCG
muscle organ development	1	83.4×	0.018	SGCG
protein folding	1	51.7×	0.023	SACS
gene expression	1	39.9×	0.025	SGCG

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 4 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
SGCG	0	0
SACS	0	0
PCOTH	0	0
LINC00362	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	4	SGCG, SACS, PCOTH, LINC00362

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SGCG	0	—
SACS	0	—
PCOTH	0	—
LINC00362	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 4.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1	2
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05973630	PHASE1	ACTIVE_NOT_RECRUITING	ATA-200 Gene Therapy Trial in Patients With LGMDR5
NCT01344798	PHASE1	COMPLETED	Clinical Study of AAV1-gamma-sarcoglycan Gene Therapy for Limb Girdle Muscular Dystrophy Type 2C
NCT05989620	Not specified	RECRUITING	Long-Term Development of Muscular Dystrophy Outcome Assessments
NCT06210672	Not specified	WITHDRAWN	Natural History Study in Patients With LGMDR5/2c