autosomal recessive limb-girdle muscular dystrophy type 2F

Summary

autosomal recessive limb-girdle muscular dystrophy type 2F (MONDO:0011028) is a disease caused by SGCD (GenCC Definitive), with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
• Causal gene: SGCD (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 549
• Phenotypes (HPO): 6
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000	0.3	Europe	Validated

Signs & symptoms

Clinical features (HPO)

6 HPO clinical features (Orphanet curated; top 6 by frequency):

HPO ID	Term	Frequency
HP:0002362	Shuffling gait	Frequent (30-79%)
HP:0003691	Scapular winging	Frequent (30-79%)
HP:0008948	Proximal upper limb amyotrophy	Frequent (30-79%)
HP:0008956	Proximal lower limb amyotrophy	Frequent (30-79%)
HP:0009055	Generalized limb muscle atrophy	Frequent (30-79%)
HP:0010628	Facial palsy	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive limb-girdle muscular dystrophy type 2F
Mondo ID	MONDO:0011028
MeSH	C535896
OMIM	601287
Orphanet	219
DOID	DOID:0110280
SNOMED CT	718177001
UMLS	C1832525
MedGen	331308
GARD	0008573
Is cancer (heuristic)	no

Also known as: autosomal recessive limb-girdle muscular dystrophy caused by mutation in SGCD · delta-sarcoglycanopathy · LGMD2F · limb-girdle muscular dystrophy due to delta-sarcoglycan deficiency · limb-girdle muscular dystrophy type 2F · muscular dystrophy limb-girdle with delta-sarcoglyan deficiency · muscular dystrophy, limb-girdle, autosomal recessive 6 · muscular dystrophy, limb-girdle, type 2F · SGCD autosomal recessive limb-girdle muscular dystrophy

Data availability: 549 ClinVar variants · 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 2F

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 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

549 retrieved; paginated sample, class counts are floors:

232 likely benign, 200 uncertain significance, 36 conflicting classifications of pathogenicity, 29 pathogenic, 25 benign/likely benign, 15 likely pathogenic, 9 benign, 3 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1068999	NC_000005.9:g.(?155935601)(156074556_?)del	SGCD	Pathogenic	criteria provided, single submitter
1394105	NM_000337.6(SGCD):c.466G>T (p.Glu156Ter)	SGCD	Pathogenic	criteria provided, single submitter
1451957	NM_000337.6(SGCD):c.97C>T (p.Arg33Ter)	SGCD	Pathogenic	criteria provided, multiple submitters, no conflicts
1455950	NM_000337.6(SGCD):c.10C>T (p.Gln4Ter)	SGCD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1677453	NM_000337.6(SGCD):c.289C>T (p.Arg97Ter)	SGCD	Pathogenic	reviewed by expert panel
1977494	NM_000337.6(SGCD):c.90G>A (p.Trp30Ter)	SGCD	Pathogenic	criteria provided, single submitter
2422916	NC_000005.9:g.(?156074454)(156074566_?)del	SGCD	Pathogenic	criteria provided, single submitter
2422917	NC_000005.9:g.(?156184572)(156184735_?)del	SGCD	Pathogenic	criteria provided, single submitter
2422918	NC_000005.9:g.(?155756587)(156074566_?)del	SGCD	Pathogenic	criteria provided, single submitter
2422920	NC_000005.9:g.(?155756587)(156184735_?)del	SGCD	Pathogenic	criteria provided, single submitter
2678700	NM_000337.6(SGCD):c.441dup (p.Leu148fs)	SGCD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2713565	NM_000337.6(SGCD):c.248_249del (p.Asp82_Ser83insTer)	SGCD	Pathogenic	criteria provided, multiple submitters, no conflicts
2741520	NM_000337.6(SGCD):c.133_172dup (p.Lys58fs)	SGCD	Pathogenic	criteria provided, single submitter
2760849	NM_000337.6(SGCD):c.414dup (p.Phe139fs)	SGCD	Pathogenic	criteria provided, single submitter
2816447	NM_000337.6(SGCD):c.654_655del (p.Glu218fs)	SGCD	Pathogenic	criteria provided, single submitter
2835886	NM_000337.6(SGCD):c.540_541del (p.Thr180_Pro181insTer)	SGCD	Pathogenic	criteria provided, single submitter
285158	NM_000337.6(SGCD):c.65dup (p.Tyr23fs)	SGCD	Pathogenic	criteria provided, multiple submitters, no conflicts
3013440	NM_000337.6(SGCD):c.481_485dup (p.Arg163fs)	SGCD	Pathogenic	criteria provided, single submitter
3641138	NM_000337.6(SGCD):c.258dup (p.Gln87fs)	SGCD	Pathogenic	criteria provided, single submitter
3669608	NM_000337.6(SGCD):c.172A>T (p.Lys58Ter)	SGCD	Pathogenic	criteria provided, single submitter
4081797	NM_000337.6(SGCD):c.506del (p.Ala169fs)	SGCD	Pathogenic	criteria provided, single submitter
411697	NM_000337.6(SGCD):c.74_77dup (p.Ile27fs)	SGCD	Pathogenic	criteria provided, single submitter
4740008	NM_000337.6(SGCD):c.491T>G (p.Leu164Ter)	SGCD	Pathogenic	criteria provided, single submitter
48118	NM_000337.6(SGCD):c.390del (p.Ala131fs)	SGCD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
584277	NC_000005.10:g.(?156757561)(156759410_?)del	SGCD	Pathogenic	criteria provided, single submitter
8171	NM_000337.6(SGCD):c.657del (p.Thr220fs)	SGCD	Pathogenic	criteria provided, multiple submitters, no conflicts
8172	NM_000337.6(SGCD):c.493C>T (p.Arg165Ter)	SGCD	Pathogenic	reviewed by expert panel
8173	NM_000337.6(SGCD):c.89G>A (p.Trp30Ter)	SGCD	Pathogenic	criteria provided, single submitter
8177	NM_000337.6(SGCD):c.391G>C (p.Ala131Pro)	SGCD	Pathogenic	no assertion criteria provided
831480	NC_000005.10:g.(?156329567)(156344687_?)del	SGCD	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
SGCD	Definitive	Autosomal recessive	autosomal recessive limb-girdle muscular dystrophy type 2F	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SGCD	Orphanet:154	Familial isolated dilated cardiomyopathy
SGCD	Orphanet:219	Delta-sarcoglycan-related limb-girdle muscular dystrophy R6

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
SGCD	HGNC:10807	ENSG00000170624	Q92629	Delta-sarcoglycan	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SGCD	Delta-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)
SGCD	Other/Unknown	no		Sarcoglycan, Sarcoglycan_gamma/delta/zeta

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
heart right ventricle	1
left ventricle myocardium	1
skeletal muscle tissue of rectus abdominis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SGCD	247	broad	marker	left ventricle myocardium, skeletal muscle tissue of rectus abdominis, heart right ventricle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SGCD	1,102

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SGCD	Q92629	81.43

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	SGCD
Non-integrin membrane-ECM interactions	1	154.3×	0.010	SGCD
Extracellular matrix organization	1	63.1×	0.016	SGCD

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
coronary vasculature morphogenesis	1	8426.0×	0.001	SGCD
cardiac muscle cell contraction	1	1685.2×	0.002	SGCD
protein-containing complex localization	1	991.3×	0.002	SGCD
cardiac muscle tissue development	1	887.0×	0.002	SGCD
heart contraction	1	766.0×	0.002	SGCD
cardiac muscle cell development	1	624.1×	0.002	SGCD
calcium ion homeostasis	1	443.5×	0.003	SGCD
calcium-mediated signaling	1	183.2×	0.006	SGCD
muscle organ development	1	166.8×	0.006	SGCD

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
SGCD	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	SGCD

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)
SGCD	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05989620	Not specified	RECRUITING	Long-Term Development of Muscular Dystrophy Outcome Assessments