Neuromuscular disease caused by qualitative or quantitative defects of perlecan

Summary

Neuromuscular disease caused by qualitative or quantitative defects of perlecan (MONDO:0016151) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	neuromuscular disease caused by qualitative or quantitative defects of perlecan
Mondo ID	MONDO:0016151
Orphanet	207101
UMLS	C5680831
MedGen	1842752
GARD	0020398
Is cancer (heuristic)	no

Also known as: qualitative or quantitative defects of perlecan

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › qualitative or quantitative protein defects in neuromuscular diseases › neuromuscular disease caused by qualitative or quantitative defects of perlecan

Related subtypes (18): sarcoglycanopathy, neuromuscular disease caused by qualitative or quantitative defects of dysferlin, caveolinopathy, neuromuscular disease caused by qualitative or quantitative defects of dystrophin, neuromuscular disease caused by qualitative or quantitative defects of TRIM32, neuromuscular disease caused by qualitative or quantitative defects of myofibrillar proteins, neuromuscular disease caused by qualitative or quantitative defects of titin, neuromuscular disease caused by qualitative or quantitative defects of telethonin, neuromuscular disease caused by qualitative or quantitative defects of alpha-actin, neuromuscular disease caused by qualitative or quantitative defects of nebulin, neuromuscular disease caused by qualitative or quantitative defects of beta-myosin heavy chain (MYH7), neuromuscular disease caused by qualitative or quantitative defects of selenoprotein N1, neuromuscular disease caused by qualitative or quantitative defects of plectin, neuromuscular disease caused by qualitative or quantitative defects of protein SERCA1, neuromuscular disease caused by qualitative or quantitative defects of tropomyosin, neuromuscular disease caused by qualitative or quantitative defects of alpha-dystroglycan, alpha-actinopathy, collagen 6-related myopathy

Subtypes (2): Silverman-Handmaker type dyssegmental dysplasia, Schwartz-Jampel syndrome

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

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1699290	NM_005529.7(HSPG2):c.7012G>A (p.Gly2338Ser)	HSPG2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HSPG2	Orphanet:1606	1p36 deletion syndrome
HSPG2	Orphanet:1865	Dyssegmental dysplasia, Silverman-Handmaker type
HSPG2	Orphanet:800	Schwartz-Jampel syndrome

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
HSPG2	HGNC:5273	ENSG00000142798	P98160	Basement membrane-specific heparan sulfate proteoglycan core protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HSPG2	Basement membrane-specific heparan sulfate proteoglycan core protein	Integral component of basement membranes.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HSPG2	Antibody/Immunoglobulin	yes		Laminin_IV, SEA_dom, EGF

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
popliteal artery	1
saphenous vein	1
tibial artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HSPG2	271	ubiquitous	marker	saphenous vein, popliteal artery, tibial artery

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HSPG2	2,463

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HSPG2	P98160	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 24. 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
Defective EXT2 causes exostoses 2	1	815.7×	0.005	HSPG2
Defective EXT1 causes exostoses 1, TRPS2 and CHDS	1	815.7×	0.005	HSPG2
Mechanical load activates signaling by PIEZO1 and integrins in osteocytes	1	671.8×	0.005	HSPG2
Attachment and Entry	1	601.0×	0.005	HSPG2
Defective B4GALT7 causes EDS, progeroid type	1	571.0×	0.005	HSPG2
Defective B3GAT3 causes JDSSDHD	1	571.0×	0.005	HSPG2
Defective B3GALT6 causes EDSP2 and SEMDJL1	1	571.0×	0.005	HSPG2
HS-GAG degradation	1	496.5×	0.005	HSPG2
Respiratory syncytial virus (RSV) attachment and entry	1	496.5×	0.005	HSPG2
Initiation of coagulation cascade	1	475.8×	0.005	HSPG2
Glycosaminoglycan-protein linkage region biosynthesis	1	393.8×	0.005	HSPG2
Laminin interactions	1	380.7×	0.005	HSPG2
HS-GAG biosynthesis	1	346.1×	0.005	HSPG2
Formation of the dystrophin-glycoprotein complex (DGC)	1	308.6×	0.006	HSPG2
Dengue Virus Attachment and Entry	1	259.6×	0.006	HSPG2
Retinoid metabolism and transport	1	248.3×	0.006	HSPG2
Regulation of clotting cascade	1	233.1×	0.006	HSPG2
RSV-host interactions	1	156.4×	0.008	HSPG2
Non-integrin membrane-ECM interactions	1	154.3×	0.008	HSPG2
ECM proteoglycans	1	150.3×	0.008	HSPG2
Integrin cell surface interactions	1	134.3×	0.009	HSPG2
Degradation of the extracellular matrix	1	117.7×	0.009	HSPG2
Amyloid fiber formation	1	102.9×	0.010	HSPG2
Dengue Virus-Host Interactions	1	45.7×	0.022	HSPG2

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
negative regulation of synaptic transmission, cholinergic	1	5617.3×	0.003	HSPG2
circulatory system development	1	1404.3×	0.006	HSPG2
protein localization to synapse	1	766.0×	0.007	HSPG2
animal organ regeneration	1	601.9×	0.007	HSPG2
negative regulation of cell adhesion	1	383.0×	0.009	HSPG2
embryo implantation	1	351.1×	0.009	HSPG2
positive regulation of endothelial cell proliferation	1	230.8×	0.010	HSPG2
receptor-mediated endocytosis	1	221.7×	0.010	HSPG2
smoothened signaling pathway	1	181.2×	0.011	HSPG2
negative regulation of angiogenesis	1	168.5×	0.011	HSPG2
response to hypoxia	1	95.8×	0.016	HSPG2
lipid metabolic process	1	91.6×	0.016	HSPG2
brain development	1	79.5×	0.017	HSPG2
response to xenobiotic stimulus	1	69.1×	0.019	HSPG2
angiogenesis	1	62.4×	0.019	HSPG2
negative regulation of cell population proliferation	1	42.1×	0.027	HSPG2
inflammatory response	1	37.7×	0.028	HSPG2
cell differentiation	1	29.1×	0.034	HSPG2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HSPG2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
HSPG2	2	Binding:2

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	1	HSPG2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
HSPG2	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.