Schwartz-Jampel syndrome type 1

Summary

Schwartz-Jampel syndrome type 1 (MONDO:0100435) is a disease caused by HSPG2 (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: HSPG2 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 121

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Schwartz-Jampel syndrome type 1
Mondo ID	MONDO:0100435
OMIM	255800
DOID	DOID:0090005
UMLS	C4551479
MedGen	1647990
GARD	0026212
Is cancer (heuristic)	no

Also known as: Schwartz-Jampel syndrome type 1 · Schwartz-Jampel syndrome, type 1 · SJA syndrome · SJS1

Data availability: 121 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Schwartz-Jampel syndrome › Schwartz-Jampel syndrome type 1

Related subtypes (1): Stüve-Wiedemann syndrome 1

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

121 retrieved; paginated sample, class counts are floors:

66 uncertain significance, 18 conflicting classifications of pathogenicity, 13 likely pathogenic, 8 pathogenic, 7 benign/likely benign, 6 benign, 3 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1323078	NM_005529.7(HSPG2):c.9033_9034del (p.Pro3011_Ser3012insTer)	HSPG2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
14917	NM_005529.7(HSPG2):c.8464+4A>G	HSPG2	Pathogenic	no assertion criteria provided
14918	NM_005529.7(HSPG2):c.4595G>A (p.Cys1532Tyr)	HSPG2	Pathogenic	no assertion criteria provided
14922	NM_005529.7(HSPG2):c.7294+4A>G	HSPG2	Pathogenic	no assertion criteria provided
14923	HSPG2, EX60/61 FUSION	HSPG2	Pathogenic	no assertion criteria provided
14924	NM_005529.7(HSPG2):c.8464G>A (p.Ala2822Thr)	HSPG2	Pathogenic	no assertion criteria provided
14925	NM_005529.7(HSPG2):c.8759-3_8764del	HSPG2	Pathogenic	no assertion criteria provided
14926	NC_000001.11:g.21816592_21823699del	HSPG2	Pathogenic	no assertion criteria provided
265454	NM_005529.7(HSPG2):c.7006+1G>A	HSPG2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3376981	NM_005529.7(HSPG2):c.3994C>T (p.Gln1332Ter)	HSPG2	Pathogenic	criteria provided, single submitter
447538	NM_005529.7(HSPG2):c.1219dup (p.Gln407fs)	HSPG2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1029973	NM_005529.7(HSPG2):c.9958T>C (p.Cys3320Arg)	HSPG2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1683425	NM_005529.7(HSPG2):c.4955+1G>C	HSPG2	Likely pathogenic	criteria provided, single submitter
2444121	NM_005529.7(HSPG2):c.1219del (p.Gln407fs)	HSPG2	Likely pathogenic	criteria provided, single submitter
2506375	NM_005529.7(HSPG2):c.5296G>A (p.Ala1766Thr)	HSPG2	Likely pathogenic	criteria provided, single submitter
2627153	NM_005529.7(HSPG2):c.12900-2A>G	HSPG2	Likely pathogenic	criteria provided, single submitter
2663848	NM_005529.7(HSPG2):c.1030T>C (p.Cys344Arg)	HSPG2	Likely pathogenic	criteria provided, single submitter
3381885	NM_005529.7(HSPG2):c.8025+1G>A	HSPG2	Likely pathogenic	criteria provided, single submitter
3600345	NM_005529.7(HSPG2):c.5112del (p.His1706fs)	HSPG2	Likely pathogenic	criteria provided, single submitter
3896882	NM_005529.7(HSPG2):c.6288+1G>A	HSPG2	Likely pathogenic	criteria provided, single submitter
4081448	NM_005529.7(HSPG2):c.5015-1G>A	HSPG2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4280629	NM_005529.7(HSPG2):c.9052+4A>G	HSPG2	Likely pathogenic	criteria provided, single submitter
982057	NM_005529.7(HSPG2):c.9970G>A (p.Gly3324Arg)	HSPG2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2506374	NM_005529.7(HSPG2):c.13163_13164del (p.Pro4388fs)	LDLRAD2	Likely pathogenic	criteria provided, single submitter
1051273	NM_005529.7(HSPG2):c.11751G>A (p.Ser3917=)	HSPG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1400608	NM_005529.7(HSPG2):c.6161A>G (p.Lys2054Arg)	HSPG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1444590	NM_005529.7(HSPG2):c.5273G>A (p.Arg1758Gln)	HSPG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
295739	NM_005529.7(HSPG2):c.10280G>A (p.Arg3427Gln)	HSPG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
295756	NM_005529.7(HSPG2):c.9564G>C (p.Gln3188His)	HSPG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
295802	NM_005529.7(HSPG2):c.6966G>T (p.Thr2322=)	HSPG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 11 · 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
HSPG2	Definitive	Autosomal recessive	Schwartz-Jampel syndrome type 1	10

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
GNA11	Orphanet:101049	Familial hypocalciuric hypercalcemia type 2
GNA11	Orphanet:1556	Cutis marmorata telangiectatica congenita
GNA11	Orphanet:39044	Uveal melanoma
GNA11	Orphanet:428	Autosomal dominant hypocalcemia
GNA11	Orphanet:675359	Anastomosing haemangioma
GNA11	Orphanet:714737	Diffuse capillary malformation with overgrowth
GNA11	Orphanet:79483	Phakomatosis cesioflammea
GNA11	Orphanet:79484	Phakomatosis cesiomarmorata

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
HSPG2	HGNC:5273	ENSG00000142798	P98160	Basement membrane-specific heparan sulfate proteoglycan core protein	gencc,clinvar
LDLRAD2	HGNC:32071	ENSG00000187942	Q5SZI1	Low-density lipoprotein receptor class A domain-containing protein 2	clinvar
GNA11	HGNC:4379	ENSG00000088256	P29992	Guanine nucleotide-binding protein subunit alpha-11	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.
GNA11	Guanine nucleotide-binding protein subunit alpha-11	Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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	9.7×	0.199
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HSPG2	Antibody/Immunoglobulin	yes		Laminin_IV, SEA_dom, EGF
LDLRAD2	Other/Unknown	no		LDrepeatLR_classA_rpt, Sperma_CUB_dom_sf, LDL_receptor-like_sf
GNA11	Other/Unknown	no		Gprotein_alpha_Q, Gprotein_alpha_su, GproteinA_insert

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
popliteal artery	2
tibial artery	2
saphenous vein	1
sural nerve	1
ileal mucosa	1
jejunal mucosa	1
pancreatic ductal cell	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
LDLRAD2	132		marker	sural nerve, popliteal artery, tibial artery
GNA11	299	ubiquitous	marker	ileal mucosa, jejunal mucosa, pancreatic ductal cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HSPG2	2,463
GNA11	1,873
LDLRAD2	196

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GNA11	P29992	13
HSPG2	P98160	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LDLRAD2	Q5SZI1	79.62

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 35. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion	1	713.8×	0.010	GNA11
Acetylcholine regulates insulin secretion	1	571.0×	0.010	GNA11
Defective EXT2 causes exostoses 2	1	407.9×	0.010	HSPG2
Defective EXT1 causes exostoses 1, TRPS2 and CHDS	1	407.9×	0.010	HSPG2
Mechanical load activates signaling by PIEZO1 and integrins in osteocytes	1	335.9×	0.010	HSPG2
Attachment and Entry	1	300.5×	0.010	HSPG2
Defective B4GALT7 causes EDS, progeroid type	1	285.5×	0.010	HSPG2
Defective B3GAT3 causes JDSSDHD	1	285.5×	0.010	HSPG2
Defective B3GALT6 causes EDSP2 and SEMDJL1	1	285.5×	0.010	HSPG2
HS-GAG degradation	1	248.3×	0.010	HSPG2
Respiratory syncytial virus (RSV) attachment and entry	1	248.3×	0.010	HSPG2
G-protein activation	1	237.9×	0.010	GNA11
Thromboxane signalling through TP receptor	1	237.9×	0.010	GNA11
Initiation of coagulation cascade	1	237.9×	0.010	HSPG2
ADP signalling through P2Y purinoceptor 1	1	228.4×	0.010	GNA11
Glycosaminoglycan-protein linkage region biosynthesis	1	196.9×	0.010	HSPG2
Laminin interactions	1	190.3×	0.010	HSPG2
Thrombin signalling through proteinase activated receptors (PARs)	1	178.4×	0.010	GNA11
Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells	1	178.4×	0.010	GNA11
HS-GAG biosynthesis	1	173.0×	0.010	HSPG2
Formation of the dystrophin-glycoprotein complex (DGC)	1	154.3×	0.011	HSPG2
Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding	1	150.3×	0.011	GNA11
PLC beta mediated events	1	132.8×	0.011	GNA11
Dengue Virus Attachment and Entry	1	129.8×	0.011	HSPG2
Retinoid metabolism and transport	1	124.1×	0.011	HSPG2
Regulation of clotting cascade	1	116.5×	0.012	HSPG2
High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells	1	80.4×	0.015	GNA11
RSV-host interactions	1	78.2×	0.015	HSPG2
Non-integrin membrane-ECM interactions	1	77.2×	0.015	HSPG2
ECM proteoglycans	1	75.1×	0.015	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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of melanocyte differentiation	1	8426.0×	0.004	GNA11
negative regulation of synaptic transmission, cholinergic	1	2808.7×	0.005	HSPG2
entrainment of circadian clock	1	1404.3×	0.005	GNA11
phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway	1	1053.2×	0.005	GNA11
developmental pigmentation	1	1053.2×	0.005	GNA11
phospholipase C-activating dopamine receptor signaling pathway	1	1053.2×	0.005	GNA11
cellular response to pH	1	1053.2×	0.005	GNA11
ligand-gated ion channel signaling pathway	1	936.2×	0.005	GNA11
endothelin receptor signaling pathway	1	842.6×	0.005	GNA11
circulatory system development	1	702.2×	0.005	HSPG2
phototransduction, visible light	1	648.1×	0.005	GNA11
G protein-coupled acetylcholine receptor signaling pathway	1	526.6×	0.006	GNA11
cranial skeletal system development	1	468.1×	0.006	GNA11
protein localization to synapse	1	383.0×	0.007	HSPG2
animal organ regeneration	1	300.9×	0.008	HSPG2
negative regulation of cell adhesion	1	191.5×	0.012	HSPG2
action potential	1	179.3×	0.012	GNA11
embryo implantation	1	175.5×	0.012	HSPG2
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1	168.5×	0.012	GNA11
positive regulation of insulin secretion	1	127.7×	0.014	GNA11
positive regulation of endothelial cell proliferation	1	115.4×	0.014	HSPG2
receptor-mediated endocytosis	1	110.9×	0.014	HSPG2
regulation of blood pressure	1	110.9×	0.014	GNA11
smoothened signaling pathway	1	90.6×	0.017	HSPG2
negative regulation of angiogenesis	1	84.3×	0.018	HSPG2
phospholipase C-activating G protein-coupled receptor signaling pathway	1	65.8×	0.022	GNA11
skeletal system development	1	62.9×	0.022	GNA11
response to hypoxia	1	47.9×	0.027	HSPG2
lipid metabolic process	1	45.8×	0.028	HSPG2
brain development	1	39.8×	0.030	HSPG2

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 3 evidence-associated genes (67%) 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
LDLRAD2	0	0
GNA11	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
GNA11	18	Binding:18
HSPG2	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	2	LDLRAD2, GNA11

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
HSPG2	2	—
LDLRAD2	0	—
GNA11	18	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.