HSPG2

heparan sulfate proteoglycan 2, the group of Proteoglycans|I-set domain containing

Basic information

Region (hg38): 1:21822243-21937310

Previous symbols: [ "SJS1" ]

Links

ENSG00000142798 ∙ NCBI:3339 ∙ OMIM:142461 ∙ HGNC:5273 ∙ Uniprot:P98160 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Silverman-Handmaker type dyssegmental dysplasia (Definitive), mode of inheritance: AR
• Schwartz-Jampel syndrome (Supportive), mode of inheritance: AR
• Silverman-Handmaker type dyssegmental dysplasia (Supportive), mode of inheritance: AR
• Schwartz-Jampel syndrome type 1 (Definitive), mode of inheritance: AR
• Silverman-Handmaker type dyssegmental dysplasia (Strong), mode of inheritance: AR
• Schwartz-Jampel syndrome type 1 (Strong), mode of inheritance: AR
• Schwartz-Jampel syndrome type 1 (Definitive), mode of inheritance: AR
• Silverman-Handmaker type dyssegmental dysplasia (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Schwartz-Jampel syndrome, type 1	AD/AR	General; Pharmacogenomic	An increased risk of malignant hyperthermia has been described; Variants may have additional pharmacogenomic importance (eg, related to tardive dyskinesia); Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal	13909723; 4953364; 11101850; 11038441; 11279527; 11941538; 16927315; 20072119; 20542149; 21808285

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HSPG2 gene.

• not provided (2157 variants)
• Lethal Kniest-like syndrome (502 variants)
• Schwartz-Jampel syndrome (498 variants)
• Inborn genetic diseases (319 variants)
• not specified (157 variants)
• Connective tissue disorder (101 variants)
• Schwartz-Jampel syndrome type 1 (25 variants)
• Lethal Kniest-like syndrome;Schwartz-Jampel syndrome type 1 (18 variants)
• HSPG2-related condition (13 variants)
• Schwartz-Jampel syndrome type 1;Lethal Kniest-like syndrome (11 variants)
• Lethal Kniest-like syndrome;Schwartz-Jampel syndrome (6 variants)
• Microcephaly (4 variants)
• Schwartz-Jampel syndrome;Lethal Kniest-like syndrome (2 variants)
• HSPG2-Related Disorders (2 variants)
• HSPG2-realted disorder (2 variants)
• See cases (2 variants)
• Abnormal facial shape (2 variants)
• Qualitative or quantitative defects of perlecan (1 variants)
• Reduced muscle fiber perlecan (1 variants)
• Childhood-onset schizophrenia (1 variants)
• Stuve-Wiedemann syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HSPG2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			59	405	36	500
missense	1	5	1084	53	24	1167
nonsense	11	6				17
start loss			1			1
frameshift	14	6	1			21
inframe indel			6			6
splice donor/acceptor (+/-2bp)	3	14	2	1		20
splice region		3	53	63	10	129
non coding			47	239	168	454
Total	29	31	1200	698	228

Highest pathogenic variant AF is 0.0000657

Variants in HSPG2

This is a list of pathogenic ClinVar variants found in the HSPG2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-21822248-G-A		Schwartz-Jampel syndrome • Lethal Kniest-like syndrome	Uncertain significance (Jan 13, 2018)
1-21822298-T-G		Lethal Kniest-like syndrome • Schwartz-Jampel syndrome	Likely benign (Jan 12, 2018)
1-21822324-G-A		Schwartz-Jampel syndrome • Lethal Kniest-like syndrome	Benign (Jan 12, 2018)
1-21822381-G-C		Schwartz-Jampel syndrome • Lethal Kniest-like syndrome	Uncertain significance (Jan 13, 2018)
1-21822412-C-T		Schwartz-Jampel syndrome • Lethal Kniest-like syndrome	Uncertain significance (Jan 13, 2018)
1-21822491-C-G		Schwartz-Jampel syndrome • Lethal Kniest-like syndrome	Likely benign (Jan 12, 2018)
1-21822492-G-A		Schwartz-Jampel syndrome • Lethal Kniest-like syndrome	Uncertain significance (Jan 12, 2018)
1-21822499-C-T		Schwartz-Jampel syndrome • Lethal Kniest-like syndrome	Uncertain significance (Jan 13, 2018)
1-21822580-G-A		Schwartz-Jampel syndrome • Lethal Kniest-like syndrome	Benign (Jan 13, 2018)
1-21822635-G-A		Lethal Kniest-like syndrome • Schwartz-Jampel syndrome	Uncertain significance (Jan 13, 2018)
1-21822666-C-T		Lethal Kniest-like syndrome • Schwartz-Jampel syndrome	Uncertain significance (Jan 13, 2018)
1-21822690-G-C		Schwartz-Jampel syndrome • Lethal Kniest-like syndrome	Benign (Jan 13, 2018)
1-21822693-G-C		Lethal Kniest-like syndrome • Schwartz-Jampel syndrome	Likely benign (Jan 12, 2018)
1-21822717-T-G		Schwartz-Jampel syndrome • Lethal Kniest-like syndrome	Uncertain significance (Jan 13, 2018)
1-21822723-G-A		Lethal Kniest-like syndrome • Schwartz-Jampel syndrome	Likely benign (Jan 12, 2018)
1-21822766-T-C		Schwartz-Jampel syndrome • Lethal Kniest-like syndrome	Uncertain significance (Jan 13, 2018)
1-21822787-G-A		Lethal Kniest-like syndrome • Schwartz-Jampel syndrome	Uncertain significance (Jan 12, 2018)
1-21822886-C-T		Schwartz-Jampel syndrome • Lethal Kniest-like syndrome	Benign (Jan 13, 2018)
1-21822917-G-T		Schwartz-Jampel syndrome • Lethal Kniest-like syndrome	Uncertain significance (Jan 13, 2018)
1-21822925-C-T		Lethal Kniest-like syndrome • Schwartz-Jampel syndrome	Likely benign (Jan 13, 2018)
1-21822977-G-T		Lethal Kniest-like syndrome • Schwartz-Jampel syndrome	Uncertain significance (Jan 12, 2018)
1-21823012-C-T		Lethal Kniest-like syndrome • Schwartz-Jampel syndrome	Uncertain significance (Jan 13, 2018)
1-21823098-C-T		Schwartz-Jampel syndrome • Lethal Kniest-like syndrome	Uncertain significance (Jan 13, 2018)
1-21823108-C-G		Lethal Kniest-like syndrome • Schwartz-Jampel syndrome	Uncertain significance (Jan 12, 2018)
1-21823213-C-T		Schwartz-Jampel syndrome • Lethal Kniest-like syndrome	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HSPG2	protein_coding	protein_coding	ENST00000374695	97	115053

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.04e-19	1.00	125592	0	156	125748	0.000620

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.14	2571	2.74e+3	0.939	0.000197	27883
Missense in Polyphen		954	1108.8	0.86041		11675
Synonymous	-1.39	1249	1.19e+3	1.05	0.0000935	9231
Loss of Function	9.23	78	229	0.341	0.0000126	2387

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00177	0.00174
Ashkenazi Jewish	0.000204	0.000198
East Asian	0.000607	0.000598
Finnish	0.000326	0.000323
European (Non-Finnish)	0.000588	0.000571
Middle Eastern	0.000607	0.000598
South Asian	0.000743	0.000719
Other	0.000667	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Integral component of basement membranes. Component of the glomerular basement membrane (GBM), responsible for the fixed negative electrostatic membrane charge, and which provides a barrier which is both size- and charge-selective. It serves as an attachment substrate for cells. Plays essential roles in vascularization. Critical for normal heart development and for regulating the vascular response to injury. Also required for avascular cartilage development.; FUNCTION: The LG3 peptide has anti-angiogenic properties that require binding of calcium ions for full activity.
• Disease: DISEASE: Schwartz-Jampel syndrome (SJS1) [MIM:255800]: Rare autosomal recessive disorder characterized by permanent myotonia (prolonged failure of muscle relaxation) and skeletal dysplasia, resulting in reduced stature, kyphoscoliosis, bowing of the diaphyses and irregular epiphyses. {ECO:0000269|PubMed:11101850}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Dyssegmental dysplasia Silverman-Handmaker type (DDSH) [MIM:224410]: The dyssegmental dysplasias are rare, autosomal recessive skeletal dysplasias with anisospondyly and micromelia. There are two recognized types: the severe, lethal DDSH and the milder Rolland-Desbuquois form. Individuals with DDSH also have a flat face, micrognathia, cleft palate and reduced joint mobility, and frequently have an encephalocoele. The endochondral growth plate is short, the calcospherites (which are spherical calcium- phosphorus crystals produced by hypertrophic chondrocytes) are unfused, and there is mucoid degeneration of the resting cartilage. {ECO:0000269|PubMed:11279527}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: ECM-receptor interaction - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Signaling by GPCR;Signal Transduction;Metabolism of fat-soluble vitamins;Metabolism of carbohydrates;A tetrasaccharide linker sequence is required for GAG synthesis;HS-GAG biosynthesis;HS-GAG degradation;Heparan sulfate/heparin (HS-GAG) metabolism;Integrin cell surface interactions;Chondroitin sulfate/dermatan sulfate metabolism;Glycosaminoglycan metabolism;Laminin interactions;Metabolism of proteins;Extracellular matrix organization;Metabolism;Amyloid fiber formation;Metabolism of vitamins and cofactors;Integrin;Degradation of the extracellular matrix;Retinoid metabolism and transport;Non-integrin membrane-ECM interactions;G alpha (i) signalling events;Visual phototransduction;ECM proteoglycans;GPCR downstream signalling;Wnt Canonical;Wnt Mammals (Consensus)

Recessive Scores

• pRec: 0.695

Intolerance Scores

• loftool: 0.588
• rvis_EVS: -0.31
• rvis_percentile_EVS: 32.07

Haploinsufficiency Scores

• pHI: 0.830
• hipred: Y
• hipred_score: 0.595
• ghis: 0.589

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.854

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Hspg2
• Phenotype: growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); craniofacial phenotype; muscle phenotype; homeostasis/metabolism phenotype; immune system phenotype; cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; embryo phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); vision/eye phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; skeleton phenotype

Zebrafish Information Network

• Gene name: hspg2
• Affected structure: blood vessel
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: retinoid metabolic process;angiogenesis;glycosaminoglycan biosynthetic process;glycosaminoglycan catabolic process;lipid metabolic process;receptor-mediated endocytosis;inflammatory response;brain development;negative regulation of angiogenesis;cell differentiation;extracellular matrix organization;cellular protein metabolic process;cardiovascular system development
• Cellular component: extracellular region;basement membrane;extracellular space;Golgi lumen;plasma membrane;focal adhesion;lysosomal lumen;collagen-containing extracellular matrix;extracellular exosome;plasma membrane protein complex
• Molecular function: amyloid-beta binding;calcium ion binding;protein binding;protein C-terminus binding;extracellular matrix structural constituent conferring compression resistance;low-density lipoprotein particle receptor binding