CSPG4

chondroitin sulfate proteoglycan 4, the group of Proteoglycans

Basic information

Region (hg38): 15:75674321-75712848

Links

ENSG00000173546 ∙ NCBI:1464 ∙ OMIM:601172 ∙ HGNC:2466 ∙ Uniprot:Q6UVK1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• schizophrenia (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CSPG4 gene.

• Inborn genetic diseases (127 variants)
• not provided (20 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CSPG4 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				9	2	11
missense			125	9	2	136
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	0	125	19	4

Variants in CSPG4

This is a list of pathogenic ClinVar variants found in the CSPG4 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-75675558-A-G		not specified	Uncertain significance (Mar 01, 2023)
15-75675593-C-T		not specified	Uncertain significance (Dec 28, 2022)
15-75675684-C-T		not specified	Uncertain significance (Dec 14, 2021)
15-75675702-C-T		not specified	Uncertain significance (Jun 27, 2023)
15-75675720-C-G		not specified	Uncertain significance (May 05, 2022)
15-75675737-G-T			Likely benign (Jun 19, 2018)
15-75675897-C-T		not specified	Likely benign (Sep 20, 2023)
15-75675972-G-A		not specified	Uncertain significance (Feb 14, 2024)
15-75675981-C-T		not specified	Uncertain significance (Jan 04, 2022)
15-75676004-C-T		not specified	Uncertain significance (Oct 12, 2022)
15-75676014-G-A		not specified	Uncertain significance (Jun 22, 2021)
15-75676068-C-T		not specified	Uncertain significance (Aug 18, 2021)
15-75676116-G-A		not specified	Uncertain significance (Mar 07, 2024)
15-75676148-C-G		not specified	Uncertain significance (Feb 09, 2023)
15-75676190-A-G		not specified	Uncertain significance (Nov 08, 2022)
15-75676233-G-A		not specified	Uncertain significance (Dec 07, 2023)
15-75676286-C-T		not specified	Uncertain significance (Jan 03, 2022)
15-75676292-C-T		not specified	Uncertain significance (Apr 28, 2022)
15-75676580-C-T			Likely benign (Aug 01, 2022)
15-75676619-C-T		not specified	Likely benign (Dec 07, 2022)
15-75676646-C-T		not specified	Uncertain significance (Aug 02, 2022)
15-75676800-C-T		not specified	Uncertain significance (Feb 15, 2023)
15-75676812-G-A		not specified	Uncertain significance (Jul 26, 2023)
15-75676844-G-C		not specified	Uncertain significance (Jan 23, 2024)
15-75676854-C-G		not specified	Uncertain significance (Nov 17, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CSPG4	protein_coding	protein_coding	ENST00000308508	10	38527

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000262	1.00	125654	0	90	125744	0.000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.41	1244	1.39e+3	0.894	0.0000903	14643
Missense in Polyphen		289	369.89	0.78131		4294
Synonymous	0.651	614	635	0.967	0.0000423	5264
Loss of Function	5.13	21	65.9	0.318	0.00000364	646

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00110	0.00109
Ashkenazi Jewish	0.000101	0.0000992
East Asian	0.000491	0.000435
Finnish	0.000239	0.000231
European (Non-Finnish)	0.000369	0.000360
Middle Eastern	0.000491	0.000435
South Asian	0.000294	0.000294
Other	0.000330	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Proteoglycan playing a role in cell proliferation and migration which stimulates endothelial cells motility during microvascular morphogenesis. May also inhibit neurite outgrowth and growth cone collapse during axon regeneration. Cell surface receptor for collagen alpha 2(VI) which may confer cells ability to migrate on that substrate. Binds through its extracellular N- terminus growth factors, extracellular matrix proteases modulating their activity. May regulate MPP16-dependent degradation and invasion of type I collagen participating in melanoma cells invasion properties. May modulate the plasminogen system by enhancing plasminogen activation and inhibiting angiostatin. Functions also as a signal transducing protein by binding through its cytoplasmic C-terminus scaffolding and signaling proteins. May promote retraction fiber formation and cell polarization through Rho GTPase activation. May stimulate alpha-4, beta-1 integrin- mediated adhesion and spreading by recruiting and activating a signaling cascade through CDC42, ACK1 and BCAR1. May activate FAK and ERK1/ERK2 signaling cascades. {ECO:0000269|PubMed:10587647, ECO:0000269|PubMed:11278606, ECO:0000269|PubMed:15210734}.
• Pathway: Spinal Cord Injury;Metabolism of carbohydrates;A tetrasaccharide linker sequence is required for GAG synthesis;Heparan sulfate/heparin (HS-GAG) metabolism;Chondroitin sulfate biosynthesis;Dermatan sulfate biosynthesis;Chondroitin sulfate/dermatan sulfate metabolism;Glycosaminoglycan metabolism;Metabolism;Beta1 integrin cell surface interactions (Consensus)

Recessive Scores

• pRec: 0.142

Intolerance Scores

• loftool: 0.654
• rvis_EVS: 0.35
• rvis_percentile_EVS: 73.79

Haploinsufficiency Scores

• pHI: 0.143
• hipred: Y
• hipred_score: 0.595
• ghis: 0.497

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.619

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cspg4
• Phenotype: hearing/vestibular/ear 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); immune system phenotype; liver/biliary system phenotype; hematopoietic system phenotype; normal phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: activation of MAPK activity;angiogenesis;transmembrane receptor protein tyrosine kinase signaling pathway;cell population proliferation;glial cell migration;chondroitin sulfate biosynthetic process;chondroitin sulfate catabolic process;dermatan sulfate biosynthetic process;intracellular signal transduction;tissue remodeling;positive regulation of peptidyl-tyrosine phosphorylation
• Cellular component: extracellular region;Golgi lumen;integral component of plasma membrane;focal adhesion;cell surface;apical plasma membrane;lamellipodium membrane;lysosomal lumen;collagen-containing extracellular matrix;extracellular exosome
• Molecular function: protein kinase binding