CSPG4

protein-coding

chondroitin sulfate proteoglycan 4, the group of Proteoglycans

Gene summary

A human melanoma-associated chondroitin sulfate proteoglycan plays a role in stabilizing cell-substratum interactions during early events of melanoma cell spreading on endothelial basement membranes. CSPG4 represents an integral membrane chondroitin sulfate proteoglycan expressed by human malignant melanoma cells. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001897.5

Inheritance

ClinVar variants

U:392B:48

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.32

Max pathogenic AF

—

Genomic locus

chr15:75,674,322-75,712,848

External References & Databases

Ensembl (ENSG00000173546)

Transcript & Mutation Effects

hg38 • Region Span ~38.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

schizophreniaLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005090

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CSPG4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 404

not providedTotal: 27

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001897.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	10 clinvar	2 clinvar	15
missense			384 clinvar	34 clinvar	2 clinvar	420
nonsense			2 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	392	44	4	440

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001897.5	RefSeq	NP_001888.2	10	MANE Select
ENST00000308508.5	Ensembl	ENSP00000312506.5	10	MANE Select
ENST00000900311.1	Ensembl	ENSP00000570370.1	9	Standard
ENST00000900311.2	Ensembl	ENSP00000570370.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Spinal Cord Injury
Metabolism of carbohydrates
A tetrasaccharide linker sequence is required for GAG synthesis
Heparan sulfate/heparin (HS-GAG) metabolism
Chondroitin sulfate biosynthesis

Biological Process

activation of MAPK activity
angiogenesis
transmembrane receptor protein tyrosine kinase signaling pathway
cell population proliferation
glial cell migration

Molecular Function

protein kinase binding

Cellular Component

extracellular region
Golgi lumen
integral component of plasma membrane
focal adhesion
cell surface

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000308508
Coding exons: 10
Length: 38527
Individuals with no LoFs: 125654
Homozygous LoFs: 0
Heterozygous LoFs: 90
Defined: 125744
p: 0.000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.41	1244	1.39e+3	0.894	0.0000903	14643
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00069	0.00068	rare
Latino/Admixed American	0.00041	0.00038	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00049	0.00044	rare
Finnish	0.00024	0.00023	rare
European (Non-Finnish)	0.00037	0.00036	rare
South Asian	0.00029	0.00029	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.142

Intolerance Scores

LoFtool: 0.654
RVIS EVS: 0.35
RVIS percentile EVS: 73.79

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.619

Gene Damage Prediction

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