CSPG4

Summary

CSPG4 (chondroitin sulfate proteoglycan 4, HGNC:2466) is a protein-coding gene on chromosome 15q24.2, encoding Chondroitin sulfate proteoglycan 4 (Q6UVK1). Proteoglycan playing a role in cell proliferation and migration which stimulates endothelial cells motility during microvascular morphogenesis.

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.

Source: NCBI Gene 1464 — RefSeq curated summary.

At a glance

• Gene–disease (curated): schizophrenia (Limited, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 443 total — 1 pathogenic
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• MANE Select transcript: NM_001897

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2466
Approved symbol	CSPG4
Name	chondroitin sulfate proteoglycan 4
Location	15q24.2
Locus type	gene with protein product
Status	Approved
Aliases	MCSPG, MEL-CSPG, MSK16, NG2, MCSP, HMW-MAA, CSPG4A
Ensembl gene	ENSG00000173546
Ensembl biotype	protein_coding
OMIM	601172
Entrez	1464

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000308508, ENST00000900311, ENST00000941445

RefSeq mRNA: 1 — MANE Select: NM_001897 NM_001897

CCDS: CCDS10284

Canonical transcript exons

ENST00000308508 — 10 exons

Exon	Start	End
ENSE00001208330	75677703	75677886
ENSE00001208333	75682293	75682459
ENSE00001208338	75682607	75682741
ENSE00001208357	75685219	75685701
ENSE00001208364	75687276	75690812
ENSE00001290681	75684736	75684912
ENSE00001302009	75712668	75712848
ENSE00001329270	75674322	75677384
ENSE00002436140	75693070	75693233
ENSE00002471306	75682843	75683041

Expression profiles

Bgee: expression breadth ubiquitous, 200 present calls, max score 98.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.3115 / max 353.4353, expressed in 1065 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151000	14.5903	1040
150999	1.7211	651

Top tissues by expression

279 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	98.19	gold quality
cartilage tissue	UBERON:0002418	97.85	gold quality
tibia	UBERON:0000979	97.00	gold quality
popliteal artery	UBERON:0002250	96.98	gold quality
tibial artery	UBERON:0007610	96.98	gold quality
aorta	UBERON:0000947	96.37	gold quality
right coronary artery	UBERON:0001625	96.16	gold quality
descending thoracic aorta	UBERON:0002345	95.95	gold quality
thoracic aorta	UBERON:0001515	95.69	gold quality
ascending aorta	UBERON:0001496	95.68	gold quality
left coronary artery	UBERON:0001626	94.20	gold quality
coronary artery	UBERON:0001621	94.14	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.73	gold quality
lower esophagus	UBERON:0013473	93.66	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.02	gold quality
muscle layer of sigmoid colon	UBERON:0035805	92.35	gold quality
blood vessel layer	UBERON:0004797	90.28	gold quality
periodontal ligament	UBERON:0008266	90.27	gold quality
sural nerve	UBERON:0015488	89.93	gold quality
mucosa of stomach	UBERON:0001199	89.83	gold quality
right lung	UBERON:0002167	89.01	gold quality
gastrocnemius	UBERON:0001388	87.44	gold quality
hair follicle	UBERON:0002073	87.39	silver quality
tibial nerve	UBERON:0001323	87.33	gold quality
body of uterus	UBERON:0009853	87.09	gold quality
stromal cell of endometrium	CL:0002255	86.95	gold quality
saphenous vein	UBERON:0007318	86.83	gold quality
subcutaneous adipose tissue	UBERON:0002190	86.03	gold quality
sigmoid colon	UBERON:0001159	85.76	gold quality
muscle of leg	UBERON:0001383	85.70	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	27.24
E-ANND-3	yes	5.28
E-ENAD-20	no	450.03

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1

miRNA regulators (miRDB)

33 targeting CSPG4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-4724-5P	98.87	67.75	1324
HSA-MIR-331-3P	98.76	64.91	793
HSA-MIR-4763-5P	98.75	63.89	854
HSA-MIR-7113-3P	98.75	65.71	1120
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-5047	98.64	68.62	1035
HSA-MIR-1301-3P	98.64	68.27	1071
HSA-MIR-4463	98.56	66.05	1071
HSA-MIR-532-5P	98.43	67.53	760
HSA-MIR-3179	98.22	65.90	1445
HSA-MIR-6867-3P	98.12	66.07	1305
HSA-MIR-4469	97.93	65.81	1319
HSA-MIR-4660	97.79	67.44	1328
HSA-MIR-4287	97.55	67.24	1247
HSA-MIR-4685-3P	97.55	67.35	1255
HSA-MIR-939-5P	97.10	65.80	1579

Literature-anchored findings (GeneRIF, showing 40)

• identified a novel repeat named CSPG in the central ectodomain (PMID:12220645)
• Data suggest that MCSP is a novel marker for epidermal stem cells that contributes to their patterned distribution by promoting stem cell clustering. (PMID:14573520)
• MCSP coexpression with a subset of beta 1 integrin basal keratinocytes within the epidermis suggests that MCSP colocalizes with epidermal stem cells, MSCP expression within the hair follicle was more complex (PMID:15009727)
• MCSP may facilitate primary melanoma progression by enhancing the activation of key signaling pathways important for tumor invasion and growth. (PMID:15210734)
• PKC-alpha-mediated NG2 phosphorylation at Thr(2256) is a key step for initiating cell polarization and motility (PMID:15504744)
• MCSP/NG2 proteoglycan may be considered an important receptor mediating COL6-sarcolemma interactions, a relationship that is disrupted by the pathogenesis of UCMD muscle. (PMID:16169245)
• tumour cells can regulate both the function and structure of the host-derived tumour vasculature through NG2 expression (PMID:16253523)
• Co-expression and interaction of NG2 and galectin-3 in human glioma cells establish a molecular basis for the NG2/galectin-3 interaction. (PMID:16365873)
• dendritic cell-based immunization represents an effective strategy to implement T cell-based immunotherapy targeting high molecular weight-melanoma-associated antigen (HMW-MAA) in patients with HMW-MAA-bearing tumors [HMW-MAA] (PMID:16455987)
• NG2 is abundantly distributed in the intestinal subepithelial myofibroblasts layer of the mouse and human intestines. (PMID:16625365)
• Colocalization of chondroitin sulfate proteoglycan 4 (NG2) with type VI collagen in the pericellular area suggests that NG2 may play an important role in cell-matrix interactions. (PMID:17268261)
• Differential phosphorylation of NG2 proteoglycan by ERK and PKCA helps balance cell proliferation and cell movement. (PMID:17591920)
• NG2 expression was uniformly positive on a cell line derived from angiomyolipoma. (PMID:17592550)
• NG2 antigen diagnosis of MLL rearrangements in pediatric patients (PMID:17851550)
• Data show that NG2 and integrin alpha4 oppositely regulate anoikis in fibroblasts, and that NG2 and integrin alpha4 regulate FAK phosphorylation by PKCalpha-dependent and -independent pathways, respectively. (PMID:18292781)
• High NG2/MPG expression correlated with multidrug resistance mediated by increased activation of alpha3beta1 integrin/PI3K signaling and their downstream targets, promoting cell survival (PMID:18469852)
• High molecular weight-melanoma-associated antigen is more sensitive and specific than MART-1, S-100p, and HMB-45 for immunohistochemistry-based detection of malignant melanoma sentinel lymph nodes micrometastases (PMID:18519770)
• NG2 has a role in metastasis formation in soft-tissue sarcoma patients (PMID:18634019)
• the coexpression of KOR-SA35443 (kappa opioid receptor) and NG2 (chondroitin sulfate proteoglycan) in result of karyotype abnormal changes may predict a poor prognosis in Pro-B acute lymphoblastic leukemia (PMID:18767415)
• A Lm-based vaccine against HMW-MAA can trigger cell-mediated immune responses to this antigen that can target not only tumor cells but also pericytes in the tumor vasculature. (PMID:18829565)
• NG2 expression on culture-expanded mesenchymal stromal cells was investigated by flow cytometry. (PMID:19462316)
• NG2 was present in the evolving astroglial scar after human traumatic spinal cord injury, and, therefore, might play an important role in the blockade of successful CNS regeneration. (PMID:19604403)
• Human skin aging is associated with reduced expression of the stem cell markers beta1 integrin and MCSP (PMID:19776755)
• Staining intensity of HMW-MAA in acral lentiginous melanoma lesions was weaker than in superficial spreading melanoma where it was found to be higher than previously reported. (PMID:20448346)
• in squamous cell carcinoma of head and neck and in basal breast carcinoma, CSPG4 is expressed by cancer stem cells (PMID:20455858)
• Results showed the expression of MCSP and PRAME in conjunctival melanoma and benign conjunctival nevi and showed that MCSP and PRAME were differentially expressed in both and can help to differentiate the lesions diagnostically. (PMID:20805128)
• Functional and clinical relevance of chondroitin sulfate proteoglycan 4. (PMID:21070915)
• In regions of spinal cord neurodegeneration of amyotrophic lateral sclerosis model mice, NG2-positive cells exhibit enhanced proliferation and accelerated differentiation into oligodendrocytes but remained committed to the oligodendrocyte lineage. (PMID:21092857)
• Cells that express NG2 proteoglycan act predominantly as a reservoir of new oligodendrocytes in the demyelinated spinal cord. (PMID:21123584)
• Cell surface P-selectin binding depends on CHST11 gene expression. CSPG4 serves as a P-selectin ligand through its CS chain and participates in P-selectin binding to the highly metastatic breast cancer cells. (PMID:21658254)
• High NG2 expression is associated with glioblastoma. (PMID:21798846)
• REVIEW outlines recent advances in our understanding of CSPG4-associated cell signaling, describing the central role it plays in melanoma tumor cell growth, motility, and survival, and explores how modifying CSPG4 function and protein-protein interactions may provide us with novel combinatorial therapies for the treatment of advanced melanoma (PMID:22004131)
• Findings define the CSPG4-specific fully human scFv-FcC21 antibody as a candidate therapeutic agent to target the many types of tumors that express CSPG4. (PMID:22021902)
• NG2 mediates activation of Rho leading to amoeboid invasiveness in sarcoma cell line. (PMID:22699001)
• Although transgenic nestin-GFP-expressing progenitor cells share morphological and molecular markers with NG2-glia, they do not express other pericyte markers nor do they differentiate into the muscle lineage. (PMID:22999866)
• NG2-positive adipose stem cells loaded on scaffolds fabricate skeletal muscle tissue in vivo without the need of a myogenic pre-differentiation step in vitro. (PMID:23359523)
• tThis study demonistrated taht human infants, Western blot analyses exhibited trends for lower NG2 levels in the germinal matrix and white matter of infants with Intraventricular hemorrhage relative to controls without Intraventricular hemorrhage. (PMID:23474192)
• NG2-Col VI interplay as putatively involved in the regulation of the cancer cell-host microenvironment interactions sustaining sarcoma progression (PMID:23559515)
• cell polarity complexes as new effectors of NG2 signaling in the establishment of front-rear polarity (PMID:23804106)
• NG2 knockdown results in loss of beta1 integrin activation in endothelial cells, revealing a mechanism for NG2-dependent cross talk between pericytes and endothelial cells. (PMID:23925489)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cspg4	ENSDARG00000078227
mus_musculus	Cspg4	ENSMUSG00000032911
rattus_norvegicus	Cspg4	ENSRNOG00000017208
drosophila_melanogaster	kon	FBGN0032683
caenorhabditis_elegans	C48E7.6	WBGENE00016751

Protein

Protein identifiers

Chondroitin sulfate proteoglycan 4 — Q6UVK1 (reviewed: Q6UVK1)

Alternative names: Chondroitin sulfate proteoglycan NG2, Melanoma chondroitin sulfate proteoglycan, Melanoma-associated chondroitin sulfate proteoglycan

All UniProt accessions (1): Q6UVK1

UniProt curated annotations — full annotation on UniProt →

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. Also functions 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.

Subunit / interactions. Interacts with the first PDZ domain of MPDZ. Interacts with PRKCA. Binds TNC, laminin-1, COL5A1 and COL6A2. Interacts with PLG and angiostatin. Binds FGF2 and PDGFA. Interacts with GRIP1, GRIP2 and GRIA2. Forms a ternary complex with GRIP1 and GRIA2. Interacts with LGALS3 and the integrin composed of ITGB1 and ITGA3. Interacts with ITGA4 through its chondroitin sulfate glycosaminoglycan. Interacts with BCAR1, CDC42 and ACK1. Interacts with MMP16. (Microbial infection) Interacts with C.difficile toxin TcdB, suggesting that it may act as a receptor for TcdB.

Subcellular location. Cell membrane. Apical cell membrane. Cell projection. Lamellipodium membrane. Cell surface.

Tissue specificity. Detected in fibroblasts (at protein level). Detected in placenta (at protein level). Detected in malignant melanoma cells.

Post-translational modifications. O-glycosylated; contains glycosaminoglycan chondroitin sulfate which are required for proper localization and function in stress fiber formation. Involved in interaction with MMP16 and ITGA4. Phosphorylation by PRKCA regulates its subcellular location and function in cell motility.

Miscellaneous. Valuable marker for several incompletely differentiated precursor cells.

RefSeq proteins (1): NP_001888* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001791	Laminin_G	Domain
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR039005	CSPG_rpt	Repeat
IPR051561	FRAS1_ECM	Family

Pfam: PF02210, PF16184

UniProt features (74 total): glycosylation site 16, repeat 15, sequence conflict 9, strand 9, region of interest 7, helix 4, topological domain 2, disulfide bond 2, domain 2, turn 2, signal peptide 1, chain 1, short sequence motif 1, transmembrane region 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7ML7	ELECTRON MICROSCOPY	3.17
7N8X	ELECTRON MICROSCOPY	3.4
7N9Y	ELECTRON MICROSCOPY	4.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UVK1-F1	75.35	0.07

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 2252

Disulfide bonds (2): 169–192, 354–380

Glycosylation sites (16): 130, 348, 427, 685, 772, 995, 1131, 1202, 1364, 1449, 1645, 1909, 2016, 2034, 2040, 2075

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-1971475	Glycosaminoglycan-protein linkage region biosynthesis
R-HSA-2022870	CS-GAG biosynthesis
R-HSA-2022923	DS-GAG biosynthesis
R-HSA-2024101	CS/DS degradation
R-HSA-3560783	Defective B4GALT7 causes EDS, progeroid type
R-HSA-3560801	Defective B3GAT3 causes JDSSDHD
R-HSA-3595172	Defective CHST3 causes SEDCJD
R-HSA-3595174	Defective CHST14 causes EDS, musculocontractural type
R-HSA-3595177	Defective CHSY1 causes TPBS
R-HSA-4420332	Defective B3GALT6 causes EDSP2 and SEMDJL1
R-HSA-9725554	Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin

MSigDB gene sets: 208 (showing top): GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_PHOSPHORYLATION, MODULE_45, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOCC_CELL_SURFACE, GOBP_NEUROGENESIS, GOCC_RUFFLE, MODULE_70, GOBP_POSITIVE_REGULATION_OF_PEPTIDYL_TYROSINE_PHOSPHORYLATION, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, ONKEN_UVEAL_MELANOMA_UP, ROSS_LEUKEMIA_WITH_MLL_FUSIONS, ROZANOV_MMP14_TARGETS_UP, GOBP_POSITIVE_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, FISCHER_G2_M_CELL_CYCLE

GO Biological Process (11): angiogenesis (GO:0001525), substrate-dependent cell migration (GO:0006929), glial cell migration (GO:0008347), intracellular signal transduction (GO:0035556), positive regulation of MAPK cascade (GO:0043410), platelet-derived growth factor receptor signaling pathway (GO:0048008), tissue remodeling (GO:0048771), positive regulation of peptidyl-tyrosine phosphorylation (GO:0050731), ruffle assembly (GO:0097178), signal transduction (GO:0007165), cell differentiation (GO:0030154)

GO Molecular Function (2): coreceptor activity (GO:0015026), protein kinase binding (GO:0019901)

GO Cellular Component (14): ruffle (GO:0001726), extracellular region (GO:0005576), nucleoplasm (GO:0005654), Golgi lumen (GO:0005796), plasma membrane (GO:0005886), focal adhesion (GO:0005925), cell surface (GO:0009986), apical plasma membrane (GO:0016324), extracellular matrix (GO:0031012), lamellipodium membrane (GO:0031258), lysosomal lumen (GO:0043202), extracellular exosome (GO:0070062), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Diseases associated with glycosaminoglycan metabolism	6
Chondroitin sulfate/dermatan sulfate metabolism	3
Glycosaminoglycan metabolism	1
Developmental Cell Lineages of the Integumentary System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cell migration	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
gliogenesis	1
intracellular anatomical structure	1
signal transduction	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
cell surface receptor protein tyrosine kinase signaling pathway	1
multicellular organismal process	1
positive regulation of protein phosphorylation	1
peptidyl-tyrosine phosphorylation	1
regulation of peptidyl-tyrosine phosphorylation	1
ruffle organization	1
plasma membrane bounded cell projection assembly	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cellular developmental process	1
signaling receptor activity	1
kinase binding	1
cell leading edge	1
plasma membrane bounded cell projection	1
nuclear lumen	1
Golgi apparatus	1
intracellular organelle lumen	1
membrane	1
cell periphery	1
cell-substrate junction	1
apical part of cell	1
plasma membrane region	1
external encapsulating structure	1
lamellipodium	1
cell projection membrane	1
leading edge membrane	1
lysosome	1

Protein interactions and networks

STRING

1880 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CSPG4	OLIG2	Q13516	897
CSPG4	LGALS3	P17931	867
CSPG4	OLIG1	Q8TAK6	820
CSPG4	PDGFRA	P16234	751
CSPG4	PDGFRB	P09619	735
CSPG4	FGF2	P09038	725
CSPG4	MPDZ	O75970	656
CSPG4	PRG4	Q92954	633
CSPG4	NECTIN3	Q9NQS3	626
CSPG4	DCN	P07585	620
CSPG4	FN1	P02751	606
CSPG4	GFAP	P14136	594
CSPG4	PLP1	P04400	594
CSPG4	EGFR	P00533	580
CSPG4	CDH2	P19022	570

IntAct

207 interactions, top by confidence:

A	B	Type	Score
TSPAN15	ADAM10	psi-mi:“MI:0914”(association)	0.840
TSPAN5	ADAM10	psi-mi:“MI:0914”(association)	0.800
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
FBXO6	MAN2B1	psi-mi:“MI:0914”(association)	0.640
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
LGALS3	PODXL	psi-mi:“MI:0914”(association)	0.530
CRP	QSOX1	psi-mi:“MI:0914”(association)	0.530
LGALS1	LAMA5	psi-mi:“MI:0914”(association)	0.530
SPCS3	ENTPD6	psi-mi:“MI:0914”(association)	0.530
ANTXR1	WFS1	psi-mi:“MI:0914”(association)	0.530
CCT8L2	ACSL4	psi-mi:“MI:0914”(association)	0.530
GRIP2	CSPG4	psi-mi:“MI:0407”(direct interaction)	0.440
CSPG4	GORASP2	psi-mi:“MI:0407”(direct interaction)	0.440
CSPG4	GRIP1	psi-mi:“MI:0407”(direct interaction)	0.440
CSPG4	HTRA3	psi-mi:“MI:0407”(direct interaction)	0.440
CSPG4	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440
CSPG4	GORASP1	psi-mi:“MI:0407”(direct interaction)	0.440
CSPG4	LNX2	psi-mi:“MI:0407”(direct interaction)	0.440
CSPG4	RADIL	psi-mi:“MI:0407”(direct interaction)	0.440
CSPG4	HTRA1	psi-mi:“MI:0407”(direct interaction)	0.440
CSPG4	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
CSPG4	TJP3	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (100): CSPG4 (Affinity Capture-MS), CSPG4 (Affinity Capture-MS), CSPG4 (Affinity Capture-MS), CSPG4 (Affinity Capture-MS), CSPG4 (Affinity Capture-MS), CSPG4 (Affinity Capture-MS), CSPG4 (Affinity Capture-MS), CSPG4 (Affinity Capture-MS), GRIP2 (Two-hybrid), CSPG4 (Affinity Capture-MS), CSPG4 (Affinity Capture-MS), CSPG4 (Affinity Capture-MS), CSPG4 (Affinity Capture-MS), CSPG4 (Affinity Capture-MS), CSPG4 (Reconstituted Complex)

ESM2 similar proteins: A0A140LHF2, A6H8M9, A7LCJ3, A8E0Y8, D3YX43, D3YZF7, O14498, O15197, O70394, O70540, P01877, P0C0K6, P0C788, P0DP72, P35590, P40223, P43121, P50895, P70289, Q00657, Q06418, Q06805, Q15109, Q28173, Q5BK54, Q5NVQ6, Q5TJE4, Q61790, Q61826, Q62151, Q62230, Q63495, Q64612, Q6UVK1, Q6UWB1, Q7Z442, Q86VR7, Q8IZF5, Q8R2Y2, Q8VHY0

Diamond homologs: Q00657, Q6UVK1, Q8VHY0, O00468, O14786, O15537, O18806, O35474, O43854, O60494, O88783, P00451, P12259, P21956, P28824, P70490, P79385, P79795, P97333, P98092, Q06194, Q08431, Q0V8S9, Q0V8T0, Q0V8T3, Q0V8T4, Q0V8T5, Q0V8T6, Q0V8T7, Q0V8T8, Q0V8T9, Q1WIM2, Q28107, Q2PC93, Q58L90, Q58L91, Q593B6, Q5R7K9, Q5RD64, Q6AYP5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PRKCA	“up-regulates activity”	CSPG4	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 180 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Dopamine Neurotransmitter Release Cycle	5	21.2×	3e-04
Assembly and cell surface presentation of NMDA receptors	9	19.5×	1e-07
Neurexins and neuroligins	11	18.5×	6e-09
Protein-protein interactions at synapses	7	15.9×	4e-05
Formation of the dystrophin-glycoprotein complex (DGC)	5	13.2×	2e-03
Non-integrin membrane-ECM interactions	6	7.9×	4e-03
Extracellular matrix organization	10	5.4×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	8	28.9×	2e-07
protein localization to synapse	6	28.6×	1e-05
receptor clustering	7	27.1×	3e-06
regulation of postsynaptic membrane neurotransmitter receptor levels	6	18.5×	1e-04
cell-cell adhesion	12	7.6×	1e-05
protein-containing complex assembly	10	7.1×	2e-04
protein localization to plasma membrane	9	6.1×	2e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — BRCA.

Clinical variants and AI predictions

ClinVar

443 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	372
Likely benign	43
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
625749	GRCh37/hg19 15q24.2(chr15:75648132-76102251)	Pathogenic

SpliceAI

1453 predictions. Top by Δscore:

Variant	Effect	Δscore
15:75677690:T:C	donor_gain	1.0000
15:75677698:TTCAC:T	donor_loss	1.0000
15:75677699:TCA:T	donor_loss	1.0000
15:75677700:CACCT:C	donor_loss	1.0000
15:75677701:ACCTT:A	donor_loss	1.0000
15:75677702:CCTTT:C	donor_loss	1.0000
15:75682292:CCT:C	donor_gain	1.0000
15:75682458:CC:C	acceptor_gain	1.0000
15:75682459:CC:C	acceptor_gain	1.0000
15:75682460:C:CC	acceptor_gain	1.0000
15:75682464:C:CT	acceptor_gain	1.0000
15:75682604:CA:C	donor_loss	1.0000
15:75682605:A:T	donor_loss	1.0000
15:75684730:TCTCA:T	donor_loss	1.0000
15:75684731:CTCA:C	donor_loss	1.0000
15:75684732:TCAC:T	donor_loss	1.0000
15:75684733:CA:C	donor_loss	1.0000
15:75684734:A:AT	donor_loss	1.0000
15:75684735:C:A	donor_loss	1.0000
15:75693066:TCAC:T	donor_loss	1.0000
15:75693067:CAC:C	donor_loss	1.0000
15:75693068:A:AC	donor_gain	1.0000
15:75693068:A:AT	donor_loss	1.0000
15:75693069:C:CC	donor_gain	1.0000
15:75693069:CCTG:C	donor_gain	1.0000
15:75693230:GAAG:G	acceptor_gain	1.0000
15:75693231:AAG:A	acceptor_gain	1.0000
15:75693231:AAGC:A	acceptor_loss	1.0000
15:75693233:GC:G	acceptor_loss	1.0000
15:75693234:C:CC	acceptor_gain	1.0000

AlphaMissense

14906 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:75689584:A:G	F494S	0.997
15:75687823:A:G	F1081S	0.995
15:75688151:A:C	Y972D	0.995
15:75688121:C:G	D982H	0.994
15:75689656:A:G	F470S	0.994
15:75687600:G:C	N1155K	0.992
15:75687600:G:T	N1155K	0.992
15:75689548:A:G	F506S	0.992
15:75687751:A:G	L1105P	0.991
15:75687787:A:G	F1093S	0.991
15:75687808:A:G	L1086P	0.991
15:75676838:A:G	F1894S	0.990
15:75677126:A:G	F1798S	0.990
15:75688009:G:T	P1019H	0.990
15:75689584:A:C	F494C	0.990
15:75687740:C:G	D1109H	0.989
15:75687808:A:T	L1086H	0.989
15:75687822:G:C	F1081L	0.989
15:75687822:G:T	F1081L	0.989
15:75687824:A:G	F1081L	0.989
15:75687933:G:C	F1044L	0.989
15:75687933:G:T	F1044L	0.989
15:75687935:A:G	F1044L	0.989
15:75688186:A:G	F960S	0.989
15:75677120:A:G	F1800S	0.988
15:75687787:A:C	F1093C	0.988
15:75688151:A:T	Y972N	0.988
15:75689506:A:G	L520P	0.988
15:75689725:A:T	L447H	0.988
15:75677273:A:G	F1749S	0.987

dbSNP variants (sampled 300 via entrez): RS1000106936 (15:75709006 A>T), RS1000269184 (15:75703294 G>A,C), RS1000351347 (15:75715137 C>T), RS1000533353 (15:75693079 T>A,G), RS1000703405 (15:75702897 C>A,T), RS1000881475 (15:75682120 C>T), RS1000952732 (15:75713817 G>A), RS1000953313 (15:75713474 C>A,T), RS1000967703 (15:75692831 C>T), RS1001103993 (15:75707194 T>G), RS1001109624 (15:75678071 T>C), RS1001135055 (15:75707007 G>A), RS1001316054 (15:75697020 C>T), RS1001421114 (15:75697145 C>A), RS1001472486 (15:75691680 G>A)

Disease associations

OMIM: gene MIM:601172 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
schizophrenia	Limited	Autosomal dominant

Mondo (1): schizophrenia (MONDO:0005090)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005580_170	Intraocular pressure	1.000000e-08
GCST007876_30	Estimated glomerular filtration rate	3.000000e-25
GCST008551_2	Simvastatin-induced myopathy	9.000000e-06
GCST90020026_402	Hip index	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1127648	CSPG4		0.00	0

CTD chemical–gene interactions

48 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Doxorubicin	increases expression	3
bisphenol A	increases expression	2
sodium arsenite	decreases expression, increases abundance, increases expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Benzo(a)pyrene	increases expression, increases methylation	2
Aflatoxin B1	increases expression	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, increases expression	2
FR900359	decreases phosphorylation	1
2,4,6-tribromophenol	increases expression	1
decabromobiphenyl ether	increases expression	1
trimellitic anhydride	decreases expression	1
sulforaphane	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
zinc chromate	decreases expression, increases abundance	1
tobacco tar	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
nickel sulfate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
epigallocatechin gallate	increases expression, affects cotreatment, decreases expression	1
cyanoginosin LR	increases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
tebuconazole	decreases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
bisphenol S	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	decreases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8E7	Abcam HCT 116 CSPG4 KO	Cancer cell line	Male
CVCL_B9GF	Abcam A-549 CSPG4 KO	Cancer cell line	Male
CVCL_D2EM	Abcam MCF-7 CSPG4 KO	Cancer cell line	Female

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety