VCAN

Summary

VCAN (versican, HGNC:2464) is a protein-coding gene on chromosome 5q14.2-q14.3, encoding Versican core protein (P13611). May play a role in intercellular signaling and in connecting cells with the extracellular matrix.

This gene is a member of the aggrecan/versican proteoglycan family. The protein encoded is a large chondroitin sulfate proteoglycan and is a major component of the extracellular matrix. This protein is involved in cell adhesion, proliferation, proliferation, migration and angiogenesis and plays a central role in tissue morphogenesis and maintenance. Mutations in this gene are the cause of Wagner syndrome type 1. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 1462 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Wagner disease (Definitive, ClinGen)
• GWAS associations: 34
• Clinical variants (ClinVar): 2,367 total — 14 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 21
• MANE Select transcript: NM_004385

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2464
Approved symbol	VCAN
Name	versican
Location	5q14.2-q14.3
Locus type	gene with protein product
Status	Approved
Aliases	PG-M
Ensembl gene	ENSG00000038427
Ensembl biotype	protein_coding
OMIM	118661
Entrez	1462

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000265077, ENST00000342785, ENST00000343200, ENST00000502527, ENST00000503923, ENST00000505615, ENST00000507162, ENST00000512590, ENST00000513016, ENST00000513960, ENST00000513984, ENST00000515397

RefSeq mRNA: 4 — MANE Select: NM_004385 NM_001126336, NM_001164097, NM_001164098, NM_004385

CCDS: CCDS4060, CCDS47242, CCDS54875, CCDS54876

Canonical transcript exons

ENST00000265077 — 15 exons

Exon	Start	End
ENSE00000915433	83537007	83542268
ENSE00001163618	83519349	83522309
ENSE00001952868	83471744	83472023
ENSE00002261977	83493546	83493720
ENSE00002264573	83493804	83493931
ENSE00002285743	83512103	83512396
ENSE00003460852	83572416	83572560
ENSE00003473576	83490098	83490472
ENSE00003501562	83483513	83483588
ENSE00003565617	83554956	83555038
ENSE00003638554	83547971	83548084
ENSE00003647958	83553364	83553522
ENSE00003648087	83545537	83545650
ENSE00003683529	83579980	83580162
ENSE00003847506	83580307	83582302

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 98.3819 / max 2647.0895, expressed in 1303 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
57398	39.2216	1193
57399	36.6140	1216
57394	9.9859	1092
57397	8.3874	1081
57396	3.3195	906
57395	0.5269	326
57407	0.3266	164

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.53	gold quality
mononuclear cell	CL:0000842	99.53	gold quality
leukocyte	CL:0000738	99.50	gold quality
pericardium	UBERON:0002407	99.46	gold quality
right coronary artery	UBERON:0001625	99.42	gold quality
ventricular zone	UBERON:0003053	99.37	gold quality
synovial joint	UBERON:0002217	99.34	gold quality
saphenous vein	UBERON:0007318	99.25	gold quality
tendon of biceps brachii	UBERON:0008188	99.25	gold quality
descending thoracic aorta	UBERON:0002345	99.07	gold quality
trabecular bone tissue	UBERON:0002483	99.04	gold quality
thoracic aorta	UBERON:0001515	99.03	gold quality
ascending aorta	UBERON:0001496	99.02	gold quality
skin of hip	UBERON:0001554	98.82	gold quality
calcaneal tendon	UBERON:0003701	98.72	gold quality
granulocyte	CL:0000094	98.71	gold quality
layer of synovial tissue	UBERON:0007616	98.69	gold quality
blood vessel layer	UBERON:0004797	98.59	gold quality
decidua	UBERON:0002450	98.49	gold quality
visceral pleura	UBERON:0002401	98.34	gold quality
coronary artery	UBERON:0001621	98.31	gold quality
embryo	UBERON:0000922	98.25	gold quality
left coronary artery	UBERON:0001626	98.17	gold quality
tendon	UBERON:0000043	98.15	gold quality
ganglionic eminence	UBERON:0004023	98.07	gold quality
placenta	UBERON:0001987	97.87	gold quality
aorta	UBERON:0000947	97.64	gold quality
periodontal ligament	UBERON:0008266	97.29	gold quality
urethra	UBERON:0000057	97.27	gold quality
bone marrow cell	CL:0002092	97.26	gold quality

Single-cell (SCXA)

Detected in 50 experiment(s), a significant marker in 47.

Experiment	Marker?	Max mean expression
E-GEOD-150728	yes	9133.02
E-CURD-112	yes	7797.82
E-GEOD-84465	yes	4666.86
E-MTAB-9221	yes	4079.55
E-HCAD-56	yes	3459.71
E-CURD-122	yes	3457.65
E-GEOD-180759	yes	2953.42
E-MTAB-9801	yes	2647.09
E-MTAB-8530	yes	2455.84
E-HCAD-15	yes	2444.40
E-GEOD-75688	yes	2341.42
E-GEOD-149689	yes	2224.96
E-HCAD-35	yes	2178.56
E-GEOD-135922	yes	2151.65
E-HCAD-32	yes	1908.67

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, AR, CTNNB1, EGR1, FOXQ1, HNF4A, JUN, PAX3, PAX6, RUNX2, SLC2A10, TCF4, TCF7L2, TP53

miRNA regulators (miRDB)

105 targeting VCAN, 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-9-5P	100.00	72.28	2361
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-9983-3P	99.94	71.48	3631

Literature-anchored findings (GeneRIF, showing 40)

• PDGF stimulates the formation of versican-hyaluronan aggregates and pericellular matrix expansion in arterial smooth muscle cells (PMID:11566024)
• beta 1-Integrin-mediated glioma cell adhesion and free radical-induced apoptosis are regulated by binding to a C-terminal domain of PG-M/versican (PMID:11805102)
• involved in the progression of melanomas and may be a reliable marker for clinical diagnosis (PMID:11839575)
• Cleavage of the carboxyl tail from the G3 domain of aggrecan but not versican and identification of the amino acids involved in the degradation (PMID:11932252)
• independent of the degree of vascularization, human adult tissues show a limited expression of versican isoforms V0, V2, and V3 (PMID:12221092)
• CSPG2 contains a bona fide p53 binding site in its first intron and its expression highly correlates with TP53 dosage. Using in vitro and in vivo assays, we showed CSPG2 to be directly transactivated by p53. (PMID:12438652)
• Synthesis and expression of mRNA encoding for different versican splice variants is related to the aggregation of human epithelial mesothelioma cells. (PMID:12553048)
• versican/PG-M binds to hyaluronan (PMID:12888576)
• All melanoma cell lines with an early or intermediate degree of differentiation expressed V0 and V1 versican isoforms, whereas V2 and V3 expression was shown only by undifferentiated cell lines. (PMID:12972299)
• humoral immunity to versican as well as immunity to aggrecan may be of importance in the development of the spinal pathology characteristic of spondylarthropathies. (PMID:14558097)
• the interaction between versican and hyaluronan in many tissues is stabilized by Link protein (PMID:14724283)
• versican and tenascin have roles in preventing relapse of node-negative breast cancer (PMID:15073129)
• Versican is 1 of the main genes upregulated after vascular injury. It is a main component in stented & nonstented restenotic lesions. It influences the assembly of ECM & elastic fiber fibrillogenesis of basic importance in vascular disease ECM remodeling. (PMID:15142969)
• Malignant cells can actively influence the composition of the extracellular matrix through TGFbeta1 and other soluble factors. (PMID:15336555)
• PG-M/versican binds to P-selectin glycoprotein ligand-1 and has a role in mediating leukocyte aggregation (PMID:15522894)
• Cartilage link protein and versican did not bind directly to each other in solution yet formed ternary complexes with hyaluronan (PMID:15590670)
• negative effect of TGFbeta1 on ADAMTS-1, -5, -9, and -15 coupled with increases in their inhibitor, TIMP-3 may aid the accumulation of versican in the stromal compartment of the prostate in BPH and prostate cancer (PMID:15599946)
• versican is related to higher tumor recurrence rate and more advanced disease (PMID:15712181)
• versican plays an important role in reducing oxidant injury through an enhancement of cell-matrix interaction (PMID:15748997)
• Specific expression of versican in the anagen hair follicles suggests its importance to maintain the normal growing phase of humans. (PMID:15871917)
• Results of RT-PCR analysis indicated that the c.4004-2 A–>G mutation activates a cryptic splice site, located 39 bp downstream from the authentic 3’ splice acceptor site. (PMID:16043844)
• This is the first report about the presence of various forms of versican in the anterior segment of the eye and the alterations in the mRNA patterns of these forms when cells are placed in culture (PMID:16110303)
• We suggest that upregulation of versican in the infarcted myocardium may have a role in the inflammatory reaction, which mediates subsequent chemotaxis in the infarcted heart. (PMID:16311904)
• Versican G3 domain promotes blood coagulation through suppressing the activity of tissue factor pathway inhibitor-1 (PMID:16431924)
• although the exact interaction between tenascin-C and PG-M/versican remains not entirely clear, these two molecules appear to play significant roles in the (PMID:16493581)
• The splice site mutation described here may lead to a complete lack of exon 8 in CSPG2 transcripts, which shortens the predicted protein by 1754 amino acids and leads to severe reduction of glycosaminoglycan attachment sites. (PMID:16636652)
• the versican G3 domain regulates neuronal attachment, neurite outgrowth, and synaptic function of hippocampal neurons via EGFR-dependent and -independent signaling pathways (PMID:16648628)
• Wagner disease and ERVR (erosive vitreoretinopathy) may belong to a largely overlooked group of diseases that are caused by mRNA isoform balance shifts, representing a novel disease mechanism. (PMID:16877430)
• (Single nucleotide polymorphisms)SNPs in strong linkage disequilibrium and haplotypes constituting these SNPs in versican gene are associated with intracranial aneurysms(IAs). Variation in or near versican gene may play role in susceptibility to IAs. (PMID:16917090)
• Epithelial versican expression was significantly higher in patients with lymph node metastasis of endometrial cancer (PMID:17065588)
• versican in the umbilical cord vein wall is elevated in pre-eclampsia in comparison to the corresponding control vessels (PMID:17097211)
• Loss of the hyaluronan (HA)-binding ability of versican followed by HA exclusion may be responsible for the pathological and phenotypical changes observed in solar elastosis. (PMID:17363913)
• TGF-beta2 triggers the malignant phenotype of high-grade gliomas by induction of migration, and that this effect is, at least in part, mediated by versican V0/V1. (PMID:17453002)
• Using transient transfection assays in prostate cancer LNCaP and HeLa cells engineered to express the AR, study shows that synthetic androgen R1881 and dihydrotestosterone stimulate expression of a versican promoter-driven luciferase reporter vector. (PMID:17728259)
• Excess decorin, biglycan, and versican may be associated with the remodeling of other matrix components in myxomatous mitral valves. (PMID:18621549)
• Report deregulation of versican and elastin binding protein in solar elastosis. (PMID:18704747)
• High steady state levels of versican variants V0, V1, and V3 mRNA transcript and gene product are detected in the nodular tissues than in the non-nodular parenchyma of benign prostatic hyperplasia. (PMID:18819099)
• superficial spreading melanoma is associated with a significant overexpression of peritumoral versican suggesting a role for versican in the pathogenesis of melanoma (PMID:19073385)
• versican plays a role in cancer invasion and metastasis [review] (PMID:19160015)
• AP-1 and TCF-4 binding sites are the main regulatory regions directing versican production provide new insights into versican promoter regulation during melanoma progression. (PMID:19269971)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	vcanb	ENSDARG00000009401
danio_rerio	vcana	ENSDARG00000103515
mus_musculus	Vcan	ENSMUSG00000021614
rattus_norvegicus	Vcan	ENSRNOG00000029212

Paralogs (7): NCAN (ENSG00000130287), BCAN (ENSG00000132692), HAPLN2 (ENSG00000132702), HAPLN3 (ENSG00000140511), HAPLN1 (ENSG00000145681), ACAN (ENSG00000157766), HAPLN4 (ENSG00000187664)

Protein

Protein identifiers

Versican core protein — P13611 (reviewed: P13611)

Alternative names: Chondroitin sulfate proteoglycan core protein 2, Glial hyaluronate-binding protein, Large fibroblast proteoglycan, PG-M

All UniProt accessions (4): D6RGZ6, E9PF17, P13611, Q86W61

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in intercellular signaling and in connecting cells with the extracellular matrix. May take part in the regulation of cell motility, growth and differentiation. Binds hyaluronic acid.

Subunit / interactions. Interacts with FBLN1.

Subcellular location. Secreted. Extracellular space. Extracellular matrix. Cell projection. Cilium. Photoreceptor outer segment. Interphotoreceptor matrix.

Tissue specificity. Detected in placenta (at protein level). Detected in cerebrospinal fluid, fibroblasts and urine (at protein level). Expressed in the retina (at protein level). Cerebral white matter and plasma. Isoform V0: Expressed in normal brain, gliomas, medulloblastomas, schwannomas, neurofibromas, and meningiomas. Isoform V1: Expressed in normal brain, gliomas, medulloblastomas, schwannomas, neurofibromas, and meningiomas. Isoform V2: Restricted to normal brain and gliomas. Isoform V3: Found in all these tissues except medulloblastomas.

Post-translational modifications. Phosphorylated by FAM20C in the extracellular medium. Proteolytically cleaved by ADAMTS5 and ADAMTS15 in the pericellular matrix surrounding myoblasts, facilitating myoblast contact and fusion which is required for skeletal muscle development and regeneration.

Disease relevance. Wagner vitreoretinopathy (WGVRP) [MIM:143200] A rare vitreoretinopathy characterized by an optically empty vitreous cavity with fibrillary condensations and a preretinal avascular membrane. Other optical features include progressive chorioretinal atrophy, perivascular sheating, subcapsular cataract and myopia. The disease is caused by variants affecting the gene represented in this entry. The pathological mechanism involves a quantitative imbalance of the normally occurring splice variants.

Similarity. Belongs to the aggrecan/versican proteoglycan family.

Isoforms (5)

UniProt ID	Names	Canonical?
P13611-1	V0	yes
P13611-2	V1
P13611-3	V2
P13611-4	V3
P13611-5	Vint

RefSeq proteins (4): NP_001119808, NP_001157569, NP_001157570, NP_004376* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000436	Sushi_SCR_CCP_dom	Domain
IPR000538	Link_dom	Domain
IPR000742	EGF	Domain
IPR001304	C-type_lectin-like	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR016186	C-type_lectin-like/link_sf	Homologous_superfamily
IPR016187	CTDL_fold	Homologous_superfamily
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR018378	C-type_lectin_CS	Conserved_site
IPR033987	CSPG_CTLD	Domain
IPR035976	Sushi/SCR/CCP_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050691	Hyaluronan_bind_Proteoglycan	Family

Pfam: PF00008, PF00059, PF00084, PF00193, PF07686

UniProt features (116 total): glycosylation site 34, region of interest 21, disulfide bond 16, compositionally biased region 14, sequence variant 8, domain 7, splice variant 5, sequence conflict 5, modified residue 3, signal peptide 1, chain 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for P13611 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

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

Catalytic / active sites (1): 1428–1429 (cleavage; by adamts15)

Post-translational modifications (3): 2116, 2608, 2617

Disulfide bonds (16): 44–130, 172–243, 196–217, 270–345, 294–315, 3093–3104, 3098–3113, 3115–3124, 3131–3142, 3136–3151, 3153–3162, 3169–3180, 3197–3289, 3265–3281, 3296–3339, 3325–3352

Glycosylation sites (34): 57, 330, 615, 659, 782, 809, 1332, 1398, 1442, 1468, 1548, 1631, 1663, 1898, 1935, 1959, 2179, 2247, 2254, 2272 …

Function

Pathways and Gene Ontology

Reactome pathways

13 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-3000178	ECM proteoglycans
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-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-4420332	Defective B3GALT6 causes EDSP2 and SEMDJL1
R-HSA-8957275	Post-translational protein phosphorylation

MSigDB gene sets: 555 (showing top): E2F_Q4, TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, LOPEZ_MESOTHELIOMA_SURVIVAL_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, LUCAS_HNF4A_TARGETS_DN, E2F4DP1_01, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, PAL_PRMT5_TARGETS_UP, MODULE_45, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_DN, GOBP_OSTEOBLAST_DIFFERENTIATION, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, GOBP_NEUROGENESIS

GO Biological Process (7): skeletal system development (GO:0001501), osteoblast differentiation (GO:0001649), cell adhesion (GO:0007155), central nervous system development (GO:0007417), cell recognition (GO:0008037), glial cell migration (GO:0008347), system development (GO:0048731)

GO Molecular Function (7): calcium ion binding (GO:0005509), glycosaminoglycan binding (GO:0005539), hyaluronic acid binding (GO:0005540), protein tyrosine phosphatase activator activity (GO:0008160), extracellular matrix structural constituent conferring compression resistance (GO:0030021), carbohydrate binding (GO:0030246), protein binding (GO:0005515)

GO Cellular Component (12): photoreceptor outer segment (GO:0001750), extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), Golgi lumen (GO:0005796), membrane (GO:0016020), extracellular matrix (GO:0031012), interphotoreceptor matrix (GO:0033165), lysosomal lumen (GO:0043202), synapse (GO:0045202), perineuronal net (GO:0072534), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Diseases associated with glycosaminoglycan metabolism	6
Chondroitin sulfate/dermatan sulfate metabolism	3
Glycosaminoglycan metabolism	1
Extracellular matrix organization	1
Metabolism of proteins	1
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
system development	2
cellular process	2
binding	2
intracellular organelle lumen	2
ossification	1
cell differentiation	1
nervous system development	1
cell migration	1
gliogenesis	1
multicellular organism development	1
anatomical structure development	1
metal ion binding	1
carbohydrate derivative binding	1
carboxylic acid binding	1
protein tyrosine phosphatase activity	1
protein phosphatase activator activity	1
extracellular matrix structural constituent	1
photoreceptor cell cilium	1
endoplasmic reticulum	1
Golgi apparatus	1
external encapsulating structure	1
specialized extracellular matrix	1
lysosome	1
vacuolar lumen	1
cell junction	1
perisynaptic extracellular matrix	1

Protein interactions and networks

STRING

2718 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VCAN	CD44	P16070	993
VCAN	ACAN	P16112	980
VCAN	DCN	P07585	966
VCAN	PTPRZ1	P23471	951
VCAN	NCAN	O14594	946
VCAN	BGN	P13247	913
VCAN	TLR2	O60603	912
VCAN	BCAN	Q96GW7	909
VCAN	SELL	P14151	885
VCAN	ELN	P15502	865
VCAN	FBN1	P35555	860
VCAN	FN1	P02751	858
VCAN	FBLN1	P23142	828
VCAN	LYVE1	Q9Y5Y7	807
VCAN	TNFAIP6	P98066	747

IntAct

35 interactions, top by confidence:

A	B	Type	Score
CRIPTO	AIP	psi-mi:“MI:0914”(association)	0.640
MMP9	VCAN	psi-mi:“MI:0407”(direct interaction)	0.600
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
TAFA4	NRP1	psi-mi:“MI:0914”(association)	0.530
VCAN	SRGN	psi-mi:“MI:0915”(physical association)	0.520
FAM20C	VCAN	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
	VCAN	psi-mi:“MI:0407”(direct interaction)	0.440
VCAN		psi-mi:“MI:0915”(physical association)	0.370
DND1	RPSA2	psi-mi:“MI:0914”(association)	0.350
PA	ESYT2	psi-mi:“MI:0914”(association)	0.350
HEATR3	TIMM44	psi-mi:“MI:0914”(association)	0.350
RACK1	RPS3A	psi-mi:“MI:0914”(association)	0.350
SRP9	RPS3A	psi-mi:“MI:0914”(association)	0.350
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
CD44	TCAF2	psi-mi:“MI:0914”(association)	0.350
ST14	LIPT2	psi-mi:“MI:0914”(association)	0.350
SLURP1	MANBA	psi-mi:“MI:0914”(association)	0.350
IL17F	TBL1X	psi-mi:“MI:0914”(association)	0.350
MSMB	ADAM11	psi-mi:“MI:0914”(association)	0.350
TNFAIP6	ZMYM6	psi-mi:“MI:0914”(association)	0.350
LY86	TMEM131L	psi-mi:“MI:0914”(association)	0.350
IL17F	POTEF	psi-mi:“MI:0914”(association)	0.350
NCR3	POTEF	psi-mi:“MI:0914”(association)	0.350
PRG2	QSOX1	psi-mi:“MI:0914”(association)	0.350
SDF2L1	MANBA	psi-mi:“MI:0914”(association)	0.350
GGH	MANBA	psi-mi:“MI:0914”(association)	0.350
BCAN	LAMA5	psi-mi:“MI:0914”(association)	0.350
ATF3	TMEM223	psi-mi:“MI:0914”(association)	0.350
CASP3	TMEM223	psi-mi:“MI:0914”(association)	0.350

BioGRID (53): VCAN (Affinity Capture-MS), Hapln1 (Affinity Capture-Western), VCAN (Affinity Capture-MS), VCAN (Affinity Capture-MS), VCAN (Affinity Capture-MS), VCAN (Affinity Capture-MS), VCAN (Affinity Capture-MS), HAPLN1 (Reconstituted Complex), VCAN (Reconstituted Complex), RAB19 (Two-hybrid), FBLN2 (Reconstituted Complex), FBN1 (Reconstituted Complex), VCAN (Affinity Capture-MS), VCAN (Affinity Capture-RNA), VCAN (Reconstituted Complex)

ESM2 similar proteins: A0JPP4, B7ZCC9, B9EKR1, E9Q7X6, J3KML8, O00592, O57604, P13611, P23471, P30005, P34910, P52549, P70628, Q01036, Q06093, Q1XI86, Q28858, Q2TA21, Q2TBJ9, Q3MIW9, Q3TNW5, Q3TYV2, Q5XI99, Q62059, Q62656, Q62781, Q68FD9, Q69558, Q6MG22, Q6R8J2, Q7TST5, Q80XH2, Q86TY3, Q8BT18, Q8BUE7, Q8C633, Q8IZF6, Q8N3K9, Q8VD58, Q8WXI7

Diamond homologs: A0ZT93, B0VXV2, B4XT08, B5U6Y6, B5U6Y7, C0HKZ7, O60449, P05140, P06027, P06734, P0DJL5, P10716, P13611, P14371, P20693, P34472, P55066, P55067, P81018, P81282, P81996, Q01758, Q02988, Q26627, Q28062, Q28670, Q28858, Q4PRD0, Q4TU93, Q4V885, Q61830, Q62059, Q64449, Q66S03, Q6X5S2, Q6X5S3, Q6X5S5, Q6X5S6, Q6X5S7, Q6X5S8

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
TP53	“up-regulates quantity by expression”	VCAN	“transcriptional regulation”
miRNA-30a-5p	“down-regulates quantity by destabilization”	VCAN	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 49 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
Degradation of the extracellular matrix	5	17.8×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

2367 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	14
Likely pathogenic	7
Uncertain significance	1515
Likely benign	581
Benign	102

Top pathogenic / likely-pathogenic (21)

Variant ID	HGVS	Classification
1070172	NM_004385.5(VCAN):c.9740_9741del (p.Gln3246_Tyr3247insTer)	Pathogenic
1451690	NM_004385.5(VCAN):c.8113G>T (p.Glu2705Ter)	Pathogenic
1459411	NM_004385.5(VCAN):c.4006C>T (p.Arg1336Ter)	Pathogenic
17494	NM_004385.5(VCAN):c.4004-2A>G	Pathogenic
2129440	NM_004385.5(VCAN):c.6412_6415del (p.Thr2138fs)	Pathogenic
21405	NM_004385.5(VCAN):c.4004-1G>A	Pathogenic
21408	NM_004385.5(VCAN):c.9265+1G>A	Pathogenic
219011	NM_004385.5(VCAN):c.4004-1G>T	Pathogenic
2425099	NC_000005.9:g.(?82400739)(82876253_?)del	Pathogenic
2765729	NM_004385.5(VCAN):c.9265+2T>C	Pathogenic
2797760	NM_004385.5(VCAN):c.5731C>T (p.Arg1911Ter)	Pathogenic
3638168	NM_004385.5(VCAN):c.8116del (p.Ile2706fs)	Pathogenic
3643781	NM_004385.5(VCAN):c.4876C>T (p.Gln1626Ter)	Pathogenic
41879	NM_004385.5(VCAN):c.4004-1G>C	Pathogenic
2024338	NM_004385.5(VCAN):c.4004-350_4461del	Likely pathogenic
219010	NM_004385.5(VCAN):c.9265+1G>T	Likely pathogenic
3246509	NC_000005.9:g.(?82836129)(82838461_?)del	Likely pathogenic
3255113	NM_004385.5(VCAN):c.9265G>C (p.Gly3089Arg)	Likely pathogenic
3775172	NM_004385.5(VCAN):c.3455C>A (p.Ser1152Ter)	Likely pathogenic
4814165	NM_004385.5(VCAN):c.1011del (p.Asp338fs)	Likely pathogenic
866367	NM_004385.5(VCAN):c.1720del (p.Asp574fs)	Likely pathogenic

SpliceAI

2636 predictions. Top by Δscore:

Variant	Effect	Δscore
5:83483507:TTCTA:T	acceptor_loss	1.0000
5:83483508:TCTA:T	acceptor_loss	1.0000
5:83483511:A:AG	acceptor_gain	1.0000
5:83483511:A:G	acceptor_loss	1.0000
5:83483512:G:GT	acceptor_gain	1.0000
5:83483586:AAGG:A	donor_loss	1.0000
5:83483587:AGG:A	donor_loss	1.0000
5:83483589:G:A	donor_loss	1.0000
5:83483589:G:GG	donor_gain	1.0000
5:83483590:T:G	donor_loss	1.0000
5:83490096:A:AG	acceptor_gain	1.0000
5:83490097:G:GT	acceptor_gain	1.0000
5:83490097:GTC:G	acceptor_gain	1.0000
5:83490097:GTCA:G	acceptor_gain	1.0000
5:83490097:GTCAA:G	acceptor_gain	1.0000
5:83490468:GGATG:G	donor_gain	1.0000
5:83490469:GATGG:G	donor_gain	1.0000
5:83490472:GGTAA:G	donor_loss	1.0000
5:83490473:G:T	donor_loss	1.0000
5:83490474:T:A	donor_loss	1.0000
5:83493544:AGG:A	acceptor_gain	1.0000
5:83493545:GGG:G	acceptor_gain	1.0000
5:83493717:TCAGG:T	donor_loss	1.0000
5:83493718:CAGG:C	donor_loss	1.0000
5:83493719:AGGTA:A	donor_loss	1.0000
5:83493720:GGTA:G	donor_loss	1.0000
5:83493721:G:C	donor_loss	1.0000
5:83493722:T:A	donor_loss	1.0000
5:83512099:CCAG:C	acceptor_loss	1.0000
5:83512100:CAG:C	acceptor_loss	1.0000

AlphaMissense

22255 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:83490223:T:A	W66R	1.000
5:83490223:T:C	W66R	1.000
5:83493686:T:A	C196S	1.000
5:83493687:G:C	C196S	1.000
5:83493698:T:A	W200R	1.000
5:83493698:T:C	W200R	1.000
5:83493700:G:C	W200C	1.000
5:83493700:G:T	W200C	1.000
5:83493832:T:A	C217S	1.000
5:83493833:G:C	C217S	1.000
5:83512248:G:C	W298C	1.000
5:83512248:G:T	W298C	1.000
5:83553440:G:C	W3190C	1.000
5:83553440:G:T	W3190C	1.000
5:83572473:T:C	C3265R	1.000
5:83572475:T:G	C3265W	1.000
5:83572506:T:A	W3276R	1.000
5:83572506:T:C	W3276R	1.000
5:83572508:G:C	W3276C	1.000
5:83572508:G:T	W3276C	1.000
5:83490225:G:C	W66C	0.999
5:83490225:G:T	W66C	0.999
5:83493564:G:T	R155M	0.999
5:83493615:G:A	C172Y	0.999
5:83493616:T:G	C172W	0.999
5:83493654:T:C	L185P	0.999
5:83493686:T:C	C196R	0.999
5:83493687:G:A	C196Y	0.999
5:83493687:G:T	C196F	0.999
5:83493688:T:G	C196W	0.999

dbSNP variants (sampled 300 via entrez): RS1000015442 (5:83513052 T>A), RS1000081437 (5:83488439 CAT>C), RS1000125977 (5:83540381 G>A), RS1000136634 (5:83558010 T>C), RS1000159610 (5:83581999 C>T), RS1000221855 (5:83506310 C>T), RS1000229833 (5:83494619 G>A), RS1000245754 (5:83486842 G>A,C,T), RS1000266031 (5:83582425 A>G), RS1000314825 (5:83575320 T>C,G), RS1000318716 (5:83580780 T>C), RS1000377369 (5:83545163 C>A,T), RS1000466430 (5:83557721 C>T), RS1000479285 (5:83568294 G>A), RS1000486609 (5:83526542 C>T)

Disease associations

OMIM: gene MIM:118661 | disease phenotypes: MIM:143200, MIM:268000, MIM:108300, MIM:617238

GenCC curated gene-disease

Disease	Classification	Inheritance
Wagner disease	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Wagner disease	Definitive	AD

Mondo (8): congenital heart disease (MONDO:0005453), Wagner disease (MONDO:0007740), inherited retinal dystrophy (MONDO:0019118), retinitis pigmentosa (MONDO:0019200), prostate cancer (MONDO:0008315), vitreoretinal degeneration (MONDO:0020248), Stickler syndrome (MONDO:0019354), myopia 25, autosomal dominant (MONDO:0014982)

Orphanet (6): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Retinitis pigmentosa (Orphanet:791), Wagner disease (Orphanet:898), Familial prostate cancer (Orphanet:1331), Stickler syndrome (Orphanet:828), OBSOLETE: Vitreoretinal degeneration (Orphanet:98670)

HPO phenotypes

21 total (23 of 21 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000501	Glaucoma
HP:0000518	Cataract
HP:0000533	Chorioretinal atrophy
HP:0000541	Retinal detachment
HP:0000545	Myopia
HP:0000572	Visual loss
HP:0000580	Pigmentary retinopathy
HP:0000648	Optic atrophy
HP:0000662	Nyctalopia
HP:0001123	Visual field defect
HP:0007643	Peripheral tractional retinal detachment
HP:0007663	Reduced visual acuity
HP:0007722	Retinal pigment epithelial atrophy
HP:0007773	Vitreoretinopathy
HP:0007819	Presenile cataracts
HP:0012122	Anterior uveitis
HP:0025007	Ectopic fovea
HP:0030466	Abnormal full-field electroretinogram
HP:0030490	Exudative vitreoretinopathy
HP:0030663	Optically empty vitreous
HP:0000556	Retinal dystrophy
HP:0007964	Degenerative vitreoretinopathy

GWAS associations

34 associations (top):

Study	Trait	p-value
GCST000689_2	Major depressive disorder	7.000000e-06
GCST002597_4	Laryngeal squamous cell carcinoma	7.000000e-08
GCST002875_12	Diisocyanate-induced asthma	9.000000e-06
GCST003998_14	Joint mobility (Beighton score)	3.000000e-08
GCST004075_12	Vertical cup-disc ratio	3.000000e-07
GCST004075_13	Vertical cup-disc ratio	7.000000e-09
GCST005036_2	Lean body mass	5.000000e-07
GCST005037_2	Appendicular lean mass	2.000000e-08
GCST006062_1	White matter hyperintensity volume	4.000000e-06
GCST006062_2	White matter hyperintensity volume	3.000000e-06
GCST006063_1	White matter integrity (fractional anisotropy)	5.000000e-10
GCST006063_2	White matter integrity (fractional anisotropy)	1.000000e-14
GCST006064_1	White matter integrity (mean diffusivity)	6.000000e-13
GCST006064_2	White matter integrity (mean diffusivity)	4.000000e-18
GCST007294_165	Body fat distribution (trunk fat ratio)	1.000000e-21
GCST007294_51	Body fat distribution (trunk fat ratio)	8.000000e-21
GCST007295_150	Body fat distribution (leg fat ratio)	8.000000e-19
GCST007295_67	Body fat distribution (leg fat ratio)	1.000000e-16
GCST008832_23	Gastroesophageal reflux disease	2.000000e-08
GCST009462_60	Optic disc size	2.000000e-12
GCST009724_46	Vertical cup-disc ratio (multi-trait analysis)	2.000000e-09
GCST009921_12	Carotid intima media thickness (mean)	9.000000e-10
GCST010102_4	White matter integrity (fractional anisotropy)	3.000000e-25
GCST010103_1	White matter integrity (mean diffusivity)	2.000000e-34
GCST010242_67	HDL cholesterol levels	4.000000e-09
GCST010244_315	Triglyceride levels	1.000000e-11
GCST010701_24	Cortical surface area (MOSTest)	2.000000e-38
GCST010702_27	Subcortical volume (MOSTest)	3.000000e-36
GCST010703_120	Brain morphology (MOSTest)	2.000000e-17
GCST011616_60	Cortical volume	3.000000e-10

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0006995	response to diisocyanate
EFO:0007905	joint hypermobility measurement
EFO:0006939	cup-to-disc ratio measurement
EFO:0004995	lean body mass
EFO:0004980	appendicular lean mass
EFO:0005665	white matter hyperintensity measurement
EFO:0004641	white matter integrity
EFO:0004341	body fat distribution
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C536075	Hyaloideoretinal degeneration of Wagner (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects expression, decreases expression, increases expression, increases methylation, increases mutagenesis	6
Valproic Acid	increases expression, affects expression, decreases expression, affects cotreatment	6
sodium arsenite	affects methylation, decreases expression, increases expression	4
Tetrachlorodibenzodioxin	affects expression, decreases expression, increases expression	4
Aflatoxin B1	affects expression, increases expression, increases methylation	4
trichostatin A	affects cotreatment, increases expression	3
Silicon Dioxide	affects secretion, decreases expression, increases expression	3
Tobacco Smoke Pollution	affects expression, decreases expression	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
bisphenol A	decreases expression, affects cotreatment	2
cobaltous chloride	decreases expression, decreases secretion	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	2
Acetaminophen	decreases expression, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Cisplatin	affects expression, increases expression	2
Dexamethasone	decreases expression, affects cotreatment	2
Estradiol	increases expression, affects cotreatment, decreases expression	2
Nickel	increases expression	2
Progesterone	affects cotreatment, decreases expression, increases expression	2
Rotenone	decreases expression, increases expression	2
Triclosan	decreases expression, increases expression	2
Cyclosporine	decreases expression, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
Palmitic Acid	increases expression, affects cotreatment, affects expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
aristolochic acid I	decreases expression	1
2,4,6-tribromophenol	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
deoxynivalenol	decreases expression	1
decabromobiphenyl ether	decreases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8AE	Abcam Raji VCAN KO	Cancer cell line	Male
CVCL_C0B9	Abcam THP-1 VCAN KO	Cancer cell line	Male
CVCL_C7CW	Abcam PC-3 VCAN KO	Cancer cell line	Male
CVCL_D1UV	Abcam U-87MG VCAN KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00115375	PHASE2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	PHASE2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	PHASE2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	PHASE2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	PHASE2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	PHASE2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	PHASE2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	PHASE2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	PHASE2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	PHASE2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	PHASE2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	PHASE2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	PHASE2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE