VCAN

versican, the group of C-type lectin domain containing|V-set domain containing|Sushi domain containing|Hyalectan proteoglycans

Basic information

Region (hg38): 5:83471618-83582303

Previous symbols: [ "CSPG2" ]

Links

ENSG00000038427 ∙ NCBI:1462 ∙ OMIM:118661 ∙ HGNC:2464 ∙ Uniprot:P13611 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Wagner disease (Moderate), mode of inheritance: AD
• Wagner disease (Supportive), mode of inheritance: AD
• Wagner disease (Definitive), mode of inheritance: AD
• Wagner disease (Strong), mode of inheritance: AD
• Wagner disease (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Wagner vitreoretinopathy	AD	General	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	Ophthalmologic	9098284; 16043844; 16636652; 19901218; 20301747; 21738396; 22739342

ClinVar

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

• not provided (13 variants)
• Wagner syndrome (7 variants)
• Inborn genetic diseases (1 variants)
• Retinal dystrophy (1 variants)
• Stickler syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VCAN 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			17	443	37	497
missense			1180	58	23	1261
nonsense	3		3			6
start loss						0
frameshift	2	1	6	2		11
inframe indel			15	2		17
splice donor/acceptor (+/-2bp)	8	2				10
splice region	1		13	13	4	31
non coding			29	43	27	99
Total	13	3	1250	548	87

Variants in VCAN

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

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

Position	Type	Phenotype	Significance	ClinVar
5-83471696-C-T		Wagner syndrome • Vitreoretinopathy	Uncertain significance (Jun 14, 2016)
5-83471771-C-T		Wagner syndrome • Vitreoretinopathy	Uncertain significance (Jan 13, 2018)
5-83471895-G-A		Wagner syndrome • Vitreoretinopathy	Uncertain significance (Jan 12, 2018)
5-83471911-A-C		Wagner syndrome • Vitreoretinopathy	Benign/Likely benign (Jan 13, 2018)
5-83471941-T-C		Vitreoretinopathy • Wagner syndrome	Uncertain significance (Jan 13, 2018)
5-83471943-A-G		Wagner syndrome • Vitreoretinopathy	Uncertain significance (Jan 12, 2018)
5-83471955-A-G		Vitreoretinopathy • Wagner syndrome	Uncertain significance (Jan 12, 2018)
5-83483532-T-C			Uncertain significance (Jun 20, 2022)
5-83483549-A-T			Uncertain significance (Nov 06, 2023)
5-83483564-A-G			Uncertain significance (Apr 03, 2019)
5-83483572-C-A			Likely benign (Oct 15, 2023)
5-83483573-C-T			Uncertain significance (Jul 21, 2023)
5-83483575-T-G			Uncertain significance (May 20, 2022)
5-83483578-G-A			Likely benign (Jun 13, 2023)
5-83483579-C-T			Likely benign (Dec 31, 2019)
5-83483582-C-T			Uncertain significance (Apr 08, 2022)
5-83483587-A-T			Uncertain significance (Apr 08, 2022)
5-83483600-A-G			Likely benign (Jul 18, 2021)
5-83483603-A-T			Likely benign (Jun 30, 2023)
5-83483604-A-G			Likely benign (Jul 27, 2023)
5-83483605-T-C			Likely benign (Dec 21, 2023)
5-83489922-G-T			Benign (May 16, 2021)
5-83490080-A-G			Benign (Jan 22, 2024)
5-83490085-C-A			Likely benign (Oct 01, 2020)
5-83490085-C-T			Likely benign (May 09, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VCAN	protein_coding	protein_coding	ENST00000265077	14	110839

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	4.71e-8	125636	0	2	125638	0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.139	1708	1.72e+3	0.991	0.0000896	22173
Missense in Polyphen		291	370.08	0.78632		4484
Synonymous	-0.179	637	631	1.01	0.0000352	6862
Loss of Function	8.27	13	104	0.125	0.00000510	1490

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000905	0.0000905
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:16043844, ECO:0000269|PubMed:22739342}. Note=The disease is caused by mutations affecting the gene represented in this entry. The pathological mechanism involves a quantitave imbalance of the normally occurring splice variants (PubMed:22739342). {ECO:0000269|PubMed:22739342}.
• Pathway: Cell adhesion molecules (CAMs) - Homo sapiens (human);Spinal Cord Injury;Hair Follicle Development- Induction (Part 1 of 3);Metabolism of carbohydrates;Post-translational protein phosphorylation;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;Post-translational protein modification;Metabolism of proteins;Extracellular matrix organization;Metabolism;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);Integrin;Direct p53 effectors;ECM proteoglycans;Regulation of nuclear beta catenin signaling and target gene transcription;Endogenous TLR signaling (Consensus)

Recessive Scores

• pRec: 0.747

Intolerance Scores

• loftool: 0.00813
• rvis_EVS: -0.55
• rvis_percentile_EVS: 19.96

Haploinsufficiency Scores

• pHI: 0.995
• hipred: N
• hipred_score: 0.381
• ghis: 0.540

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.683

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Vcan
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; embryo phenotype; skeleton 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); limbs/digits/tail 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); normal 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)

Zebrafish Information Network

• Gene name: vcana
• Affected structure: pronephric podocyte
• Phenotype tag: abnormal
• Phenotype quality: increased width

Gene ontology

• Biological process: skeletal system development;osteoblast differentiation;cell adhesion;multicellular organism development;central nervous system development;cell recognition;extracellular matrix organization;chondroitin sulfate biosynthetic process;chondroitin sulfate catabolic process;dermatan sulfate biosynthetic process;post-translational protein modification;cellular protein metabolic process
• Cellular component: extracellular region;extracellular space;endoplasmic reticulum lumen;Golgi lumen;membrane;extracellular matrix;lysosomal lumen;collagen-containing extracellular matrix
• Molecular function: calcium ion binding;protein binding;glycosaminoglycan binding;hyaluronic acid binding;extracellular matrix structural constituent conferring compression resistance;carbohydrate binding