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WISP3 (WNT-1 inducible signaling pathway protein 3)

Identity

Other namesPPD
CCN6
LIBC
PPAC
Wnt1 signaling pathway protein 3
HGNC (Hugo) WISP3
LocusID (NCBI) 8838
Location 6q21
Location_base_pair Starts at 112375278 and ends at 112390887 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

Description 5 exons spanning 967kb of genomic
Transcription Alternative splicing generates at least three transcript variants, their sizes are 1212bp, 1307 bp and 1068 bp

Protein

 
Description WISP3 contains four conserved cysteine-rich domains: insulin-like growth factor-binding domain, von Willebrand factor type C module, thrombospondin domain and C-terminal cystine knot-like domain. It has three isoforms: 1) variant 1, 354 aa, 39292 Da; 2) variant 2, 331 aa, This variant differs from variant 1 in two regions. It has an alternate 5' end which results in a different N-terminus. It also uses two alternative donor and acceptor sites in the middle coding region which result in a few internal aa differences between variant 1 and 2. 3) variant 3, 372 aa, This variant differs in the 5' UTR and CDS, compared to variant 1. The resulting protein is longer and has a distinct N-terminus, compared to variant 1.
Expression Predominant expression in adult kidney and testis and fetal kidney. Weaker expression found in placenta, ovary, prostate and small intestine. Also expressed in skeletally-derived cells such as synoviocytes and articular cartilage chondrocytes.
Localisation Secreted (Probable).
Function It is a member of the WNT1 inducible signaling pathway (WISP) protein subfamily, which belongs to the connective tissue growth factor (CTGF) family and may be downstream in the WNT1 signaling pathway that is relevant to malignant transformation. It is over-expressed in colon tumors. It is essential for normal postnatal skeletal growth and cartilage homeostasis. It acts as a putative growth regulator contributing to the inflammatory breast cancer by regulating tumor cell growth, invasion and angiogenesis.
Homology Wnt1-inducible signaling proteins

Mutations

Germinal Various types of mutations have been described, dispersed throughout the gene, including nucleotide substitutions, small deletions and small insertions. There are patients who are compound heterozygous, heterozygous or homozygous. The mutations cause progressive pseudorheumatoid dysplasia.
Somatic Somatic mutations that cause reading frameshifts at a polyadenosine tract within the WISP3 coding sequence have been observed at higher-than-expected rates in gastrointestinal tumors from patients with mutations in the mismatch repair pathway.

Implicated in

Entity Arthropathy, progressive pseudorheumatoid, of childhood
Disease Mutations in the WISP3 gene result in an arthropathy of childhood beginning at about age 3-8. Usually several joints were affected with pain and soft tissue swelling. The proximal interphalangeal joints of the hand were most commonly affected and the hips and elbows next most often involved.
  
Entity Inflammatory breast cancer
Oncogenesis Loss of WISP3 is one of the key genetic alterations in the development of IBC.
  
Entity Rheumatoid arthritis
  
Entity Colon cancer
Oncogenesis Frameshifts, non-sense mutations and non-synonymous changes involving cysteines or affect a splice-donor site.
  

Other Solid tumors implicated (Data extracted from papers in the Atlas)

Solid Tumors AmeloblastomID5945

External links

Nomenclature
HGNC (Hugo)WISP3   12771
Cards
AtlasWISP3ID469ch6q22
Entrez_Gene (NCBI)WISP3  8838  WNT1 inducible signaling pathway protein 3
GeneCards (Weizmann)WISP3
Ensembl (Hinxton)ENSG00000112761 [Gene_View]  chr6:112375278-112390887 [Contig_View]  WISP3 [Vega]
ICGC DataPortalENSG00000112761
cBioPortalWISP3
AceView (NCBI)WISP3
Genatlas (Paris)WISP3
WikiGenes8838
SOURCE (Princeton)NM_003880 NM_130396 NM_198239
Genomic and cartography
GoldenPath (UCSC)WISP3  -  6q21   chr6:112375278-112390887 +  6q21   [Description]    (hg19-Feb_2009)
EnsemblWISP3 - 6q21 [CytoView]
Mapping of homologs : NCBIWISP3 [Mapview]
OMIM208230   603400   
Gene and transcription
Genbank (Entrez)AB075040 AF100781 AF143679 AY358349 AY358350
RefSeq transcript (Entrez)NM_003880 NM_130396 NM_198239
RefSeq genomic (Entrez)AC_000138 NC_000006 NC_018917 NG_011748 NT_025741 NW_001838990 NW_004929328
Consensus coding sequences : CCDS (NCBI)WISP3
Cluster EST : UnigeneHs.558428 [ NCBI ]
CGAP (NCI)Hs.558428
Alternative Splicing : Fast-db (Paris)GSHG0025976
Alternative Splicing GalleryENSG00000112761
Gene ExpressionWISP3 [ NCBI-GEO ]     WISP3 [ SEEK ]   WISP3 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO95389 (Uniprot)
NextProtO95389  [Medical]
With graphics : InterProO95389
Splice isoforms : SwissVarO95389 (Swissvar)
Domaine pattern : Prosite (Expaxy)CTCK_2 (PS01225)    IGFBP_N_1 (PS00222)    IGFBP_N_2 (PS51323)    TSP1 (PS50092)   
Domains : Interpro (EBI)Cys_knot_C [organisation]   Glyco_hormone_CN [organisation]   Growth_fac_rcpt_N_dom [organisation]   IGFBP-like [organisation]   IGFBP_CNN [organisation]   Insulin_GF-bd_Cys-rich_CS [organisation]   Thrombospondin_1_rpt [organisation]  
Related proteins : CluSTrO95389
Domain families : Pfam (Sanger)Cys_knot (PF00007)    IGFBP (PF00219)    TSP_1 (PF00090)   
Domain families : Pfam (NCBI)pfam00007    pfam00219    pfam00090   
Domain families : Smart (EMBL)CT (SM00041)  IB (SM00121)  TSP1 (SM00209)  
DMDM Disease mutations8838
Blocks (Seattle)O95389
Human Protein AtlasENSG00000112761 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasO95389
HPRD04550
IPIIPI00022051   IPI00419732   IPI00383246   IPI00412939   IPI00917794   IPI00515003   IPI01010374   
Protein Interaction databases
DIP (DOE-UCLA)O95389
IntAct (EBI)O95389
FunCoupENSG00000112761
BioGRIDWISP3
InParanoidO95389
Interologous Interaction database O95389
IntegromeDBWISP3
STRING (EMBL)WISP3
Ontologies - Pathways
Ontology : AmiGOregulation of cell growth  insulin-like growth factor binding  extracellular space  signal transduction  cell-cell signaling  growth factor activity  
Ontology : EGO-EBIregulation of cell growth  insulin-like growth factor binding  extracellular space  signal transduction  cell-cell signaling  growth factor activity  
Protein Interaction DatabaseWISP3
Wikipedia pathwaysWISP3
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)WISP3
snp3D : Map Gene to Disease8838
SNP (GeneSNP Utah)WISP3
SNP : HGBaseWISP3
Genetic variants : HAPMAPWISP3
Exome VariantWISP3
1000_GenomesWISP3 
ICGC programENSG00000112761 
Somatic Mutations in Cancer : COSMICWISP3 
CONAN: Copy Number AnalysisWISP3 
Mutations and Diseases : HGMDWISP3
Mutations and Diseases : intOGenWISP3
Genomic VariantsWISP3  WISP3 [DGVbeta]
dbVarWISP3
ClinVarWISP3
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM208230    603400   
MedgenWISP3
GENETestsWISP3
Disease Genetic AssociationWISP3
Huge Navigator WISP3 [HugePedia]  WISP3 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneWISP3
Homology/Alignments : Family Browser (UCSC)WISP3
Phylogenetic Trees/Animal Genes : TreeFamWISP3
Chemical/Protein Interactions : CTD8838
Chemical/Pharm GKB GenePA37374
Clinical trialWISP3
Cancer Resource (Charite)ENSG00000112761
Other databases
Probes
Litterature
PubMed39 Pubmed reference(s) in Entrez
CoreMineWISP3
iHOPWISP3
OncoSearchWISP3

Bibliography

WISP genes are members of the connective tissue growth factor family that are up-regulated in wnt-1-transformed cells and aberrantly expressed in human colon tumors.
Pennica D, Swanson TA, Welsh JW, Roy MA, Lawrence DA, Lee J, Brush J, Taneyhill LA, Deuel B, Lew M, Watanabe C, Cohen RL, Melhem MF, Finley GG, Quirke P, Goddard AD, Hillan KJ, Gurney AL, Botstein D, Levine AJ
Proceedings of the National Academy of Sciences of the United States of America. 1998 ; 95 (25) : 14717-14722.
PMID 9843955
 
Mutations in the CCN gene family member WISP3 cause progressive pseudorheumatoid dysplasia.
Hurvitz JR, Suwairi WM, Van Hul W, El-Shanti H, Superti-Furga A, Roudier J, Holderbaum D, Pauli RM, Herd JK, Van Hul EV, Rezai-Delui H, Legius E, Le Merrer M, Al-Alami J, Bahabri SA, Warman ML
Nature genetics. 1999 ; 23 (1) : 94-98.
PMID 10471507
 
A novel putative low-affinity insulin-like growth factor-binding protein, LIBC (lost in inflammatory breast cancer), and RhoC GTPase correlate with the inflammatory breast cancer phenotype.
van Golen KL, Davies S, Wu ZF, Wang Y, Bucana CD, Root H, Chandrasekharappa S, Strawderman M, Ethier SP, Merajver SD
Clinical cancer research : an official journal of the American Association for Cancer Research. 1999 ; 5 (9) : 2511-2519.
PMID 10499627
 
WNT1 inducible signaling pathway protein 3, WISP-3, a novel target gene in colorectal carcinomas with microsatellite instability.
Thorstensen L, Diep CB, Meling GI, Aagesen TH, Ahrens CH, Rognum TO, Lothe RA
Gastroenterology. 2001 ; 121 (6) : 1275-1280.
PMID 11729105
 
WISP3 is a novel tumor suppressor gene of inflammatory breast cancer.
Kleer CG, Zhang Y, Pan Q, van Golen KL, Wu ZF, Livant D, Merajver SD
Oncogene. 2002 ; 21 (20) : 3172-3180.
PMID 12082632
 
Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF, Zeeberg B, Buetow KH, Schaefer CF, Bhat NK, Hopkins RF, Jordan H, Moore T, Max SI, Wang J, Hsieh F, Diatchenko L, Marusina K, Farmer AA, Rubin GM, Hong L, Stapleton M, Soares MB, Bonaldo MF, Casavant TL, Scheetz TE, Brownstein MJ, Usdin TB, Toshiyuki S, Carninci P, Prange C, Raha SS, Loquellano NA, Peters GJ, Abramson RD, Mullahy SJ, Bosak SA, McEwan PJ, McKernan KJ, Malek JA, Gunaratne PH, Richards S, Worley KC, Hale S, Garcia AM, Gay LJ, Hulyk SW, Villalon DK, Muzny DM, Sodergren EJ, Lu X, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madan A, Young AC, Shevchenko Y, Bouffard GG, Blakesley RW, Touchman JW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Krzywinski MI, Skalska U, Smailus DE, Schnerch A, Schein JE, Jones SJ, Mammalian Gene Collection Program Team, Marra MA
Proceedings of the National Academy of Sciences of the United States of America. 2002 ; 99 (26) : 16899-16903.
PMID 12477932
 
Variant WISPs as targets for gastrointestinal carcinomas.
Tanaka S, Sugimachi K, Shimada M, Maehara Y, Sugimachi K
Gastroenterology. 2002 ; 123 (1) : 392-393.
PMID 12105881
 
The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.
Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A
Genome research. 2003 ; 13 (10) : 2265-2270.
PMID 12975309
 
WISP3 (CCN6) is a secreted tumor-suppressor protein that modulates IGF signaling in inflammatory breast cancer.
Kleer CG, Zhang Y, Pan Q, Merajver SD
Neoplasia (New York, N.Y.). 2004 ; 6 (2) : 179-185.
PMID 15140407
 
WISP3-dependent regulation of type II collagen and aggrecan production in chondrocytes.
Sen M, Cheng YH, Goldring MB, Lotz MK, Carson DA
Arthritis and rheumatism. 2004 ; 50 (2) : 488-497.
PMID 14872491
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written03-2005Celina G Kleer, Lei Ding
Department of Pathology, 2G332 University Hospital, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0054, USA

Citation

This paper should be referenced as such :
Kleer, CG ; Ding, L
WISP3 (wnt-1 inducible signaling pathway protein 3)
Atlas Genet Cytogenet Oncol Haematol. 2005;9(2):145-146.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/WISP3ID469ch6q22.html

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