This gene encodes a member of the WNT1 inducible signaling pathway (WISP) protein subfamily, which belongs to the connective tissue growth factor (CTGF) family. WNT1 is a member of a family of cysteine-rich, glycosylated signaling proteins that mediate diverse developmental processes. The CTGF family members are characterized by four conserved cysteine-rich domains: insulin-lik... See more...

Aliases for CCN6 Gene

Aliases for CCN6 Gene

  • Cellular Communication Network Factor 6 2 3 4 5
  • WISP-3 2 3 4
  • WNT1 Inducible Signaling Pathway Protein 3 2 3
  • CCN Family Member 6 3 4
  • WISP3 3 4
  • Epididymis Secretory Sperm Binding Protein 3
  • WNT1-Inducible-Signaling Pathway Protein 3 4
  • LIBC 3
  • PPAC 3
  • PPRD 3
  • CCN6 5
  • PPD 3

External Ids for CCN6 Gene

Previous HGNC Symbols for CCN6 Gene

  • WISP3

Summaries for CCN6 Gene

Entrez Gene Summary for CCN6 Gene

  • This gene encodes a member of the WNT1 inducible signaling pathway (WISP) protein subfamily, which belongs to the connective tissue growth factor (CTGF) family. WNT1 is a member of a family of cysteine-rich, glycosylated signaling proteins that mediate diverse developmental processes. The CTGF family members are characterized by 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. This gene is overexpressed in colon tumors. It may be downstream in the WNT1 signaling pathway that is relevant to malignant transformation. Mutations of this gene are associated with progressive pseudorheumatoid dysplasia, an autosomal recessive skeletal disorder, indicating that the gene is essential for normal postnatal skeletal growth and cartilage homeostasis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GeneCards Summary for CCN6 Gene

CCN6 (Cellular Communication Network Factor 6) is a Protein Coding gene. Diseases associated with CCN6 include Progressive Pseudorheumatoid Dysplasia and Spondyloepiphyseal Dysplasia Tarda, Autosomal Recessive. An important paralog of this gene is CCN4.

UniProtKB/Swiss-Prot Summary for CCN6 Gene

  • Plays a role in mitochondrial electron transport and mitochondrial respiration (PubMed:27252383). Through its regulation of the mitochondrial function may play a role in normal postnatal skeletal growth and cartilage homeostasis (PubMed:27252383, PubMed:10471507).

Gene Wiki entry for CCN6 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CCN6 Gene

Genomics for CCN6 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for CCN6 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH06J112054 Promoter 0.8 EPDnew Ensembl 275.4 +1.8 1788 0.8 RNF2 CREB1 CCN6 HSALNG0052824 lnc-TUBE1-2 piR-50444-406 HSALNG0052825 TUBE1
GH06J112055 Promoter 0.4 EPDnew 274.5 +1.3 1272 0.1 CREB1 CCN6 HSALNG0052824 lnc-TUBE1-2 piR-50444-406 TUBE1
GH06J112061 Promoter 0.3 EPDnew 250.4 +8.4 8413 0.1 HSALNG0052825 CCN6 HSALNG0052826 TUBE1
GH06J112086 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas 22.3 +34.4 34388 2.8 MYC ZNF600 JUND POLR2A CEBPA YY1 MXD4 CEBPB KLF11 SMAD5 FAM229B HSALNG0052828 TUBE1 lnc-TUBE1-1 MFSD4B ENSG00000220506 CCN6 FCF1P5 ENSG00000237234 ENSG00000272356
GH06J112041 Promoter/Enhancer 1.7 FANTOM5 ENCODE CraniofacialAtlas dbSUPER 23.1 -8.8 -8848 4.4 BCLAF1 ZNF207 ZNF654 NCOR1 ATF2 CEBPA BRCA1 POLR2A CHD4 ZBTB10 lnc-TUBE1-8 CCN6 FAM229B TUBE1 FYN ENSG00000255389 TRAF3IP2 piR-43583-486 lnc-TUBE1-2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CCN6 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CCN6

Genomic Locations for CCN6 Gene

Latest Assembly
chr6:112,052,813-112,069,686
(GRCh38/hg38)
Size:
16,874 bases
Orientation:
Plus strand

Previous Assembly
chr6:112,375,307-112,390,889
(GRCh37/hg19 by Entrez Gene)
Size:
15,583 bases
Orientation:
Plus strand

chr6:112,375,275-112,392,171
(GRCh37/hg19 by Ensembl)
Size:
16,897 bases
Orientation:
Plus strand

Genomic View for CCN6 Gene

Genes around CCN6 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CCN6 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CCN6 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CCN6 Gene

Proteins for CCN6 Gene

  • Protein details for CCN6 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O95389-CCN6_HUMAN
    Recommended name:
    Cellular communication network factor 6
    Protein Accession:
    O95389
    Secondary Accessions:
    • Q3KR29
    • Q5H8W4
    • Q6UXH6

    Protein attributes for CCN6 Gene

    Size:
    354 amino acids
    Molecular mass:
    39293 Da
    Quaternary structure:
    No Data Available

    Alternative splice isoforms for CCN6 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CCN6 Gene

Post-translational modifications for CCN6 Gene

  • Glycosylation at Asn178 and Asn308
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for CCN6 Gene

Domains & Families for CCN6 Gene

Gene Families for CCN6 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins
  • Predicted secreted proteins

Protein Domains for CCN6 Gene

Suggested Antigen Peptide Sequences for CCN6 Gene

GenScript: Design optimal peptide antigens:
  • WNT1 inducible signaling pathway protein 3, isoform CRA_d (O95958_HUMAN)
  • WNT1 inducible signaling pathway protein 3 (Q3T1A9_HUMAN)
  • CCN family member 6 (WISP3_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O95389

UniProtKB/Swiss-Prot:

CCN6_HUMAN :
  • Belongs to the CCN family.
Family:
  • Belongs to the CCN family.
genes like me logo Genes that share domains with CCN6: view

Function for CCN6 Gene

Molecular function for CCN6 Gene

UniProtKB/Swiss-Prot Function:
Plays a role in mitochondrial electron transport and mitochondrial respiration (PubMed:27252383). Through its regulation of the mitochondrial function may play a role in normal postnatal skeletal growth and cartilage homeostasis (PubMed:27252383, PubMed:10471507).

Phenotypes From GWAS Catalog for CCN6 Gene

Gene Ontology (GO) - Molecular Function for CCN6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005178 integrin binding IBA 21873635
GO:0005520 insulin-like growth factor binding IEA --
GO:0008083 growth factor activity IEA --
GO:0008201 heparin binding IBA 21873635
genes like me logo Genes that share ontologies with CCN6: view
genes like me logo Genes that share phenotypes with CCN6: view

Human Phenotype Ontology for CCN6 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for CCN6 Gene

MGI Knock Outs for CCN6:
  • Ccn6 Ccn6<tm2Mawa>

Animal Models for research

  • Taconic Biosciences Mouse Models for CCN6

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CCN6

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for CCN6 Gene

Localization for CCN6 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CCN6 Gene

Secreted. Mitochondrion. Note=Associated with membranes. {ECO:0000269 PubMed:27252383}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CCN6 gene
Compartment Confidence
extracellular 5
mitochondrion 5
endoplasmic reticulum 4
plasma membrane 3
cytoskeleton 2
nucleus 2
cytosol 1
peroxisome 0
lysosome 0
golgi apparatus 0

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for CCN6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space NAS 9843955
GO:0005739 mitochondrion IEA,IDA 27252383
GO:0031012 extracellular matrix IBA 21873635
genes like me logo Genes that share ontologies with CCN6: view

Pathways & Interactions for CCN6 Gene

PathCards logo

SuperPathways for CCN6 Gene

No Data Available

Gene Ontology (GO) - Biological Process for CCN6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007155 cell adhesion IBA 21873635
GO:0007165 signal transduction IEA,IBA 21873635
GO:0007267 cell-cell signaling TAS 9843955
GO:0008285 negative regulation of cell proliferation IDA 12082632
GO:0016525 negative regulation of angiogenesis IDA 12082632
genes like me logo Genes that share ontologies with CCN6: view

No data available for Pathways by source and SIGNOR curated interactions for CCN6 Gene

Drugs & Compounds for CCN6 Gene

(2) Drugs for CCN6 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(1) Additional Compounds for CCN6 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with CCN6: view

Transcripts for CCN6 Gene

mRNA/cDNA for CCN6 Gene

3 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
11 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CCN6

Alternative Splicing Database (ASD) splice patterns (SP) for CCN6 Gene

No ASD Table

Relevant External Links for CCN6 Gene

GeneLoc Exon Structure for
CCN6

Expression for CCN6 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CCN6

SOURCE GeneReport for Unigene cluster for CCN6 Gene:

Hs.558428

mRNA Expression by UniProt/SwissProt for CCN6 Gene:

O95389-CCN6_HUMAN
Tissue specificity: Predominant expression in adult kidney and testis and fetal kidney. Weaker expression found in placenta, ovary, prostate and small intestine (PubMed:9843955, PubMed:10471507). Also expressed in skeletally-derived cells such as synoviocytes and articular cartilage chondrocytes (PubMed:10471507).

Evidence on tissue expression from TISSUES for CCN6 Gene

  • Bone marrow(4.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for CCN6 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • head
  • jaw
  • mandible
  • maxilla
  • mouth
  • neck
  • skull
Thorax:
  • chest wall
  • clavicle
  • lung
  • rib
  • rib cage
  • scapula
  • sternum
Pelvis:
  • pelvis
Limb:
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
General:
  • peripheral nerve
  • peripheral nervous system
  • spinal column
  • vertebrae

Primer products for research

No data available for mRNA expression in normal human tissues , mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein differential expression in normal tissues , Protein expression and Protein tissue co-expression partners for CCN6 Gene

Orthologs for CCN6 Gene

This gene was present in the common ancestor of animals.

Orthologs for CCN6 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia WISP3 29 30
  • 99.1 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia WISP3 29 30
  • 87.48 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Wisp3 29 30
  • 82.39 (n)
OneToOne
Ccn6 16
Dog
(Canis familiaris)
Mammalia WISP3 30
  • 82 (a)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Wisp3 29
  • 80.79 (n)
Oppossum
(Monodelphis domestica)
Mammalia WISP3 30
  • 77 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia WISP3 30
  • 74 (a)
OneToOne
Chicken
(Gallus gallus)
Aves WISP3 29 30
  • 70.9 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia WISP3 30
  • 65 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia wisp3 29
  • 65.73 (n)
Zebrafish
(Danio rerio)
Actinopterygii wisp3 29 30
  • 60.48 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta Ccn 30
  • 14 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 28 (a)
OneToOne
Species where no ortholog for CCN6 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for CCN6 Gene

ENSEMBL:
Gene Tree for CCN6 (if available)
TreeFam:
Gene Tree for CCN6 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CCN6: view image
Alliance of Genome Resources:
Additional Orthologs for CCN6

Paralogs for CCN6 Gene

Paralogs for CCN6 Gene

genes like me logo Genes that share paralogs with CCN6: view

Variants for CCN6 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CCN6 Gene

SNP ID Clinical significance and condition Chr 06 pos Variation AA Info Type
1006632 Uncertain Significance: not provided 112,068,263(+) G/C
NM_198239.2(CCN6):c.648G>C (p.Trp216Cys)
MISSENSE_VARIANT,NON_CODING_TRANSCRIPT
1018220 Uncertain Significance: not provided 112,054,400(+) G/A
NM_198239.2(CCN6):c.43G>A (p.Ala15Thr)
MISSENSE_VARIANT,NON_CODING_TRANSCRIPT
1030720 Uncertain Significance: Progressive pseudorheumatoid dysplasia 112,054,386(+) T/C
NM_198239.2(CCN6):c.29T>C (p.Leu10Pro)
MISSENSE_VARIANT,NON_CODING_TRANSCRIPT
869151 Pathogenic: Progressive pseudorheumatoid dysplasia 112,069,349(+) G/GA
NM_198239.2(CCN6):c.799dup (p.Thr267fs)
FRAMESHIFT_VARIANT,NON_CODING_TRANSCRIPT
903725 Uncertain Significance: Progressive pseudorheumatoid dysplasia 112,064,943(+) T/G
NM_198239.2(CCN6):c.535T>G (p.Cys179Gly)
MISSENSE_VARIANT,NON_CODING_TRANSCRIPT

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for CCN6 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for CCN6 Gene

Variant ID Type Subtype PubMed ID
esv3352560 CNV insertion 20981092
nsv830774 CNV gain 17160897

Variation tolerance for CCN6 Gene

Residual Variation Intolerance Score: 78.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.00; 60.17% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CCN6 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
CCN6
Leiden Open Variation Database (LOVD)
CCN6

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CCN6 Gene

Disorders for CCN6 Gene

MalaCards: The human disease database

(11) MalaCards diseases for CCN6 Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

Disorder Aliases PubMed IDs
progressive pseudorheumatoid dysplasia
  • pprd
spondyloepiphyseal dysplasia tarda, autosomal recessive
  • autosomal recessive spondyloepiphyseal dysplasia tarda
arthropathy
  • ankylosis of ankle and foot joint
inflammatory breast carcinoma
  • inflammatory carcinoma of breast
spondyloepiphyseal dysplasia tarda, x-linked
  • sedt
- elite association - COSMIC cancer census association via MalaCards
Search CCN6 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

CCN6_HUMAN
  • Progressive pseudorheumatoid arthropathy of childhood (PPAC) [MIM:208230]: Autosomal recessive disorder characterized by stiffness and swelling of joints, motor weakness and joint contractures. Signs and symptoms of the disease develop typically between three and eight years of age. This progressive disease is a primary disorder of articular cartilage with continued cartilage loss and destructive bone changes with aging. {ECO:0000269 PubMed:10471507, ECO:0000269 PubMed:16152649, ECO:0000269 PubMed:19064006, ECO:0000269 PubMed:22685593, ECO:0000269 PubMed:22987568, ECO:0000269 PubMed:25738435, ECO:0000269 PubMed:25794430, ECO:0000269 PubMed:25988854, ECO:0000269 PubMed:27436824, ECO:0000269 PubMed:29092958}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for CCN6

genes like me logo Genes that share disorders with CCN6: view

No data available for Genatlas for CCN6 Gene

Publications for CCN6 Gene

  1. 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. (PMID: 9843955) Pennica D … Levine AJ (Proceedings of the National Academy of Sciences of the United States of America 1998) 2 3 4 22
  2. WISP3 mutation associated with pseudorheumatoid dysplasia. (PMID: 29092958) Sailani MR … Snyder MP (Cold Spring Harbor molecular case studies 2018) 3 4 72
  3. Novel and recurrent mutations in WISP3 and an atypical phenotype. (PMID: 25988854) Bhavani GS … Girisha KM (American journal of medical genetics. Part A 2015) 3 4 72
  4. Analysis of the WISP3 gene in Indian families with progressive pseudorheumatoid dysplasia. (PMID: 22987568) Dalal A … Girisha KM (American journal of medical genetics. Part A 2012) 3 4 72
  5. Identification of novel mutations in WISP3 gene in two unrelated Chinese families with progressive pseudorheumatoid dysplasia. (PMID: 19064006) Yue H … He JW (Bone 2009) 3 4 22

Products for CCN6 Gene

Sources for CCN6 Gene