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    CCN6 cellular communication network factor 6 [ Homo sapiens (human) ]

    Gene ID: 8838, updated on 3-Apr-2024

    Summary

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    Official Symbol
    CCN6provided by HGNC
    Official Full Name
    cellular communication network factor 6provided by HGNC
    Primary source
    HGNC:HGNC:12771
    See related
    Ensembl:ENSG00000112761 MIM:603400; AllianceGenome:HGNC:12771
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    PPD; LIBC; PPAC; PPRD; WISP3; WISP-3
    Summary
    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]
    Expression
    Biased expression in testis (RPKM 1.0), skin (RPKM 0.5) and 4 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    6q21
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (112052813..112069686)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (113236232..113253104)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (112375307..112390889)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:112229311-112229997 Neighboring gene long intergenic non-protein coding RNA 2527 Neighboring gene uncharacterized LOC105377947 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24958 Neighboring gene Sharpr-MPRA regulatory region 11311 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17484 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24959 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:112408399-112408930 Neighboring gene tubulin epsilon 1 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr6:112421446-112422235 Neighboring gene family with sequence similarity 229 member B

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. CCN6 improves hepatic steatosis, inflammation, and fibrosis in non-alcoholic steatohepatitis. Song Y, et al. Liver Int, 2023 Feb. PMID 36156376
    2. CCN6 regulates mitochondrial respiratory complex assembly and activity. Padhan DK, et al. FASEB J, 2020 Sep. PMID 32686858
    3. CCN6 mutation detection in Chinese patients with progressive pseudo-rheumatoid dysplasia and identification of four novel mutations. Wang Y, et al. Mol Genet Genomic Med, 2020 Jul. PMID 32351055, Free PMC Article
    4. Skeletal phenotype/genotype in progressive pseudorheumatoid chondrodysplasia. Al Kaissi A, et al. Clin Rheumatol, 2020 Feb. PMID 31628567
    5. Progressive Pseudorheumatoid Dysplasia resolved by whole exome sequencing: a novel mutation in WISP3 and review of the literature. Pode-Shakked B, et al. BMC Med Genet, 2019 Mar 29. PMID 30922245, Free PMC Article

    See all (74) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Dual roles of cellular communication network factor 6 (CCN6) in the invasion and metastasis of oral cancer cells to bone via binding to BMP2 and RANKL.
      Title: Dual roles of cellular communication network factor 6 (CCN6) in the invasion and metastasis of oral cancer cells to bone via binding to BMP2 and RANKL.
    2. Directed differentiation of human pluripotent stem cells into articular cartilage reveals effects caused by absence of WISP3, the gene responsible for progressive pseudorheumatoid arthropathy of childhood.
      Title: Directed differentiation of human pluripotent stem cells into articular cartilage reveals effects caused by absence of WISP3, the gene responsible for progressive pseudorheumatoid arthropathy of childhood.
    3. OTUB1 inhibits breast cancer by non-canonically stabilizing CCN6.
      Title: OTUB1 inhibits breast cancer by non-canonically stabilizing CCN6.
    4. Effects of CCN6 overexpression on the cell motility and activation of p38/bone morphogenetic protein signaling pathways in pancreatic cancer cells.
      Title: Effects of CCN6 overexpression on the cell motility and activation of p38/bone morphogenetic protein signaling pathways in pancreatic cancer cells.
    5. CCN6 influences transcription and controls mitochondrial mass and muscle organization.
      Title: CCN6 influences transcription and controls mitochondrial mass and muscle organization.
    6. CCN6 improves hepatic steatosis, inflammation, and fibrosis in non-alcoholic steatohepatitis.
      Title: CCN6 improves hepatic steatosis, inflammation, and fibrosis in non-alcoholic steatohepatitis.
    7. LncRNA RNA XIST binding to GATA1 contributes to rheumatoid arthritis through its effects on proliferation of synovial fibroblasts and angiogenesis via regulation of CCN6.
      Title: LncRNA RNA XIST binding to GATA1 contributes to rheumatoid arthritis through its effects on proliferation of synovial fibroblasts and angiogenesis via regulation of CCN6.
    8. WISP3 suppresses ESCC progression by inhibiting the IGF-2-IGF1R-AKT signaling cascade.
      Title: WISP3 suppresses ESCC progression by inhibiting the IGF-2-IGF1R-AKT signaling cascade.
    9. CCN6 mutation detection in Chinese patients with progressive pseudo-rheumatoid dysplasia and identification of four novel mutations.
      Title: CCN6 mutation detection in Chinese patients with progressive pseudo-rheumatoid dysplasia and identification of four novel mutations.
    10. CCN6 regulates mitochondrial respiratory complex assembly and activity.
      Title: CCN6 regulates mitochondrial respiratory complex assembly and activity.
    Submit: New GeneRIF Correction See all GeneRIFs (60)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Progressive pseudorheumatoid dysplasia
    MedGen: C0432215 OMIM: 208230 GeneReviews: Progressive Pseudorheumatoid Dysplasia
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC125987, MGC125988, MGC125989

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables growth factor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables heparin binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables integrin binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in cell adhesion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cell-cell signaling TAS
    Traceable Author Statement
    more info
    		 PubMed 
    acts_upstream_of_or_within negative regulation of angiogenesis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within negative regulation of cell population proliferation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of cell differentiation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of mitochondrial membrane potential IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of reactive oxygen species biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    is_active_in extracellular matrix IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in extracellular space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in extracellular space NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    cellular communication network factor 6
    Names
    CCN family member 6
    WNT1 inducible signaling pathway protein 3
    epididymis secretory sperm binding protein

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_011748.1 RefSeqGene

      Range
      5030..20612
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_003880.4 → NP_003871.1  cellular communication network factor 6 isoform 1 precursor

      See identical proteins and their annotated locations for NP_003871.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) has an alternate splice pattern near the 5' end and uses a downstream start codon, compared to variant 3. The resulting isoform (1) has a shorter N-terminus, compared to isoform 3.
      Source sequence(s)
      AL512299, BC012028, BC035250, BC105941
      Consensus CDS
      CCDS5098.1
      UniProtKB/Swiss-Prot
      O95389, Q3KR29, Q5H8W4, Q6UXH6
      UniProtKB/TrEMBL
      A0A384NYW3, O95958
      Related
      ENSP00000230529.5, ENST00000230529.9
      Conserved Domains (3) summary
      pfam00219
      Location:48 → 100
      IGFBP; Insulin-like growth factor binding protein
      pfam19035
      Location:209 → 252
      TSP1_CCN; CCN3 Nov like TSP1 domain
      cl21545
      Location:275 → 341
      GHB_like; Glycoprotein hormone beta chain homologues

    2. NM_198239.2 → NP_937882.2  cellular communication network factor 6 isoform 1 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) represents the longer transcript and encodes the longer isoform (3).
      Source sequence(s)
      AL512299, Z99289
      Consensus CDS
      CCDS5098.1
      UniProtKB/Swiss-Prot
      O95389, Q3KR29, Q5H8W4, Q6UXH6
      UniProtKB/TrEMBL
      A0A384NYW3, O95958
      Related
      ENSP00000357655.4, ENST00000368666.7
      Conserved Domains (3) summary
      pfam00219
      Location:48 → 100
      IGFBP; Insulin-like growth factor binding protein
      pfam19035
      Location:209 → 252
      TSP1_CCN; CCN3 Nov like TSP1 domain
      cl21545
      Location:275 → 341
      GHB_like; Glycoprotein hormone beta chain homologues

    RNA

    1. NR_125353.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) contains an alternate internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AL512299, BC035250, BC105940
      Related
      ENST00000368664.7

    2. NR_125354.3 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) contains an alternate internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      BC012028, BC035250, BG928545
      Related
      ENST00000454589.5

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      112052813..112069686
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047419469.1 → XP_047275425.1  cellular communication network factor 6 isoform X2

    2. XM_011536222.2 → XP_011534524.2  cellular communication network factor 6 isoform X4

      Conserved Domains (1) summary
      pfam00219
      Location:69 → 121
      IGFBP; Insulin-like growth factor binding protein

    3. XM_011536220.1 → XP_011534522.1  cellular communication network factor 6 isoform X1

      See identical proteins and their annotated locations for XP_011534522.1

      UniProtKB/Swiss-Prot
      O95389, Q3KR29, Q5H8W4, Q6UXH6
      UniProtKB/TrEMBL
      A0A384NYW3, O95958
      Conserved Domains (3) summary
      pfam00219
      Location:48 → 100
      IGFBP; Insulin-like growth factor binding protein
      pfam19035
      Location:209 → 252
      TSP1_CCN; CCN3 Nov like TSP1 domain
      cl21545
      Location:275 → 341
      GHB_like; Glycoprotein hormone beta chain homologues

    4. XM_011536223.4 → XP_011534525.1  cellular communication network factor 6 isoform X3

      UniProtKB/TrEMBL
      Q3T1A9
      Conserved Domains (1) summary
      cl21545
      Location:81 → 147
      GHB_like; Glycoprotein hormone beta chain homologues

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      113236232..113253104
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054356669.1 → XP_054212644.1  cellular communication network factor 6 isoform X2

    2. XM_054356671.1 → XP_054212646.1  cellular communication network factor 6 isoform X4

    3. XM_054356668.1 → XP_054212643.1  cellular communication network factor 6 isoform X1

      UniProtKB/Swiss-Prot
      O95389, Q3KR29, Q5H8W4, Q6UXH6
      UniProtKB/TrEMBL
      A0A384NYW3

    4. XM_054356670.1 → XP_054212645.1  cellular communication network factor 6 isoform X3

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_130396.1: Suppressed sequence

      Description
      NM_130396.1: This RefSeq was permanently suppressed because currently there is not sufficient data to support this transcript.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O95389.1 GenPept UniProtKB/Swiss-Prot:O95389

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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