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

Gene ID: 8838, updated on 2-Nov-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
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Genomic context

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See CCN6 in Genome Data Viewer
Location:
6q21
Exon count:
10
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (112052813..112069686)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (113236232..113253104)
RS_2024_09 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 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. A novel compound WISP3 mutation in a Chinese family with progressive pseudorheumatoid dysplasia. Luo H, et al. Gene, 2015 Jun 10. PMID 25794430
  2. Cellular and molecular responses in progressive pseudorheumatoid dysplasia articular cartilage associated with compound heterozygous WISP3 gene mutation. Zhou HD, et al. J Mol Med (Berl), 2007 Sep. PMID 17483925
  3. Identification of novel mutations in WISP3 gene in two unrelated Chinese families with progressive pseudorheumatoid dysplasia. Yue H, et al. Bone, 2009 Apr. PMID 19064006
  4. Frameshift mutation of WISP3 gene and its regional heterogeneity in gastric and colorectal cancers. Lee JH, et al. Hum Pathol, 2016 Apr. PMID 26997449
  5. Early severe scoliosis in a patient with atypical progressive pseudorheumatoid dysplasia (PPD): Identification of two WISP3 mutations, one previously unreported. Montané LS, et al. Am J Med Genet A, 2016 Jun. PMID 26991965

See all (77) 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
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Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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_2024_08

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

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