CCN6

Protein identityUniProt · HPA

UniProt accession

O95389

Gene

CCN6

Ensembl

ENSG00000112761

Chromosome

6

Canonical length

354 aa

Protein class

Disease related genes, Human disease related genes, Predicted secreted proteins

Subcellular location

Mitochondria

Secretome location

Secreted to extracellular matrix

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

354 residues, UniProt reviewed canonical sequence.

>O95389|CCN6
     1  MQGLLFSTLL LAGLAQFCCR VQGTGPLDTT PEGRPGEVSD APQRKQFCHW PCKCPQQKPR
    61  CPPGVSLVRD GCGCCKICAK QPGEICNEAD LCDPHKGLYC DYSVDRPRYE TGVCAYLVAV
   121  GCEFNQVHYH NGQVFQPNPL FSCLCVSGAI GCTPLFIPKL AGSHCSGAKG GKKSDQSNCS
   181  LEPLLQQLST SYKTMPAYRN LPLIWKKKCL VQATKWTPCS RTCGMGISNR VTNENSNCEM
   241  RKEKRLCYIQ PCDSNILKTI KIPKGKTCQP TFQLSKAEKF VFSGCSSTQS YKPTFCGICL
   301  DKRCCIPNKS KMITIQFDCP NEGSFKWKML WITSCVCQRN CREPGDIFSE LKIL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CCN6 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.42

Highest tissue expression

9.6 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CCN6.

Disease | AllUniProt

Conditions CCN6 is implicated in, by any mechanism.

• Progressive pseudorheumatoid dysplasia (PPRD) MIM:208230

Disease | GeneticClinVar

68 pathogenic / likely-pathogenic of 255 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Progressive pseudorheumatoid dysplasia
• CCN6-related disorder
• Inborn genetic diseases
• See cases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.84

gnomAD pLI

0

DepMap mean gene effect

-0.04

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell adhesion
• cell-cell signaling
• negative regulation of angiogenesis
• negative regulation of cell population proliferation
• positive regulation of cell differentiation
• regulation of mitochondrial membrane potential
• regulation of reactive oxygen species biosynthetic process
• signal transduction

Molecular functions

• growth factor activity
• heparin binding
• integrin binding

Cellular components

• extracellular matrix
• extracellular space
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Insulin-like growth factor-binding protein, IGFBP
• Thrombospondin type-1 (TSP1) repeat
• Cystine knot, C-terminal
• Glycoprotein hormone subunit beta
• Growth factor receptor cysteine-rich domain superfamily
• IGFBP-related, CNN
• Insulin-like growth factor binding protein, N-terminal, Cys-rich conserved site
• Thrombospondin type-1 repeat superfamily
• CCN, TSP1 domain
• Cellular Communication Network Factor
• Cystine-knot domain
• Insulin-like growth factor binding protein
• CCN3 Nov like TSP1 domain

KeywordsUniProt

• Disulfide bond
• Glycoprotein
• Growth factor
• Mitochondrion
• Secreted
• Signal