CCN6 (cellular communication network factor 6)

Gene

• Entrez ID: 8838
• Gene name: Cellular communication network factor 6
• Gene symbol: CCN6
• Synonyms (NCBI Gene): LIBC, PPAC, PPD, PPRD, WISP-3, WISP3
• Chromosome: 6
• Chromosome location: 6q21
• 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 di

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121908899	G>A,C	Pathogenic	Non coding transcript variant, intron variant, 5 prime UTR variant, missense variant, coding sequence variant
rs121908900	G>A	Pathogenic	Genic downstream transcript variant, non coding transcript variant, stop gained, coding sequence variant
rs121908901	C>A,T	Pathogenic	Non coding transcript variant, upstream transcript variant, synonymous variant, genic upstream transcript variant, stop gained, coding sequence variant
rs121908902	T>C	Pathogenic	Non coding transcript variant, upstream transcript variant, genic upstream transcript variant, missense variant, coding sequence variant
rs121908903	T>C	Pathogenic	Genic downstream transcript variant, non coding transcript variant, missense variant, coding sequence variant
rs727503755	GT>-	Pathogenic-likely-pathogenic	Downstream transcript variant, frameshift variant, coding sequence variant, non coding transcript variant, genic downstream transcript variant
rs781838640	AG>-	Pathogenic	Non coding transcript variant, genic downstream transcript variant, frameshift variant, coding sequence variant
rs781986930	G>A,C	Pathogenic	Non coding transcript variant, genic downstream transcript variant, missense variant, coding sequence variant
rs797044438	A>-	Pathogenic	Coding sequence variant, frameshift variant, upstream transcript variant, genic upstream transcript variant, non coding transcript variant
rs797044439	->T	Pathogenic	Genic upstream transcript variant, splice donor variant
rs797044440	T>-	Pathogenic	Genic downstream transcript variant, frameshift variant, coding sequence variant, non coding transcript variant
rs863223286	->AC	Pathogenic	Genic downstream transcript variant, frameshift variant, coding sequence variant, non coding transcript variant
rs879255273	G>A	Pathogenic	Intron variant, splice donor variant
rs1554311394	GC>-	Pathogenic	Frameshift variant, coding sequence variant, non coding transcript variant, genic upstream transcript variant
rs1554313639	G>A,C	Likely-pathogenic	Missense variant, coding sequence variant, non coding transcript variant, intron variant
rs1554314738	->C	Pathogenic	Genic downstream transcript variant, coding sequence variant, non coding transcript variant, frameshift variant
rs1562595388	G>A	Pathogenic	Coding sequence variant, upstream transcript variant, non coding transcript variant, genic upstream transcript variant, missense variant
rs1562599153	T>-	Pathogenic	Coding sequence variant, frameshift variant, genic downstream transcript variant, non coding transcript variant, downstream transcript variant
rs1583586843	G>-	Pathogenic	Downstream transcript variant, frameshift variant, non coding transcript variant, genic downstream transcript variant, coding sequence variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005178	Function	Integrin binding	IBA
GO:0005576	Component	Extracellular region	IEA
GO:0005615	Component	Extracellular space	IBA
GO:0005615	Component	Extracellular space	IDA	27252383
GO:0005615	Component	Extracellular space	NAS	9843955
GO:0005739	Component	Mitochondrion	IDA	27252383
GO:0005739	Component	Mitochondrion	IEA
GO:0007155	Process	Cell adhesion	IBA
GO:0007165	Process	Signal transduction	IBA
GO:0007165	Process	Signal transduction	IEA
GO:0007165	Process	Signal transduction	TAS	9843955
GO:0007267	Process	Cell-cell signaling	TAS	9843955
GO:0008083	Function	Growth factor activity	IEA
GO:0008201	Function	Heparin binding	IBA
GO:0008285	Process	Negative regulation of cell population proliferation	IDA	12082632
GO:0016525	Process	Negative regulation of angiogenesis	IDA	12082632
GO:0031012	Component	Extracellular matrix	IBA
GO:0045597	Process	Positive regulation of cell differentiation	IBA
GO:0050793	Process	Regulation of developmental process	IEA
GO:0051881	Process	Regulation of mitochondrial membrane potential	IMP	27252383
GO:1903426	Process	Regulation of reactive oxygen species biosynthetic process	IMP	27252383

Other IDs

• MIM: 603400
• HGNC: 12771
• e!Ensembl: ENSG00000112761

Protein

• UniProt ID: O95389
• Protein name: Cellular communication network factor 6 (CCN family member 6) (WNT1-inducible-signaling pathway protein 3) (WISP-3)
• Protein 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:10471507
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00219	IGFBP	48 → 100	Insulin-like growth factor binding protein	Domain
  PF19035	TSP1_CCN	209 → 252	CCN3 Nov like TSP1 domain	Domain
  PF00007	Cys_knot	265 → 353	Cystine-knot domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Predominant expression in adult kidney and testis and fetal kidney. Weaker expression found in placenta, ovary, prostate and small intestine (PubMed:10471507, PubMed:9843955). Also expressed in skeletally-derived cells such as synovioc
• Sequence:

  MQGLLFSTLLLAGLAQFCCRVQGTGPLDTTPEGRPGEVSDAPQRKQFCHWPCKCPQQKPR
  CPPGVSLVRDGCGCCKICAKQPGEICNEADLCDPHKGLYCDYSVDRPRYETGVCAYLVAV
  GCEFNQVHYHNGQVFQPNPLFSCLCVSGAIGCTPLFIPKLAGSHCSGAKGGKKSDQSNCS
  LEPLLQQLSTSYKTMPAYRNLPLIWKKKCLVQATKWTPCSRTCGMGISNRVTNENSNCEM
  RKEKRLCYIQPCDSNILKTIKIPKGKTCQPTFQLSKAEKFVFSGCSSTQSYKPTFCGICL
  DKRCCIPNKSKMITIQFDCPNEGSFKWKMLWITSCVCQRNCREPGDIFSELKIL

• Sequence length: 354

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
CCN6-related disorder	Likely pathogenic; Pathogenic	rs863223286, rs2546928903	RCV003415669 RCV003393115
Progressive pseudorheumatoid dysplasia	Pathogenic; Likely pathogenic	rs781790231, rs2114469138, rs1776281365, rs2114473419, rs927750682, rs2114444927, rs727503755, rs782813346, rs2546929184, rs782172825, rs121908900, rs121908901, rs121908902, rs797044438, rs797044439, rs863223286, rs1554311394, rs121908903, rs797044440, rs2546914056, rs879255273, rs2546930511, rs2546920176, rs781864926, rs2546919773, rs2546929180, rs1776627236, rs781838640, rs781986930, rs1562599153, rs1562595388, rs1554313639, rs1583586843, rs1776805400	RCV002298943 RCV001785145 RCV005860302 RCV002238738 RCV002249330 RCV002251201 RCV000152703 RCV002470048 RCV002470575 RCV005433301 RCV000006752 RCV000006753 RCV000006754 RCV000006755 RCV000006756 RCV000006757 RCV000006758 RCV000006760 RCV000006761 RCV003155619 RCV000239146 RCV003230994 RCV003324475 RCV004821336 RCV005864688 RCV004579634 RCV004577145 RCV000520702 RCV000790883 RCV000770938 RCV000778771 RCV000789044 RCV001269330 RCV001078180
See cases	Likely pathogenic; Pathogenic	rs121908901	RCV001196832

Associations from Text Mining
Disease Name	Relationship Type	References
Arthritis	Associate	26183434
Arthritis Juvenile	Associate	16255026, 32894151
Arthritis Rheumatoid	Associate	22736089
Arthropathy progressive pseudorheumatoid of childhood	Associate	22294415, 22685593, 27291587, 29092958, 29246200, 29258992, 30075503, 30200995, 30635069, 30922245, 32430353, 32894151, 34749805, 35462544, 36550675
Breast Neoplasms	Inhibit	16457688, 18321996, 20395207
Breast Neoplasms	Associate	18593979, 21525039, 23226100, 37608493
Carcinogenesis	Associate	15802015, 22685593
Cartilage Diseases	Associate	30200995
Chondromatosis Synovial	Associate	32430353
Colorectal Neoplasms	Associate	20372786
Diabetes Mellitus	Associate	34951048
Disease Progression	Associate	32351055
Dwarfism	Associate	22685593
Edema	Associate	22685593
Genetic Diseases Inborn	Associate	22685593
HEM dysplasia	Associate	29246200, 30922245
IgA Vasculitis	Associate	32351055
Inflammation	Inhibit	16457688
Inflammation	Associate	18321996
Inflammatory Breast Neoplasms	Associate	14696649, 19198217
Inflammatory Breast Neoplasms	Inhibit	20395207
Joint Diseases	Associate	32894151
Lymphatic Metastasis	Inhibit	18321996, 20395207
Mammary Neoplasms Animal	Inhibit	16457688
Microsatellite Instability	Associate	15802015
Mouth Neoplasms	Associate	37590989
Neoplasm Metastasis	Associate	25400723, 37590989
Neoplasms	Inhibit	14696649, 18321996, 19198217, 21525039, 23226100, 37608493
Neoplasms	Associate	18593979, 25400723
Pleural Effusion	Associate	6982389
Spondyloepiphyseal Dysplasia Tarda Autosomal Recessive	Associate	36550675
Squamous Cell Carcinoma of Head and Neck	Associate	37590989
Stomach Neoplasms	Associate	25400723, 27633176
Tuberculosis	Associate	10691916, 11872098
Tuberculosis Pleural	Associate	6982389