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

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
CCN6-related disorder	Likely pathogenic; Pathogenic	rs863223286, rs2546928903	RCV003415669 RCV003393115	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
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	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ARTHROPATHY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DESBUQUOIS SYNDROME	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OLIGODENDROGLIOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PARKINSON DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PULMONARY EDEMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCOLIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPONDYLOEPIPHYSEAL DYSPLASIA, CONGENITA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acquired Kyphoscoliosis	Acquired Kyphoscoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Amyloidosis cutis dyschromia	Amyloidosis Cutis Dyschromia	BEFREE	28889150		★☆☆☆☆ Found in Text Mining only
Arthritis	Arthritis	BEFREE	15517620, 26183434, 30922245		★☆☆☆☆ Found in Text Mining only
Arthritis	Arthritis	Pubtator	26183434	Associate	★☆☆☆☆ Found in Text Mining only
Arthritis Juvenile	Juvenile arthritis	Pubtator	16255026, 32894151	Associate	★☆☆☆☆ Found in Text Mining only
Arthritis Rheumatoid	Rheumatoid arthritis	Pubtator	22736089	Associate	★☆☆☆☆ Found in Text Mining only
Arthropathy	Arthropathy	BEFREE	21528827		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Arthropathy	Arthropathy	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autistic Disorder	Autism	BEFREE	11916331		★☆☆☆☆ Found in Text Mining only
Avellino corneal dystrophy	Avellino Corneal Dystrophy	BEFREE	28889150		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	17406949, 17587813, 18321996, 20014943, 21525039, 22911819, 23226100, 27819674, 29357008		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	16457688, 18321996, 20395207	Inhibit	★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	18593979, 21525039, 23226100, 37608493	Associate	★☆☆☆☆ Found in Text Mining only
Buruli Ulcer	Buruli Ulcer	BEFREE	10756149		★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	15802015, 22685593	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma	Carcinoma	BEFREE	18593979, 27819674, 29357008, 30220054		★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Cardiovascular Diseases	BEFREE	15899484		★☆☆☆☆ Found in Text Mining only
Cartilage Diseases	Cartilage disease	Pubtator	30200995	Associate	★☆☆☆☆ Found in Text Mining only
Chondrosarcoma	Chondrosarcoma	BEFREE	21391218, 28465477, 30237403		★☆☆☆☆ Found in Text Mining only
Colonic Neoplasms	Colonic Neoplasms	BEFREE	9843955		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	11729105, 20372786, 20403915, 26997449		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	20372786	Associate	★☆☆☆☆ Found in Text Mining only
Congenital Dysplasia Of The Hip	Developmental dysplasia of the hip	BEFREE	29680248		★☆☆☆☆ Found in Text Mining only
Congenital kyphoscoliosis	Congenital kyphoscoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Contact Dermatitis	Dermatitis	BEFREE	7233093		★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	BEFREE	15517620, 25986313		★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	LHGDN	15517620		★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Depression, Postpartum	Mental Depression	BEFREE	31533685		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes mellitus	Pubtator	34951048	Associate	★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	BEFREE	22685593		★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	Pubtator	22685593	Associate	★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Edema	Edema	Pubtator	22685593	Associate	★☆☆☆☆ Found in Text Mining only
FG syndrome	FG Syndrome	BEFREE	9475086		★☆☆☆☆ Found in Text Mining only
Fibrosis, Liver	Liver Fibrosis	BEFREE	29929367		★☆☆☆☆ Found in Text Mining only
Greig cephalopolysyndactyly syndrome	Greig Cephalopolysyndactyly Syndrome	BEFREE	22903559		★☆☆☆☆ Found in Text Mining only
Hypercholesterolemia, Familial	Hypercholesterolemia	BEFREE	15026427, 15899484		★☆☆☆☆ Found in Text Mining only
Hyperlipoproteinemia Type IIa	Hyperlipoproteinemia	BEFREE	15026427, 15899484		★☆☆☆☆ Found in Text Mining only
Inflammatory Breast Carcinoma	Breast Cancer	BEFREE	12082632, 14696649, 16457688, 18321996, 19198217, 20014943, 20131997, 29357008		★☆☆☆☆ Found in Text Mining only
Juvenile arthritis	Arthritis	BEFREE	16255026		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	LHGDN	15650268		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	30793395		★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung Neoplasms	BEFREE	24954872		★☆☆☆☆ Found in Text Mining only
Lymphadenitis	Lymphadenitis	BEFREE	30055739		★☆☆☆☆ Found in Text Mining only
Lymphatic Metastasis	Lymphatic metastasis	Pubtator	18321996, 20395207	Inhibit	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	17406949, 17587813, 18321996, 20014943, 21525039, 22911819, 23226100, 29357008		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of liver	Liver Cancer	BEFREE	30793395		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of pancreas	Pancreatic cancer	BEFREE	19203832		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	18253123		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of stomach	Stomach Neoplasms	BEFREE	25400723, 26428367		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	24954872, 29357008, 31382131		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	LHGDN	18321996		★☆☆☆☆ Found in Text Mining only
Mood Disorders	Mood Disorder	BEFREE	8297808		★☆☆☆☆ Found in Text Mining only
Mouth Neoplasms	Mouth neoplasm	Pubtator	37590989	Associate	★☆☆☆☆ Found in Text Mining only
Movement Disorders	Movement Disorders	CLINVAR_DG	22791401, 22987568, 23270760, 25988854, 29092958		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	11729105, 12082632, 14696649, 17587813, 18253123, 18321996, 19198217, 20014943, 21525039, 26997449, 27819674, 29357008, 29473838, 30220054, 30793395, 31571900		★☆☆☆☆ Found in Text Mining only
Non-Small Cell Lung Carcinoma	Lung carcinoma	BEFREE	31571900		★☆☆☆☆ Found in Text Mining only
Osteochondrodysplasias	Osteochondrodysplasia	LHGDN	17363178		★☆☆☆☆ Found in Text Mining only
Osteopenia	Osteopenia	BEFREE	29843053, 30389428		★☆☆☆☆ Found in Text Mining only
Osteoporosis	Osteoporosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pallister-Hall syndrome	Pallister-Hall Syndrome	BEFREE	10441570, 22903559		★☆☆☆☆ Found in Text Mining only
Pancreatic carcinoma	Pancreatic carcinoma	BEFREE	19203832		★☆☆☆☆ Found in Text Mining only
Paratuberculosis	Paratuberculosis	BEFREE	29483289		★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	BEFREE	23485738		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Periodontal Diseases	Periodontal Diseases	BEFREE	25280920, 27727278		★☆☆☆☆ Found in Text Mining only
Polydactyly	Polydactyly	BEFREE	12837695		★☆☆☆☆ Found in Text Mining only
POLYDACTYLY, POSTAXIAL	Polydactyly	BEFREE	15811011		★☆☆☆☆ Found in Text Mining only
Progressive pseudorheumatoid arthropathy of childhood	Pseudorheumatoid Arthropath	Orphanet			★☆☆☆☆ Found in Text Mining only
Progressive pseudorheumatoid dysplasia	Progressive Pseudorheumatoid Dysplasia	BEFREE	10471507, 15601861, 16152649, 17363178, 17483925, 17823661, 19064006, 21993478, 22294415, 22685593, 22791401, 22987568, 25553839, 25738435, 25794430, 26183434, 26991965, 27291587, 28802407, 29246200, 29312328, 29680248, 30096296, 30635069, 30922245		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Progressive pseudorheumatoid dysplasia	Progressive Pseudorheumatoid Dysplasia	UNIPROT_DG	10471507, 16152649, 19064006, 22685593, 22987568, 25738435, 25794430, 25988854, 27436824, 29092958		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Progressive pseudorheumatoid dysplasia	Progressive Pseudorheumatoid Dysplasia	CLINVAR_DG	10471507, 12819927, 16152649, 22791401, 22987568, 23270760, 25988854, 27436824, 29092958		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Progressive pseudorheumatoid dysplasia	Progressive Pseudorheumatoid Dysplasia	ORPHANET_DG	10471507, 22987568		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Progressive pseudorheumatoid dysplasia	Progressive Pseudorheumatoid Dysplasia	GENOMICS_ENGLAND_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Progressive pseudorheumatoid dysplasia	Progressive Pseudorheumatoid Dysplasia	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Prostate carcinoma	Prostate cancer	BEFREE	18253123		★☆☆☆☆ Found in Text Mining only
Pulmonary Fibrosis	Pulmonary Fibrosis	BEFREE	29353205		★☆☆☆☆ Found in Text Mining only
Radial polydactyly	Radial Polydactyly	BEFREE	15811011		★☆☆☆☆ Found in Text Mining only
Rheumatoid Arthritis	Rheumatoid arthritis	BEFREE	15517620, 25986313		★☆☆☆☆ Found in Text Mining only
Rheumatoid Arthritis	Rheumatoid arthritis	LHGDN	15517620		★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	8297808		★☆☆☆☆ Found in Text Mining only
Scoliosis, unspecified	Scoliosis	BEFREE	26991965		★☆☆☆☆ Found in Text Mining only
Scoliosis, unspecified	Scoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Spondyloepiphyseal Dysplasia	Spondyloepiphyseal dysplasia	BEFREE	26183434		★☆☆☆☆ Found in Text Mining only
Spondyloepiphyseal dysplasia, congenita	Spondyloepiphyseal dysplasia congenita	BEFREE	26183434		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	37590989	Associate	★☆☆☆☆ Found in Text Mining only
Stomach Carcinoma	Stomach Carcinoma	BEFREE	25400723, 26428367		★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	25400723, 27633176	Associate	★☆☆☆☆ Found in Text Mining only
Syndactyly	Syndactyly	BEFREE	15811011		★☆☆☆☆ Found in Text Mining only
Triple Negative Breast Neoplasms	Triple Negative Breast Neoplasms	BEFREE	30220054		★☆☆☆☆ Found in Text Mining only