Atlas of Genetics and Cytogenetics in Oncology and Haematology

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CTHRC1 (Collagen Triple Helix Repeat Containing 1)

Written2008-11Renee J LeClair, Tahir Durmus, Volkhard Lindner
Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA

(Note : for Links provided by Atlas : click)


Other aliasNMTC1
LocusID (NCBI) 115908
Atlas_Id 40193
Location 8q22.3  [Link to chromosome band 8q22]
Location_base_pair Starts at 103371515 and ends at 103383004 bp from pter ( according to hg19-Feb_2009)  [Mapping CTHRC1.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)


Description CTHRC1 spans 4 exons and is a 1.2 kb transcript.


Description Collagen Triple Helix Repeat Containing-1, CTHRC1, is a 30kDa secreted protein that has the ability to inhibit collagen matrix synthesis. CTHRC1 is glycosylated and retains a signal sequence consistent with it being secreted from the cell. Activity of the protein is reliant on removal of the propeptide and while CTHRC1 does not contain a predictable consensus propeptide cleavage site, there is direct evidence demonstrating the ability of plasmin to cleave the secreted protein at residues E46 and R96.
Expression The expression patterns of Cthrc1 during murine embryonic development and in postnatal tissues have been characterized with in situ hybridization and immunohistochemistry (see Durmus et al., 2007 for a complete review). Cthrc1 expression levels are induced in the adventitia and intimal smooth muscle after balloon catheter injury of arteries. Additionally, Cthrc1 is highly expressed in cartilage and developing bones as well as in myofibroblasts during skin wound healing. Indirect evidence for the expression of Cthrc1 by hair cells of the inner ear has been reported in a Cthrc1 mutant mouse with a beta-galactosidase expression construct replacing the first exon of Cthrc1. Expression of Cthrc1 is increased in fibroblasts and chondrocytic cells in response to TGF-beta family members including BMP4, BMP2 and TGF-beta. Cthrc1 is also upregulated during tumorigenesis and metastasis; its role during this process is unknown.
Localisation CTHRC1 has a signal peptide that targets it to the ER-Golgi pathway for secretion. In the extracellular environment the molecule is sensitive to cleavage by proteases such as plasmin. While CTHRC1 is abundant in cartilage matrix, the CTHRC1 protein has been observed in the cytoplasm of select cell types such as certain neuronal populations and parafollicular cells of the thyroid gland despite the presence of the signal peptide.
Function CTHRC1 has been linked to major signaling pathways such as Wnt and TGF-beta. The ability of CTHRC1 to inhibit TGF-beta signaling via a reduction in Smad 2/Smad 3 phosphorylation has been demonstrated both in vivo and in vitro models. This inhibition translates into a reduction in collagen type I deposition during vascular remodeling.
Characterization of Cthrc1 deficient mice indicated that the gene is not essential for normal development. Evidence from in vitro studies suggested that Cthrc1 may play a role in the Planar Cell Polarity (PCP) pathway of non-canonical Wnt signaling. Combinatorial mutations in both Cthrc1 alleles and a single allele of Vangl2, a gene previously shown to be involved in noncanonical Wnt signaling, resulted in animals lacking proper orientation of inner and outer ear hair cells. Further biochemical analysis showed Cthrc1 associated with several of the Frizzled family of receptors suggesting it may stabilize the receptor ligand complex on the cell surface. Cthrc1 deficient mice also demonstrated a reduction in bone density that was attributable to a reduction in osteoblast number and coverage. Mechanistically, it is unclear how this occurs but was shown to be due to a reduction in osteoblast proliferation rather than an increase in osteoclasts.
Homology CTHRC1 is a unique protein, displaying an extremely high level of conservation among vertebrates, but showing very little homology to other currently known proteins. Structurally, it contains a short collagen-like motif similar to the collagen domains present in the C1q/tumor necrosis factor-a-related proteins (CTRPs). Both CTHRC1 and CTRP members share a conserved and post-translationally modified lysine residue present in the collagen domain, but currently there are no data to suggest that the collagen domain of CTHRC1 leads to trimerization.

Implicated in

Entity Breast cancer
Disease Lobular carcinoma and invasive ductal carcinoma
Prognosis Undetermined. Suggested that CTHRC1 expression in these tumors is associated with cancer tissue invasion and metastasis.
Entity Solid cancers
Disease Melanomas, cancers of the rectum, small intestine, colon, liver, lung, ovary, breast, thyroid gland and cervix.
Prognosis CTHRC1 is upregulated in solid tumors. Linked expression levels to prognosis is undetermined.


Expression analysis of the novel gene collagen triple helix repeat containing-1 (Cthrc1).
Durmus T, LeClair RJ, Park KS, Terzic A, Yoon JK, Lindner V.
Gene Expr Patterns. 2006 Oct;6(8):935-40.
PMID 16678498
Differential gene expression profiling in HELLP syndrome placentas.
Kang BY, Tsoi S, Zhu S, Su S, Kay HH.
Reprod Sci. 2008 Apr;15(3):285-94.
PMID 18421023
Leading Wnt down a PCP path: Cthrc1 acts as a coreceptor in the Wnt-PCP pathway.
Kelley MW.
Dev Cell. 2008 Jul;15(1):7-8.
PMID 18606135
Cthrc1 is a positive regulator of osteoblastic bone formation.
Kimura H, Kwan KM, Zhang Z, Deng JM, Darnay BG, Behringer RR, Nakamura T, de Crombrugghe B, Akiyama H.
PLoS ONE. 2008 Sep 9;3(9):e3174.
PMID 18779865
The role of collagen triple helix repeat containing 1 in injured arteries, collagen expression, and transforming growth factor beta signaling.
LeClair R, Lindner V.
Trends Cardiovasc Med. 2007 Aug;17(6):202-5.
PMID 17662915
Cthrc1 is a novel inhibitor of transforming growth factor-beta signaling and neointimal lesion formation.
LeClair RJ, Durmus T, Wang Q, Pyagay P, Terzic A, Lindner V.
Circ Res. 2007 Mar 30;100(6):826-33.
PMID 17322174
Intracellular localization of Cthrc1 characterizes differentiated smooth muscle.
Leclair RJ, Wang Q, Benson MA, Prudovsky I, Lindner V.
Arterioscler Thromb Vasc Biol. 2008 Jul;28(7):1332-8.
PMID 18467647
Collagen triple helix repeat containing 1, a novel secreted protein in injured and diseased arteries, inhibits collagen expression and promotes cell migration.
Pyagay P, Heroult M, Wang Q, Lehnert W, Belden J, Liaw L, Friesel RE, Lindner V.
Circ Res. 2005 Feb 4;96(2):261-8.
PMID 15618538
Aberrant expression of collagen triple helix repeat containing 1 in human solid cancers.
Tang L, Dai DL, Su M, Martinka M, Li G, Zhou Y.
Clin Cancer Res. 2006 Jun 15;12(12):3716-22.
PMID 16778098
Novel markers for differentiation of lobular and ductal invasive breast carcinomas by laser microdissection and microarray analysis.
Turashvili G, Bouchal J, Baumforth K, Wei W, Dziechciarkova M, Ehrmann J, Klein J, Fridman E, Skarda J, Srovnal J, Hajduch M, Murray P, Kolar Z.
BMC Cancer. 2007 Mar 27;7:55.
PMID 17389037
[Construction of a subtracted cDNA library of chronic intermittent hypoxia rabbit liver by suppression subtractive hybridization].
Wu YT, Liu RH, Yang Y, Luo YQ, Rong Y.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2007 Dec;32(6):1013-9.
PMID 18182719
Cthrc1 selectively activates the planar cell polarity pathway of Wnt signaling by stabilizing the Wnt-receptor complex.
Yamamoto S, Nishimura O, Misaki K, Nishita M, Minami Y, Yonemura S, Tarui H, Sasaki H.
Dev Cell. 2008 Jul;15(1):23-36.
PMID 18606138


This paper should be referenced as such :
LeClair, R ; Durmus, T ; Lindner, V
CTHRC1 (Collagen Triple Helix Repeat Containing 1)
Atlas Genet Cytogenet Oncol Haematol. 2009;13(10):719-720.
Free journal version : [ pdf ]   [ DOI ]
On line version :

External links

HGNC (Hugo)CTHRC1   18831
Entrez_Gene (NCBI)CTHRC1  115908  collagen triple helix repeat containing 1
GeneCards (Weizmann)CTHRC1
Ensembl hg19 (Hinxton)ENSG00000164932 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000164932 [Gene_View]  ENSG00000164932 [Sequence]  chr8:103371515-103383004 [Contig_View]  CTHRC1 [Vega]
ICGC DataPortalENSG00000164932
Genatlas (Paris)CTHRC1
SOURCE (Princeton)CTHRC1
Genetics Home Reference (NIH)CTHRC1
Genomic and cartography
GoldenPath hg38 (UCSC)CTHRC1  -     chr8:103371515-103383004 +  8q22.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CTHRC1  -     8q22.3   [Description]    (hg19-Feb_2009)
EnsemblCTHRC1 - 8q22.3 [CytoView hg19]  CTHRC1 - 8q22.3 [CytoView hg38]
Mapping of homologs : NCBICTHRC1 [Mapview hg19]  CTHRC1 [Mapview hg38]
OMIM610635   614266   
Gene and transcription
Genbank (Entrez)AF395488 AI743774 AK130063 AK300273 AY136825
RefSeq transcript (Entrez)NM_001256099 NM_138455
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)CTHRC1
Cluster EST : UnigeneHs.405614 [ NCBI ]
CGAP (NCI)Hs.405614
Alternative Splicing GalleryENSG00000164932
Gene ExpressionCTHRC1 [ NCBI-GEO ]   CTHRC1 [ EBI - ARRAY_EXPRESS ]   CTHRC1 [ SEEK ]   CTHRC1 [ MEM ]
Gene Expression Viewer (FireBrowse)CTHRC1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)115908
GTEX Portal (Tissue expression)CTHRC1
Human Protein AtlasENSG00000164932-CTHRC1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ96CG8   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ96CG8  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ96CG8
Splice isoforms : SwissVarQ96CG8
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)CTHRC1
DMDM Disease mutations115908
Blocks (Seattle)CTHRC1
Human Protein Atlas [tissue]ENSG00000164932-CTHRC1 [tissue]
Peptide AtlasQ96CG8
IPIIPI00060423   IPI00336091   IPI00909154   IPI00983832   
Protein Interaction databases
IntAct (EBI)Q96CG8
Ontologies - Pathways
Ontology : AmiGOfrizzled binding  extracellular region  collagen trimer  extracellular space  cytoplasm  cell migration  Wnt-protein binding  extracellular matrix  positive regulation of protein binding  positive regulation of osteoblast proliferation  ossification involved in bone remodeling  positive regulation of osteoblast differentiation  Wnt signaling pathway, planar cell polarity pathway  inner ear receptor cell stereocilium organization  negative regulation of canonical Wnt signaling pathway  cochlea morphogenesis  establishment of planar polarity involved in neural tube closure  
Ontology : EGO-EBIfrizzled binding  extracellular region  collagen trimer  extracellular space  cytoplasm  cell migration  Wnt-protein binding  extracellular matrix  positive regulation of protein binding  positive regulation of osteoblast proliferation  ossification involved in bone remodeling  positive regulation of osteoblast differentiation  Wnt signaling pathway, planar cell polarity pathway  inner ear receptor cell stereocilium organization  negative regulation of canonical Wnt signaling pathway  cochlea morphogenesis  establishment of planar polarity involved in neural tube closure  
NDEx NetworkCTHRC1
Atlas of Cancer Signalling NetworkCTHRC1
Wikipedia pathwaysCTHRC1
Orthology - Evolution
GeneTree (enSembl)ENSG00000164932
Phylogenetic Trees/Animal Genes : TreeFamCTHRC1
Homologs : HomoloGeneCTHRC1
Homology/Alignments : Family Browser (UCSC)CTHRC1
Gene fusions - Rearrangements
Fusion : QuiverCTHRC1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCTHRC1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CTHRC1
Exome Variant ServerCTHRC1
ExAC (Exome Aggregation Consortium)ENSG00000164932
GNOMAD BrowserENSG00000164932
Varsome BrowserCTHRC1
Genetic variants : HAPMAP115908
Genomic Variants (DGV)CTHRC1 [DGVbeta]
DECIPHERCTHRC1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisCTHRC1 
ICGC Data PortalCTHRC1 
TCGA Data PortalCTHRC1 
Broad Tumor PortalCTHRC1
OASIS PortalCTHRC1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICCTHRC1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDCTHRC1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch CTHRC1
DgiDB (Drug Gene Interaction Database)CTHRC1
DoCM (Curated mutations)CTHRC1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)CTHRC1 (select a term)
NCG5 (London)CTHRC1
Cancer3DCTHRC1(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
OMIM610635    614266   
Genetic Testing Registry CTHRC1
NextProtQ96CG8 [Medical]
Target ValidationCTHRC1
Huge Navigator CTHRC1 [HugePedia]
snp3D : Map Gene to Disease115908
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD115908
Chemical/Pharm GKB GenePA38701
Clinical trialCTHRC1
canSAR (ICR)CTHRC1 (select the gene name)
PubMed49 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Oct 12 17:54:58 CEST 2018

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