CTHRC1
protein-codingcollagen triple helix repeat containing 1
Gene summary
This locus encodes a protein that may play a role in the cellular response to arterial injury through involvement in vascular remodeling. Mutations at this locus have been associated with Barrett esophagus and esophageal adenocarcinoma. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~11.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0013662
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Gastrointestinal; Oncologic
Intervention: Gastrointestinal; Oncologic
Rationale: Awareness of disease risk may allow surveillance, preventive measures (eg, related to Barrett esophagus) and early treatment of malignancy, which may reduce morbidity and mortality
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CTHRC1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_138455.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 3 | ||||
| missense | 1 | 37 | 38 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 1 | 0 | 40 | 3 | 0 | 44 |
Highest pathogenic variant AF is 0.000100454134
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_612464.1 | 4 | MANE Select | |
| Ensembl | ENSP00000330523.5 | 4 | MANE Select | |
| RefSeq | NP_001243028.1 | 4 | Standard | |
| Ensembl | ENSP00000416045.2 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Noncanonical Wnt signaling pathway
- Wnt signaling network
Biological Process
- cell migration
- positive regulation of protein binding
- positive regulation of osteoblast proliferation
- ossification involved in bone remodeling
- positive regulation of osteoblast differentiation
Molecular Function
- frizzled binding
- extracellular matrix structural constituent
- Wnt-protein binding
Cellular Component
- extracellular region
- collagen trimer
- extracellular space
- cytoplasm
- collagen-containing extracellular matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000330295
- Coding exons
- 4
- Length
- 11483
- Individuals with no LoFs
- 125696
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 51
- Defined
- 125748
- p
- 0.000207
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.633 | 107 | 127 | 0.842 | 0.00000687 | 1525 |
| Missense (PolyPhen) | 35 | 45.967 | 0.76142 | 460 | ||
| Synonymous | 0.161 | 44 | 45.4 | 0.970 | 0.00000221 | 504 |
| Loss of Function | 0.659 | 8 | 10.3 | 0.778 | 4.83e-7 | 136 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00064 | 0.00064 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00092 | 0.00087 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000089 | 0.000088 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May act as a negative regulator of collagen matrix deposition. {ECO:0000250}.;
- Disease
- DISEASE: Barrett esophagus (BE) [MIM:614266]: A condition characterized by a metaplastic change in which normal esophageal squamous epithelium is replaced by a columnar and intestinal-type epithelium. Patients with Barrett esophagus have an increased risk of esophageal adenocarcinoma. The main cause of Barrett esophagus is gastroesophageal reflux. The retrograde movement of acid and bile salts from the stomach into the esophagus causes prolonged injury to the esophageal epithelium and induces chronic esophagitis, which in turn is believed to trigger the pathologic changes. {ECO:0000269|PubMed:21791690}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.145
Intolerance Scores
- LoFtool
- 0.651
- RVIS EVS
- -0.14
- RVIS percentile EVS
- 43.29
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.245
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |