CTHRC1

Summary

CTHRC1 (collagen triple helix repeat containing 1, HGNC:18831) is a protein-coding gene on chromosome 8q22.3, encoding Collagen triple helix repeat-containing protein 1 (Q96CG8). May act as a negative regulator of collagen matrix deposition.

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.

Source: NCBI Gene 115908 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Barrett esophagus (Limited, GenCC)
• Clinical variants (ClinVar): 49 total — 1 pathogenic
• Phenotypes (HPO): 5
• MANE Select transcript: NM_138455

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18831
Approved symbol	CTHRC1
Name	collagen triple helix repeat containing 1
Location	8q22.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000164932
Ensembl biotype	protein_coding
OMIM	610635
Entrez	115908

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000330295, ENST00000415886, ENST00000520337, ENST00000520880, ENST00000891015

RefSeq mRNA: 2 — MANE Select: NM_138455 NM_001256099, NM_138455

CCDS: CCDS59110, CCDS6299

Canonical transcript exons

ENST00000330295 — 4 exons

Exon	Start	End
ENSE00001088746	103375738	103375959
ENSE00001162157	103371538	103371806
ENSE00002118765	103382458	103382989
ENSE00003596572	103378027	103378243

Expression profiles

Bgee: expression breadth ubiquitous, 228 present calls, max score 99.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.1942 / max 409.7047, expressed in 1130 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
90115	22.3817	1072
90114	2.8528	750
90117	1.7800	549
205281	0.6548	393
90116	0.5249	256

Top tissues by expression

250 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	99.71	gold quality
skin of hip	UBERON:0001554	99.35	gold quality
visceral pleura	UBERON:0002401	98.83	gold quality
cartilage tissue	UBERON:0002418	98.44	gold quality
upper arm skin	UBERON:0004263	98.36	gold quality
gall bladder	UBERON:0002110	97.37	gold quality
parietal pleura	UBERON:0002400	97.28	gold quality
upper leg skin	UBERON:0004262	96.77	gold quality
placenta	UBERON:0001987	96.45	gold quality
stromal cell of endometrium	CL:0002255	96.26	gold quality
saphenous vein	UBERON:0007318	94.76	gold quality
synovial joint	UBERON:0002217	94.42	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.22	gold quality
ascending aorta	UBERON:0001496	93.97	gold quality
thoracic aorta	UBERON:0001515	93.97	gold quality
right coronary artery	UBERON:0001625	93.44	gold quality
descending thoracic aorta	UBERON:0002345	93.10	gold quality
penis	UBERON:0000989	92.72	gold quality
urethra	UBERON:0000057	92.61	gold quality
parotid gland	UBERON:0001831	92.46	gold quality
thoracic mammary gland	UBERON:0005200	91.11	gold quality
epithelial cell of pancreas	CL:0000083	90.84	gold quality
mammary gland	UBERON:0001911	90.84	gold quality
adipose tissue	UBERON:0001013	90.77	gold quality
amniotic fluid	UBERON:0000173	90.63	gold quality
aorta	UBERON:0000947	90.37	gold quality
mammary duct	UBERON:0001765	90.30	gold quality
epithelium of mammary gland	UBERON:0003244	90.01	gold quality
skin of leg	UBERON:0001511	89.59	gold quality
smooth muscle tissue	UBERON:0001135	87.89	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-CURD-126	yes	2456.78
E-MTAB-8410	yes	2238.38
E-MTAB-7407	yes	1125.35
E-MTAB-6701	yes	74.71
E-CURD-112	yes	17.68
E-CURD-46	yes	14.48
E-MTAB-9388	yes	13.26
E-MTAB-10290	no	766.48
E-GEOD-124858	no	213.91
E-MTAB-6678	no	3.77
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

48 targeting CTHRC1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4302	99.89	67.94	1187

Literature-anchored findings (GeneRIF, showing 40)

• CTHRC1 is transiently expressed in the arterial wall in response to injury where it may contribute to vascular remodeling by limiting collagen matrix deposition and promoting cell migration. (PMID:15618538)
• Aberrant expression of CTHRC1 is widely present in human solid cancers and seems to be associated with cancer tissue invasion and metastasis. (PMID:16778098)
• Intracellular localization of Cthrc1 characterizes differentiated smooth muscle. (PMID:18467647)
• Three major genes, MSR1, ASCC1, and CTHRC1 were associated with Barrett esophagus/esophageal adenocarcinoma (PMID:21791690)
• Data indicate that the upregulated expression of collagen triple helix repeat containing 1 (CTHRC1) in gastric carcinogenesis contributes to tumor cell invasion and metastasis. (PMID:22590977)
• CTHRC1 has a role in pancreatic cancer progression and metastasis by regulating migration and adhesion activities of cancer cells. (PMID:23222813)
• this is the first demonstration of Cthrc1 as a marker of the severity of the disease progression in the dystrophic muscles. (PMID:23274062)
• the results of our study suggest that increased expression of CTHRC1 is associated with peritoneal carcinomatosis in Colorectal cancer patients (PMID:23359115)
• Studied CTHRC1 expression in human breast cancer tissue. A significant increase of CTHRC1 mRNA expression was seen in breast cancer tissue compared to the normal tissue from the same patients using RT-PCR and real-time PCR. (PMID:23658133)
• Data suggest that in oral squamous cell carcinoma (OSCC), dysregulation of canonical Wnt signaling and DPAGT1-dependent N-glycosylation induces CTHRC1, thereby driving OSCC cell migration and tumor spread. (PMID:23703614)
• Overexpression of CTHRC1 in hepatocellular carcinoma promotes tumor invasion and predicts poor prognosis. (PMID:23922981)
• Rs35500845 in the CTHRC1 gene was associated with Paget’s disease of bone in the French-Canadian population. (PMID:24370779)
• CTHRC1 expression is elevated in human colon cancer cell lines and clinical specimens, and promotes cancer cell invasivity through ERK-dependent induction of MMP9 expression. (PMID:24504172)
• CTHRC1 acts as a prognostic factor and promotes invasiveness of gastrointestinal stromal tumors by activating Wnt/PCP-Rho signaling. (PMID:24726140)
• high Cthrc1 expression was an independent prognostic factor for both overall survival and disease-free survival of patients with gastric carcinoma (PMID:24746208)
• CTHRC1 has the potential to be a new biomarker for the aggressive hepatocellular carcinoma (PMID:24841500)
• Cthrc1 is a pituitary hormone with significantly elevated levels in subjects carrying variant alleles of the melanocortin-1 receptor as wells as in patients with inflammatory conditions. (PMID:24945147)
• Cthrc1 overexpression was associated with non-small cell lung cancers. (PMID:25139095)
• CTHRC1 was overexpressed in human non-small cell lung cancer tissues and non-small cell lung cancer cell lines at the protein and mRNA level. (PMID:25238260)
• HBV facilitates HCC development through activating the oncoprotein CTHRC1. (PMID:25263696)
• let-7b may directly target Cthrc1 and function as a tumor suppressor gene in gastric cancer. (PMID:25510669)
• CTHRC1 has a novel role in viral infection. (PMID:26180054)
• Authors showed that ectopic transfection of CTHRC1 in EOC cells up-regulated the expression of EMT markers such as N-cadherin and vimentin, and EMT-associated transcriptional factor Snail. (PMID:26452130)
• determined the mRNA and protein expression of CTHRC1 in oral squamous cell carcinoma and evaluated the clinical and prognostic impact of CTHRC1 overexpression (PMID:26664254)
• CTHRC1 is secreted both by colorectal epithelia cells and stromal fibroblasts. CTHRC1 overexpression promotes colorectal cancer cell migration, invasion and proliferation in vitro. (PMID:26722469)
• High CTHRC1 expression is associated with metastatic melanomas. (PMID:26918341)
• High CTHRC1 expression is associated with Osteosarcoma. (PMID:27043295)
• Expression of CTHRC1 was significantly higher in Wilms’ tumor compared to the expression in the adjacent non-cancerous tissues. High tumor expression of CTHRC1 was associated with tumor size, clinical stage, histopathological type, and vascular invasion/metastasis. Patients with high CTHRC1 expression also exhibited a shorter survival. (PMID:27230801)
• increased CTHRC1 expression is associated with advanced TNM stage, increased LN metastasis and tumor size, and decreased OS and DFS, indicating that CTHRC1 may be a biomarker for prognosis of cancer patients (PMID:27323076)
• CTHRC1 was established as a novel marker of activated synoviocytes in murine experimental arthritis and rheumatoid arthritis (PMID:27430622)
• Gene expression levels of three randomly selected DEGs, VCAN, COL5A1 and KCNJ16, were examined using RT-PCR in 10 ATC samples.. angiogenesis was activated by the high expression of CTHRC1, VCAN and POSTN, providing necessary nutrition for tumor cells (PMID:27599582)
• this study shows that the serum CTHRC1 level was significantly higher in the influenza A virus infection patients than in the healthy individuals; the influenza A virus non-structural protein NS1 upregulates the expression of CTHRC1 protein (PMID:27718266)
• CTHRC1 may play a role in the progression of ovarian cancer. (PMID:27779718)
• The negative and sensitivity-predictive values of CTHRC1 staining were excellent for both lymph node and peritoneal metastases. (PMID:27870703)
• CTHRC1 expression is significantly upregulated in human masticatory mucosa during wound healing. (PMID:28005267)
• The knockdown of CTHRC1 exerts inhibitory effects on the proliferation and migration ability of glioblastoma cells. (PMID:28277194)
• CTHRC1 downregulation inhibited proliferation. (PMID:28281968)
• E6/E7-p53-POU2F1-CTHRC1 axis promotes cervical cancer cell invasion and metastasis (PMID:28303973)
• Our data suggest that CTHRC1 may act as an oncogenic driver in progression and metastasis of ESCC, and may serve as a potential biomarker for prognosis and personalized therapy. (PMID:28645305)
• CTHRC1, negatively regulated by miR-30c, promoted cell proliferation, invasion and migration and suppressed cell apoptosis in breast cancer, which might be by activating GSK-3beta/beta-catenin signaling and inhibiting Bax/Caspase-9/Caspase-3 signaling respectively. (PMID:28697793)

Cross-species orthologs

16 orthologs

Organism	Symbol	Gene ID
danio_rerio	cthrc1b	ENSDARG00000001971
danio_rerio	cthrc1a	ENSDARG00000087198
mus_musculus	Cthrc1	ENSMUSG00000054196
rattus_norvegicus	Cthrc1	ENSRNOG00000004578
caenorhabditis_elegans		WBGENE00000599
caenorhabditis_elegans	col-35	WBGENE00000612
caenorhabditis_elegans	col-47	WBGENE00000624
caenorhabditis_elegans	col-50	WBGENE00000627
caenorhabditis_elegans		WBGENE00000661
caenorhabditis_elegans		WBGENE00000700
caenorhabditis_elegans		WBGENE00000701
caenorhabditis_elegans		WBGENE00000717
caenorhabditis_elegans		WBGENE00000718
caenorhabditis_elegans		WBGENE00000721
caenorhabditis_elegans		WBGENE00000757
caenorhabditis_elegans		WBGENE00000760

Paralogs (2): METTL24 (ENSG00000053328), SCARA3 (ENSG00000168077)

Protein

Protein identifiers

Collagen triple helix repeat-containing protein 1 — Q96CG8 (reviewed: Q96CG8)

All UniProt accessions (3): E5RK99, E7EVQ5, Q96CG8

UniProt curated annotations — full annotation on UniProt →

Function. May act as a negative regulator of collagen matrix deposition.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Isoform 1 is expressed in calcified atherosclerotic plaque and chondrocyte-like cells.

Post-translational modifications. N-glycosylated.

Disease relevance. 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. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96CG8-1	1	yes
Q96CG8-2	2
Q96CG8-3	3

RefSeq proteins (2): NP_001243028, NP_612464* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR057873	CTHRC1_C	Domain

Pfam: PF25815

UniProt features (9 total): splice variant 2, signal peptide 1, chain 1, domain 1, region of interest 1, glycosylation site 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96CG8-F1	79.78	0.52

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (1): 186

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 251 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOCC_COLLAGEN_TRIMER, GOBP_NON_CANONICAL_WNT_SIGNALING_PATHWAY, GOZGIT_ESR1_TARGETS_DN, GOBP_OSTEOBLAST_DIFFERENTIATION, AREB6_01, GAUSSMANN_MLL_AF4_FUSION_TARGETS_E_UP

GO Biological Process (11): osteoblast differentiation (GO:0001649), cyclooxygenase pathway (GO:0019371), osteoblast proliferation (GO:0033687), positive regulation of osteoblast proliferation (GO:0033690), ossification involved in bone remodeling (GO:0043932), positive regulation of osteoblast differentiation (GO:0045669), Wnt signaling pathway, planar cell polarity pathway (GO:0060071), inner ear receptor cell stereocilium organization (GO:0060122), negative regulation of canonical Wnt signaling pathway (GO:0090090), cochlea morphogenesis (GO:0090103), establishment of planar polarity involved in neural tube closure (GO:0090177)

GO Molecular Function (4): prostaglandin-endoperoxide synthase activity (GO:0004666), frizzled binding (GO:0005109), Wnt-protein binding (GO:0017147), extracellular matrix structural constituent (GO:0005201)

GO Cellular Component (7): extracellular region (GO:0005576), collagen trimer (GO:0005581), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), sarcoplasm (GO:0016528), extracellular matrix (GO:0031012), neuron projection (GO:0043005)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ossification	2
embryonic morphogenesis	2
cellular anatomical structure	2
cell differentiation	1
prostaglandin biosynthetic process	1
arachidonate metabolic process	1
cell population proliferation	1
positive regulation of cell population proliferation	1
osteoblast proliferation	1
regulation of osteoblast proliferation	1
bone remodeling	1
osteoblast differentiation	1
positive regulation of cell differentiation	1
regulation of osteoblast differentiation	1
non-canonical Wnt signaling pathway	1
neuron projection development	1
inner ear receptor cell development	1
negative regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
inner ear morphogenesis	1
cochlea development	1
neural tube closure	1
establishment of planar polarity of embryonic epithelium	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	1
G protein-coupled receptor binding	1
protein binding	1
structural molecule activity	1
extracellular matrix	1
protein-containing complex	1
intracellular anatomical structure	1
cytoplasm	1
external encapsulating structure	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

810 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTHRC1	FZD3	Q9NPG1	769
CTHRC1	FZD9	O00144	729
CTHRC1	COL1A1	P02452	706
CTHRC1	VANGL2	Q9ULK5	661
CTHRC1	TGFB1	P01137	658
CTHRC1	MMP2	P08253	628
CTHRC1	POSTN	Q15063	589
CTHRC1	PTBP3	O95758	588
CTHRC1	HMMR	O75330	553
CTHRC1	COL1A2	P02464	545
CTHRC1	VCAN	P13611	529
CTHRC1	MMP9	P14780	527
CTHRC1	COL15A1	P39059	518
CTHRC1	CDH1	P12830	515
CTHRC1	COL6A6	A6NMZ7	508

IntAct

15 interactions, top by confidence:

A	B	Type	Score
KLHL22	METTL15	psi-mi:“MI:0914”(association)	0.640
PLAUR	PLAU	psi-mi:“MI:0914”(association)	0.560
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
CTHRC1	VAPA	psi-mi:“MI:0915”(physical association)	0.400
CTHRC1	ZDHHC17	psi-mi:“MI:0915”(physical association)	0.370
CTHRC1	TFAP2C	psi-mi:“MI:0915”(physical association)	0.370
CD48	POTEF	psi-mi:“MI:0914”(association)	0.350
GPIHBP1	SAC3D1	psi-mi:“MI:0914”(association)	0.350
PRG2	QSOX1	psi-mi:“MI:0914”(association)	0.350
CBLN4	AGRN	psi-mi:“MI:0914”(association)	0.350
C1QTNF3	PLOD2	psi-mi:“MI:0914”(association)	0.350
CNTNAP3	ADAM10	psi-mi:“MI:0914”(association)	0.350
NXPH2	VGF	psi-mi:“MI:0914”(association)	0.350
NXPH1	RAD51C	psi-mi:“MI:0914”(association)	0.350

BioGRID (21): CTHRC1 (Two-hybrid), CTHRC1 (Affinity Capture-MS), VAPA (Proximity Label-MS), CTHRC1 (Affinity Capture-MS), CTHRC1 (Affinity Capture-MS), CTHRC1 (Affinity Capture-RNA), CTHRC1 (Affinity Capture-MS), CTHRC1 (Affinity Capture-MS), CTHRC1 (Affinity Capture-MS), CTHRC1 (Affinity Capture-MS), CTHRC1 (Affinity Capture-MS), CTHRC1 (Affinity Capture-MS), CTHRC1 (Affinity Capture-MS), CTHRC1 (Affinity Capture-MS), CTHRC1 (Affinity Capture-MS)

ESM2 similar proteins: A1A5X5, A4IH36, D4AB34, O93449, O95150, O97605, O97626, P04088, P04924, P09529, P10600, P15203, P16047, P17125, P17491, P27093, P36939, P36940, P41047, P42917, P48023, P50591, P50592, P59694, P59695, P63306, P63307, P63308, Q04999, Q07258, Q5UBV8, Q5XIG2, Q6PGN1, Q80WL1, Q861W5, Q8BGU2, Q8BMF8, Q8IUK8, Q8K3Y7, Q8R2Z0

Diamond homologs: Q8CG08, Q96CG8, Q9D1D6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 25 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Neutrophil degranulation	6	9.2×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

49 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	38
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
30848	NM_138455.4(CTHRC1):c.131A>C (p.Gln44Pro)	Pathogenic

SpliceAI

896 predictions. Top by Δscore:

Variant	Effect	Δscore
8:103371792:G:T	donor_gain	1.0000
8:103382456:A:AG	acceptor_gain	1.0000
8:103382456:AGT:A	acceptor_gain	1.0000
8:103382457:G:GG	acceptor_gain	1.0000
8:103382457:GTG:G	acceptor_gain	1.0000
8:103371764:G:GT	donor_gain	0.9900
8:103371764:G:T	donor_gain	0.9900
8:103371796:T:TA	donor_gain	0.9900
8:103371797:G:GA	donor_gain	0.9900
8:103371804:CTGG:C	donor_loss	0.9900
8:103371806:GGT:G	donor_loss	0.9900
8:103371807:G:GG	donor_gain	0.9900
8:103371807:GTGA:G	donor_loss	0.9900
8:103371808:TGAG:T	donor_loss	0.9900
8:103371818:G:GT	donor_gain	0.9900
8:103372077:G:GT	donor_gain	0.9900
8:103372086:G:GT	donor_gain	0.9900
8:103375733:TATA:T	acceptor_loss	0.9900
8:103375734:ATAG:A	acceptor_loss	0.9900
8:103375735:TA:T	acceptor_loss	0.9900
8:103375736:A:AG	acceptor_gain	0.9900
8:103375737:G:GA	acceptor_gain	0.9900
8:103375737:GT:G	acceptor_gain	0.9900
8:103375737:GTAT:G	acceptor_gain	0.9900
8:103375737:GTATA:G	acceptor_gain	0.9900
8:103375956:TGCGG:T	donor_loss	0.9900
8:103375957:GCGGT:G	donor_loss	0.9900
8:103375958:CGG:C	donor_loss	0.9900
8:103375959:GGTA:G	donor_loss	0.9900
8:103375960:G:A	donor_loss	0.9900

AlphaMissense

1543 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:103375912:T:A	C109S	1.000
8:103375913:G:C	C109S	1.000
8:103375920:G:C	W111C	1.000
8:103375920:G:T	W111C	1.000
8:103378030:T:C	C126R	1.000
8:103378070:T:A	V139D	1.000
8:103378091:G:C	R146P	1.000
8:103378115:G:A	C154Y	1.000
8:103378116:T:G	C154W	1.000
8:103378121:G:C	R156P	1.000
8:103378123:T:A	W157R	1.000
8:103378123:T:C	W157R	1.000
8:103378125:G:C	W157C	1.000
8:103378125:G:T	W157C	1.000
8:103378150:T:A	C166S	1.000
8:103378150:T:C	C166R	1.000
8:103378151:G:C	C166S	1.000
8:103378224:T:A	N190K	1.000
8:103378224:T:G	N190K	1.000
8:103378228:C:G	H192D	1.000
8:103378232:G:C	R193P	1.000
8:103382463:G:A	G199R	1.000
8:103382463:G:C	G199R	1.000
8:103382469:T:A	C201S	1.000
8:103382469:T:C	C201R	1.000
8:103382470:G:A	C201Y	1.000
8:103382470:G:C	C201S	1.000
8:103382471:T:G	C201W	1.000
8:103382520:T:A	C218S	1.000
8:103382520:T:C	C218R	1.000

dbSNP variants (sampled 300 via entrez): RS1000194128 (8:103371544 C>A,G,T), RS1000206159 (8:103380349 A>G), RS1000209899 (8:103378851 C>CA), RS1001036925 (8:103375775 C>G), RS1001651056 (8:103381286 C>T), RS1001767173 (8:103381610 G>A), RS1002607940 (8:103373889 A>C), RS1002698625 (8:103371223 C>A,T), RS1003168106 (8:103380988 C>A), RS1003557646 (8:103375326 C>G), RS1003607478 (8:103370450 C>T), RS1004862499 (8:103374879 A>T), RS1005049748 (8:103382011 A>C,G), RS1005201270 (8:103376686 C>T), RS1005219817 (8:103383392 T>C)

Disease associations

OMIM: gene MIM:610635 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
Barrett esophagus	Limited	Autosomal dominant

Mondo (1): Barrett esophagus (MONDO:0013662)

Orphanet (0):

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0001442	Typified by somatic mosaicism
HP:0002020	Gastroesophageal reflux
HP:0004791	Esophageal ulceration
HP:0011459	Esophageal carcinoma
HP:0100580	Barrett esophagus

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001471	Barrett Esophagus	C04.834.154; C06.405.117.102

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

59 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	10
Cyclosporine	increases expression	4
trichostatin A	affects cotreatment, increases expression	3
Aflatoxin B1	affects expression, increases expression	3
mono-(2-ethylhexyl)phthalate	decreases expression	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression	2
belinostat	increases expression, affects cotreatment	2
(+)-JQ1 compound	increases expression, decreases expression	2
Decitabine	affects expression, decreases expression, decreases reaction	2
Vorinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Tretinoin	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
propionaldehyde	increases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	increases expression	1
deoxynivalenol	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	affects expression	1
trimellitic anhydride	decreases expression	1
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	increases expression, increases secretion, affects cotreatment	1

Clinical trials (associated diseases)

269 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00352261	PHASE4	COMPLETED	An Open Label pH Comparison of Esomeprazole and Lansoprazole in Barrett’s Esophagus Patients
NCT00526786	PHASE4	TERMINATED	Study of CryoSpray Ablation of Low Grade or High Grade Dysplasia Within Barrett’s Esophagus
NCT00628784	PHASE4	UNKNOWN	Endoesophageal Cryotherapy For Ablating Barrett’s Esophagus and Early Stage Esophageal Cancer
NCT00637559	PHASE4	COMPLETED	Barrett’s Esophagus - 315 - 3 Way Cross-Over
NCT00637988	PHASE4	COMPLETED	Barrett’s Esophagus - 315 - 3 Way Cross Over
NCT00754468	PHASE4	COMPLETED	Study of CryoSpray Ablation(TM)to Determine Treatment Effect, Depth of Injury, and Side Effects in the Esophagus.
NCT00872755	PHASE4	COMPLETED	Nissen and Gastroplasty in Gastroesophageal Reflux Disease (GERD)
NCT01030263	PHASE4	TERMINATED	A Trial Comparing Yield of Confocal Endomicroscopy Guided Biopsies
NCT01093755	PHASE4	COMPLETED	Does Intensive Acid Suppression Reduce Esophageal Inflammation and Recurrent Barrett’s Esophagus Following Ablation?
NCT01733147	PHASE4	COMPLETED	Modulation of Esophageal Inflammation in Barrett’s Esophagus by Omega-3 Fatty Acids
NCT02004782	PHASE4	WITHDRAWN	Barretts oEsophageal Resection With Steroid Therapy Trial
NCT00487695	PHASE3	COMPLETED	Confocal Endomicroscopy for Barrett’s Esophagus
NCT01209013	PHASE3	WITHDRAWN	Safety of Photodynamic Therapy (PDT) in the Ablation of High-grade Dysplasia (HGD) in Barrett’s Esophagus (BE)
NCT01566474	PHASE3	COMPLETED	Melatonin Associated to Acid Inhibition for Chemoprevention in Barret Esophagus: a Pilot Study
NCT00217087	PHASE2	COMPLETED	Endoscopic Therapy of Early Cancer in Barretts Esophagus
NCT00220103	PHASE2	COMPLETED	Pre-operative Epirubicin, Cisplatin, and Capecitabine in Patients With Newly Diagnosed Localised Oesophageal Adenocarcinoma
NCT00411151	PHASE2	COMPLETED	Efficacy and Safety of Sunitinib in Metastatic Gastric Cancer
NCT00474903	PHASE2	COMPLETED	Esomeprazole Magnesium With or Without Aspirin in Preventing Esophageal Cancer in Patients With Barrett Esophagus
NCT01097304	PHASE2	COMPLETED	Ursodiol in Treating Patients With Barrett Esophagus and Low-Grade Dysplasia
NCT01298999	PHASE2	COMPLETED	Trial of a Gastrin Receptor Antagonist in Barrett’s Esophagus
NCT01360541	PHASE2	COMPLETED	Radiofrequency Ablation for Barrett Oesophagus With Low Grade Dysplasia
NCT01447927	PHASE2	COMPLETED	Metformin Hydrochloride in Preventing Esophageal Cancer in Patients With Barrett Esophagus
NCT02018367	PHASE2	UNKNOWN	Accuracy, Yield and Clinical Impact of a Low-Cost HRME in the Early Diagnosis of Esophageal Adenocarcinoma
NCT02162758	PHASE2	TERMINATED	Effect of Dexlansoprazole 60 mg QD and 60 mg BID on Recurrence of Intestinal Metaplasia in Subjects Who Have Achieved Complete Eradication of Barrett’s Esophagus With Radiofrequency Ablation
NCT02521285	PHASE2	ACTIVE_NOT_RECRUITING	Aspirin in Preventing Disease Recurrence in Patients With Barrett Esophagus After Successful Elimination by Radiofrequency Ablation
NCT02597712	PHASE2	COMPLETED	YF476 in Barrett’s Esophagus
NCT03877601	PHASE2	UNKNOWN	Detection of Early Esophageal Cancer by NIR-FME.
NCT04939051	PHASE2	RECRUITING	Obeticholic Acid for Prevention in Barrett’s Esophagus
NCT06732388	PHASE2	NOT_YET_RECRUITING	Itraconazole in Combination With Ablation for the Prevention of Esophageal Cancer in Patients With High-risk Barrett’s Esophagus
NCT07260877	PHASE2	RECRUITING	A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 2a Study With an Open-Label Extension Evaluating the Efficacy and Safety of VENT-03 in Adult Participants With Active Cutaneous Lupus Erythematosus With or Without Systemic Lupus Erythematosus
NCT00216788	PHASE1	UNKNOWN	The Effect of Nexium on Transmucosal Esophageal Leak
NCT00233935	PHASE1	COMPLETED	Defined Green Tea Catechin Extract in Preventing Esophageal Cancer in Patients With Barrett’s Esophagus
NCT00573911	PHASE1	COMPLETED	Acid Reflux and Stromal Fibroblasts in Barrett’s Esophagus
NCT01236443	PHASE1	COMPLETED	Study of Photodynamic Therapy (PDT) Using HPPH in Barrett’s Esophagus
NCT01238042	PHASE1	COMPLETED	Study To Determine The Maximum Range of Light Doses At Two HPPH Doses With Acceptable Normal Tissue Toxicity For PDT Treatment Of High Grade Dysplasia,CIS or Early Adenocarcinoma In Barrett’s Esophagus
NCT01391208	PHASE1	COMPLETED	Esophageal Protocol for Detection of Neoplasia in the Digestive Tract
NCT01630798	PHASE1	COMPLETED	A In-Vivo Esophageal Protocol for Detection of Neoplasia in the Digestive Tract
NCT01905202	PHASE1	UNKNOWN	The Safety and Tolerability of Secretrol in Patients With Barrett’s Esophagus
NCT03205501	PHASE1	COMPLETED	Molecular Fluorescence Endoscopy of (Pre)Malignant Esophageal Lesions
NCT03589443	PHASE1	COMPLETED	Study of Multiplexed Heptapeptides for Detection of Neoplasia in the Esophagus