ALTERED WNT SIGNALING, CANONICAL PATHWAY (PW:0000599)

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Description

Wnt signaling pathways initiated by the Wnt family of secreted glycoproteins play important roles in the control of embryonic development, tissue regeneration, cell polarity, proliferation and cell fate determination. The canonical, beta-catenin dependent pathway is the best understood system. Altered canonical Wnt signaling has been implicated in several conditions, primarily tumorigenesis and bone malformations. Hyperactive Wnt signaling is found in more than 90% of colorectal cancer (CRC). In

Pathway Diagram:

Elsevier Inc. Lrp5 ---> eye defects Lrp5 ---> bone malformations eye defects Lrp5 bone malformations Wnt target genes ---> Colorectal Neoplasms Colorectal Neoplasms Wnt target genes Wnt target genes ---> colorectal cancer pathway colorectal cancer pathway translocated Ctnnb1 Axin1 Axin2 Apc Wls Csnk1g1 Wnt_ligands_secreted Sostdc1 Ndp Sost Crebbp palmitate Wnt_ligands Rnf43 ---| Fzd_receptors Rnf43 ---| Fzd_receptors Znrf3 ---| Fzd_receptors Znrf3 ---| Fzd_receptors sFRPs ---| Wnt_ligands_secreted Wif1 ---| Wnt_ligands_secreted Znrf3 ---| Lrp6 Csnk1g1 --+> Lrp6 Gsk3b --+> Lrp6 RSPOs ---> Wnt signal potentiation Ndp ---> Wnt signal potentiation Gsk3b Lrp6 Kremen2 Kremen1 Wif1 Porcn Lef1 Smarca4 Csnk1a1 Rnf43 Znrf3 Lgr4 Lgr5 RSPOs Btrc Dvls Wnt signal potentiation Dkk members Axin1 ---- Lrp6 Dvls ---- Fzd_receptors sFRPs sFRPs ---- Wnt_ligands_secreted sFRPs ---> Fzd_receptors Fzd_receptors Fzd_receptors ---- sFRPs Axin1 ---- Gsk3b Lgr4 ---- Ndp RSPOs ---> Znrf3 Lrp6 ---- Sost Lrp5 ---- Sost Lrp6 ---- Sostdc1 Dkk members ---- Lrp5 Dkk members ---> Lrp5 Dkk members ---> Lrp6 Dkk members ---- Lrp6 Lrp5 ---- Ndp Lgr4 ---- RSPOs Lgr5 ---- RSPOs Fzd_receptors ---- Wnt_ligands_secreted Lrp5 ---- Wnt_ligands_secreted Kremen2 ---> Dkk members Kremen1 ---> Dkk members Dkk members ---- Kremen1 Dkk members ---- Kremen2 Lrp6 ---- Wnt_ligands_secreted Wif1 ---- Wnt_ligands_secreted translocated Ctnnb1 ---> Wnt target genes Porcn ---> Wnt_ligands Wls ---- Wnt_ligands Wnt_ligands ---> Wnt_ligands_secreted Fzd_receptors ---- Ndp Axin1 ---- Csnk1a1 Tcf_factors Csnk1a1 ---> Axin1 Gsk3b ---> Axin1
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Genes in Pathway:

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altered Wnt signaling, canonical pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G Apc APC, WNT signaling pathway regulator JBrowse link 18 27,011,710 27,106,323 RGD:2293188
G Axin1 axin 1 RGD:2293188
G Axin2 axin 2 JBrowse link 10 97,212,483 97,238,824 RGD:2293188
G Ctnnb1 catenin beta 1 JBrowse link 8 129,601,511 129,628,378 RGD:2293188
RGD:4143515
G Lrp5 LDL receptor related protein 5 JBrowse link 1 218,816,833 218,920,147 RGD:2293188
G Tcf7l2 transcription factor 7 like 2 JBrowse link 1 276,686,911 276,730,517 RGD:5490966
G Wnt9a Wnt family member 9A JBrowse link 10 45,659,045 45,686,103 RGD:5490966

Additional Elements in Pathway:

(includes Gene Groups, Small Molecules, Other Pathways..etc.)
Object TypePathway ObjectPathway Object Description
Functional ClassDkk membersdickkopf homolog 1 (Xenopus laevis)
Functional ClassDvlsdisheveled, dsh homolog family of proteins
Functional ClassFzd_receptorsfrizzled homolog family of proteins
Functional ClassRSPOsRSPOs family of agonists
Functional ClasssFRPssFRP famikly of antagonists
Functional ClassTcf_factorsTcf family of transcription factors
Functional ClassWnt_ligandswingless related family of proteins

Pathway Gene Annotations

Disease Annotations Associated with Genes in the altered Wnt signaling, canonical pathway
Disease TermsGene Symbols
Aberrant Crypt FociApc , Ctnnb1
acinar cell carcinomaApc
adenocarcinomaApc , Ctnnb1 , Tcf7l2
adenomaApc , Ctnnb1
Adenomatous Polyposis Coli, AttenuatedApc
Adenomatous PolypsApc
adrenal carcinomaCtnnb1
Adrenal Gland NeoplasmsCtnnb1
adrenocortical carcinomaCtnnb1
adult respiratory distress syndromeApc
Aggressive FibromatosisApc
Alzheimer's diseaseApc , Ctnnb1
angiosarcomaCtnnb1
Animal Mammary NeoplasmsApc
anodontiaAxin2
ascending colon cancerApc
autistic disorderApc , Ctnnb1
autosomal dominant non-syndromic intellectual disability 19Ctnnb1
autosomal dominant osteopetrosis 1Lrp5
autosomal recessive limb-girdle muscular dystrophy type 2BApc
bladder urothelial carcinomaCtnnb1
Bone FracturesLrp5
Brain NeoplasmsCtnnb1
breast cancerApc
Breast Cancer, FamilialApc
Breast NeoplasmsCtnnb1 , Wnt9a
calcinosisCtnnb1
Caudal Duplication AnomalyAxin1
Cecal NeoplasmsCtnnb1
Cell Transformation, NeoplasticApc
Chemical and Drug Induced Liver InjuryCtnnb1
cholangiocarcinomaApc
colon adenocarcinomaApc
colon cancerApc , Ctnnb1
colon carcinomaApc , Axin2 , Ctnnb1
Colonic NeoplasmsApc , Axin2 , Ctnnb1 , Tcf7l2
colorectal adenomaApc
colorectal cancerApc , Axin2 , Ctnnb1 , Tcf7l2
Colorectal NeoplasmsApc , Axin1 , Axin2 , Ctnnb1 , Tcf7l2
Coronary DiseaseTcf7l2
Craniofacial AbnormalitiesCtnnb1
craniopharyngiomaApc , Ctnnb1
craniosynostosisAxin2
diabetes mellitusTcf7l2
Diabetic CardiomyopathiesCtnnb1
Diabetic NephropathiesTcf7l2
Digestive System NeoplasmsApc
dilated cardiomyopathyCtnnb1
diseaseCtnnb1
disease of cellular proliferationApc , Ctnnb1
Disease ProgressionCtnnb1
duodenum adenocarcinomaApc
endodermal sinus tumorCtnnb1
endometrial cancerApc
endometrial carcinomaApc
Endometrial NeoplasmsApc , Axin2 , Ctnnb1
Endometrioid CarcinomasApc , Ctnnb1
esophageal carcinomaCtnnb1
esophagus squamous cell carcinomaCtnnb1
Experimental Liver NeoplasmsCtnnb1
exudative vitreoretinopathyLrp5
Exudative Vitreoretinopathy 1Ctnnb1 , Lrp5
Exudative Vitreoretinopathy 4Lrp5
exudative vitreoretinopathy 7Ctnnb1
Eye AbnormalitiesApc
familial adenomatous polyposisApc
familial hyperlipidemiaApc
Familial Prostate CancerTcf7l2
Femur Head NecrosisLrp5
Fibromatosis, AbdominalApc
fundus dystrophyLrp5
Gallbladder NeoplasmsApc
Gardner SyndromeApc
gastric adenocarcinomaCtnnb1
Gastrointestinal HemorrhageApc
Gastrointestinal NeoplasmsApc
gastrointestinal stromal tumorApc
genetic diseaseAxin2 , Ctnnb1 , Lrp5
gestational diabetesTcf7l2
glioblastoma multiformeApc
granulosa cell tumorCtnnb1
head and neck squamous cell carcinomaCtnnb1
heart valve diseaseLrp5
hepatoblastomaApc , Ctnnb1
Hepatoblastoma Caused By Somatic MutationApc , Ctnnb1
hepatocellular adenomaCtnnb1
hepatocellular carcinomaApc , Axin1 , Ctnnb1
Hereditary Desmoid DiseaseApc , Ctnnb1
Hereditary Neoplastic SyndromesApc , Axin2
HyperplasiaApc , Tcf7l2
hypertrophic cardiomyopathyCtnnb1
idiopathic juvenile osteoporosisLrp5
imperforate anusCtnnb1
in situ carcinomaCtnnb1
inflammatory bowel diseaseApc
Insulin ResistanceTcf7l2
intellectual disabilityApc , Ctnnb1
Intestinal NeoplasmsApc , Ctnnb1
Intestinal PolypsApc
intrahepatic cholangiocarcinomaApc
invasive lobular carcinomaCtnnb1
juvenile rheumatoid arthritisTcf7l2
Klatskin's tumorApc
Knee OsteoarthritisCtnnb1
Leber congenital amaurosisLrp5
LeukocytosisApc
liver benign neoplasmApc , Ctnnb1
liver cancerApc , Axin1 , Ctnnb1
liver cirrhosisCtnnb1
lung adenocarcinomaApc , Ctnnb1
Lung NeoplasmsApc , Ctnnb1
lung squamous cell carcinomaCtnnb1
Lymphatic MetastasisCtnnb1
Lynch syndromeApc
macrocytic anemiaApc
malignant mesotheliomaCtnnb1
Mammary Neoplasms, ExperimentalCtnnb1
Mandibular NeoplasmsCtnnb1
mantle cell lymphomaCtnnb1
medulloblastomaApc , Ctnnb1
melanomaApc , Ctnnb1
MesotheliomaApc
Metabolic Bone DiseasesLrp5
MetaplasiaAxin2
microphthalmiaLrp5
Miyoshi muscular dystrophyApc
Miyoshi muscular dystrophy 1Apc
Monoclonal B-Cell LymphocytosisApc
Multiple AbnormalitiesCtnnb1 , Lrp5
muscular atrophyCtnnb1
Myopathy, Distal, with Anterior Tibial OnsetApc
Neoplasm InvasivenessCtnnb1
Neoplasm MetastasisCtnnb1
nephroblastomaCtnnb1
Nerve DegenerationCtnnb1
Neurodevelopmental DisordersCtnnb1 , Tcf7l2
No-Reflow PhenomenonCtnnb1
non-small cell lung carcinomaApc
Oligodontia-Colorectal Cancer SyndromeAxin2
osteogenesis imperfectaLrp5
osteopetrosisLrp5
osteoporosisLrp5
osteoporosis-pseudoglioma syndromeLrp5
ovarian cancerApc , Ctnnb1
Ovarian NeoplasmsCtnnb1
pancreatic adenocarcinomaCtnnb1
pancreatic cancerApc , Ctnnb1 , Tcf7l2 , Wnt9a
papillary renal cell carcinomaCtnnb1
papillary thyroid carcinomaCtnnb1
Parathyroid NeoplasmsCtnnb1
periampullary adenomaApc
Peritoneal NeoplasmsCtnnb1
Phyllodes TumorCtnnb1
pilomatrixomaCtnnb1
polycystic kidney disease 1Lrp5
polycystic liver diseaseLrp5
Polycystic Liver Disease 1Lrp5
Polycystic Liver Disease 4 with or without Kidney CystsLrp5
Polyposis, GastricApc
Postmenopausal OsteoporosisLrp5
Potter Type III Polycystic Kidney DiseaseLrp5
Progressive Osseous HeteroplasiaCtnnb1
proliferative vitreoretinopathyLrp5
prostate adenocarcinomaCtnnb1
prostate cancerApc , Ctnnb1 , Tcf7l2
Prostatic NeoplasmsApc , Ctnnb1
rectal neoplasmApc
rectum adenocarcinomaApc
renal cell carcinomaApc , Ctnnb1
Serrated PolyposisApc
sigmoid colon cancerApc
skin melanomaCtnnb1
Skin NeoplasmsCtnnb1
Smith-Magenis syndromeAxin2
SOST-related sclerosing bone dysplasiaLrp5
Spinal Cord InjuriesLrp5
Spine OsteoarthritisLrp5
SplenomegalyApc
Stevens-Johnson syndromeCtnnb1
stomach cancerApc
Stomach NeoplasmsApc , Ctnnb1
StrokeCtnnb1
tendinitisLrp5
teratomaCtnnb1
tooth agenesisAxin2
transitional cell carcinomaApc , Ctnnb1
Tumor Predisposition SyndromeApc
Turcot SyndromeApc
type 2 diabetes mellitusTcf7l2
urinary bladder cancerCtnnb1
Uterine Cervical NeoplasmsCtnnb1
Uterine NeoplasmsCtnnb1
Vascular CalcificationCtnnb1
Worth SyndromeLrp5
Worth's syndromeLrp5
Pathway Annotations Associated with Genes in the altered Wnt signaling, canonical pathway

References Associated with the altered Wnt signaling, canonical pathway:

Ontology Path Diagram:

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