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
Abnormalities, MultipleCtnnb1 , Lrp5
AdenocarcinomaApc , Ctnnb1 , Tcf7l2
Adenocarcinoma of LungApc , Ctnnb1
ADENOCARCINOMA OF STOMACHCtnnb1
Adenocarcinoma, ProstaticCtnnb1
AdenomaApc , Ctnnb1
Adenoma, ColorectalApc
Adenoma, Liver CellCtnnb1
Adenomatous Polyposis ColiApc
Adenomatous Polyposis Coli, AttenuatedApc
Adenomatous PolypsApc
Adrenal Gland NeoplasmsCtnnb1
Adrenocortical CarcinomaCtnnb1
Alzheimer DiseaseApc , Ctnnb1
Anemia, MacrocyticApc
AnodontiaAxin2
Arthritis, JuvenileTcf7l2
Autistic DisorderApc
bladder urothelial carcinomaCtnnb1
Bone Diseases, MetabolicLrp5
Brain NeoplasmsCtnnb1
Breast NeoplasmsApc , Ctnnb1 , Wnt9a
CalcinosisCtnnb1
Carcinoma in SituCtnnb1
Carcinoma, Acinar CellApc
Carcinoma, EndometrioidCtnnb1
Carcinoma, HepatocellularApc , Axin1 , Ctnnb1
Carcinoma, LobularCtnnb1
Carcinoma, Non-Small-Cell LungApc
Carcinoma, Renal CellApc , Ctnnb1
Carcinoma, Squamous Cell of Head and NeckCtnnb1
Carcinoma, Transitional CellApc , Ctnnb1
Cardiomyopathy, HypertrophicCtnnb1
Caudal Duplication AnomalyAxin1
Cecal NeoplasmsCtnnb1
Cell Transformation, NeoplasticApc
Chemical and Drug Induced Liver InjuryCtnnb1
CholangiocarcinomaApc
colon cancerApc , Axin2 , Ctnnb1
Colonic NeoplasmsApc , Axin2 , Ctnnb1 , Tcf7l2
colorectal cancerApc , Axin2 , Ctnnb1
Colorectal NeoplasmsApc , Axin1 , Axin2 , Ctnnb1 , Tcf7l2
Colorectal Neoplasms, Hereditary NonpolyposisApc
Craniofacial AbnormalitiesCtnnb1
CraniopharyngiomaCtnnb1
Desmoid Disease, HereditaryApc , Ctnnb1
Diabetes MellitusTcf7l2
Diabetes Mellitus, Type 2Tcf7l2
Diabetes, GestationalTcf7l2
Diabetic NephropathiesTcf7l2
Digestive System NeoplasmsApc
DiseaseCtnnb1
Endodermal Sinus TumorCtnnb1
Endometrial NeoplasmsApc , Axin2 , Ctnnb1
Esophageal NeoplasmsCtnnb1
Esophageal Squamous Cell CarcinomaCtnnb1
Exudative vitreoretinopathy 1Ctnnb1 , Lrp5
Exudative Vitreoretinopathy 4Lrp5
Eye AbnormalitiesApc
Familial Exudative VitreoretinopathyLrp5
Femur Head NecrosisLrp5
Fibromatosis, AbdominalApc
Fibromatosis, AggressiveApc
Fractures, BoneLrp5
Gallbladder NeoplasmsApc
Gardner SyndromeApc
Gastrointestinal HemorrhageApc
Gastrointestinal NeoplasmsApc
Genetic Diseases, InbornCtnnb1 , Lrp5
GlioblastomaApc
Granulosa Cell TumorCtnnb1
Heart Valve DiseasesLrp5
HemangiosarcomaCtnnb1
HepatoblastomaApc , Ctnnb1
Hepatoblastoma Caused By Somatic MutationApc , Ctnnb1
HyperlipidemiasApc
HyperplasiaApc , Tcf7l2
InfectionCtnnb1
Inflammatory Bowel DiseasesApc
Insulin ResistanceTcf7l2
Intellectual DisabilityApc
Intestinal NeoplasmsApc , Ctnnb1
Intestinal PolypsApc
Juvenile osteoporosisLrp5
Leber Congenital AmaurosisLrp5
LeukocytosisApc
liver cancerApc , Axin1 , Ctnnb1
Liver CirrhosisCtnnb1
Liver NeoplasmsApc , Axin1 , Ctnnb1
Liver Neoplasms, ExperimentalCtnnb1
Lung NeoplasmsApc , Ctnnb1
Lymphatic MetastasisCtnnb1
Lymphoma, Mantle-CellCtnnb1
Mammary Neoplasms, AnimalApc
Mammary Neoplasms, ExperimentalCtnnb1
MedulloblastomaApc , Ctnnb1
MelanomaCtnnb1
Melanoma, Cutaneous Malignant, Susceptibility To, 1Ctnnb1
Mental Retardation, Autosomal Dominant 19Ctnnb1
MesotheliomaApc
Mesothelioma, MalignantCtnnb1
MetaplasiaAxin2
MicrophthalmosLrp5
Miyoshi MyopathyApc
Monoclonal B-Cell LymphocytosisApc
Muscular AtrophyCtnnb1
Muscular Dystrophy, Limb-Girdle, Type 2BApc
Myopathy, Distal, with Anterior Tibial OnsetApc
Neoplasm InvasivenessCtnnb1
Neoplasm MetastasisCtnnb1
NeoplasmsApc , Ctnnb1
Neoplastic Syndromes, HereditaryApc , Axin2
Nerve DegenerationCtnnb1
Neurodevelopmental DisordersCtnnb1 , Tcf7l2
Niemann-Pick Disease, Type BApc
No-Reflow PhenomenonCtnnb1
Oligodontia-Colorectal Cancer SyndromeAxin2
Osseous Heteroplasia, ProgressiveCtnnb1
Osteoarthritis, KneeCtnnb1
Osteoarthritis, SpineLrp5
OsteochondrodysplasiasLrp5
Osteogenesis ImperfectaLrp5
OsteopetrosisLrp5
Osteopetrosis Autosomal Dominant Type 1Lrp5
OsteoporosisLrp5
Osteoporosis, PostmenopausalLrp5
Osteoporosis-Pseudoglioma SyndromeLrp5
Ovarian NeoplasmsCtnnb1
Pancreatic AdenocarcinomaCtnnb1
Pancreatic NeoplasmsApc , Ctnnb1 , Tcf7l2 , Wnt9a
Periampullary AdenomaApc
Peritoneal NeoplasmsCtnnb1
Phyllodes TumorCtnnb1
PilomatrixomaCtnnb1
Polycystic Kidney DiseasesLrp5
Polycystic Kidney, Autosomal DominantLrp5
Potter Type III Polycystic Kidney DiseaseLrp5
Prostatic NeoplasmsApc , Ctnnb1
Rectal NeoplasmsApc
Respiratory Distress Syndrome, AdultApc
Retinal DystrophiesLrp5
Skin NeoplasmsCtnnb1
Smith-Magenis SyndromeAxin2
Spinal Cord InjuriesLrp5
Spinocerebellar Ataxia, Autosomal Recessive 8Apc
SplenomegalyApc
Squamous Cell Carcinoma of the LungCtnnb1
Stevens-Johnson SyndromeCtnnb1
Stomach NeoplasmsApc , Ctnnb1
StrokeCtnnb1
TendinopathyLrp5
TeratomaCtnnb1
Tumor Predisposition SyndromeApc
Turcot SyndromeApc
Urinary Bladder NeoplasmsCtnnb1
Uterine Cervical NeoplasmsCtnnb1
Uterine NeoplasmsCtnnb1
Van Buchem Disease Type 2Lrp5
Vascular CalcificationCtnnb1
Vitreoretinopathy, ProliferativeLrp5
Wilms TumorCtnnb1
Worth 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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