ALTERED WNT SIGNALING, CANONICAL PATHWAY (PW:0000599)
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 addition to mutations in components of the pathway, aberrant splicing of these components has recently been associated with neoplasms, including CRC. The role mutations in core components of the pathway play in colorectal cancer has been extensively reviewed and will be summarized here. In the normal Wnt signaling, the level and thus the functioning of beta-catenin - the core component of the canonical Wnt pathway - are highly regulated. In the absence of Wnt signal, beta-catenin is recruited to a multi-protein complex known as the 'destruction complex' comprising Apc, Axin and kinases where it is phosphorylated and targeted for degradation. The interaction of Wnt ligands with receptors and recruitment of Dvl (disheveled) eventually lead to destabilization of the complex and translocation of beta-catenin to the nucleus where in conjunction with the Tcf/Lef effector complex transcription factors and recruited co-activators, it turns on the expression of target genes.
To access the diagram for the normal canonical Wnt signaling, click here . Apc gene is mutated in both the sporadic and the inherited form of colorectal cancer; frameshift, nonsense or splice-site mutations result in a truncated Apc protein. Axin1 and 2 loss-of-function mutations in colorectal cancer have been reported but they are relatively rare. Beta-catenin mutations cluster in a region of the amino-terminus; they either result in a deletion of an N-terminal fragment or disrupt the phosphorylation of key residues within this region. Mutated beta-catenin has been found in colorectal cancer and with a lower frequency in other types of cancer. For instance, mutations in beta-catenin have been associated with type 1 endometrial cancer. Apc, Axins and beta-catenin mutations result in a constitutively active beta-catenin in the nucleus leading to deregulated expression of Wnt target genes. Other mutations involve the Lrp5 receptor and link to osteoarthritis and low bone mass syndrome as well as eye defects. Mutations in some of the Wnt ligands and/or frizzled receptors (not shown) have been associated with renal failure, cardiovascular and neurodegenerative diseases. A member of Tcf family, Tcf72l, known as Tcf-4 is a strong susceptibility locus for type 2 diabetes. Mutated genes are color coded.
To see the ontology report for Gviewer, annotations and download, click here ...(less)
Pathway Diagram:
Genes in Pathway:
G
Apc
APC regulator of WNT signaling pathway
ISO
RGD
PMID:18432252 RGD:2293188
NCBI chr18:26,138,382...26,196,021
G
Axin1
axin 1
ISO
RGD
PMID:18432252 RGD:2293188
NCBI chr10:15,667,894...15,720,092
G
Axin2
axin 2
ISO
RGD
PMID:18432252 RGD:2293188
NCBI chr10:94,393,379...94,426,579
G
Ctnnb1
catenin beta 1
ISO
RGD
PMID:18432252 PMID:19078924 RGD:2293188 , RGD:4143515
NCBI chr 8:129,517,576...129,544,661
G
Lrp5
LDL receptor related protein 5
ISO
RGD
PMID:18432252 RGD:2293188
NCBI chr 1:210,243,499...210,346,886
G
Map3k1
mitogen-activated protein kinase kinase kinase 1
IMP
RGD
PMID:20128690 RGD:150573713
NCBI chr 2:45,081,889...45,150,555
G
Tcf7l2
transcription factor 7 like 2
ISO
RGD
PMID:18772397 RGD:5490966
NCBI chr 1:264,791,335...264,984,225
G
Wnt9a
Wnt family member 9A
ISO
RGD
PMID:18772397 RGD:5490966
NCBI chr10:44,593,691...44,620,682
Pathway Gene Annotations
Disease Annotations Associated with Genes in the altered Wnt signaling, canonical pathway
Apc Abdominal Fibromatosis , Aberrant Crypt Foci , acinar cell carcinoma , adenocarcinoma , adenoma , Adenomatous Polyps , adult respiratory distress syndrome , Aggressive Fibromatosis , Alzheimer's disease , amenorrhea , anemia , Animal Mammary Neoplasms , ascending colon cancer , Attenuated Adenomatous Polyposis Coli , Attenuated Familial Adenomatous Polyposis , autism spectrum disorder , autistic disorder , breast cancer , Breast Cancer, Familial , breast carcinoma , cholangiocarcinoma , colon adenocarcinoma , colon cancer , colon carcinoma , Colonic Neoplasms , Colonic Polyps , colorectal adenoma , colorectal cancer , Colorectal Neoplasms , craniopharyngioma , desmoid tumor , Digestive System Neoplasms , duodenum adenocarcinoma , endometrial cancer , endometrial carcinoma , Endometrial Intraepithelial Neoplasia , Endometrial Neoplasms , Endometrioid Carcinomas , Eye Abnormalities , familial adenomatous polyposis , familial adenomatous polyposis 1 , familial adenomatous polyposis 2 , familial hyperlipidemia , gallbladder cancer , Gallbladder Neoplasms , Gardner Syndrome , Gastric Adenocarcinoma and Proximal Polyposis of the Stomach , Gastric Polyposis , Gastrointestinal Hemorrhage , Gastrointestinal Neoplasms , gastrointestinal stromal tumor , glioblastoma , hepatoblastoma , hepatocellular carcinoma , hereditary breast ovarian cancer syndrome , hereditary desmoid disease , Hereditary Neoplastic Syndromes , high grade glioma , Hyperplasia , inflammatory bowel disease , intellectual disability , Intestinal Neoplasms , Intestinal Polyposis, Osteomas, Sebaceous Cysts , Intestinal Polyps , intrahepatic cholangiocarcinoma , Jaw Neoplasms , kidney disease , Klatskin's tumor , Leukocytosis , liver disease , Liver Neoplasms , lung adenocarcinoma , Lung Neoplasms , lung non-small cell carcinoma , Lynch syndrome , macrocytic anemia , medulloblastoma , Mesothelioma , mismatch repair cancer syndrome , Monoclonal B-Cell Lymphocytosis , Neoplastic Cell Transformation , ovarian cancer , pancreatic cancer , periampullary adenoma , prostate cancer , Prostatic Neoplasms , rectal benign neoplasm , rectum adenocarcinoma , renal cell carcinoma , sigmoid colon cancer , sigmoid neoplasm , splenic disease , Splenomegaly , squamous cell carcinoma , stomach cancer , Stomach Neoplasms , transitional cell carcinoma , Weight Loss Axin1 Caudal Duplication Anomaly , colon cancer , Colorectal Neoplasms , CRANIOMETADIAPHYSEAL OSTEOSCLEROSIS WITH HIP DYSPLASIA , esophagus squamous cell carcinoma , hepatocellular carcinoma , liver cirrhosis , lung cancer , lung non-small cell carcinoma , oral squamous cell carcinoma , urinary bladder cancer Axin2 Animal Disease Models , anodontia , autosomal recessive limb-girdle muscular dystrophy type 2J , breast cancer , colon adenoma , colon carcinoma , Colonic Neoplasms , colorectal cancer , colorectal carcinoma , Colorectal Neoplasms , craniosynostosis , Craniosynostosis Syndrome, Autosomal Recessive , dilated cardiomyopathy , endometrial adenocarcinoma , familial adenomatous polyposis , familial adenomatous polyposis 2 , gallbladder cancer , hepatoblastoma , hepatocellular carcinoma , Hereditary Neoplastic Syndromes , Hirschsprung's disease , Intestinal Polyps , lung adenocarcinoma , lung cancer , lung small cell carcinoma , Metaplasia , Myocardial Ischemia , Oligodontia-Colorectal Cancer Syndrome , oral mucosa leukoplakia , oral squamous cell carcinoma , orofacial cleft , ovarian cancer , Parkinson's disease , Pulmonary Arterial Hypertension , Selective Tooth Agenesis 1 , short-rib thoracic dysplasia 6 with or without polydactyly , tooth agenesis , transient cerebral ischemia , Ventilator-Induced Lung Injury , Ventricular Remodeling Ctnnb1 Aberrant Crypt Foci , adenocarcinoma , adenoma , Adrenal Cortex Neoplasms , Adrenal Gland Neoplasms , adrenocortical carcinoma , Alazami Syndrome , Alzheimer's disease , Angiofibroma , angiosarcoma , Animal Disease Models , atherosclerosis , autism spectrum disorder , autosomal dominant intellectual developmental disorder 19 , Breast Neoplasms , calcinosis , Cecal Neoplasms , Chemical and Drug Induced Liver Injury , colon adenocarcinoma , colon carcinoma , Colonic Neoplasms , colorectal cancer , Colorectal Neoplasms , Craniofacial Abnormalities , craniopharyngioma , desmoid tumor , Developmental Disabilities , Developmental Disease , Diabetic Cardiomyopathies , dilated cardiomyopathy , Disease Progression , endodermal sinus tumor , Endometrial Intraepithelial Neoplasia , Endometrial Neoplasms , Endometrioid Carcinomas , endometriosis , Experimental Liver Neoplasms , Experimental Mammary Neoplasms , Experimental Neoplasms , exudative vitreoretinopathy , exudative vitreoretinopathy 1 , exudative vitreoretinopathy 7 , fibrolamellar carcinoma , Fibrosis , gallbladder cancer , genetic disease , granulosa cell tumor , head and neck squamous cell carcinoma , hepatitis B , hepatoblastoma , hepatocellular adenoma , hepatocellular carcinoma , hereditary desmoid disease , heroin dependence , hyperekplexia , hypertrophic cardiomyopathy , imperforate anus , in situ carcinoma , intellectual disability , Intestinal Neoplasms , invasive lobular carcinoma , Knee Osteoarthritis , left ventricular failure , Left Ventricular Hypertrophy , liver cirrhosis , Liver Neoplasms , lung adenocarcinoma , lung cancer , lung carcinoma , Lung Neoplasms , lung squamous cell carcinoma , Lymphatic Metastasis , malignant mesothelioma , Mandibular Neoplasms , mantle cell lymphoma , medulloblastoma , Metaplasia , Multiple Abnormalities , muscular atrophy , Myocardial Ischemia , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplastic Cell Transformation , nephroblastoma , Nerve Degeneration , Nervous System Malformations , Neurodevelopmental Disorders , No-Reflow Phenomenon , osteosclerosis , ovarian cancer , Ovarian Neoplasms , pancreatic cancer , papillary thyroid carcinoma , Peritoneal Neoplasms , Phyllodes Tumor , pilomatrixoma , polycystic liver disease , progressive osseous heteroplasia , prostate adenocarcinoma , prostate cancer , Prostatic Neoplasms , Recurrence , renal cell carcinoma , Renal Cell Carcinoma 1 , skin melanoma , Skin Neoplasms , Stevens-Johnson syndrome , Stiff-Person syndrome , stomach cancer , stroke , teratoma , Thyroid Neoplasms , transitional cell carcinoma , traumatic brain injury , urinary bladder cancer , Uterine Cervical Neoplasms , Uterine Neoplasms , Vascular Calcification , Ventricular Remodeling Lrp5 autosomal dominant osteopetrosis 1 , autosomal dominant polycystic kidney disease , BCARD syndrome , Bone Fractures , Camurati-Engelmann disease , Desbuquois dysplasia , exudative vitreoretinopathy , exudative vitreoretinopathy 1 , exudative vitreoretinopathy 4 , Femur Head Necrosis , fundus dystrophy , genetic disease , heart valve disease , idiopathic juvenile osteoporosis , Leber congenital amaurosis , Metabolic Bone Diseases , microcephaly , microphthalmia , neovascular inflammatory vitreoretinopathy , osteogenesis imperfecta , osteopetrosis , osteoporosis , osteoporosis-pseudoglioma syndrome , osteosclerosis , polycystic kidney disease , polycystic kidney disease 1 , polycystic liver disease , polycystic liver disease 1 , polycystic liver disease 4 , Postmenopausal Osteoporosis , retinitis pigmentosa 1 , Spinal Cord Injuries , Spine Osteoarthritis , tendinitis , Worth syndrome Map3k1 46,XY sex reversal 6 , breast cancer , Breast Neoplasms , diffuse gastric cancer , disorder of sexual development , esophagus squamous cell carcinoma , genetic disease , Hearing Loss , hepatocellular carcinoma , Hereditary Neoplastic Syndromes , lung metastasis , lung non-small cell carcinoma , Ovarian Neoplasms , Prostatic Neoplasms , rectum cancer , stomach cancer , syndromic microphthalmia 5 Tcf7l2 adenocarcinoma , Animal Disease Models , autistic disorder , breast cancer , Colonic Neoplasms , colorectal cancer , Colorectal Neoplasms , Coronary Disease , diabetes mellitus , Diabetic Nephropathies , dilated cardiomyopathy , Familial Prostate Cancer , genetic disease , gestational diabetes , Hyperalgesia , Hyperplasia , Insulin Resistance , intellectual disability , juvenile rheumatoid arthritis , maturity-onset diabetes of the young type 1 , Myocardial Ischemia , Neurodevelopmental Disorders , pancreatic cancer , prostate cancer , type 2 diabetes mellitus , Ventricular Remodeling Wnt9a breast cancer , cholangiocarcinoma , pancreatic cancer
46,XY sex reversal 6 Map3k1 Abdominal Fibromatosis Apc Aberrant Crypt Foci Apc , Ctnnb1 acinar cell carcinoma Apc adenocarcinoma Apc , Ctnnb1 , Tcf7l2 adenoma Apc , Ctnnb1 Adenomatous Polyps Apc Adrenal Cortex Neoplasms Ctnnb1 Adrenal Gland Neoplasms Ctnnb1 adrenocortical carcinoma Ctnnb1 adult respiratory distress syndrome Apc Aggressive Fibromatosis Apc Alazami Syndrome Ctnnb1 Alzheimer's disease Apc , Ctnnb1 amenorrhea Apc anemia Apc Angiofibroma Ctnnb1 angiosarcoma Ctnnb1 Animal Disease Models Axin2 , Ctnnb1 , Tcf7l2 Animal Mammary Neoplasms Apc anodontia Axin2 ascending colon cancer Apc atherosclerosis Ctnnb1 Attenuated Adenomatous Polyposis Coli Apc Attenuated Familial Adenomatous Polyposis Apc autism spectrum disorder Apc , Ctnnb1 autistic disorder Apc , Tcf7l2 autosomal dominant intellectual developmental disorder 19 Ctnnb1 autosomal dominant osteopetrosis 1 Lrp5 autosomal dominant polycystic kidney disease Lrp5 autosomal recessive limb-girdle muscular dystrophy type 2J Axin2 BCARD syndrome Lrp5 Bone Fractures Lrp5 breast cancer Apc , Axin2 , Map3k1 , Tcf7l2 , Wnt9a Breast Cancer, Familial Apc breast carcinoma Apc Breast Neoplasms Ctnnb1 , Map3k1 calcinosis Ctnnb1 Camurati-Engelmann disease Lrp5 Caudal Duplication Anomaly Axin1 Cecal Neoplasms Ctnnb1 Chemical and Drug Induced Liver Injury Ctnnb1 cholangiocarcinoma Apc , Wnt9a colon adenocarcinoma Apc , Ctnnb1 colon adenoma Axin2 colon cancer Apc , Axin1 colon carcinoma Apc , Axin2 , Ctnnb1 Colonic Neoplasms Apc , Axin2 , Ctnnb1 , Tcf7l2 Colonic Polyps Apc colorectal adenoma Apc colorectal cancer Apc , Axin2 , Ctnnb1 , Tcf7l2 colorectal carcinoma Axin2 Colorectal Neoplasms Apc , Axin1 , Axin2 , Ctnnb1 , Tcf7l2 Coronary Disease Tcf7l2 Craniofacial Abnormalities Ctnnb1 CRANIOMETADIAPHYSEAL OSTEOSCLEROSIS WITH HIP DYSPLASIA Axin1 craniopharyngioma Apc , Ctnnb1 craniosynostosis Axin2 Craniosynostosis Syndrome, Autosomal Recessive Axin2 Desbuquois dysplasia Lrp5 desmoid tumor Apc , Ctnnb1 Developmental Disabilities Ctnnb1 Developmental Disease Ctnnb1 diabetes mellitus Tcf7l2 Diabetic Cardiomyopathies Ctnnb1 Diabetic Nephropathies Tcf7l2 diffuse gastric cancer Map3k1 Digestive System Neoplasms Apc dilated cardiomyopathy Axin2 , Ctnnb1 , Tcf7l2 Disease Progression Ctnnb1 disorder of sexual development Map3k1 duodenum adenocarcinoma Apc endodermal sinus tumor Ctnnb1 endometrial adenocarcinoma Axin2 endometrial cancer Apc endometrial carcinoma Apc Endometrial Intraepithelial Neoplasia Apc , Ctnnb1 Endometrial Neoplasms Apc , Ctnnb1 Endometrioid Carcinomas Apc , Ctnnb1 endometriosis Ctnnb1 esophagus squamous cell carcinoma Axin1 , Map3k1 Experimental Liver Neoplasms Ctnnb1 Experimental Mammary Neoplasms Ctnnb1 Experimental Neoplasms Ctnnb1 exudative vitreoretinopathy Ctnnb1 , Lrp5 exudative vitreoretinopathy 1 Ctnnb1 , Lrp5 exudative vitreoretinopathy 4 Lrp5 exudative vitreoretinopathy 7 Ctnnb1 Eye Abnormalities Apc familial adenomatous polyposis Apc , Axin2 familial adenomatous polyposis 1 Apc familial adenomatous polyposis 2 Apc , Axin2 familial hyperlipidemia Apc Familial Prostate Cancer Tcf7l2 Femur Head Necrosis Lrp5 fibrolamellar carcinoma Ctnnb1 Fibrosis Ctnnb1 fundus dystrophy Lrp5 gallbladder cancer Apc , Axin2 , Ctnnb1 Gallbladder Neoplasms Apc Gardner Syndrome Apc Gastric Adenocarcinoma and Proximal Polyposis of the Stomach Apc Gastric Polyposis Apc Gastrointestinal Hemorrhage Apc Gastrointestinal Neoplasms Apc gastrointestinal stromal tumor Apc genetic disease Ctnnb1 , Lrp5 , Map3k1 , Tcf7l2 gestational diabetes Tcf7l2 glioblastoma Apc granulosa cell tumor Ctnnb1 head and neck squamous cell carcinoma Ctnnb1 Hearing Loss Map3k1 heart valve disease Lrp5 hepatitis B Ctnnb1 hepatoblastoma Apc , Axin2 , Ctnnb1 hepatocellular adenoma Ctnnb1 hepatocellular carcinoma Apc , Axin1 , Axin2 , Ctnnb1 , Map3k1 hereditary breast ovarian cancer syndrome Apc hereditary desmoid disease Apc , Ctnnb1 Hereditary Neoplastic Syndromes Apc , Axin2 , Map3k1 heroin dependence Ctnnb1 high grade glioma Apc Hirschsprung's disease Axin2 Hyperalgesia Tcf7l2 hyperekplexia Ctnnb1 Hyperplasia Apc , Tcf7l2 hypertrophic cardiomyopathy Ctnnb1 idiopathic juvenile osteoporosis Lrp5 imperforate anus Ctnnb1 in situ carcinoma Ctnnb1 inflammatory bowel disease Apc Insulin Resistance Tcf7l2 intellectual disability Apc , Ctnnb1 , Tcf7l2 Intestinal Neoplasms Apc , Ctnnb1 Intestinal Polyposis, Osteomas, Sebaceous Cysts Apc Intestinal Polyps Apc , Axin2 intrahepatic cholangiocarcinoma Apc invasive lobular carcinoma Ctnnb1 Jaw Neoplasms Apc juvenile rheumatoid arthritis Tcf7l2 kidney disease Apc Klatskin's tumor Apc Knee Osteoarthritis Ctnnb1 Leber congenital amaurosis Lrp5 left ventricular failure Ctnnb1 Left Ventricular Hypertrophy Ctnnb1 Leukocytosis Apc liver cirrhosis Axin1 , Ctnnb1 liver disease Apc Liver Neoplasms Apc , Ctnnb1 lung adenocarcinoma Apc , Axin2 , Ctnnb1 lung cancer Axin1 , Axin2 , Ctnnb1 lung carcinoma Ctnnb1 lung metastasis Map3k1 Lung Neoplasms Apc , Ctnnb1 lung non-small cell carcinoma Apc , Axin1 , Map3k1 lung small cell carcinoma Axin2 lung squamous cell carcinoma Ctnnb1 Lymphatic Metastasis Ctnnb1 Lynch syndrome Apc macrocytic anemia Apc malignant mesothelioma Ctnnb1 Mandibular Neoplasms Ctnnb1 mantle cell lymphoma Ctnnb1 maturity-onset diabetes of the young type 1 Tcf7l2 medulloblastoma Apc , Ctnnb1 Mesothelioma Apc Metabolic Bone Diseases Lrp5 Metaplasia Axin2 , Ctnnb1 microcephaly Lrp5 microphthalmia Lrp5 mismatch repair cancer syndrome Apc Monoclonal B-Cell Lymphocytosis Apc Multiple Abnormalities Ctnnb1 muscular atrophy Ctnnb1 Myocardial Ischemia Axin2 , Ctnnb1 , Tcf7l2 Neoplasm Invasiveness Ctnnb1 Neoplasm Metastasis Ctnnb1 Neoplastic Cell Transformation Apc , Ctnnb1 neovascular inflammatory vitreoretinopathy Lrp5 nephroblastoma Ctnnb1 Nerve Degeneration Ctnnb1 Nervous System Malformations Ctnnb1 Neurodevelopmental Disorders Ctnnb1 , Tcf7l2 No-Reflow Phenomenon Ctnnb1 Oligodontia-Colorectal Cancer Syndrome Axin2 oral mucosa leukoplakia Axin2 oral squamous cell carcinoma Axin1 , Axin2 orofacial cleft Axin2 osteogenesis imperfecta Lrp5 osteopetrosis Lrp5 osteoporosis Lrp5 osteoporosis-pseudoglioma syndrome Lrp5 osteosclerosis Ctnnb1 , Lrp5 ovarian cancer Apc , Axin2 , Ctnnb1 Ovarian Neoplasms Ctnnb1 , Map3k1 pancreatic cancer Apc , Ctnnb1 , Tcf7l2 , Wnt9a papillary thyroid carcinoma Ctnnb1 Parkinson's disease Axin2 periampullary adenoma Apc Peritoneal Neoplasms Ctnnb1 Phyllodes Tumor Ctnnb1 pilomatrixoma Ctnnb1 polycystic kidney disease Lrp5 polycystic kidney disease 1 Lrp5 polycystic liver disease Ctnnb1 , Lrp5 polycystic liver disease 1 Lrp5 polycystic liver disease 4 Lrp5 Postmenopausal Osteoporosis Lrp5 progressive osseous heteroplasia Ctnnb1 prostate adenocarcinoma Ctnnb1 prostate cancer Apc , Ctnnb1 , Tcf7l2 Prostatic Neoplasms Apc , Ctnnb1 , Map3k1 Pulmonary Arterial Hypertension Axin2 rectal benign neoplasm Apc rectum adenocarcinoma Apc rectum cancer Map3k1 Recurrence Ctnnb1 renal cell carcinoma Apc , Ctnnb1 Renal Cell Carcinoma 1 Ctnnb1 retinitis pigmentosa 1 Lrp5 Selective Tooth Agenesis 1 Axin2 short-rib thoracic dysplasia 6 with or without polydactyly Axin2 sigmoid colon cancer Apc sigmoid neoplasm Apc skin melanoma Ctnnb1 Skin Neoplasms Ctnnb1 Spinal Cord Injuries Lrp5 Spine Osteoarthritis Lrp5 splenic disease Apc Splenomegaly Apc squamous cell carcinoma Apc Stevens-Johnson syndrome Ctnnb1 Stiff-Person syndrome Ctnnb1 stomach cancer Apc , Ctnnb1 , Map3k1 Stomach Neoplasms Apc stroke Ctnnb1 syndromic microphthalmia 5 Map3k1 tendinitis Lrp5 teratoma Ctnnb1 Thyroid Neoplasms Ctnnb1 tooth agenesis Axin2 transient cerebral ischemia Axin2 transitional cell carcinoma Apc , Ctnnb1 traumatic brain injury Ctnnb1 type 2 diabetes mellitus Tcf7l2 urinary bladder cancer Axin1 , Ctnnb1 Uterine Cervical Neoplasms Ctnnb1 Uterine Neoplasms Ctnnb1 Vascular Calcification Ctnnb1 Ventilator-Induced Lung Injury Axin2 Ventricular Remodeling Axin2 , Ctnnb1 , Tcf7l2 Weight Loss Apc Worth syndrome Lrp5
