WNT1 (wingless-type MMTV integration site family, member 1)

2013-12-01   Irini Theohari , Lydia Nakopoulou 

1st Department of Pathology, Medical School, University of Athens, Athens, Greece


Atlas Image
Genomic location of WNT1 gene at chromosome 12 (plus strand).


Atlas Image


The WNT1 gene spans a genomic region of 4161 bases on plus strand. The DNA of WNT1 consists of 4 exons and the coding sequence starts in the first exon.


The WNT1 gene has one protein coding transcript which consists of 370 amino acids.



Ligand for members of the frizzled family of seven transmembrane receptors. In some developmental processes, is also a ligand for the coreceptor RYK, thus triggering Wnt signaling.


Secreted, extracellular space, extracellular matrix.


Probable developmental protein. May be a signaling molecule important in CNS (central nervous system) development. Is likely to signal over only few cell diameters. Has a role in osteoblast function and bone development.



There are several WNT1 mutations identified related with osteogenesis imperfecta. Several confirmed somatic mutations of the WNT1 gene have also been reported, according to COSMIC, which are associated with carcinomas of the endometrium, lung, large intestine, prostate and kidney.

Implicated in

Entity name
Esophageal cancer
It has been shown, in cell cultures of esophageal cancer, that WNT1 results in cytoplasmic accumulation of beta-catenin and activates TCF-dependent transcription (Mizushima et al., 2002). Overexpression of mRNA and protein levels of WNT1 have been positively associated with lymph node metastasis, advanced pathological stage and prognosis of patients with esophageal squamous cell carcinoma (Lv et al., 2012).
Entity name
Breast cancer
WNT1 has been shown to be markedly elevated in grade I tumors, but declined as tumor grade declined (Wong et al., 2002). Ectopic expression of WNT1, triggers the DNA damage response (DDR) and an ensuing cascade of events resulting in tumorigenic conversion of primary human mammary epithelial cells. WNT1-transformed cells have high telomerase activity and compromised p53 and Rb function, grow as spheres in suspension, and in mice form tumors that closely resemble medullary carcinomas of the breast (Ayyanan et al., 2006). siRNA anti-WNT1 has been shown to induce apoptosis in human breast cancer cell lines (Wieczorek et al., 2008). WNT1 immunoreactivity has been found to be inversely related to histological grade, Ki-67 and p53, positively to , HER-2 and caspase-3 and has been correlated with favorable prognosis of patients with stage II breast cancer (Mylona et al., 2013).
Entity name
Basal cell carcinoma of head and neck
Overexpression of WNT1 has been positively associated with cytoplasmic beta-catenin (Lo Muzio et al., 2002).
Entity name
WNT1 blockade by either monoclonal antibody or siRNA induces cell death in sarcoma cells (Mikami et al., 2005).
Entity name
Non-small cell lung cancer (NSCLC)
The expression of WNT1 has been positively correlated with c-Myc, cyclin D1, VEGF-A, MMP-7, Ki-67 and intratumoral microvessel density and has been found to negatively influence patients survival (Huang et al., 2008). WNT1 overexpression has been positively associated with the Ki-67 proliferation index and c-Myc and has been found to exert an unfavorable impact on patients survival (Nakashima et al., 2008). WNT1 expression has been found to be an independent prognostic factor of poor survival (Xu et al., 2011).
Entity name
Gastric cancer
The expression levels of WNT1 are positively correlated with tumor size, tumor invasive depth, lymph node metastasis, pTNM stage and negatively influences patients 5-year survival rate (Zhang and Xue, 2008).
Entity name
Knockdown of endogenous WNT1 expression results in cell death and inhibits cell growth (Zhang et al., 2009).
Entity name
Osteogenesis imperfecta (OI)
This disease is a heritable bone fragiility disorder that is usually due to dominant mutations in COL1A1 or COL1A2 and is characterized by reduced bone mass and recurrent fractures. Genetic variations in WNT1 define the bone mineral density quantitative trait locus 16 (BMND16) [MIM:615221]. Variance in bone mineral density influences bone mass, contributes to size determination in the general population, and is a susceptibility factor for osteoporotic fractures. The disease is caused by mutations affecting the gene of WNT1 (Fahiminiya et al., 2013; Faqeih et al., 2013; Laine et al., 2013; Pyott et al., 2013).
Entity name
Osteoporosis (OSTEOP)
A systemic skeletal disorder characterized by decreased bone mass and deterioration of bone microarchitecture without alteration in the composition of bone. The result is fragile bones and an increased risk of fractures, even after minimal trauma. Osteoporosis is a chronic condition of multifactorial etiology and is usually clinically silent until a fracture occurs. Disease susceptibility is associated with variations affecting the gene of WNT1 (Keupp et al., 2013; Laine et al., 2013).


Pubmed IDLast YearTitleAuthors
165010432006Increased Wnt signaling triggers oncogenic conversion of human breast epithelial cells by a Notch-dependent mechanism.Ayyanan A et al
234347632013Mutations in WNT1 are a cause of osteogenesis imperfecta.Fahiminiya S et al
237097552013WNT1 mutation with recessive osteogenesis imperfecta and profound neurological phenotype.Faqeih E et al
187906332008Wnt1 overexpression promotes tumour progression in non-small cell lung cancer.Huang CL et al
234993092013Mutations in WNT1 cause different forms of bone fragility.Keupp K et al
236566462013WNT1 mutations in early-onset osteoporosis and osteogenesis imperfecta.Laine CM et al
120146242002WNT-1 expression in basal cell carcinoma of head and neck. An immunohistochemical and confocal study with regard to the intracellular distribution of beta-catenin.Lo Muzio L et al
212590572012Association of β-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 with the prognosis of esophageal squamous cell carcinoma.Lv J et al
159134532005Efficacy of Wnt-1 monoclonal antibody in sarcoma cells.Mikami I et al
117823882002Wnt-1 but not epidermal growth factor induces beta-catenin/T-cell factor-dependent transcription in esophageal cancer cells.Mizushima T et al
235515362013An immunohistochemical evaluation of the proteins Wnt1 and glycogen synthase kinase (GSK)-3β in invasive breast carcinomas.Mylona E et al
180975962008Wnt1 overexpression associated with tumor proliferation and a poor prognosis in non-small cell lung cancer patients.Nakashima T et al
234993102013WNT1 mutations in families affected by moderately severe and progressive recessive osteogenesis imperfecta.Pyott SM et al
180591862008Silencing of Wnt-1 by siRNA induces apoptosis of MCF-7 human breast cancer cells.Wieczorek M et al
117933652002Expression of frizzled-related protein and Wnt-signalling molecules in invasive human breast tumours.Wong SC et al
213361842011Aberrant Wnt1/β-catenin expression is an independent poor prognostic marker of non-small cell lung cancer after surgery.Xu X et al
187053442008Wnt pathway is involved in advanced gastric carcinoma.Zhang H et al
197566562009The effect on cell growth by Wnt1 RNAi in human neuroblastoma SH-SY5Y cell line.Zhang L et al

Other Information

Locus ID:

NCBI: 7471
MIM: 164820
HGNC: 12774
Ensembl: ENSG00000125084


dbSNP: 7471
ClinVar: 7471
TCGA: ENSG00000125084


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
mTOR signaling pathwayKEGGko04150
Wnt signaling pathwayKEGGko04310
Basal cell carcinomaKEGGko05217
mTOR signaling pathwayKEGGhsa04150
Wnt signaling pathwayKEGGhsa04310
Pathways in cancerKEGGhsa05200
Basal cell carcinomaKEGGhsa05217
HTLV-I infectionKEGGko05166
HTLV-I infectionKEGGhsa05166
Hippo signaling pathwayKEGGhsa04390
Hippo signaling pathwayKEGGko04390
Proteoglycans in cancerKEGGhsa05205
Proteoglycans in cancerKEGGko05205
Signaling pathways regulating pluripotency of stem cellsKEGGhsa04550
Signaling pathways regulating pluripotency of stem cellsKEGGko04550
Wnt signalingKEGGhsa_M00677
Wnt signalingKEGGM00677
Signal TransductionREACTOMER-HSA-162582
Signaling by GPCRREACTOMER-HSA-372790
GPCR ligand bindingREACTOMER-HSA-500792
Class B/2 (Secretin family receptors)REACTOMER-HSA-373080
Signaling by WntREACTOMER-HSA-195721
WNT ligand biogenesis and traffickingREACTOMER-HSA-3238698
TCF dependent signaling in response to WNTREACTOMER-HSA-201681
Disassembly of the destruction complex and recruitment of AXIN to the membraneREACTOMER-HSA-4641262
Beta-catenin independent WNT signalingREACTOMER-HSA-3858494
PCP/CE pathwayREACTOMER-HSA-4086400
Developmental BiologyREACTOMER-HSA-1266738
Transcriptional regulation of white adipocyte differentiationREACTOMER-HSA-381340
Breast cancerKEGGko05224
Breast cancerKEGGhsa05224


Pubmed IDYearTitleCitations
170723032006A Wnt-Axin2-GSK3beta cascade regulates Snail1 activity in breast cancer cells.254
196286682009Wnt/beta-catenin signaling promotes podocyte dysfunction and albuminuria.167
223929992012Wnt/β-catenin signaling promotes differentiation, not self-renewal, of human embryonic stem cells and is repressed by Oct4.117
165010432006Increased Wnt signaling triggers oncogenic conversion of human breast epithelial cells by a Notch-dependent mechanism.116
190618382008Hepatic stem-like phenotype and interplay of Wnt/beta-catenin and Myc signaling in aggressive childhood liver cancer.109
193987212009MicroRNA profiling identifies miR-34a and miR-21 and their target genes JAG1 and WNT1 in the coordinate regulation of dendritic cell differentiation.108
165650902006Mediator is a transducer of Wnt/beta-catenin signaling.106
167567202006Aberrant Wnt/beta-catenin signaling in pancreatic adenocarcinoma.91
182970602008MesP1 drives vertebrate cardiovascular differentiation through Dkk-1-mediated blockade of Wnt-signalling.91
171432992006The ups and downs of Wnt signaling in prevalent neurological disorders.89


Irini Theohari ; Lydia Nakopoulou

WNT1 (wingless-type MMTV integration site family, member 1)

Atlas Genet Cytogenet Oncol Haematol. 2013-12-01

Online version: http://atlasgeneticsoncology.org/gene/462/wnt1-(wingless-type-mmtv-integration-site-family-member-1)