WNT-1 Human Active Protein

The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It is very conserved in evolution, and the protein encoded by this gene is known to be 98% identical to the mouse Wnt1 protein at the amino acid level. The studies in mouse indicate that the Wnt1 protein functions in the induction of the mesencephalon and cerebellum. This gene was originally considered as a candidate gene for Joubert syndrome, an autosomal recessive disorder with cerebellar hypoplasia as a leading feature. However, further studies suggested that the gene mutations might not have a significant role in Joubert syndrome. This gene is clustered with another family member, WNT10B, in the chromosome 12q13 region. [provided by RefSeq, Jul 2008]

Function: 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. Probable developmental protein. May be a signaling molecule important in CNS development. Is likely to signal over only few cell diameters. Has a role in osteoblast function and bone development. Ref.6

Subunit structure: Interacts with PORCN. Interacts with RSPO1, RSPO2 and RSPO3

By similarity. Interacts with WLS

By similarity.

Subcellular location: Secreted › extracellular space › extracellular matrix.

Post-translational modification: Palmitoylation at Ser-224 is required for efficient binding to frizzled receptors. It is also required for subsequent palmitoylation at Cys-93. Palmitoylation is necessary for proper trafficking to cell surface. Ref.5

Polymorphism: 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.

Involvement in disease: Osteoporosis (OSTEOP) [MIM:166710]: 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.Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.6 Ref.7Osteogenesis imperfecta 15 (OI15) [MIM:615220]: An autosomal recessive form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI15 is characterized by early-onset recurrent fractures, bone deformity, significant reduction of bone density, short stature, and, in some patients, blue sclerae. Tooth development and hearing are normal. Learning and developmental delays and brain anomalies have been observed in some patients.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.7 Ref.8 Ref.9

Sequence similarities: Belongs to the Wnt family.