LGR4
Function
Receptor for R-spondins that potentiates the canonical Wnt signaling pathway and is involved in the formation of various organs. Upon binding to R-spondins (RSPO1, RSPO2, RSPO3 or RSPO4), associates with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. In contrast to classical G-protein coupled receptors, does not activate heterotrimeric G-proteins to transduce the signal. Its function as activator of the Wnt signaling pathway is required for the development of various organs, including liver, kidney, intestine, bone, reproductive tract and eye. May also act as a receptor for norrin (NDP), such results however require additional confirmation in vivo. Required during spermatogenesis to activate the Wnt signaling pathway in peritubular myoid cells. Required for the maintenance of intestinal stem cells and Paneth cell differentiation in postnatal intestinal crypts. Acts as a regulator of bone formation and remodeling. Involved in kidney development; required for maintaining the ureteric bud in an undifferentiated state. Involved in the development of the anterior segment of the eye. Required during erythropoiesis. Also acts as a negative regulator of innate immunity by inhibiting TLR2/TLR4 associated pattern-recognition and pro-inflammatory cytokine production. Plays an important role in regulating the circadian rhythms of plasma lipids, partially through regulating the rhythmic expression of MTTP (By similarity). Required for proper development of GnRH neurons (gonadotropin-releasing hormone expressing neurons) that control the release of reproductive hormones from the pituitary gland (By similarity).
Involvement in disease
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.
None
Disease susceptibility may be associated with variants affecting the gene represented in this entry. A LGR4 nonsense mutation creating a stop codon after position 126 (c.376C>T) is strongly associated with low bone mineral density and osteoporotic fractures (PubMed:23644456). This mutation probably causes degradation of the transcript by nonsense-mediated decay (NMD). The c.376C>T mutation is also associated with electrolyte imbalance, late onset of menarche and reduced testosterone levels, as well as an increased risk of squamous cell carcinoma of the skin and biliary tract cancer (PubMed:23644456).
Delayed puberty, self-limited
DPSL
A condition defined as the absence of testicular enlargement in boys or breast development in girls at an age that is 2-2.5 SD later than the population mean. DPSL is often familial and is highly heritable, most commonly seen with an autosomal dominant inheritance pattern.
None
The disease may be caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the G-protein coupled receptor 1 family.
Tissue Specificity
Expressed in multiple steroidogenic tissues: placenta, ovary, testis and adrenal. Expressed also in spinal cord, thyroid, stomach, trachea, heart, pancreas, kidney, prostate and spleen.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
Alternative names
GPR48, LGR4, Leucine-rich repeat-containing G-protein coupled receptor 4, G-protein coupled receptor 48