what does fgfr3 mean

What is the function of the FGFR3 gene?

Normal Function. The FGFR3 gene provides instructions for making a protein called fibroblast growth factor receptor 3. This protein is part of a family of four fibroblast growth factor receptors that share similar structures and functions. These proteins play a role in several important cellular processes, including regulation ...

What is the isoform of FGFR3?

Several versions (isoforms) of the FGFR3 protein are produced from the FGFR3 gene. The different isoforms are found in various tissues of the body, and they interact with a variety of growth factors. Many isoforms are found in the cells that form bones.

What does FGFR stand for in cancer?

FGFR stands for fibroblast growth factor receptor. FGFR helps cells grow, survive, and multiply. In certain types of cancer, like in some cases of bladder cancer, the gene that controls FGFR can change or mutate (known as an FGFR alteration).

Where is FGFR3 found in the body?

One particular isoform of the FGFR3 protein is found specifically in cells that line the surfaces of the body (epithelial cells), including the cells that form the outermost layer of skin, called the epidermis.

What does FGFR3 stand for?

fibroblast growth factor receptor 3Novel fibroblast growth factor receptor 3 (FGFR3) mutations in bladder cancer previously identified in non-lethal skeletal disorders.

What causes FGFR3?

More than 25 mutations in the FGFR3 gene have been identified in people with hypochondroplasia, another form of short-limbed dwarfism that is milder than achondroplasia. Many cases are caused by one of two specific FGFR3 gene mutations, both of which lead to the same change in the FGFR3 protein.

Where is FGFR3 found?

chromosome 4p16.3FGFR3, a tyrosine kinase receptor gene, is located at chromosome 4p16. 3 and is composed of 19 exons [14]. The extracellular portion can bind with fibroblast growth factors, initiating cascades of downstream signals that ultimately influence cell growth, migration, angiogenesis, and differentiation [14].

What type of receptor is FGFR3?

Tocris Summary for FGFR3 Gene Fibroblast growth factors (FGFs) are mitogenic signaling molecules that have roles in angiogenesis, wound healing, cell migration, neural outgrowth and embryonic development. FGF receptors (FGFRs) are transmembrane catalytic receptors with intracellular tyrosine kinase activity.

What is FGFR3 antibody?

One of the receptors, FGFR3, is known to be involved in nerve regeneration and axonal development [6]. The intracellular domain of FGFR3 was found to be a target of IgG antibodies in a subgroup of patients with sensory neuropathy, particularly in idiopathic or autoimmune-related cases [7].

Who is most likely to get achondroplasia?

Affected Populations Achondroplasia appears to affect males and females in equal numbers. This disorder begins in the developing fetus and is one of the most common forms of skeletal dysplasia that causes dwarfism. The estimated frequency of achondroplasia has ranged from about one in 15,000 to one in 35,000 births.

How does FGFR3 cause achondroplasia?

What is achondroplasia? Achondroplasia is caused by a gene alteration (mutation) in the FGFR3 gene. The FGFR3 gene makes a protein called fibroblast growth factor receptor 3 that is involved in converting cartilage to bone. FGFR3 is the only gene known to be associated with achondroplasia.

What happens to the body when you have achondroplasia?

Achondroplasia impairs the growth of bone in the limbs and causes abnormal growth in the spine and skull. Although the cause is a genetic mutation, only about one out of five cases is hereditary (passed down by a parent).

How is the FGFR3 gene affected in achondroplasia?

Mutations in the FGFR3 gene lead to a change in the FGFR3 protein, specifically, the amino acid? glycine is replaced with the amino acid arginine. This results in the FGFR3 protein being absent or damaged so that it cannot interact with external growth factors and therefore cannot control ossification.

How many people in the world have achondroplasia?

Achondroplasia is a genetic condition that affects about 1 in 15,000 to 1 in 40,000 people. It makes your arms and legs short in comparison to your head and trunk.

Is a FGFR3 a tyrosine kinase?

Fibroblast growth factor receptor 3 (FGFR3) belongs to a class of transmembrane tyrosine kinase receptors (FGFR1–4) involved in signal transduction regulating cell growth, differentiation, migration, wound healing and angiogenesis, depending on target cell type and developmental stage.

What chromosome is the FGFR3 gene on?

chromosome 4Mutations involve the gene encoding fibroblast growth factor receptor 3 (FGFR3), situated on chromosome 4. Most commonly, a point mutation causes the substitution of arginine for glycine (G380R) in the transmembrane region of the receptor.

How does FGFR3 cause achondroplasia?

What is achondroplasia? Achondroplasia is caused by a gene alteration (mutation) in the FGFR3 gene. The FGFR3 gene makes a protein called fibroblast growth factor receptor 3 that is involved in converting cartilage to bone. FGFR3 is the only gene known to be associated with achondroplasia.

How does mutation in FGFR3 cause achondroplasia?

Achondroplasia comes from the genetic point mutations in the fibroblastic growth factor receptor 3 gene (FGFR3), which enables abnormal cartilage growth-plate differentiation and insufficient bony development.

How is the FGFR3 gene affected in achondroplasia?

Mutations in the FGFR3 gene lead to a change in the FGFR3 protein, specifically, the amino acid? glycine is replaced with the amino acid arginine. This results in the FGFR3 protein being absent or damaged so that it cannot interact with external growth factors and therefore cannot control ossification.

What chromosome is the FGFR3 gene on?

chromosome 4Mutations involve the gene encoding fibroblast growth factor receptor 3 (FGFR3), situated on chromosome 4. Most commonly, a point mutation causes the substitution of arginine for glycine (G380R) in the transmembrane region of the receptor.

What is TD type 1?

There are two types. TD type I is caused by a stop codon mutation that is located in part of the gene coding for the extracellular domain of the protein. TD type II is a result of a substitution in a Lsy650Glu which is located in the tyrosine kinase area of FGFR3.

What is achondroplasia caused by?

Achondroplasia is a dominant genetic disorder caused by mutations in FGFR3 that make the resulting protein overactive. Individuals with these mutation have a head size that is larger than normal and are significantly shorter in height. Only a single copy of the mutated FGFR3 gene results in achondroplasia.

What is the primary mitogenic driver of glioblastoma?

FGFR3-TACC3 fusions have been identified as the primary mitogenic drivers in a subset of glioblastomas (approximately 4%) and other gliomas and may be associated with slightly improved overall survival. The FGFR3-TACC3 fusion represents a possible therapeutic target in glioblastoma.

What happens if you get a gain of function mutation?

Gain of function mutations in this gene can develop dysfunctional proteins "impede cartilage growth and development and affect chondrocyte proliferation and calcification" which can lead to craniosynostosis and multiple types of skeletal dysplasia ( osteochondrodysplasia ).

What family is FGFR in?

The protein encoded by this gene is a member of the fibroblast growth factor receptor family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution.

What is the function of FGFR3?

Since the different forms are found within different tissues the protein is responsible for multiple growth factor interactions.

Where is FGFR3 located?

FGFR3 has also been designated as CD333 ( cluster of differentiation 333). The gene, which is located on chromosome 4 , location p16.3, is expressed in tissues such as the cartilage, brain, intestine, and kidneys. The FGFR3 gene produces various forms of ...

What is the function of snail1?

Snail1 is a transcriptional repressor that is expressed in prehypertrophic chondrocytes and that is induced in Thanatophoric dysplasia bone tissue and in mouse models that activate FGFR3 ( de Frutos et al., 2007; Karuppaiah et al., 2016; Seki et al., 2003 ). Ectopic activation of SNAIL1 in chondrocytes decreased chondrocyte proliferation and longitudinal bone growth ( de Frutos et al., 2007 ). This phenotype required activation of STAT1 (which increases p21 Waf1/Cip1 expression) and MAPK, both of which act downstream of FGFR3 ( de Frutos et al., 2007 ). Further supporting this model, conditional inactivation of both Snail1 and Snail2 in limb bud mesenchyme also increased p21 Waf1/Cip1 and decreased chondrocyte proliferation ( Chen & Gridley, 2013 ). In cancer cells, activated ERK2 directly phosphorylates SNAIL1, leading to its nuclear accumulation and increased protein stability ( Zhang et al., 2013) and SNAIL1 promotes the nuclear localization of p-ERK ( Smith et al., 2014 ). However, it is not known if these activities occur in chondrocytes.

What mutations cause FGFR3 to be lost?

A heterozygous missense mutation of the FGFR3 that was predicted to cause a partial loss of FGFR3 function was identified in 20 of the 20 affected members tested. The observation suggested that the haploinsufficiency caused loss of FGFR3 function by a dominant negative mechanism.

What is FGFR3?

Fibroblast growth factor receptor 3 (FGFR3) disorders are a group of disorders that include thanatophoric dysplasia, achondroplasia, and hypochondroplasia. Achondroplasia is the most frequent cause of nonlethal dwarfism and is characterized by relative macrocephaly, characteristic facies, shortened long bones, relative long trunk and a distinct form of brachydactyly associated with a trident configuration to the hand. Many of these findings can be detected by prenatal ultrasound. Thanatophoric dysplasia is one of the most common lethal skeletal disorders and is associated with relative macrocephaly, frontal bossing, severe micromelia, and small, lethal appearing thorax. Achondroplasia and thanatophoric dysplasia are inherited as autosomal dominant disorders due to heterozygosity for mutations in FGFR3.

What is the skeletal phenotype of mice?

The skeletal phenotype of these mice is characterized by elongated long bones, particularly the femur, and long vertebral bodies, that pred ispose the animals to thoracic kyphoscoliosis. Only bones formed by endochondrial ossification were affected in the mice and in the patients with this syndrome and the bones most notably affected were the long bones and vertebral bodies. The mice also exhibited profound sensory neural deafness, which was caused by cochlear defects.

What is the FGFR3 receptor?

Fibroblast growth factor receptor 3 (FGFR3) is one of five distinct membrane spanning tyrosine kinases and a negative regulator of endochondral bone growth.

Where is FGFR3 found?

FGFR3 was first reported as a 110-kDa variant form lacking the transmembrane domain but with ligand-binding and kinase domain in the nuclei of breast epithelial cells ( Johnston, Cox, Gomm, & Coombes, 1995 ). Nuclear FGFR3 is also detected in malignant breast cancer ( Zammit et al., 2001 ).

Does FGFR3 suppress BMP4?

FGFR3 signaling suppresses the expression of Bmp4, BMPR1a, Ihh, and Pth1r in the postnatal growth plate ( Chen, Li, Qiao, Xu, & Deng, 2001; Naski et al., 1998; Qi et al., 2014 ). Additionally, in a chondrocyte cell line, overexpression of FGFR3 suppresses expression of both Pthlh and its receptor, Pth1r ( Li et al., 2010 ). In addition to regulation of classical signaling pathways, FGFR3 has recently been shown to affect cilia length and intraflagellar transport in chondrocytes. This in turn may modulate chondrocyte response to hedgehog signaling ( Kunova Bosakova et al., 2018 ).

Overview

Function

Mutations

Disease linkage

As a drug target

Interactions

See also

Further reading