Intraflagellar transport 122
The IFT122 gene provides instructions for making a protein that is involved in the formation and maintenance of cilia, which are microscopic, finger-like projections that stick out from the surface of cells. Cilia participate in signaling pathways that transmit information within and between cells and are important for the development and function of many types of cells and tissues, including cells in the kidneys and liver and the light-sensitive tissue at the back of the eye (the retina). Cilia also play a role in the development of the bones, although the mechanism is not well understood.
The movement of substances within cilia and similar structures called flagella is known as intraflagellar transport. This process is essential for the assembly and maintenance of these cell structures. During intraflagellar transport, cells use molecules called IFT particles to carry materials to and from the tips of cilia. Each IFT particle is made up of two groups of IFT proteins: complex A and complex B. The protein produced from the IFT122 gene forms part of IFT complex A (IFT-A). During intraflagellar transport, this complex carries materials from the tip to the base of cilia.
The IFT-A complex is essential for proper regulation of the Sonic Hedgehog signaling pathway, which is important for the growth and maturation (differentiation) of cells and the normal shaping (patterning) of many parts of the body, especially during embryonic development. The exact role of the complex in this pathway is unclear.
2. Health Conditions Related to Genetic Changes
2.1. Cranioectodermal Dysplasia
Mutations in the IFT122 gene can cause cranioectodermal dysplasia. This condition is characterized by an elongated head (dolichocephaly) with a prominent forehead and other distinctive facial features; short bones; and abnormalities of certain tissues known as ectodermal tissues, which include the teeth, hair, nails, and skin.
At least six IFT122 gene mutations have been found in people with cranioectodermal dysplasia. These mutations reduce the amount or function of the IFT122 protein. A shortage or reduction in activity of this component of the IFT-A complex impairs the function of the entire complex, disrupting transport of proteins and materials from the tips of cilia. As a result, assembly and maintenance of cilia is impaired, which leads to a smaller number of cilia and abnormalities in their shape and structure. Although the mechanism is unclear, a loss of normal cilia impedes proper development of bone and other tissues, leading to the features of cranioectodermal dysplasia. Some researchers suggest that disrupted intraflagellar transport prevents signaling through the Sonic Hedgehog pathway, which could impact cell growth and other functions in several tissues throughout the body.
3. Other Names for This Gene
intraflagellar transport 122 homolog (Chlamydomonas)
intraflagellar transport protein 122 homolog
WD repeat domain 10
WD repeat-containing protein 10
WD repeat-containing protein 140
The entry is from https://medlineplus.gov/genetics/gene/ift122
- Arts H, Knoers N. Cranioectodermal Dysplasia. 2013 Sep 12 [updated 2018 Apr12]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K,Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University ofWashington, Seattle; 1993-2020. Available fromhttp://www.ncbi.nlm.nih.gov/books/NBK154653/
- Liem KF Jr, Ashe A, He M, Satir P, Moran J, Beier D, Wicking C, Anderson KV.The IFT-A complex regulates Shh signaling through cilia structure and membraneprotein trafficking. J Cell Biol. 2012 Jun 11;197(6):789-800. doi:10.1083/jcb.201110049.
- Qin J, Lin Y, Norman RX, Ko HW, Eggenschwiler JT. Intraflagellar transportprotein 122 antagonizes Sonic Hedgehog signaling and controls ciliarylocalization of pathway components. Proc Natl Acad Sci U S A. 2011 Jan25;108(4):1456-61. doi: 10.1073/pnas.1011410108.
- Walczak-Sztulpa J, Eggenschwiler J, Osborn D, Brown DA, Emma F, Klingenberg C,Hennekam RC, Torre G, Garshasbi M, Tzschach A, Szczepanska M, Krawczynski M,Zachwieja J, Zwolinska D, Beales PL, Ropers HH, Latos-Bielenska A, Kuss AW.Cranioectodermal Dysplasia, Sensenbrenner syndrome, is a ciliopathy caused bymutations in the IFT122 gene. Am J Hum Genet. 2010 Jun 11;86(6):949-56. doi:10.1016/j.ajhg.2010.04.012.