Normal Function
The KIF21A gene provides instructions for making a protein that is part of the kinesin family. Many proteins in the kinesin family are essential for the transport of materials within cells. Kinesin proteins function like freight trains that transport cargo along a track-like system made from structures called microtubules. Some kinesins also help maintain microtubules. As well as functioning like a track, microtubules make up the structural framework of cells and help cells move.
The KIF21A protein is found in nerve cells (neurons) and many other cell types. Researchers believe that this protein plays an important role in neuron development by helping control the growth of microtubules. By blocking microtubule growth at critical times, the KIF21A protein may help direct the path of neuron extensions known as axons so they can reach their correct locations. Once in the right position, axons relay messages to and from the brain to control muscle movement and detect sensations such as touch, pain, and heat.
For proper neuron development, the KIF21A protein must be turned on and off at particular times. When a segment of the protein known as the regulatory region interacts with another segment of the protein known as the motor domain, the protein is turned off (which is known as autoinhibition).
Health Conditions Related to Genetic Changes
Congenital fibrosis of the extraocular muscles
At least 12 mutations in the KIF21A gene have been identified in people with congenital fibrosis of the extraocular muscles (CFEOM). These mutations cause the most common form of the disorder, CFEOM1, and are a rare cause of another form of the condition called CFEOM3. Individuals with CFEOM are unable to move their eyes normally. They have difficulty looking upward or, less commonly, side-to-side, and most also have droopy eyelids (ptosis). In addition, people with CFEOM3 can have intellectual disability or other neurological problems.
Each of the known KIF21A gene mutations changes a single protein building block (amino acid) in the KIF21A protein. Most of these changes occur in the regulatory region of the protein. These mutations alter the protein's structure, which interferes with its ability to turn itself off. As a result, the KIF21A protein is always on (constitutively active) and cannot regulate microtubule growth. Without proper control of microtubule elongation, the axons of nerves develop abnormally and do not reach the muscles they control. Nerves in the head and face (cranial nerves) that control muscles that surround the eyes (extraocular muscles) are particularly affected. Problems with cranial nerve development impair extraocular muscle function, resulting in the characteristic features of CFEOM such as restricted eye movement and droopy eyelids.
More About This Health ConditionOther Names for This Gene
- CFEOM
- CFEOM1
- DKFZp779C159
- FEOM
- FEOM1
- Fibrosis of extraocular muscles, congenital, 1, autosomal dominant
- fibrosis of the extraocular muscles, congenital, 1
- FLJ20052
- KI21A_HUMAN
- KIAA1708
- KIF2
- KIF21A variant protein
- Kinesin-like protein KIF2
- Kinesin-like protein KIF21A
- NY-REN-62 antigen
- Renal carcinoma antigen NY-REN-62
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Bianchi S, van Riel WE, Kraatz SH, Olieric N, Frey D, Katrukha EA, Jaussi R, Missimer J, Grigoriev I, Olieric V, Benoit RM, Steinmetz MO, Akhmanova A, Kammerer RA. Structural basis for misregulation of kinesin KIF21A autoinhibition by CFEOM1 disease mutations. Sci Rep. 2016 Aug 3;6:30668. doi: 10.1038/srep30668. Citation on PubMed or Free article on PubMed Central
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- Yamada K, Andrews C, Chan WM, McKeown CA, Magli A, de Berardinis T, Loewenstein A, Lazar M, O'Keefe M, Letson R, London A, Ruttum M, Matsumoto N, Saito N, Morris L, Del Monte M, Johnson RH, Uyama E, Houtman WA, de Vries B, Carlow TJ, Hart BL, Krawiecki N, Shoffner J, Vogel MC, Katowitz J, Goldstein SM, Levin AV, Sener EC, Ozturk BT, Akarsu AN, Brodsky MC, Hanisch F, Cruse RP, Zubcov AA, Robb RM, Roggenkaemper P, Gottlob I, Kowal L, Battu R, Traboulsi EI, Franceschini P, Newlin A, Demer JL, Engle EC. Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1). Nat Genet. 2003 Dec;35(4):318-21. doi: 10.1038/ng1261. Epub 2003 Nov 2. Citation on PubMed
- Yamada K, Chan WM, Andrews C, Bosley TM, Sener EC, Zwaan JT, Mullaney PB, Ozturk BT, Akarsu AN, Sabol LJ, Demer JL, Sullivan TJ, Gottlob I, Roggenkaemper P, Mackey DA, De Uzcategui CE, Uzcategui N, Ben-Zeev B, Traboulsi EI, Magli A, de Berardinis T, Gagliardi V, Awasthi-Patney S, Vogel MC, Rizzo JF 3rd, Engle EC. Identification of KIF21A mutations as a rare cause of congenital fibrosis of the extraocular muscles type 3 (CFEOM3). Invest Ophthalmol Vis Sci. 2004 Jul;45(7):2218-23. doi: 10.1167/iovs.03-1413. Citation on PubMed
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