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Genetics Home Reference: your guide to understanding genetic conditions
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FKRP

Reviewed August 2013

What is the official name of the FKRP gene?

The official name of this gene is “fukutin related protein.”

FKRP is the gene's official symbol. The FKRP gene is also known by other names, listed below.

What is the normal function of the FKRP gene?

The FKRP gene provides instructions for making a protein called fukutin-related protein (FKRP). This protein is present in many of the body's tissues but is particularly abundant in muscles used for movement (skeletal muscles), the brain, and the heart. Within cells, FKRP is found in a specialized structure called the Golgi apparatus, where newly produced proteins are modified.

Although the exact function of FKRP is unclear, researchers predict that it may chemically modify a protein called alpha (α)-dystroglycan. Specifically, FKRP is thought to add chains of sugar molecules to α-dystroglycan through a process known as glycosylation. Glycosylation is critical for the normal function of α-dystroglycan.

The α-dystroglycan protein helps anchor the structural framework inside each cell (cytoskeleton) to the lattice of proteins and other molecules outside the cell (extracellular matrix). In skeletal muscles, glycosylated α-dystroglycan helps stabilize and protect muscle fibers. In the brain, it helps direct the movement (migration) of nerve cells (neurons) during early development.

How are changes in the FKRP gene related to health conditions?

Walker-Warburg syndrome - caused by mutations in the FKRP gene

Mutations in the FKRP gene cause Walker-Warburg syndrome in a small number of people. This condition is the most severe form of a group of disorders known as congenital muscular dystrophies. Walker-Warburg syndrome causes muscle weakness and abnormalities of the brain and eyes. Because of the severity of the problems caused by this condition, affected individuals usually do not survive past early childhood.

Many FKRP gene mutations involved in Walker-Warburg syndrome change single protein building blocks (amino acids) in FKRP. The altered proteins cannot reach the Golgi apparatus and are instead broken down, resulting in a reduction of functional FKRP.

A shortage of FKRP likely prevents the normal glycosylation of α-dystroglycan. As a result, α-dystroglycan can no longer effectively anchor cells to the proteins and other molecules that surround them. Without functional α-dystroglycan to stabilize muscle cells, muscle fibers become damaged as they repeatedly contract and relax with use. The damaged fibers weaken and die over time, which affects the development, structure, and function of skeletal muscles in people with Walker-Warburg syndrome.

Defective α-dystroglycan also affects the migration of neurons during the early development of the brain. Instead of stopping when they reach their intended destinations, some neurons migrate past the surface of the brain into the fluid-filled space that surrounds it. Researchers believe that this problem with neuronal migration causes a brain abnormality called cobblestone lissencephaly, in which the surface of the brain lacks the normal folds and grooves and instead appears bumpy and irregular. Less is known about the effects of FKRP gene mutations in other parts of the body.

other disorders - caused by mutations in the FKRP gene

Mutations in the FKRP gene are also involved in less severe forms of muscular dystrophy. Limb-girdle muscular dystrophy type 2I (LGMD2I) is the mildest of the conditions caused by changes in this gene. Individuals with this condition have muscle weakness in the arms and legs that begins in childhood and causes difficulty walking. Some individuals with LGMD2I also have a heart condition called dilated cardiomyopathy that weakens and enlarges the heart, preventing it from pumping blood efficiently. Mutations in the FKRP gene have also been found in a small number of people with congenital muscular dystrophy type 1C (MDC1C), which causes muscle weakness, brain abnormalities, and intellectual disability but usually does not affect the eyes. It is unclear how mutations in this gene cause this range of muscular dystrophies.

Where is the FKRP gene located?

Cytogenetic Location: 19q13.32

Molecular Location on chromosome 19: base pairs 46,746,045 to 46,758,574

The FKRP gene is located on the long (q) arm of chromosome 19 at position 13.32.

The FKRP gene is located on the long (q) arm of chromosome 19 at position 13.32.

More precisely, the FKRP gene is located from base pair 46,746,045 to base pair 46,758,574 on chromosome 19.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about FKRP?

You and your healthcare professional may find the following resources about FKRP helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the FKRP gene or gene products?

  • FKRP_HUMAN
  • LGMD2I
  • MDC1C
  • MDDGA5
  • MDDGB5
  • MDDGC5

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding FKRP?

acids ; cardiomyopathy ; cell ; congenital ; cytoskeleton ; dilated ; disability ; extracellular ; extracellular matrix ; gene ; glycosylation ; Golgi apparatus ; muscle cells ; muscular dystrophy ; neuronal migration ; protein ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Beltran-Valero de Bernabé D, Voit T, Longman C, Steinbrecher A, Straub V, Yuva Y, Herrmann R, Sperner J, Korenke C, Diesen C, Dobyns WB, Brunner HG, van Bokhoven H, Brockington M, Muntoni F. Mutations in the FKRP gene can cause muscle-eye-brain disease and Walker-Warburg syndrome. J Med Genet. 2004 May;41(5):e61. (http://www.ncbi.nlm.nih.gov/pubmed/15121789?dopt=Abstract)
  • Boito CA, Melacini P, Vianello A, Prandini P, Gavassini BF, Bagattin A, Siciliano G, Angelini C, Pegoraro E. Clinical and molecular characterization of patients with limb-girdle muscular dystrophy type 2I. Arch Neurol. 2005 Dec;62(12):1894-9. (http://www.ncbi.nlm.nih.gov/pubmed/16344347?dopt=Abstract)
  • Esapa CT, Benson MA, Schröder JE, Martin-Rendon E, Brockington M, Brown SC, Muntoni F, Kröger S, Blake DJ. Functional requirements for fukutin-related protein in the Golgi apparatus. Hum Mol Genet. 2002 Dec 15;11(26):3319-31. (http://www.ncbi.nlm.nih.gov/pubmed/12471058?dopt=Abstract)
  • Esapa CT, McIlhinney RA, Blake DJ. Fukutin-related protein mutations that cause congenital muscular dystrophy result in ER-retention of the mutant protein in cultured cells. Hum Mol Genet. 2005 Jan 15;14(2):295-305. Epub 2004 Dec 1. (http://www.ncbi.nlm.nih.gov/pubmed/15574464?dopt=Abstract)
  • OMIM: FUKUTIN-RELATED PROTEIN (http://omim.org/entry/606596)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/79147)
  • Trovato R, Astrea G, Bartalena L, Ghirri P, Baldacci J, Giampietri M, Battini R, Santorelli FM, Fiorillo C. Elevated serum creatine kinase and small cerebellum prompt diagnosis of congenital muscular dystrophy due to FKRP mutations. J Child Neurol. 2014 Mar;29(3):394-8. doi: 10.1177/0883073812474951. Epub 2013 Feb 17. (http://www.ncbi.nlm.nih.gov/pubmed/23420653?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: August 2013
Published: September 29, 2014