Fukutin-related protein (FKRP) is also known as FKRP_HUMAN, LGMD2I, MDC1C, MDDGA5, MDDGB5, and MDDGC5. FKRP can be located in the brain, cardiac muscle and skeletal muscle, and in cells it is found in the Golgi apparatus. Fukutin is expressed in the mammalian retina and is located in the Golgi complex of retinal neurons.
The genomic location of the FKRP gene is on chromosome 19. FKRP is a ribitol-5-phosphate (enzyme)
glycosyltranferase, which means this enzyme helps create glycosidic linkages to an acceptor. In
glycosylation of α-
dystroglycan
Dystroglycan is a protein that in humans is encoded by the ''DAG1'' gene.
Dystroglycan is one of the dystrophin-associated glycoproteins, which is encoded by a 5.5 kb transcript in ''Homo sapiens'' on chromosome 3. There are two exons that are s ...
(sugar chain) it adds a ribitol-5-phosphate onto the M3 core O-mannosylation of α-
dystroglycan
Dystroglycan is a protein that in humans is encoded by the ''DAG1'' gene.
Dystroglycan is one of the dystrophin-associated glycoproteins, which is encoded by a 5.5 kb transcript in ''Homo sapiens'' on chromosome 3. There are two exons that are s ...
to create O-linked mannosylation. Without this linkage α-
dystroglycan
Dystroglycan is a protein that in humans is encoded by the ''DAG1'' gene.
Dystroglycan is one of the dystrophin-associated glycoproteins, which is encoded by a 5.5 kb transcript in ''Homo sapiens'' on chromosome 3. There are two exons that are s ...
will not function properly, this can cause issues with the cytoskeleton, and extracellular matrix. In skeletal muscles the α-
dystroglycan
Dystroglycan is a protein that in humans is encoded by the ''DAG1'' gene.
Dystroglycan is one of the dystrophin-associated glycoproteins, which is encoded by a 5.5 kb transcript in ''Homo sapiens'' on chromosome 3. There are two exons that are s ...
helps stabilize and protect muscle fibers, in the brain it directs movement of nerve cells. This could be caused by mutations that binds ribitol-5-phosphate to the α-
dystroglycan
Dystroglycan is a protein that in humans is encoded by the ''DAG1'' gene.
Dystroglycan is one of the dystrophin-associated glycoproteins, which is encoded by a 5.5 kb transcript in ''Homo sapiens'' on chromosome 3. There are two exons that are s ...
incorrectly. These mutations have been found to be associated with
congenital muscular dystrophy
Congenital muscular dystrophies are autosomal recessively-inherited muscle diseases. They are a group of heterogeneous disorders characterized by muscle weakness which is present at birth and the different changes on muscle biopsy that ranges fr ...
, dystroglycanopathies, and
Walker-Warburg syndrome.
The severity of these diseases are correlated to the amount of mutations occurring. Possible therapy options for FKRP mutations include small molecules,
gene delivery
Gene delivery is the process of introducing foreign genetic material, such as DNA or RNA, into host cells. Gene delivery must reach the genome of the host cell to induce gene expression. Successful gene delivery requires the foreign gene delive ...
, and
cell therapy
Cell therapy (also called cellular therapy, cell transplantation, or cytotherapy) is a therapy in which viable cells are injected, grafted or implanted into a patient in order to effectuate a medicinal effect, for example, by transplanting T-c ...
.
See also
*
Fukutin
References
External links
GeneReviews/NCBI/NIH/UW entry on Congenital Muscular Dystrophy Overview*
LOVD The Leiden Open Variation Database (LOVD) is a free, flexible web-based open source database developed in the Leiden University Medical Center in the Netherlands, designed to collect and display variants in the DNA sequence. The focus of an LOVD i ...
mutation database
FKRP
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