FKRP (Fukutin Related Protein) Gene
Key player in alpha-dystroglycan glycosylation and muscular dystrophy pathology
Gene Information Card
| Symbol | FKRP |
|---|---|
| Full Name | Fukutin Related Protein |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.32 |
| NCBI Gene ID | 79147 ncbi.nlm.nih.gov/gene/79147 |
| Ensembl ID | ENSG00000181027 |
| UniProt ID | Q9H9S5 |
| OMIM ID | 606596 |
| HGNC ID | 17997 |
| Aliases | MDDGA5, MDDGB5, MDDGC5, LGMD2I, LGMDR9, MDC1C, RP87 |
Description
The FKRP gene encodes fukutin related protein, a putative glycosyltransferase involved in the glycosylation of alpha-dystroglycan. This modification is essential for the binding of alpha-dystroglycan to extracellular matrix proteins such as laminin, neurexin, and agrin. Mutations in FKRP cause a spectrum of muscular dystrophies, including limb-girdle muscular dystrophy type 2I (LGMD2I), congenital muscular dystrophy type 1C (MDC1C), and Walker-Warburg syndrome. The gene is also associated with mild to severe forms of dystroglycanopathy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Limb-girdle muscular dystrophy type 2I (LGMD2I) | Reduced glycosylation of alpha-dystroglycan due to FKRP mutations leads to impaired laminin binding and muscle fiber degeneration | ClinVar, OMIM |
| Congenital muscular dystrophy type 1C (MDC1C) | Severe loss of FKRP function disrupts alpha-dystroglycan glycosylation, causing early-onset muscle weakness and brain involvement | OMIM, UniProt |
| Walker-Warburg syndrome (WWS) | Biallelic FKRP mutations result in complete loss of glycosyltransferase activity, leading to severe brain and eye malformations | OMIM, NCBI |
| Dystroglycanopathy, limb-girdle, type 2I (LGMDR9) | Hypomorphic FKRP variants cause a milder, later-onset form of muscular dystrophy with variable cardiac involvement | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 5.2 | Low |
| Heart | 3.8 | Low |
| Brain | 2.1 | Low |
| Placenta | 1.5 | Low |
| Lung | 1.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Skeletal muscle myoblasts | 4.5 | nTPM from GTEx |
| Cardiomyocytes | 3.2 | nTPM from GTEx |
| Fibroblasts | 1.8 | nTPM from GTEx |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.826C>A (p.Leu276Ile) | Missense | Common in LGMD2I | Reduced protein stability and glycosyltransferase activity |
| c.1364C>A (p.Ala455Asp) | Missense | Rare | Severe loss of function, associated with MDC1C |
| c.919T>A (p.Tyr307Asn) | Missense | Rare | Impaired alpha-dystroglycan glycosylation |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Complete loss of protein expression |
Mutation functional classification
Loss of Function (LOF)
Most FKRP mutations are loss-of-function, reducing or abolishing glycosyltransferase activity, leading to hypoglycosylation of alpha-dystroglycan.
Gain of Function (GOF)
No gain-of-function mutations have been reported for FKRP.
Dominant Negative (DN)
No dominant-negative mechanisms have been described; FKRP-associated diseases are recessive.
View complete mutation data：
Gene Ontology (GO)
| • acetylglucosaminyltransferase activity (GO:0008375) | • Golgi membrane (GO:0000139) |
| • protein glycosylation (GO:0006486) | • glycosyltransferase activity (GO:0016757) |
| • Golgi apparatus (GO:0005794) |
Pathways
• Dystroglycan glycosylation pathway
• Muscle contraction and extracellular matrix interaction
Protein Summary
Fukutin related protein (FKRP) is a 495-amino acid type II transmembrane protein localized to the Golgi apparatus. It functions as a putative glycosyltransferase that adds sugar moieties to alpha-dystroglycan, a key component of the dystrophin-glycoprotein complex. Proper glycosylation is critical for the binding of alpha-dystroglycan to extracellular matrix ligands. FKRP is expressed in skeletal muscle, heart, and brain, with highest levels in muscle. Mutations in FKRP disrupt this glycosylation, leading to a spectrum of muscular dystrophies ranging from mild limb-girdle to severe congenital forms.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FKRP Knockout HEK293 Cell Line | EDJ-KQ12060 | Human | 79147 | Details Get a Quote |
| FKRP Knockout A-549 Cell Line | EDJ-KQ40703 | Human | 79147 | Details Get a Quote |
| FKRP Knockout HCT 116 Cell Line | EDJ-KQ40704 | Human | 79147 | Details Get a Quote |
| FKRP Knockout HeLa Cell Line | EDJ-KQ40705 | Human | 79147 | Details Get a Quote |
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