CRPPA
CDP-L-ribitol pyrophosphorylase A; Dystroglycanopathy-associated gene
Gene Information Card
| Symbol | CRPPA |
|---|---|
| Full Name | CDP-L-ribitol pyrophosphorylase A |
| Gene Type | Protein coding |
| Chromosomal Location | 7p21.2 |
| NCBI Gene ID | 729920 ncbi.nlm.nih.gov/gene/729920 |
| Ensembl ID | ENSG00000182378 |
| UniProt ID | Q5T6W5 |
| OMIM ID | 614631 |
| HGNC ID | 37276 |
| Aliases | ISPD, MDDGA7, MDDGC7, MDDGB7 |
Description
The CRPPA gene encodes CDP-L-ribitol pyrophosphorylase A, an enzyme involved in the biosynthesis of CDP-ribitol, a nucleotide sugar required for the O-mannosylation of alpha-dystroglycan. This post-translational modification is critical for the structural integrity of the extracellular matrix and muscle cell membrane. Mutations in CRPPA disrupt this glycosylation pathway, leading to a spectrum of dystroglycanopathies, including congenital muscular dystrophy and limb-girdle muscular dystrophy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies) type A7 | Loss-of-function mutations impair CDP-ribitol synthesis, reducing alpha-dystroglycan glycosylation and disrupting basement membrane adhesion. | OMIM #614643 |
| Muscular dystrophy-dystroglycanopathy (limb-girdle) type C7 | Hypomorphic mutations lead to partial loss of enzyme activity, causing milder limb-girdle muscular dystrophy phenotype. | OMIM #616052 |
| Muscular dystrophy-dystroglycanopathy (congenital without mental retardation) type B7 | Biallelic mutations with residual enzyme activity result in congenital muscular dystrophy without significant brain involvement. | OMIM #616052 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 8.2 | Medium |
| Heart | 6.5 | Medium |
| Brain | 4.1 | Low |
| Liver | 2.3 | Low |
| Kidney | 3.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Skeletal muscle myoblasts | 7.8 | Differentiated cells show higher expression |
| Cardiomyocytes | 6.1 | Consistent with heart tissue data |
| Fibroblasts | 2.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.100G>A (p.Gly34Arg) | Missense | Rare | Reduced enzyme activity; associated with LGMD |
| c.1342C>T (p.Arg448*) | Nonsense | Rare | Loss of function; severe congenital phenotype |
| c.1A>G (p.Met1?) | Start loss | Rare | Complete loss of protein; severe dystroglycanopathy |
Mutation functional classification
Loss of Function (LOF)
Most CRPPA mutations are loss-of-function, reducing or abolishing CDP-ribitol synthesis and alpha-dystroglycan glycosylation.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • catalytic activity (GO:0003824) | • Golgi apparatus (GO:0005794) |
| • protein glycosylation (GO:0006486) | • transferase activity (GO:0016740) |
| • protein O-linked mannosylation (GO:0035269) |
Pathways
• O-mannosyl glycan biosynthesis (Reactome R-HSA-5173105)
• Dystroglycan-related disorders (KEGG hsa05310)
Protein Summary
CRPPA encodes a 448-amino acid protein localized to the Golgi apparatus. It catalyzes the formation of CDP-ribitol from CTP and ribitol-5-phosphate, providing the ribitol phosphate donor for the synthesis of the O-mannosyl glycan on alpha-dystroglycan. This modification is essential for binding to extracellular matrix proteins such as laminin. Deficiency leads to reduced glycosylation and muscular dystrophy phenotypes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CRPPA Knockout HEK293 Cell Line | EDJ-KQ13005 | Human | 729920 | Details Get a Quote |
| CRPPA Knockout HCT 116 Cell Line | EDJ-KQ41020 | Human | 729920 | Details Get a Quote |
| CRPPA Knockout A-549 Cell Line | EDJ-KQ42264 | Human | 729920 | Details Get a Quote |
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