GMPPA: GDP-Mannose Pyrophosphorylase A
A key enzyme in GDP-mannose biosynthesis, linked to congenital disorders of glycosylation and neuromuscular phenotypes.
Gene Information Card
| Symbol | GMPPA |
|---|---|
| Full Name | GDP-mannose pyrophosphorylase A |
| Gene Type | Protein coding |
| Chromosomal Location | 2q35 |
| NCBI Gene ID | 29926 ncbi.nlm.nih.gov/gene/29926 |
| Ensembl ID | ENSG00000144554 |
| UniProt ID | Q96IJ6 |
| OMIM ID | 615495 |
| HGNC ID | 22923 |
| Aliases | GMPPA, MRSD, GDP-mannose pyrophosphorylase A |
Description
GMPPA encodes GDP-mannose pyrophosphorylase A, a cytosolic enzyme that catalyzes the conversion of mannose-1-phosphate and GTP to GDP-mannose, a critical nucleotide sugar donor for protein N-glycosylation and GPI anchor biosynthesis. Mutations in GMPPA cause a congenital disorder of glycosylation with neuromuscular involvement (OMIM #615495).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital disorder of glycosylation with neuromuscular involvement (GMPPA-CDG) | Loss-of-function mutations impair GDP-mannose synthesis, leading to defective N-glycosylation and GPI anchor assembly, resulting in multisystem disease including intellectual disability, hypotonia, and seizures. | OMIM #615495; ClinVar; multiple case reports |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.3 | Medium |
| Brain | 9.8 | Medium |
| Heart | 8.5 | Medium |
| Kidney | 7.2 | Low |
| Lung | 6.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 10.5 | Ubiquitous expression |
| HEK293 | 9.2 | Moderate expression |
| HepG2 | 11.0 | High expression |
| SH-SY5Y | 8.0 | Neuronal expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1000C>T (p.Arg334*) | Nonsense | Rare (found in multiple families) | Loss of function; premature stop codon leads to truncated protein |
| c.859G>A (p.Gly287Arg) | Missense | Rare | Loss of function; disrupts catalytic activity |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function; no translation initiation |
Mutation functional classification
Loss of Function (LOF)
Most reported GMPPA mutations are loss-of-function (nonsense, missense, frameshift) leading to reduced or absent GDP-mannose pyrophosphorylase activity.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• GDP-mannose biosynthesis (Reactome: R-HSA-446193)
• N-glycosylation (Reactome: R-HSA-446203)
• GPI anchor biosynthesis (Reactome: R-HSA-162710)
Protein Summary
GMPPA is a 370-amino acid cytosolic protein that forms a homodimer and catalyzes the reversible synthesis of GDP-mannose from mannose-1-phosphate and GTP. GDP-mannose is essential for N-glycosylation, O-mannosylation, and GPI anchor formation. Deficiency leads to impaired glycosylation and multisystem disease.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GMPPA Knockout HEK293 Cell Line | EDJ-KQ9085 | Human | 29926 | Details Get a Quote |
| GMPPA Knockout HCT 116 Cell Line | EDJ-KQ34328 | Human | 29926 | Details Get a Quote |
| GMPPA Knockout A-549 Cell Line | EDJ-KQ35582 | Human | 29926 | Details Get a Quote |
| GMPPA Knockout HeLa Cell Line | EDJ-KQ35583 | Human | 29926 | Details Get a Quote |
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