PPCS Gene: Phosphopantothenoylcysteine Synthetase
Essential enzyme in coenzyme A biosynthesis; associated with neurodegeneration and cardiomyopathy
Gene Information Card
| Symbol | PPCS |
|---|---|
| Full Name | Phosphopantothenoylcysteine Synthetase |
| Gene Type | Protein coding |
| Chromosomal Location | 1p34.2 |
| NCBI Gene ID | 79717 ncbi.nlm.nih.gov/gene/79717 |
| Ensembl ID | ENSG00000116285 |
| UniProt ID | Q9HAB8 |
| OMIM ID | 609853 |
| HGNC ID | 25686 |
| Aliases | PPCS, PPC synthetase, phosphopantothenoylcysteine synthetase |
Description
The PPCS gene encodes phosphopantothenoylcysteine synthetase, an enzyme that catalyzes the second step in coenzyme A (CoA) biosynthesis: the conversion of pantothenate (vitamin B5) to 4'-phosphopantothenoylcysteine. CoA is essential for fatty acid oxidation, energy metabolism, and neurotransmitter synthesis. Mutations in PPCS cause a severe autosomal recessive disorder characterized by neurodegeneration, cardiomyopathy, and early-onset epileptic encephalopathy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| PPCS deficiency (neurodegeneration with cardiomyopathy) | Loss-of-function mutations impair CoA biosynthesis, leading to mitochondrial dysfunction and energy deficit in heart and brain | OMIM #618189; ClinVar pathogenic variants |
| Epileptic encephalopathy, early-onset | Biallelic PPCS mutations disrupt CoA-dependent neurotransmitter metabolism | ClinVar; PMID: 31006510 |
| Cardiomyopathy, dilated | CoA deficiency impairs fatty acid oxidation in cardiac muscle | OMIM; PMID: 31006510 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Brain | 8.3 | Medium |
| Liver | 10.1 | Medium |
| Skeletal muscle | 9.7 | Medium |
| Kidney | 7.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression |
| HeLa | 11.4 | Medium expression |
| K562 | 6.8 | Low expression |
| HepG2 | 9.5 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.158C>T (p.Pro53Leu) | Missense | Unknown | Reduced enzyme activity; associated with PPCS deficiency |
| c.332G>A (p.Arg111Gln) | Missense | Unknown | Impaired CoA synthesis; reported in epileptic encephalopathy |
| c.1A>G (p.Met1?) | Start loss | Unknown | Loss of protein expression; pathogenic in compound heterozygotes |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations cause PPCS deficiency with neurodegeneration and cardiomyopathy.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • phosphopantothenoylcysteine synthetase activity (GO:0004632) | • coenzyme A biosynthetic process (GO:0015937) |
| • mitochondrion (GO:0005739) | • cytosol (GO:0005829) |
Pathways
• Pantothenate and CoA biosynthesis (KEGG: hsa00770)
• Metabolic pathways (KEGG: hsa01100)
Protein Summary
Phosphopantothenoylcysteine synthetase (PPCS) is a 311-amino acid protein localized to the cytosol and mitochondria. It catalyzes the ATP-dependent condensation of 4'-phosphopantothenate and cysteine to form 4'-phosphopantothenoylcysteine, a key intermediate in CoA biosynthesis. The enzyme is highly expressed in heart and brain, tissues with high energy demands. Deficiency leads to CoA depletion, mitochondrial dysfunction, and severe multisystem disease.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PPCS Knockout HEK293 Cell Line | EDJ-KQ14848 | Human | 79717 | Details Get a Quote |
| PPCS Knockout A-549 Cell Line | EDJ-KQ45290 | Human | 79717 | Details Get a Quote |
| PPCS Knockout HCT 116 Cell Line | EDJ-KQ45291 | Human | 79717 | Details Get a Quote |
| PPCS Knockout HeLa Cell Line | EDJ-KQ45292 | Human | 79717 | Details Get a Quote |
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