PCBD1: Pterin-4 Alpha-Carbinolamine Dehydratase 1
A key enzyme in tetrahydrobiopterin (BH4) regeneration and phenylalanine metabolism, associated with BH4-deficient hyperphenylalaninemia and dopa-responsive dystonia.
Gene Information Card
| Symbol | PCBD1 |
|---|---|
| Full Name | Pterin-4 Alpha-Carbinolamine Dehydratase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q22.1 |
| NCBI Gene ID | 5092 ncbi.nlm.nih.gov/gene/5092 |
| Ensembl ID | ENSG00000120071 |
| UniProt ID | P61457 |
| OMIM ID | 126090 |
| HGNC ID | 8646 |
| Aliases | DCOH, PCD, DCOH1 |
Description
The PCBD1 gene encodes pterin-4 alpha-carbinolamine dehydratase 1, a bifunctional enzyme that catalyzes the dehydration of 4a-hydroxy-tetrahydrobiopterin (4a-OH-BH4) to quinonoid dihydrobiopterin (q-BH2) in the regeneration of tetrahydrobiopterin (BH4), an essential cofactor for aromatic amino acid hydroxylases. Additionally, the protein acts as a dimerization cofactor for hepatocyte nuclear factor 1 alpha (HNF1A), influencing transcriptional regulation. Mutations in PCBD1 cause BH4-deficient hyperphenylalaninemia type IV (HPABH4D) and have been linked to dopa-responsive dystonia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hyperphenylalaninemia, BH4-deficient, type IV (HPABH4D) | Loss-of-function mutations impair BH4 regeneration, reducing phenylalanine hydroxylase activity and causing phenylalanine accumulation. | OMIM #264070; ClinVar; multiple case reports |
| Dopa-responsive dystonia (DRD) | Impaired BH4 recycling reduces dopamine synthesis due to decreased tyrosine hydroxylase activity. | OMIM #128230; ClinVar; literature reports |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 8.3 | Medium |
| Brain | 6.1 | Low |
| Pancreas | 4.7 | Low |
| Adrenal gland | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocellular carcinoma cell line; high expression |
| HEK293 | 9.8 | Embryonic kidney cells; moderate expression |
| SH-SY5Y | 5.4 | Neuroblastoma cell line; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.259C>T (p.Arg87Trp) | Missense | Rare | Reduced enzyme activity; associated with HPABH4D |
| c.292G>A (p.Gly98Ser) | Missense | Rare | Impaired BH4 recycling; linked to dopa-responsive dystonia |
| c.1A>G (p.Met1Val) | Start loss | Rare | Loss of protein expression; severe phenotype |
Mutation functional classification
Loss of Function (LOF)
Most PCBD1 mutations are loss-of-function, reducing or abolishing dehydratase activity, leading to BH4 deficiency and hyperphenylalaninemia.
Gain of Function (GOF)
No gain-of-function mutations reported for PCBD1.
Dominant Negative (DN)
No dominant-negative mutations reported; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Tetrahydrobiopterin (BH4) recycling (Reactome: R-HSA-1474228)
• Phenylalanine and tyrosine metabolism (KEGG: hsa00360)
• Catecholamine biosynthesis (Reactome: R-HSA-209776)
Protein Summary
PCBD1 encodes a 104-amino acid protein (12 kDa) that functions as a homotetramer. It catalyzes the dehydration of 4a-hydroxy-tetrahydrobiopterin, a critical step in BH4 regeneration. BH4 is an essential cofactor for phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase. The protein also serves as a dimerization cofactor for HNF1A, modulating transcription of liver-specific genes. Deficiency leads to hyperphenylalaninemia and dopamine deficiency.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PCBD1 Knockout HEK293 Cell Line | EDJ-KQ5406 | Human | 5092 | Details Get a Quote |
| PCBD1 Knockout A-549 Cell Line | EDJ-KQ28560 | Human | 5092 | Details Get a Quote |
| PCBD1 Knockout HCT 116 Cell Line | EDJ-KQ28561 | Human | 5092 | Details Get a Quote |
| PCBD1 Knockout HeLa Cell Line | EDJ-KQ28562 | Human | 5092 | Details Get a Quote |
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