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PCBD1

pterin-4 alpha-carbinolamine dehydratase 1

The PCBD1 gene provides instructions for an enzyme essential in recycling tetrahydrobiopterin (BH4), a crucial cofactor for processing amino acids and producing neurotransmitters. PCBD1 encodes pterin-4 alpha-carbinolamine dehydratase, an enzyme vital for maintaining the supply of tetrahydrobiopterin (BH4).

Chromosome 10q22.1 Autosomal recessive HGNC:8646 Tier C
PCBD1 10q22.1 p arm q arm 10

PCBD1 is located on the long (q) arm of chromosome 10, at band 10q22.1. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 10 in the library →

Available at Jeen Health

Clinical tests that include this

Carrier Screening panel
PCBD1 is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions
Newborn Genetic Screening panel
PCBD1 is 1 of 258 genes on this panel
Genomic newborn screening for actionable paediatric conditions

Overview

The PCBD1 gene, or pterin-4 alpha-carbinolamine dehydratase 1, plays a critical role in human metabolism by encoding an enzyme involved in the recycling of tetrahydrobiopterin (BH4) [PMID:10781577]. BH4 is a vital cofactor that helps various enzymes carry out essential biochemical reactions in the body. Disruptions in the PCBD1 gene can impact these metabolic processes, leading to specific health conditions.

What the gene does

The PCBD1 gene produces an enzyme called pterin-4 alpha-carbinolamine dehydratase. This enzyme is specifically involved in one step of the biochemical pathway responsible for recycling tetrahydrobiopterin (BH4) [PMID:10781577]. BH4 acts as a cofactor, assisting enzymes in processing several amino acids, such as converting phenylalanine into tyrosine, a process crucial for proper neurological function [PMID:10781577]. Furthermore, BH4 participates in reactions that synthesise neurotransmitters, which are chemical messengers facilitating signal transmission between nerve cells. After BH4 is used in these reactions, its structure changes, and it must be recycled back into its active form. The enzyme produced from PCBD1 is one of two enzymes that facilitate this essential recycling process, ensuring a continuous supply of functional BH4 for metabolic needs.

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Chromosome location

The PCBD1 gene is located on chromosome 10, specifically at position 10q22.1. This position indicates its precise location on the long arm (q) of chromosome 10, within region 22, band 1.

Protein structure

The PCBD1 gene codes for a protein that is 104 amino acids in length. Domain architecture has not been experimentally characterised in detail for this protein.

Key variants

Variants within the PCBD1 gene can alter the function of the pterin-4 alpha-carbinolamine dehydratase enzyme. These genetic changes may disrupt the enzyme's ability to efficiently recycle tetrahydrobiopterin (BH4), leading to impaired metabolic pathways.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for PCBD1.
View all on ClinVar →

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.259G>T
single nucleotide variant
 p.Glu87Ter Pathogenic/Likely pathogenic ★★☆☆ PCBD1-related disorder
c.289G>A
single nucleotide variant
 p.Glu97Lys Pathogenic/Likely pathogenic ★★☆☆ PCBD1-related disorders
c.292C>T
single nucleotide variant
 p.Gln98Ter Pathogenic/Likely pathogenic ★★☆☆ PCBD1-related disorders
g.(?_72643707)_(72645009_?)del
Deletion
 - Pathogenic ★☆☆☆ Pterin-4 alpha-carbinolamine dehydratase 1 deficiency
g.(?_72643707)_(72648290_?)del
Deletion
 - Pathogenic ★☆☆☆ Pterin-4 alpha-carbinolamine dehydratase 1 deficiency
c.108_118del
Deletion
 p.Lys36fs Pathogenic ★☆☆☆ Pterin-4 alpha-carbinolamine dehydratase 1 deficiency
c.111del
Deletion
 p.Gln37fs Pathogenic ★☆☆☆ Pterin-4 alpha-carbinolamine dehydratase 1 deficiency
c.201dup
Duplication
 p.Asn68Ter Pathogenic ★☆☆☆ Pterin-4 alpha-carbinolamine dehydratase 1 deficiency
c.272del
Deletion
 p.Asn91fs Pathogenic ★☆☆☆ Pterin-4 alpha-carbinolamine dehydratase 1 deficiency
c.46del
Deletion
 p.Leu16fs Pathogenic ★☆☆☆ Pterin-4 alpha-carbinolamine dehydratase 1 deficiency

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Pathogenic variants in the PCBD1 gene are associated with tetrahydrobiopterin deficiency, specifically known as pterin-4 alpha-carbinolamine dehydratase (PCD) deficiency. This condition results from the impaired recycling of BH4, affecting amino acid processing and neurotransmitter synthesis. PCD deficiency accounts for approximately 5% of all tetrahydrobiopterin deficiency cases.

No disease links recorded for this gene in our reference set.

Inheritance pattern

Conditions caused by pathogenic PCBD1 variants typically follow autosomal recessive inheritance.

♀ Carrier parent 1 altered copy ♂ Carrier parent 1 altered copy Affected Carrier Carrier Unaffected Affected Carrier Unaffected Circles = females · Squares = males

When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.

Carrier frequency by population How common is heterozygous PCBD1 carrier status across ancestry groups?

UK clinical status

PCBD1 is recognised in the UK National Health Service (NHS) Genomic Medicine Service. It is included on several green-rated panels within NHS England's PanelApp, indicating strong evidence for its gene-disease association. These panels include DDG2P, Familial diabetes, Likely inborn error of metabolism (R98), Monogenic diabetes (R141), and Undiagnosed metabolic disorders.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Likely inborn error of metabolism · R98 NHS GMS → Monogenic diabetes · R141 NHS GMS → DDG2P NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the primary function of the PCBD1 gene?

The PCBD1 gene provides instructions for making an enzyme called pterin-4 alpha-carbinolamine dehydratase, which is crucial for recycling tetrahydrobiopterin (BH4). BH4 is a cofactor essential for processing amino acids and synthesising neurotransmitters.

What condition is associated with PCBD1 gene variants?

Variants in the PCBD1 gene are associated with pterin-4 alpha-carbinolamine dehydratase (PCD) deficiency, a specific type of tetrahydrobiopterin deficiency. This condition affects metabolism due to impaired BH4 recycling.

How common is PCD deficiency?

PCD deficiency, caused by PCBD1 gene variants, accounts for approximately 5% of all cases of tetrahydrobiopterin deficiency. It is considered a rare genetic condition.

References

  1. Longo N. Disorders of biopterin metabolism. Journal of inherited metabolic disease. 2009. PMID: 19234759
  2. Thöny B, Blau N. Mutations in the BH4-metabolizing genes GTP cyclohydrolase I, 6-pyruvoyl-tetrahydropterin synthase, sepiapterin reductase, carbinolamine-4a-dehydratase, and dihydropteridine reductase. Human mutation. 2006. PMID: 16917893
  3. Shintaku H. Disorders of tetrahydrobiopterin metabolism and their treatment. Current drug metabolism. 2002. PMID: 12003346
  4. Thöny B, Auerbach G, Blau N. Tetrahydrobiopterin biosynthesis, regeneration and functions. The Biochemical journal. 2000. PMID: 10727395
  5. Thöny B, Neuheiser F, Kierat L. Mutations in the pterin-4alpha-carbinolamine dehydratase (PCBD) gene cause a benign form of hyperphenylalaninemia. Human genetics. 1998. PMID: 9760199
  6. Citron BA, Kaufman S, Milstien S. Mutation in the 4a-carbinolamine dehydratase gene leads to mild hyperphenylalaninemia with defective cofactor metabolism. American journal of human genetics. 1993. PMID: 8352282
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 18 October 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .