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PTS

6-pyruvoyltetrahydropterin synthase

The *PTS* gene provides instructions for producing 6-pyruvoyltetrahydropterin synthase, an enzyme vital for the creation of tetrahydrobiopterin (BH4), a molecule essential for various metabolic processes. The *PTS* gene is responsible for an enzyme involved in the biosynthesis of tetrahydrobiopterin (BH4), a crucial cofactor for processing amino acids and producing neurotransmitters.

Chromosome 11q23.1 Autosomal recessive HGNC:9689 Tier C
PTS 11q23.1 p arm q arm 11

PTS is located on the long (q) arm of chromosome 11, at band 11q23.1. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 11 in the library →

Available at Jeen Health

Clinical tests that include this

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

Overview

The *PTS* gene, also known as 6-pyruvoyltetrahydropterin synthase, plays a fundamental role in human metabolism. It encodes an enzyme critical for the second step in the production of tetrahydrobiopterin (BH4), a molecule essential for several biochemical reactions.

Disruptions in *PTS* gene function can lead to metabolic disorders, specifically deficiencies in BH4, which affect amino acid processing and neurotransmitter synthesis.

What the gene does

The *PTS* gene provides the blueprint for an enzyme called 6-pyruvoyltetrahydropterin synthase. This enzyme is a key player in the intricate pathway that synthesises tetrahydrobiopterin (BH4). BH4 acts as a cofactor, meaning it helps other enzymes carry out their specific chemical reactions within the body.

One significant role of BH4 is in the processing of amino acids. For instance, it works in conjunction with the enzyme phenylalanine hydroxylase to convert phenylalanine into tyrosine. Additionally, BH4 is indispensable for the production of neurotransmitters, which are chemical messengers responsible for transmitting signals between nerve cells in the brain. Therefore, the proper functioning of the *PTS* gene and its encoded enzyme is crucial for normal neurological function and overall metabolic balance.

Video: Genetics 101

Chromosome location

The *PTS* gene is situated on chromosome 11, specifically at position 11q23.1. This location refers to the long (q) arm of chromosome 11, within region 23 and band 1. The precise positioning on the chromosome helps in mapping and understanding genetic disorders associated with this region.

Protein structure

The 6-pyruvoyltetrahydropterin synthase protein, encoded by the *PTS* gene, is composed of 145 amino acids. Domain architecture has not been experimentally characterised in detail for this protein.

Key variants

Variants in the *PTS* gene can alter the structure or function of the 6-pyruvoyltetrahydropterin synthase enzyme. Over 45 different variants have been identified that lead to tetrahydrobiopterin deficiency when they affect the *PTS* gene. Most of these involve changes to single amino acids within the protein, impacting its enzymatic activity.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for PTS.
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.174_175del
Deletion
 p.Val59fs Pathogenic/Likely pathogenic ★★☆☆ 6-Pyruvoyl-tetrahydrobiopterin synthase deficiency
c.186+1G>A
single nucleotide variant
 - Pathogenic ★★☆☆ 6-Pyruvoyl-tetrahydrobiopterin synthase deficiency
c.243G>A
single nucleotide variant
 p.Glu81= Pathogenic/Likely pathogenic ★★☆☆ 6-Pyruvoyl-tetrahydrobiopterin synthase deficiency
c.245A>G
single nucleotide variant
 p.Glu82Gly Pathogenic/Likely pathogenic ★★☆☆ 6-Pyruvoyl-tetrahydrobiopterin synthase deficiency
c.314+2T>C
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ 6-Pyruvoyl-tetrahydrobiopterin synthase deficiency
c.315-1G>A
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ PTS-related disorder
c.331G>A
single nucleotide variant
 p.Ala111Thr Pathogenic/Likely pathogenic ★★☆☆ 6-Pyruvoyl-tetrahydrobiopterin synthase deficiency
c.379C>T
single nucleotide variant
 p.Leu127Phe Pathogenic/Likely pathogenic ★★☆☆ 6-Pyruvoyl-tetrahydrobiopterin synthase deficiency
c.385A>G
single nucleotide variant
 p.Lys129Glu Pathogenic/Likely pathogenic ★★☆☆ 6-Pyruvoyl-tetrahydrobiopterin synthase deficiency
c.94A>G
single nucleotide variant
 p.Ser32Gly Pathogenic/Likely pathogenic ★★☆☆ 6-Pyruvoyl-tetrahydrobiopterin synthase 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 *PTS* gene are the most common cause of tetrahydrobiopterin deficiency, specifically known as 6-pyruvoyltetrahydropterin synthase (PTS) deficiency. This condition arises when the body cannot produce enough functional tetrahydrobiopterin (BH4), leading to a range of neurological and developmental issues due to impaired amino acid metabolism and neurotransmitter synthesis.

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

Inheritance pattern

Conditions caused by pathogenic PTS 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 PTS carrier status across ancestry groups?

UK clinical status

The *PTS* gene is recognised within the UK's NHS Genomic Medicine Service, featuring in several NHS national genomic test directories. It is listed on panels such as those for Dystonia, chorea or related movement disorder (childhood onset), Early onset or syndromic epilepsy, Foetal anomalies, Intellectual disability, Neurotransmitter disorders, and Undiagnosed metabolic disorders, indicating its clinical significance in diagnosing these conditions.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Dystonia, chorea or related movement disorder, childhood onset · R57 NHS GMS → Fetal anomalies · R21 NHS GMS → Likely inborn error of metabolism · R98 NHS GMS → DDG2P NHS GMS → Early onset or syndromic epilepsy NHS GMS → Intellectual disability 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 main function of the PTS gene?

The *PTS* gene provides instructions for an enzyme called 6-pyruvoyltetrahydropterin synthase, which is essential for producing tetrahydrobiopterin (BH4). BH4 is a critical cofactor involved in processing amino acids and synthesising neurotransmitters.

What condition is associated with variants in the PTS gene?

Variants in the *PTS* gene are primarily associated with 6-pyruvoyltetrahydropterin synthase (PTS) deficiency, which is the most common form of tetrahydrobiopterin deficiency. This condition can lead to neurological and developmental problems.

How common are *PTS* gene variants in causing tetrahydrobiopterin deficiency?

Variants in the *PTS* gene account for more than half of all reported cases of tetrahydrobiopterin deficiency. More than 45 different variants have been identified in the *PTS* gene that lead to this condition.

References

  1. Leuzzi V, Carducci CA, Carducci CL. Phenotypic variability, neurological outcome and genetics background of 6-pyruvoyl-tetrahydropterin synthase deficiency. Clinical genetics. 2010. PMID: 20059486
  2. Longo N. Disorders of biopterin metabolism. Journal of inherited metabolic disease. 2009. PMID: 19234759
  3. Wang L, Yu WM, He C. Long-term outcome and neuroradiological findings of 31 patients with 6-pyruvoyltetrahydropterin synthase deficiency. Journal of inherited metabolic disease. 2006. PMID: 16601879
  4. 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
  5. Kao CD, Niu DM, Chen JT. Subtle brain dysfunction in treated 6-pyruvoyl-tetrahydropterin synthase deficiency: relationship to motor tasks and neurophysiological tests. Brain & development. 2004. PMID: 15036427
  6. Shintaku H. Disorders of tetrahydrobiopterin metabolism and their treatment. Current drug metabolism. 2002. PMID: 12003346
  7. Dudesek A, Röschinger W, Muntau AC. Molecular analysis and long-term follow-up of patients with different forms of 6-pyruvoyl-tetrahydropterin synthase deficiency. European journal of pediatrics. 2001. PMID: 11388593
  8. Liu TT, Chiang SH, Wu SJ. Tetrahydrobiopterin-deficient hyperphenylalaninemia in the Chinese. Clinica chimica acta; international journal of clinical chemistry. 2001. PMID: 11694255
  9. Thöny B, Auerbach G, Blau N. Tetrahydrobiopterin biosynthesis, regeneration and functions. The Biochemical journal. 2000. PMID: 10727395
  10. Auerbach G, Nar H. The pathway from GTP to tetrahydrobiopterin: three-dimensional structures of GTP cyclohydrolase I and 6-pyruvoyl tetrahydropterin synthase. Biological chemistry. 1997. PMID: 9165069
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 27 September 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .