PTS (6-pyruvoyltetrahydropterin synthase)

Gene

• Entrez ID: 5805
• Gene name: 6-pyruvoyltetrahydropterin synthase
• Gene symbol: PTS
• Synonyms (NCBI Gene): PTPS
• Chromosome: 11
• Chromosome location: 11q23.1
• Summary: The enzyme encoded by this gene catalyzes the elimination of inorganic triphosphate from dihydroneopterin triphosphate, which is the second and irreversible step in the biosynthesis of tetrahydrobiopterin from GTP. Tetrahydrobiopterin, also known as BH(4)

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs104894273	G>A	Pathogenic	Missense variant, coding sequence variant
rs104894274	C>T	Pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs104894275	A>G	Pathogenic	Missense variant, coding sequence variant
rs104894276	C>G,T	Pathogenic	Missense variant, coding sequence variant
rs104894277	G>A,C	Pathogenic-likely-pathogenic	Missense variant, coding sequence variant
rs104894278	A>G	Pathogenic	Missense variant, coding sequence variant
rs104894279	A>G	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs104894280	G>A	Pathogenic	Missense variant, coding sequence variant
rs145882709	C>A	Likely-pathogenic	Coding sequence variant, stop gained
rs150726932	G>T	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs200712908	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs370340361	C>T	Pathogenic	Missense variant, coding sequence variant
rs747260038	TTTG>-	Pathogenic	Frameshift variant, coding sequence variant
rs750229518	A>G,T	Pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs761285716	A>G	Pathogenic	Missense variant, coding sequence variant
rs765406631	C>T	Pathogenic-likely-pathogenic	Missense variant, coding sequence variant
rs770387277	GTG>-	Likely-pathogenic	Coding sequence variant, inframe deletion
rs775426269	C>A,T	Uncertain-significance, likely-pathogenic	Coding sequence variant, missense variant
rs776543880	G>A,C	Likely-pathogenic	Splice acceptor variant
rs780332520	A>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs781197929	T>A,C,G	Pathogenic	Stop gained, coding sequence variant, synonymous variant
rs794726656	GTTCTTCCTGTAGG>-	Pathogenic	Frameshift variant, coding sequence variant
rs794726657	A>T	Pathogenic	Intron variant
rs866922524	->GG	Likely-pathogenic	Splice donor variant, coding sequence variant
rs927103678	G>A	Conflicting-interpretations-of-pathogenicity	Splice donor variant
rs1057517810	A>G	Likely-pathogenic	Missense variant, coding sequence variant
rs1057517811	A>G	Likely-pathogenic	Missense variant, coding sequence variant
rs1167104933	C>G,T	Likely-pathogenic	Coding sequence variant, missense variant, stop gained
rs1230781262	C>G,T	Pathogenic-likely-pathogenic	Intron variant
rs1256819927	G>T	Likely-pathogenic	Splice donor variant
rs1480995114	A>G	Pathogenic	Intron variant
rs1555197885	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1555198165	AAAGCACTGATAAAGTTTTTTTTTGTTGTTGTTGTTTTTTTTTTTGAGATGGAGT>-	Pathogenic	Intron variant
rs1555198233	A>G	Likely-pathogenic	Splice acceptor variant
rs1555198263	TC>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1555198451	G>T	Likely-pathogenic	Splice acceptor variant
rs1555198462	G>C	Likely-pathogenic	Splice donor variant
rs1555198483	A>G	Likely-pathogenic	Splice acceptor variant
rs1555198494	T>-	Likely-pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT024591	hsa-miR-215-5p	Microarray	19074876
MIRT026112	hsa-miR-192-5p	Microarray	19074876
MIRT049542	hsa-miR-92a-3p	CLASH	23622248
MIRT1276703	hsa-miR-3616-5p	CLIP-seq
MIRT1276704	hsa-miR-3646	CLIP-seq
MIRT1276705	hsa-miR-3647-3p	CLIP-seq
MIRT1276706	hsa-miR-3647-5p	CLIP-seq
MIRT1276707	hsa-miR-3662	CLIP-seq
MIRT1276708	hsa-miR-4775	CLIP-seq
MIRT1276709	hsa-miR-4795-5p	CLIP-seq
MIRT1276710	hsa-miR-573	CLIP-seq
MIRT1276711	hsa-miR-889	CLIP-seq
MIRT2081380	hsa-miR-1265	CLIP-seq
MIRT2081381	hsa-miR-192	CLIP-seq
MIRT2081382	hsa-miR-215	CLIP-seq
MIRT2081383	hsa-miR-224	CLIP-seq
MIRT2081384	hsa-miR-3171	CLIP-seq
MIRT2081385	hsa-miR-3177-5p	CLIP-seq
MIRT2081386	hsa-miR-3614-5p	CLIP-seq
MIRT2081387	hsa-miR-3622a-5p	CLIP-seq
MIRT2081388	hsa-miR-4423-3p	CLIP-seq
MIRT2081389	hsa-miR-4452	CLIP-seq
MIRT2081390	hsa-miR-4705	CLIP-seq
MIRT2081391	hsa-miR-508-5p	CLIP-seq
MIRT2081392	hsa-miR-520a-5p	CLIP-seq
MIRT2081393	hsa-miR-525-5p	CLIP-seq
MIRT2081394	hsa-miR-590-3p	CLIP-seq
MIRT2081395	hsa-miR-656	CLIP-seq
MIRT2081381	hsa-miR-192	CLIP-seq
MIRT2307427	hsa-miR-19a	CLIP-seq
MIRT2307428	hsa-miR-19b	CLIP-seq
MIRT2307429	hsa-miR-2113	CLIP-seq
MIRT2081382	hsa-miR-215	CLIP-seq
MIRT2307430	hsa-miR-3121-3p	CLIP-seq
MIRT2081385	hsa-miR-3177-5p	CLIP-seq
MIRT2081387	hsa-miR-3622a-5p	CLIP-seq
MIRT2307431	hsa-miR-378g	CLIP-seq
MIRT2081388	hsa-miR-4423-3p	CLIP-seq
MIRT2081390	hsa-miR-4705	CLIP-seq
MIRT2081391	hsa-miR-508-5p	CLIP-seq
MIRT2081392	hsa-miR-520a-5p	CLIP-seq
MIRT2081393	hsa-miR-525-5p	CLIP-seq
MIRT1276711	hsa-miR-889	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003874	Function	6-pyruvoyltetrahydropterin synthase activity	IEA
GO:0003874	Function	6-pyruvoyltetrahydropterin synthase activity	TAS	3308682
GO:0005515	Function	Protein binding	IPI	19060904, 25416956, 31515488, 32296183
GO:0005737	Component	Cytoplasm	IDA
GO:0005739	Component	Mitochondrion	IBA
GO:0005739	Component	Mitochondrion	IDA
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	TAS
GO:0006520	Process	Amino acid metabolic process	TAS	3308682
GO:0006729	Process	Tetrahydrobiopterin biosynthetic process	IEA
GO:0006729	Process	Tetrahydrobiopterin biosynthetic process	IEA
GO:0006729	Process	Tetrahydrobiopterin biosynthetic process	TAS	3308682
GO:0007417	Process	Central nervous system development	TAS	3308682
GO:0016829	Function	Lyase activity	IEA
GO:0042802	Function	Identical protein binding	IEA
GO:0042802	Function	Identical protein binding	IPI	16169070, 16189514, 21516116, 24599843, 25416956, 25502805, 25910212, 31515488, 32296183
GO:0046146	Process	Tetrahydrobiopterin metabolic process	IEA
GO:0046872	Function	Metal ion binding	IEA

Other IDs

• MIM: 612719
• HGNC: 9689
• e!Ensembl: ENSG00000150787

Protein

• UniProt ID: Q03393
• Protein name: 6-pyruvoyl tetrahydrobiopterin synthase (PTP synthase) (PTPS) (EC 4.2.3.12)
• Protein function: Involved in the biosynthesis of tetrahydrobiopterin, an essential cofactor of aromatic amino acid hydroxylases. Catalyzes the transformation of 7,8-dihydroneopterin triphosphate into 6-pyruvoyl tetrahydropterin.
• PDB: 3I2B
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01242	PTPS	13 → 145	6-pyruvoyl tetrahydropterin synthase	Domain

• Sequence:

  MSTEGGGRRCQAQVSRRISFSASHRLYSKFLSDEENLKLFGKCNNPNGHGHNYKVVVTVH
  GEIDPATGMVMNLADLKKYMEEAIMQPLDHKNLDMDVPYFADVVSTTENVAVYIWDNLQK
  VLPVGVLYKVKVYETDNNIVVYKGE

• Sequence length: 145

Pathways

KEGG:

Folate biosynthesis
Metabolic pathways
Biosynthesis of cofactors

Reactome:

Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
6-Pyruvoyl-tetrahydrobiopterin synthase deficiency	Likely pathogenic; Pathogenic	rs2135407114, rs2135407146, rs1328320990, rs2135409169, rs141163668, rs765777664, rs1399026048, rs1859972447, rs1317230624, rs759363496, rs2135410340, rs1859971691, rs1367077861, rs199603175, rs2135408292, rs1859971515, rs370340361, rs2135409211, rs2135408968, rs104894273, rs104894274, rs104894275, rs104894276, rs104894277, rs104894280, rs1555198165, rs2135407190, rs2135410460, rs2496567570, rs1256819927, rs1040441824, rs772285014, rs776543880, rs778932353, rs2496570916, rs1178886103, rs2496564107, rs2496567659, rs2496570703, rs2496570868, rs927103678, rs2496560615, rs2496560570, rs150726932, rs1566816174, rs2496571358, rs1474586656, rs1555198483, rs2496570663, rs2496571494, rs145882709, rs1057517811, rs1057517810, rs775426269, rs1167104933, rs1555198233, rs770387277, rs866922524, rs765406631, rs200712908, rs779681799, rs1449216377, rs200279736, rs1555198451, rs1555198458, rs1213277062, rs747260038, rs1555198232, rs1555198263, rs1555198462, rs1230781262, rs778053171, rs1555198494, rs780332520, rs781197929, rs761285716, rs1859894340, rs1859865221, rs17851590	RCV001378214 RCV001378592 RCV001379602 RCV001378238 RCV001379032 RCV001386720 RCV001389733 RCV001386869 RCV001754543 RCV001989605 RCV001936011 RCV002007379 RCV001994721 RCV002000120 RCV001976797 RCV001958661 RCV001949408 RCV001972791 RCV001881243 RCV000000505 RCV000778305 RCV000000508 RCV000000509 RCV000000510 RCV000000513 RCV000000514 RCV002226800 RCV002272739 RCV002308167 RCV003062455 RCV003037430 RCV003068334 RCV003110522 RCV003108869 RCV002876898 RCV002889372 RCV002886582 RCV003055659 RCV003131275 RCV003471750 RCV003471751 RCV003463402 RCV003471752 RCV003496201 RCV003496658 RCV003598970 RCV003598665 RCV003992136 RCV004574652 RCV004574653 RCV004574654 RCV000410240 RCV001206459 RCV001261646 RCV000984305 RCV000545224 RCV000546150 RCV000669121 RCV000666747 RCV000672251 RCV000669844 RCV000669353 RCV000667396 RCV000672206 RCV000671251 RCV000669778 RCV000666591 RCV000668893 RCV000670243 RCV000667725 RCV000665717 RCV000667242 RCV000669373 RCV000673112 RCV000674555 RCV000668151 RCV000668809 RCV000666677 RCV000666163 RCV000672138 RCV000671217 RCV000791681 RCV001004344 RCV001066231 RCV001068909 RCV001210738 RCV001261645 RCV001261647	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
GTP cyclohydrolase I deficiency with hyperphenylalaninemia	Pathogenic; Likely pathogenic	rs104894276, rs1449216377	RCV003982818 RCV003983773	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hyperphenylalaninemia due to tetrahydrobiopterin deficiency	Pathogenic	rs104894276	RCV003153291	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hyperphenylalaninemia, bh4-deficient, a, due to partial pts deficiency	Likely pathogenic; Pathogenic	rs104894274, rs794726656, rs104894278	RCV000000506 RCV000000507 RCV000000511	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Nonpapillary renal cell carcinoma	Pathogenic; Likely pathogenic	rs1256819927	RCV005930319 RCV005901497	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
PTS-related disorder	Pathogenic; Likely pathogenic	rs104894275, rs778932353, rs2496570703	RCV003924789 RCV003396891 RCV003900961	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BH4-DEFICIENT HYPERPHENYLALANINEMIA A	—	ClinGen, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BIPOLAR DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC DISEASES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Noonan syndrome 1	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
6-pyruvoyl-tetrahydropterin synthase deficiency	6-pyruvoyl-tetrahydropterin synthase deficiency	UNIPROT_DG	10220141, 10531334, 10585341, 10874306, 11388593, 7493990, 7698774, 8178819, 8707300, 9159737, 9222757, 9450907		★☆☆☆☆ Found in Text Mining only
6-pyruvoyl-tetrahydropterin synthase deficiency	6-pyruvoyl-tetrahydropterin synthase deficiency	CLINVAR_DG	10319579, 10585341, 11388593, 11438997, 11694255, 11916314, 16917893, 17160954, 18505119, 19280650, 19350512, 20059486, 21933604, 22237589, 23138986, 23942198, 25304915, 25456745, 25525159, 25758715, 27246466, 27629047, 3297709, 7493990, 8707300, 9222757, 9450907		★☆☆☆☆ Found in Text Mining only
6-pyruvoyl-tetrahydropterin synthase deficiency	6-pyruvoyl-tetrahydropterin synthase deficiency	CLINGEN_DG	11517215, 19234759, 19280650, 20059486, 21542064, 8178819, 9222757		★☆☆☆☆ Found in Text Mining only
6-pyruvoyl-tetrahydropterin synthase deficiency	6-pyruvoyl-tetrahydropterin synthase deficiency	GENOMICS_ENGLAND_DG	26919687, 27604308, 27830117, 8801112, 9450907		★☆☆☆☆ Found in Text Mining only
6-pyruvoyl-tetrahydropterin synthase deficiency	6-pyruvoyl-tetrahydropterin synthase deficiency	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
6-pyruvoyl-tetrahydropterin synthase deficiency	6-pyruvoyl-tetrahydropterin synthase deficiency	ORPHANET_DG			★☆☆☆☆ Found in Text Mining only
6-pyruvoyl-tetrahydropterin synthase deficiency	6-pyruvoyl-tetrahydropterin synthase deficiency	Orphanet			★☆☆☆☆ Found in Text Mining only
Amnesia	Amnesia	BEFREE	30055470		★☆☆☆☆ Found in Text Mining only
AMYOTROPHIC LATERAL SCLEROSIS 1	Lateral Sclerosis	BEFREE	11772995		★☆☆☆☆ Found in Text Mining only
Amyotrophic Lateral Sclerosis, Familial	Amyotrophic lateral sclerosis	BEFREE	11772995		★☆☆☆☆ Found in Text Mining only
Aromatic amino acid decarboxylase deficiency	Aromatic amino acid decarboxylase deficiency	BEFREE	29116116		★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	BEFREE	28957509		★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	Pubtator	19674121	Associate	★☆☆☆☆ Found in Text Mining only
Bipolar Disorder	Bipolar Disorder	GWASCAT_DG	26503763		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Blepharoptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Choreoathetosis	Choreoathetosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Classical phenylketonuria	Phenylketonuria	BEFREE	11772995, 1588014		★☆☆☆☆ Found in Text Mining only
Clumsiness - motor delay	Motor delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Colitis	Colitis	BEFREE	31036600		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	31628042		★☆☆☆☆ Found in Text Mining only
Deep Vein Thrombosis	Thrombosis	BEFREE	27664152, 28760416		★☆☆☆☆ Found in Text Mining only
Deficiency of aromatic-L-amino-acid decarboxylase	Deficiency Of Aromatic-L-Amino-Acid Decarboxylase	BEFREE	29116116		★☆☆☆☆ Found in Text Mining only
Deglutition Disorders	Dysphagia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dystonia	Dystonia	Pubtator	36054588	Associate	★☆☆☆☆ Found in Text Mining only
Dystonia, Dopa-Responsive, due to Sepiapterin Reductase Deficiency	Dopa-responsive dystonia	BEFREE	29116116		★☆☆☆☆ Found in Text Mining only
Familial Alzheimer Disease (FAD)	Alzheimer disease	BEFREE	11772995		★☆☆☆☆ Found in Text Mining only
Familial Dystonia	Dystonia	BEFREE	9159737		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hyperphenylalaninaemia	Hyperphenylalaninemia	BEFREE	10585341, 10874306, 1588014, 28915855, 30926181, 8841415		★☆☆☆☆ Found in Text Mining only
Hyperphenylalaninaemia	Hyperphenylalaninemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hyperphenylalaninemia, Non-Phenylketonuric	Hyperphenylalaninemia	BEFREE	10874306, 11916314, 23138986, 25304915, 8841415		★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	BEFREE	31154885		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	GENOMICS_ENGLAND_DG	27604308		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	9222757		★☆☆☆☆ Found in Text Mining only
Liver neoplasms	Liver neoplasms	BEFREE	9222757		★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus Systemic	Systemic lupus erythematosus	Pubtator	31616406	Associate	★☆☆☆☆ Found in Text Mining only
Metabolic Diseases	Metabolic Diseases	BEFREE	27798097, 30926181		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Metabolic Diseases	Metabolic syndrome	Pubtator	27798097	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mixed anxiety and depressive disorder	Mixed Anxiety And Depressive Disorder	BEFREE	31686574		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	31628042		★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	Pubtator	17270157	Inhibit	★☆☆☆☆ Found in Text Mining only
Parkinson Disease Secondary	Secondary parkinson disease	Pubtator	36054588	Associate	★☆☆☆☆ Found in Text Mining only
Parkinsonian Disorders	Parkinson Disease	HPO_DG			★☆☆☆☆ Found in Text Mining only
Phenylketonuria II	Phenylketonuria	BEFREE	29116116		★☆☆☆☆ Found in Text Mining only
Phenylketonurias	Phenylketonuria	BEFREE	11772995, 1588014, 24705691		★☆☆☆☆ Found in Text Mining only
Post-Traumatic Stress Disorder	Stress Disorder	BEFREE	30055470		★☆☆☆☆ Found in Text Mining only
Primary Hyperoxaluria	Hyperoxaluria	BEFREE	25689234		★☆☆☆☆ Found in Text Mining only
Ptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Transient hyperphenylalaninemia	Transient hyperphenylalaninemia	BEFREE	9222757		★☆☆☆☆ Found in Text Mining only