PTS Gene

Name	6-pyruvoyltetrahydropterin synthase
Description	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), is an essential cofactor and regulator of various enzyme activities, including enzymes involved in serotonin biosynthesis and NO synthase activity. Mutations in this gene result in hyperphenylalaninemia. [provided by RefSeq, Oct 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n6‐Pyruvoyl‐tetrahydropterin synthase (PTS) is a key enzyme in the de novo synthesis of tetrahydrobiopterin (BH4). It catalyzes the conversion of its precursor into 6‐pyruvoyl‐tetrahydropterin, a critical intermediate that leads to the production of BH4—a cofactor essential for nitric oxide synthases and aromatic amino acid hydroxylases, including tyrosine hydroxylase. This biochemical activity underlies the synthesis of neurotransmitters and the regulation of vascular functions, with PTS expression also modulated by cytokine signals in endothelial cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nMutations in the PTS gene disrupt BH4 biosynthesis and are a major cause of BH4 deficiency syndromes, in which hyperphenylalaninemia is often observed along with varied neurological disturbances. Detailed studies in patient cohorts and animal models have documented a wide spectrum of PTS mutations – with founder effects noted in certain populations – that affect both enzyme stability and activity. These genetic alterations have been linked not only to classical metabolic presentations such as dopa‐responsive dystonia and severe hyperphenylalaninemia but also to subtler neurodevelopmental conditions, suggesting that deficits in PTS activity can impact dopaminergic neuronal function and even contribute to the risk of disorders like autism."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "13"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its mechanistic role, PTS is of considerable clinical importance. Newborn screening programs and metabolic analyses routinely assess BH4 status, since identifying PTS deficiency is crucial for early therapeutic intervention. Treatment regimens—including supplementation with BH4 and the use of L‐Dopa/carbidopa (with adjustments guided by biomarkers such as serum prolactin levels)—have been optimized based on genotype–phenotype correlations from extensive mutational analyses. Such precision medicine approaches underscore the enzyme’s dual role as both a pivotal metabolic catalyst and a valuable diagnostic marker in disorders of BH4 metabolism"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "16"}]}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Y H Chien, S C Chiang, A Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Treatment and outcome of Taiwanese patients with 6-pyruvoyltetrahydropterin synthase gene mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Inherit Metab Dis (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1023/a:1013984022994"}], "href": "https://doi.org/10.1023/a:1013984022994"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11916314"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11916314"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Nicola Franscini, Nenad Blau, Roland B Walter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Critical role of interleukin-1beta for transcriptional regulation of endothelial 6-pyruvoyltetrahydropterin synthase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/01.ATV.0000099785.65848.F1"}], "href": "https://doi.org/10.1161/01.ATV.0000099785.65848.F1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14551150"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14551150"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yen-Hui Chiu, Ying-Chen Chang, Yu-Hsin Chang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutation spectrum of and founder effects affecting the PTS gene in East Asian populations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hum Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jhg.2011.146"}], "href": "https://doi.org/10.1038/jhg.2011.146"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22237589"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22237589"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Chiho Sumi-Ichinose, Fumi Urano, Atsushi Shimomura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetically rescued tetrahydrobiopterin-depleted mice survive with hyperphenylalaninemia and region-specific monoaminergic abnormalities."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurochem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1471-4159.2005.03402.x"}], "href": "https://doi.org/10.1111/j.1471-4159.2005.03402.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16135092"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16135092"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jennifer E Tobin, Jing Cui, Jemma B Wilk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sepiapterin reductase expression is increased in Parkinson's disease brain tissue."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.brainres.2007.01.001"}], "href": "https://doi.org/10.1016/j.brainres.2007.01.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17270157"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17270157"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jun Ye, Xiao-qing Liu, Wen-juan Qiu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[Screening for tetrahydrobiopterin metabolic disorders and related gene analysis among the patients with motor disturbance and mental retardation]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Zhonghua Yi Xue Yi Chuan Xue Za Zhi (2007)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17407085"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17407085"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Atsushi Ogawa, Masaki Kanazawa, Masaki Takayanagi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A case of 6-pyruvoyl-tetrahydropterin synthase deficiency demonstrates a more significant correlation of L-Dopa dosage with serum prolactin levels than CSF homovanillic acid levels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain Dev (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.braindev.2007.05.011"}], "href": "https://doi.org/10.1016/j.braindev.2007.05.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17590551"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17590551"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yu-Jin Qu, Fang Song, Yu-Wei Jin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[Mutation analysis and one novel mutation detection of 6-pyruvoyl tetrahydropterin synthase gene in children with tetrahydrobiopterin deficiency]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Zhongguo Yi Xue Ke Xue Yuan Xue Bao (2008)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18505119"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18505119"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Mei-qing Gu, Jun Ye, Wen-juan Qiu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[Mutational analysis of patients with 6-pyruvoyltetrahydrobiopterin synthesis deficiency]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Zhonghua Yi Xue Yi Chuan Xue Za Zhi (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3760/cma.j.issn.1003-9406.2009.02.014"}], "href": "https://doi.org/10.3760/cma.j.issn.1003-9406.2009.02.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19350512"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19350512"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "B M Anderson, N Schnetz-Boutaud, J Bartlett, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Examination of association to autism of common genetic variationin genes related to dopamine."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Autism Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/aur.55"}], "href": "https://doi.org/10.1002/aur.55"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19360691"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19360691"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "N Vatanavicharn, C Kuptanon, S Liammongkolkul, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel mutation affecting the pterin-binding site of PTS gene and review of PTS mutations in Thai patients with 6-pyruvoyltetrahydropterin synthase deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Inherit Metab Dis (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10545-009-1221-x"}], "href": "https://doi.org/10.1007/s10545-009-1221-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19830588"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19830588"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Polina Gundorova, Irina A Kuznetcova, Galina V Baydakova, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Long-term clinical outcome of 6-pyruvoyl-tetrahydropterin synthase-deficient patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Metab (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymgme.2020.06.009"}], "href": "https://doi.org/10.1016/j.ymgme.2020.06.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32651154"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32651154"}]}]}]}
Synonyms	PTPS
Proteins	PTPS_HUMAN
NCBI Gene ID	5805
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PTS has 7,087 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 133 datasets.

Click the + buttons to view associations for PTS from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PTS Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by PTS gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PTS gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of PTS gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of PTS gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of PTS gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of PTS gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PTS gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of PTS gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PTS gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PTS gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of PTS gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PTS gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of PTS gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PTS protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PTS gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PTS gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PTS gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of PTS gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with PTS gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with PTS gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of PTS gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PTS protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PTS protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing PTS protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with PTS protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with PTS protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of PTS gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PTS gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PTS gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PTS gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of PTS protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by PTS gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving PTS gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving PTS gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with PTS gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with PTS gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with PTS gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PTS gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for PTS protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at PTS gene from the ENCODE Histone Modification Site Profiles dataset.