ATIC Gene

Name	5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase
Description	This gene encodes a bifunctional protein that catalyzes the last two steps of the de novo purine biosynthetic pathway. The N-terminal domain has phosphoribosylaminoimidazolecarboxamide formyltransferase activity, and the C-terminal domain has IMP cyclohydrolase activity. A mutation in this gene results in AICA-ribosiduria. [provided by RefSeq, Sep 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ATIC is a bifunctional enzyme that catalyzes the final two steps in the de novo purine biosynthetic pathway through its AICAR transformylase and IMP cyclohydrolase activities. This dual‐function enzyme is critical for maintaining nucleotide pool balance and thus supports both normal cellular proliferation and oncogenic growth. In the context of rheumatoid arthritis, inhibition of ATIC—mediated in part by methotrexate polyglutamates—contributes to the anti‐inflammatory and disease‐modifying effects of methotrexate. Moreover, genetic polymorphisms in ATIC have been associated with variability in methotrexate efficacy and toxicity, suggesting that ATIC may serve as a pharmacogenetic biomarker for patient response (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Detailed kinetic analyses of human ATIC have revealed key rate‐limiting steps and substrate interactions that further our understanding of its catalytic mechanism, information that is crucial in designing selective inhibitors (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In addition, in certain cancers ATIC can contribute to oncogenesis not only by sustaining the high nucleotide demand of rapidly proliferating tumor cells but also when aberrantly fused to receptor tyrosine kinases such as ALK. The ATIC–ALK fusion protein, identified in a subset of anaplastic large‐cell lymphomas, underscores a dual role for ATIC as both a metabolic enzyme and an oncogenic fusion partner. In these settings, post‐fusion phosphorylation of ATIC has been shown to enhance its enzymatic activity and may influence resistance to antifolate drugs (see"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies highlight the multifaceted role of ATIC in health and disease. Its central function in purine biosynthesis makes it a key regulator of cell growth and survival, while its inhibition is pivotal for the pharmacologic action of methotrexate in inflammatory diseases. In addition, the involvement of ATIC in oncogenic fusion events implicates it as a potential target for therapeutic intervention in certain cancers. This convergence of metabolic control and oncogenic signaling makes ATIC a promising candidate for both biomarker development and drug targeting.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Thierry Dervieux, Daniel Furst, Diana Orentas Lein, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier, aminoimidazole carboxamide ribonucleotide transformylase, and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arthritis Rheum (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/art.20460"}], "href": "https://doi.org/10.1002/art.20460"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15457444"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15457444"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Cheom-Gil Cheong, Dennis W Wolan, Samantha E Greasley, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Crystal structures of human bifunctional enzyme aminoimidazole-4-carboxamide ribonucleotide transformylase/IMP cyclohydrolase in complex with potent sulfonyl-containing antifolates."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M313691200"}], "href": "https://doi.org/10.1074/jbc.M313691200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14966129"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14966129"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yvonne C Lee, Jing Cui, Karen H Costenbader, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Investigation of candidate polymorphisms and disease activity in rheumatoid arthritis patients on methotrexate."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Rheumatology (Oxford) (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/rheumatology/ken513"}], "href": "https://doi.org/10.1093/rheumatology/ken513"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19193698"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19193698"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Aurea Lima, Joaquim Monteiro, Miguel Bernardes, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Prediction of methotrexate clinical response in Portuguese rheumatoid arthritis patients: implication of MTHFR rs1801133 and ATIC rs4673993 polymorphisms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Res Int (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2014/368681"}], "href": "https://doi.org/10.1155/2014/368681"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24967362"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24967362"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Karen G Bulock, G Peter Beardsley, Karen S Anderson "}, {"type": "b", "children": [{"type": "t", "text": "The kinetic mechanism of the human bifunctional enzyme ATIC (5-amino-4-imidazolecarboxamide ribonucleotide transformylase/inosine 5'-monophosphate cyclohydrolase). A surprising lack of substrate channeling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111964200"}], "href": "https://doi.org/10.1074/jbc.M111964200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11948179"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11948179"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jan Cools, Iwona Wlodarska, Riet Somers, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of novel fusion partners of ALK, the anaplastic lymphoma kinase, in anaplastic large-cell lymphoma and inflammatory myofibroblastic tumor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Chromosomes Cancer (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/gcc.10033"}], "href": "https://doi.org/10.1002/gcc.10033"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12112524"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12112524"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Francesco E Boccalatte, Claudia Voena, Chiara Riganti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The enzymatic activity of 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase is enhanced by NPM-ALK: new insights in ALK-mediated pathogenesis and the treatment of ALCL."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2008-06-161018"}], "href": "https://doi.org/10.1182/blood-2008-06-161018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18845790"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18845790"}]}]}]}
Synonyms	AICARFT, HEL-S-70P, AICAR, PURH, IMPCHASE
Proteins	PUR9_HUMAN
NCBI Gene ID	471
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ATIC has 9,120 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 137 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

ATIC 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 ATIC 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 ATIC 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 ATIC 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 ATIC 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 ATIC 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 ATIC 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 ATIC 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 ATIC 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 ATIC 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 ATIC 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 ATIC gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ATIC 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 ATIC gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with ATIC gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ATIC protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ATIC 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 ATIC gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ATIC 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 ATIC gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with ATIC gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of ATIC gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of ATIC gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ATIC protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing ATIC protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with ATIC 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 ATIC protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ATIC gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ATIC gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ATIC gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with ATIC gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of ATIC 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 ATIC gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for ATIC protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving ATIC gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving ATIC gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with ATIC gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with ATIC 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 ATIC 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 ATIC gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ATIC gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.