PAICS Gene

Name	phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase
Description	This gene encodes a bifunctional enzyme containing phosphoribosylaminoimidazole carboxylase activity in its N-terminal region and phosphoribosylaminoimidazole succinocarboxamide synthetase in its C-terminal region. It catalyzes steps 6 and 7 of purine biosynthesis. The gene is closely linked and divergently transcribed with a locus that encodes an enzyme in the same pathway, and transcription of the two genes is coordinately regulated. The human genome contains several pseudogenes of this gene. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPhosphoribosylaminoimidazole carboxylase/succinocarboxamide synthetase (PAICS) is a bifunctional enzyme that catalyzes two sequential reactions in the de novo purine biosynthesis pathway. Structural and mechanistic studies have revealed that PAICS not only mediates the carboxylation of aminoimidazole ribonucleotide (AIR) and the subsequent conversion to SAICAR but also facilitates substrate channeling between its two enzymatic domains. In addition, PAICS participates in the formation of a dynamic multi‐protein assembly—often referred to as the purinosome—through selective protein–protein interactions and post‐translational modifications (including K6-polyubiquitination) that drive phase separation, thereby enhancing pathway flux under metabolic stress conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDysregulation of PAICS expression is emerging as a common feature across several cancer types. Increased PAICS levels have been associated with aggressive lung adenocarcinoma, where its altered expression influences metabolic enzymes such as pyruvate kinase, thereby promoting cell proliferation and invasion. Similarly, PAICS is overexpressed in bladder cancer and prostate cancer, and its upregulation in neuroblastoma (under MYCN regulation), gastric cancer, and glioma correlates with enhanced epithelial-to-mesenchymal transition, impaired DNA damage repair, and overall tumor progression. In many of these malignancies, PAICS serves as a prognostic biomarker and its expression is intricately modulated through mechanisms such as genomic amplification, microRNA-mediated silencing, and interplay with co-substrates like L-glutamine."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its biochemical and oncogenic roles, emerging pharmacogenomic approaches underscore the potential for identifying genetic variants that influence drug responses related to PAICS activity. These insights, together with detailed structural information and evidence of its involvement in substrate channeling, pave the way for the rational design of targeted inhibitors. Collectively, the integrated findings highlight PAICS as a multifaceted enzyme that not only orchestrates purine nucleotide production but also contributes to cancer cell metabolic reprogramming and genomic maintenance, rendering it a promising diagnostic marker and therapeutic target."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jana Škerlová, Judith Unterlass, Mona Göttmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Crystal structures of human PAICS reveal substrate and product binding of an emerging cancer target."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA120.013695"}], "href": "https://doi.org/10.1074/jbc.RA120.013695"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32571877"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32571877"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hyungjoo Shon, Elena A Matveeva, Ella C Jull, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evidence Supporting Substrate Channeling between Domains of Human PAICS: A Time-Course Analysis of "}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "13"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": "C-Bicarbonate Incorporation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/acs.biochem.1c00803"}], "href": "https://doi.org/10.1021/acs.biochem.1c00803"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35285625"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35285625"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jingxuan He, Ling-Nan Zou, Vidhi Pareek, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Multienzyme interactions of the de novo purine biosynthetic protein PAICS facilitate purinosome formation and metabolic channeling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jbc.2022.101853"}], "href": "https://doi.org/10.1016/j.jbc.2022.101853"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35331738"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35331738"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ming-Chieh Chou, Yi-Hsuan Wang, Fei-Yun Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PAICS ubiquitination recruits UBAP2 to trigger phase separation for purinosome assembly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2023.09.028"}], "href": "https://doi.org/10.1016/j.molcel.2023.09.028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37848033"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37848033"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Moloy T Goswami, Guoan Chen, Balabhadrapatruni V S K Chakravarthi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role and regulation of coordinately expressed de novo purine biosynthetic enzymes PPAT and PAICS in lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.4352"}], "href": "https://doi.org/10.18632/oncotarget.4352"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26140362"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26140362"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Balabhadrapatruni V S K Chakravarthi, Maria Del Carmen Rodriguez Pena, Sumit Agarwal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Role for De Novo Purine Metabolic Enzyme PAICS in Bladder Cancer Progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neoplasia (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neo.2018.07.006"}], "href": "https://doi.org/10.1016/j.neo.2018.07.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30121007"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30121007"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Shuyi Zhou, Yuanliang Yan, Xi Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Roles of highly expressed PAICS in lung adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2018.12.064"}], "href": "https://doi.org/10.1016/j.gene.2018.12.064"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30641222"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30641222"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Chantal Hoi Yin Cheung, Chia-Lang Hsu, Chao-Yin Tsuei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Combinatorial targeting of MTHFD2 and PAICS in purine synthesis as a novel therapeutic strategy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-019-2033-z"}], "href": "https://doi.org/10.1038/s41419-019-2033-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31624245"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31624245"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Nan Huang, Chang Xu, Liang Deng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PAICS contributes to gastric carcinogenesis and participates in DNA damage response by interacting with histone deacetylase 1/2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-020-2708-5"}], "href": "https://doi.org/10.1038/s41419-020-2708-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32632107"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32632107"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Baoshun Du, Zheying Zhang, Wenyu Di, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PAICS is related to glioma grade and can promote glioma growth and migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.16647"}], "href": "https://doi.org/10.1111/jcmm.16647"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34173716"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34173716"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Masashi Ikeda, Yasuyuki Tomita, Akihiro Mouri, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of novel candidate genes for treatment response to risperidone and susceptibility for schizophrenia: integrated analysis among pharmacogenomics, mouse expression, and genetic case-control association approaches."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Psychiatry (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopsych.2009.08.030"}], "href": "https://doi.org/10.1016/j.biopsych.2009.08.030"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19850283"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19850283"}]}]}]}
Synonyms	ADE2H1, AIRC, ADE2
Proteins	PUR6_HUMAN
NCBI Gene ID	10606
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PAICS has 11,790 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 131 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

PAICS 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 PAICS 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 PAICS 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 PAICS 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 PAICS 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 PAICS 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 PAICS 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 PAICS 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 PAICS 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 PAICS 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 PAICS 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 PAICS gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PAICS 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 PAICS gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PAICS protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PAICS 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 PAICS gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PAICS 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 PAICS gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of PAICS gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PAICS protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PAICS protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing PAICS 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 PAICS 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 PAICS 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 PAICS gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PAICS gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PAICS gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PAICS gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with PAICS 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 PAICS protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with PAICS 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 PAICS 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 PAICS gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PAICS gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for PAICS protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at PAICS gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PAICS gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PAICS gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing PAICS from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with PAICS gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.