RPIA Gene

Name	ribose 5-phosphate isomerase A
Description	The protein encoded by this gene is an enzyme, which catalyzes the reversible conversion between ribose-5-phosphate and ribulose-5-phosphate in the pentose-phosphate pathway. This gene is highly conserved in most organisms. The enzyme plays an essential role in the carbohydrate metabolism. Mutations in this gene cause ribose 5-phosphate isomerase deficiency. A pseudogene is found on chromosome 18. [provided by RefSeq, Mar 2010]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRibose-5-phosphate isomerase A (RPIA) is a pivotal enzyme in the nonoxidative branch of the pentose phosphate pathway, catalyzing the reversible conversion of ribose-5-phosphate to ribulose-5-phosphate. Loss-of-function mutations in RPIA result in the accumulation of polyols such as ribitol and D-arabitol, a metabolic imbalance that is linked to neurological manifestations including leukoencephalopathy and peripheral neuropathy. These clinical findings underscore RPIA’s essential role in maintaining nucleotide synthesis and redox homeostasis, which are critical for neural integrity and overall metabolic stability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nConversely, dysregulation of RPIA has been strongly implicated in oncogenesis. Elevated RPIA expression is observed in various cancers—including hepatocellular carcinoma, lung cancer, and endometrial cancer—where its overactivity promotes tumor cell proliferation, colony formation, and enhanced metabolic flux through glycolysis and the pentose phosphate pathway. Mechanistically, RPIA facilitates oncogenic signaling via upregulation of the ERK pathway and concomitant modulation of PP2A activity, while its suppression leads to increased reactive oxygen species that trigger autophagy, apoptosis, and cellular senescence. In addition, emerging evidence suggests that microRNAs may further fine-tune RPIA-mediated metabolic reprogramming in cancer cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nComparative structural analyses further illuminate RPIA’s functional versatility. In contrast to the parasite-specific analog RpiB—which displays distinct active site residues and reaction mechanisms—human RPIA exhibits unique structural features that underpin its catalytic efficiency and regulatory capabilities in central carbon metabolism. These insights not only advance our fundamental understanding of the enzyme’s role within the pentose phosphate pathway but also pave the way for the development of selective therapeutic agents aimed at targeting parasitic infections without adversely affecting human cellular metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jojanneke H J Huck, Nanda M Verhoeven, Eduard A Struys, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ribose-5-phosphate isomerase deficiency: new inborn error in the pentose phosphate pathway associated with a slowly progressive leukoencephalopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/383204"}], "href": "https://doi.org/10.1086/383204"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14988808"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14988808"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Parneet Kaur, Mirjam M C Wamelink, Marjo S van der Knaap, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Confirmation of a Rare Genetic Leukoencephalopathy due to a Novel Bi-allelic Variant in RPIA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Med Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejmg.2019.103708"}], "href": "https://doi.org/10.1016/j.ejmg.2019.103708"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31247379"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31247379"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Shih-Ci Ciou, Yu-Ting Chou, Yu-Ling Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ribose-5-phosphate isomerase A regulates hepatocarcinogenesis via PP2A and ERK signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.29361"}], "href": "https://doi.org/10.1002/ijc.29361"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25429733"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25429733"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Zhaoping Qiu, Weijie Guo, Qifeng Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-124 reduces the pentose phosphate pathway and proliferation by targeting PRPS1 and RPIA mRNAs in human colorectal cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gastroenterology (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1053/j.gastro.2015.07.050"}], "href": "https://doi.org/10.1053/j.gastro.2015.07.050"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26248089"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26248089"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jacob Heintze, Joana R Costa, Melanie Weber, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ribose 5-phosphate isomerase inhibits LC3 processing and basal autophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2016.06.015"}], "href": "https://doi.org/10.1016/j.cellsig.2016.06.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27328773"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27328773"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Maria M Szwarc, Ramakrishna Kommagani, Vasanta Putluri, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Steroid Receptor Coactivator-2 Controls the Pentose Phosphate Pathway through RPIA in Human Endometrial Cancer Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-018-31372-y"}], "href": "https://doi.org/10.1038/s41598-018-31372-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30177747"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30177747"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yu-Chin Nieh, Yu-Ting Chou, Yu-Ting Chou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Suppression of Ribose-5-Phosphate Isomerase a Induces ROS to Activate Autophagy, Apoptosis, and Cellular Senescence in Lung Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms23147883"}], "href": "https://doi.org/10.3390/ijms23147883"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35887232"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35887232"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Priscila V S Z Capriles, Luiz Phillippe R Baptista, Isabella A Guedes, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural modeling and docking studies of ribose 5-phosphate isomerase from Leishmania major and Homo sapiens: a comparative analysis for Leishmaniasis treatment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Graph Model (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmgm.2014.11.002"}], "href": "https://doi.org/10.1016/j.jmgm.2014.11.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25528729"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25528729"}]}]}]}
Synonyms	RPI, RPIAD
Proteins	RPIA_HUMAN
NCBI Gene ID	22934
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

RPIA has 8,925 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 135 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

RPIA Gene

Functional Associations

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

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of RPIA gene relative to other tissues from the Allen Brain Atlas Adult Human 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 RPIA 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 RPIA 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 RPIA 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 RPIA 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 RPIA 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 RPIA 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 RPIA 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 RPIA gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of RPIA 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 RPIA gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with RPIA protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with RPIA 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 RPIA gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of RPIA 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 RPIA 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 RPIA gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with RPIA gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of RPIA gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing RPIA protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of RPIA gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing RPIA protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing RPIA protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing RPIA protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing RPIA 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 RPIA 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 RPIA 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 RPIA gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with RPIA gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with RPIA gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with RPIA gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of RPIA 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 RPIA gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving RPIA gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with RPIA 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 RPIA 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 RPIA gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with RPIA gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for RPIA protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at RPIA gene from the ENCODE Histone Modification Site Profiles dataset.