REPS2 Gene

HGNC Family	EF-hand domain containing
Name	RALBP1 associated Eps domain containing 2
Description	The product of this gene is part of a protein complex that regulates the endocytosis of growth factor receptors. The encoded protein directly interacts with a GTPase activating protein that functions downstream of the small G protein Ral. Its expression can negatively affect receptor internalization and inhibit growth factor signaling. 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": "\nREPS2 (also known as POB1) is an adaptor protein that plays a critical role in modulating receptor‐mediated endocytosis and intracellular signaling. In non‐small cell lung cancer cells, REPS2 cooperates with other factors (for example, Hsf‑1) to inhibit the transport activity of Ralbp1, thereby triggering apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In prostate cancer, REPS2 is implicated in switching growth control from androgens to growth factors; its relatively high expression in androgen‑dependent cells contributes to controlled growth factor signaling, whereas its downregulation is associated with a loss of such control."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In esophageal squamous cell carcinoma, REPS2 is directly targeted by miR‑675‑5p; suppression of REPS2 relieves an inhibitory effect on the RalBP1/RAC1/CDC42 pathway, which in turn promotes tumor cell proliferation, migration, and metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nREPS2 also directly regulates the transport function of RalBP1. Over‑expression of REPS2 in prostate and lung cancer cells has been shown to inhibit RLIP76‑mediated transport of doxorubicin and glutathione conjugates, leading to intracellular drug accumulation and apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, its potential as a biomarker is highlighted in studies that include REPS2 among several prognostic and predictive candidates in breast cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In addition, REPS2 interacts with other signaling proteins such as PAG2 through a proline‑rich motif, an interaction that modulates cell migration and focal adhesion dynamics."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of growth factor receptor signaling, REPS2 exerts an inhibitory effect on receptor internalization and downstream signaling cascades. Induced REPS2 expression in prostate cancer models was found to reduce EGF receptor internalization and attenuate the expression of several EGF‑responsive genes, an effect that may contribute to the transition toward androgen independence."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Furthermore, REPS2 binds the NF‑κB subunit p65 through its EH domain, and loss of this interaction in advanced prostate cancer is associated with increased NF‑κB activity and resistance to apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Additional studies support a tumor‑suppressive role for REPS2, showing its involvement in inhibiting cell proliferation and migration, and underscoring its utility as a favorable prognostic biomarker in hormone‑related cancers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond cancer, REPS2 function extends to non‑neoplastic conditions. In lens epithelial cells, for example, reduced REPS2 levels have been observed in cataract patients and in experimental models, where its downregulation enhances FGF‑induced extracellular matrix synthesis, epithelial–mesenchymal transition, cytoskeletal reorganization, and cell migration via activation of FAK/Cdc42 signaling. Such findings suggest that REPS2 normally acts as a negative regulator of growth factor–induced cellular changes, with its loss contributing to pathologies such as posterior capsular opacification following cataract surgery."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sharad S Singhal, Sushma Yadav, Kenneth Drake, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hsf-1 and POB1 induce drug sensitivity and apoptosis by inhibiting Ralbp1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M708703200"}], "href": "https://doi.org/10.1074/jbc.M708703200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18474607"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18474607"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Josien K Oosterhoff, Fred Penninkhof, Albert O Brinkmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "REPS2/POB1 is downregulated during human prostate cancer progression and inhibits growth factor signalling in prostate cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1206397"}], "href": "https://doi.org/10.1038/sj.onc.1206397"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12771942"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12771942"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yan-Wu Zhou, Hang Zhang, Chao-Jun Duan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-675-5p enhances tumorigenesis and metastasis of esophageal squamous cell carcinoma by targeting REPS2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.8950"}], "href": "https://doi.org/10.18632/oncotarget.8950"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27120794"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27120794"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Sushma Yadav, Ewa Zajac, Sharad S Singhal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "POB1 over-expression inhibits RLIP76-mediated transport of glutathione-conjugates, drugs and promotes apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2005.01.055"}], "href": "https://doi.org/10.1016/j.bbrc.2005.01.055"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15707977"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15707977"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "P Doolan, M Clynes, S Kennedy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMEM25, REPS2 and Meis 1: favourable prognostic and predictive biomarkers for breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tumour Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000239795"}], "href": "https://doi.org/10.1159/000239795"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19776672"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19776672"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Takafumi Oshiro, Shinya Koyama, Shinichiro Sugiyama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interaction of POB1, a downstream molecule of small G protein Ral, with PAG2, a paxillin-binding protein, is involved in cell migration."}]}, {"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.M203453200"}], "href": "https://doi.org/10.1074/jbc.M203453200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12149250"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12149250"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Josien K Oosterhoff, Liesbeth C Kühne, J Anton Grootegoed, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EGF signalling in prostate cancer cell lines is inhibited by a high expression level of the endocytosis protein REPS2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.20612"}], "href": "https://doi.org/10.1002/ijc.20612"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15455380"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15455380"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Fred Penninkhof, J Anton Grootegoed, Leen J Blok "}, {"type": "b", "children": [{"type": "t", "text": "Identification of REPS2 as a putative modulator of NF-kappaB activity in prostate cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1207750"}], "href": "https://doi.org/10.1038/sj.onc.1207750"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15184881"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15184881"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Hang Zhang, Chao-Jun Duan, Heng Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression and clinical significance of REPS2 in human esophageal squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Asian Pac J Cancer Prev (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7314/apjcp.2013.14.5.2851"}], "href": "https://doi.org/10.7314/apjcp.2013.14.5.2851"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23803043"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23803043"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Chan Wen, Chen Wang, Conghui Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "REPS2 downregulation facilitates FGF-induced adhesion and migration in human lens epithelial cells through FAK/Cdc42 signaling and contributes to posterior capsule opacification."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2022.110378"}], "href": "https://doi.org/10.1016/j.cellsig.2022.110378"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35690292"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35690292"}]}]}]}
Synonyms	POB1
Proteins	REPS2_HUMAN
NCBI Gene ID	9185
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

REPS2 has 4,831 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 111 datasets.

Click the + buttons to view associations for REPS2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

REPS2 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 REPS2 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 REPS2 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 REPS2 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 REPS2 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 REPS2 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 REPS2 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 REPS2 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 REPS2 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of REPS2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of REPS2 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 REPS2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with REPS2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with REPS2 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 REPS2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of REPS2 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 REPS2 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 REPS2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing REPS2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with REPS2 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 REPS2 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 REPS2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with REPS2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with REPS2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of REPS2 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 REPS2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with REPS2 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 REPS2 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 REPS2 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 REPS2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with REPS2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at REPS2 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 REPS2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of REPS2 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 REPS2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of REPS2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with REPS2 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing REPS2 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of REPS2 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of REPS2 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Kinase Perturbations	kinase perturbations changing expression of REPS2 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.