ABCC5 Gene

HGNC Family	ATP binding cassette transporters (ABC)
Name	ATP-binding cassette, sub-family C (CFTR/MRP), member 5
Description	The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MRP subfamily which is involved in multi-drug resistance. This protein functions in the cellular export of its substrate, cyclic nucleotides. This export contributes to the degradation of phosphodiesterases and possibly an elimination pathway for cyclic nucleotides. Studies show that this protein provides resistance to thiopurine anticancer drugs, 6-mercatopurine and thioguanine, and the anti-HIV drug 9-(2-phosphonylmethoxyethyl)adenine. This protein may be involved in resistance to thiopurines in acute lymphoblastic leukemia and antiretroviral nucleoside analogs in HIV-infected patients. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ABCC5 (also known as MRP5) is an ATP‐binding cassette efflux transporter with multifaceted functions in both normal physiology and disease. In non‐malignant tissues, ABCC5 mediates the ATP‐dependent export of cyclic nucleotides such as cGMP and cAMP—even though it operates with low affinity and appears to serve as an “overflow” pump—to help rapidly restore intracellular homeostasis without contributing to prostaglandin transport, a property that distinguishes it from some related transporters."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In addition, ABCC5 is expressed in several other normal tissues, including the heart and placenta, where in the heart it facilitates cGMP export—a process that is notably increased in ischemic cardiomyopathy"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "—and in the placenta its expression is modulated during trophoblast differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of cancer, ABCC5 contributes to chemoresistance through its efflux function. It mediates the export of nucleoside analogs and related compounds, thereby reducing intracellular drug accumulation and diminishing the efficacy of chemotherapeutic agents. Overexpression of ABCC5 has been implicated in resistance to treatments in pancreatic carcinoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "and in acquired sorafenib resistance in hepatocellular carcinoma, where activation of the PI3K/AKT/NRF2 axis increases its expression and promotes survival via enhanced intracellular glutathione levels and inhibition of ferroptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Moreover, transcriptional upregulation of ABCC5 by FOXM1 has been shown to drive paclitaxel resistance in nasopharyngeal carcinoma by enhancing drug efflux"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", and genetic polymorphisms in ABCC5 have been linked to adverse outcomes such as anthracycline‐induced cardiotoxicity in pediatric leukemia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in drug disposition, ABCC5 expression and function can be modulated by alternative splicing events. Mutations in splicing regulators (for example, SF3B1) result in aberrant splicing of several genes including ABCC5 in uveal melanoma and breast cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " In addition, recent studies have identified a novel role for ABCC5 in the export of hyaluronan from fibroblasts, suggesting that its function is not limited to handling drug or signaling molecule substrates but also extends to contributing to extracellular matrix regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings illustrate that ABCC5 is a versatile transporter that helps maintain cellular cyclic nucleotide balance under physiological conditions and, when dysregulated, facilitates drug resistance in various cancers. Its expression and activity are influenced by transcriptional, post‐transcriptional, and genetic mechanisms, thereby presenting a potential target for overcoming chemoresistance and modulating tissue homeostasis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Glen Reid, Peter Wielinga, Noam Zelcer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1033060100"}], "href": "https://doi.org/10.1073/pnas.1033060100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12835412"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12835412"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Peter R Wielinga, Ingrid van der Heijden, Glen Reid, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of the MRP4- and MRP5-mediated transport of cyclic nucleotides from intact cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M212723200"}], "href": "https://doi.org/10.1074/jbc.M212723200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12637526"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12637526"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yassine Sassi, Larissa Lipskaia, Grégoire Vandecasteele, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Multidrug resistance-associated protein 4 regulates cAMP-dependent signaling pathways and controls human and rat SMC proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI35067"}], "href": "https://doi.org/10.1172/JCI35067"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18636120"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18636120"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Peter Dazert, Konrad Meissner, Silke Vogelgesang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression and localization of the multidrug resistance protein 5 (MRP5/ABCC5), a cellular export pump for cyclic nucleotides, in human heart."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/S0002-9440(10)63513-4"}], "href": "https://doi.org/10.1016/S0002-9440(10"}, {"type": "t", "text": "63513-4) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14507663"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14507663"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Henriette E U Meyer Zu Schwabedissen, Markus Grube, Björn Heydrich, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression, localization, and function of MRP5 (ABCC5), a transporter for cyclic nucleotides, in human placenta and cultured human trophoblasts: effects of gestational age and cellular differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/S0002-9440(10)62230-4"}], "href": "https://doi.org/10.1016/S0002-9440(10"}, {"type": "t", "text": "62230-4) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15631998"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15631998"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Lorella Pascolo, Cristina Fernetti, Doroti Pirulli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effects of maturation on RNA transcription and protein expression of four MRP genes in human placenta and in BeWo cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0006-291x(03)00327-9"}], "href": "https://doi.org/10.1016/s0006-291x(03"}, {"type": "t", "text": "00327-9) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12646196"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12646196"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Wolfgang Hagmann, Ralf Jesnowski, Ralf Faissner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ATP-binding cassette C transporters in human pancreatic carcinoma cell lines. Upregulation in 5-fluorouracil-resistant cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pancreatology (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000178884"}], "href": "https://doi.org/10.1159/000178884"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19077464"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19077464"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Wenbin Huang, Kunling Chen, Yishi Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ABCC5 facilitates the acquired resistance of sorafenib through the inhibition of SLC7A11-induced ferroptosis in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neoplasia (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neo.2021.11.002"}], "href": "https://doi.org/10.1016/j.neo.2021.11.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34768109"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34768109"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Youxiang Hou, Qianling Zhu, Zheng Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The FOXM1-ABCC5 axis contributes to paclitaxel resistance in nasopharyngeal carcinoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cddis.2017.53"}], "href": "https://doi.org/10.1038/cddis.2017.53"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28277541"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28277541"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "M Krajinovic, J Elbared, S Drouin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphisms of ABCC5 and NOS3 genes influence doxorubicin cardiotoxicity in survivors of childhood acute lymphoblastic leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pharmacogenomics J (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/tpj.2015.63"}], "href": "https://doi.org/10.1038/tpj.2015.63"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26345518"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26345518"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Simon J Furney, Malin Pedersen, David Gentien, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SF3B1 mutations are associated with alternative splicing in uveal melanoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Discov (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/2159-8290.CD-13-0330"}], "href": "https://doi.org/10.1158/2159-8290.CD-13-0330"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23861464"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23861464"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Sarah L Maguire, Andri Leonidou, Patty Wai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SF3B1 mutations constitute a novel therapeutic target in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Pathol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/path.4483"}], "href": "https://doi.org/10.1002/path.4483"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25424858"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25424858"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Tobias Schulz, Udo Schumacher, Peter Prehm "}, {"type": "b", "children": [{"type": "t", "text": "Hyaluronan export by the ABC transporter MRP5 and its modulation by intracellular cGMP."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M700915200"}], "href": "https://doi.org/10.1074/jbc.M700915200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17540771"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17540771"}]}]}]}
Synonyms	EST277145, PABC11, MOAT-C, MOATC, SMRP, ABC33, MRP5
Proteins	MRP5_HUMAN
NCBI Gene ID	10057
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ABCC5 has 10,947 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 134 datasets.

Click the + buttons to view associations for ABCC5 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ABCC5 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 ABCC5 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 ABCC5 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 ABCC5 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 ABCC5 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 ABCC5 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 ABCC5 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 ABCC5 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 ABCC5 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 ABCC5 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 ABCC5 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 ABCC5 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ABCC5 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 ABCC5 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ABCC5 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ABCC5 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 ABCC5 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ABCC5 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 ABCC5 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of ABCC5 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 ABCC5 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ABCC5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing ABCC5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with ABCC5 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 ABCC5 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 ABCC5 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ABCC5 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ABCC5 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ABCC5 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with ABCC5 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 ABCC5 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 ABCC5 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for ABCC5 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with ABCC5 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 ABCC5 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 ABCC5 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 ABCC5 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ABCC5 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for ABCC5 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at ABCC5 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 ABCC5 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.