ARF4 Gene

HGNC Family	Ras small GTPases superfamily
Name	ADP-ribosylation factor 4
Description	This gene is a member of the human ARF gene family whose members encode small guanine nucleotide-binding proteins that stimulate the ADP-ribosyltransferase activity of cholera toxin and play a role in vesicular trafficking and as activators of phospholipase D. The gene products include 5 ARF proteins and 11 ARF-like proteins and constitute one family of the RAS superfamily. The ARF proteins are categorized as class I, class II and class III; this gene is a class II member. The members of each class share a common gene organization. The ARF4 gene spans approximately 12kb and contains six exons and five introns. This gene is the most divergent member of the human ARFs. Conflicting map positions at 3p14 or 3p21 have been reported for this gene. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ARF4 is a small GTPase belonging to the ADP‐ribosylation factor family that has emerged as a multifunctional regulator of intracellular trafficking. Under stress conditions that compromise Golgi structure—for example, upon treatment with brefeldin A—ARF4 expression is induced, and its depletion helps preserve Golgi integrity and maintain cargo trafficking, an effect that also confers increased resistance to certain pathogens."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, ARF4 interacts with the intracellular domain of the epidermal growth factor receptor (EGFR) to mediate EGF‐dependent activation of phospholipase D2 and subsequent activation of AP‑1–dependent transcription."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " ARF4 also plays a key role in membrane trafficking, as demonstrated by its involvement—together with other class II ARFs—in maintaining recycling endosome integrity and regulating retrograde transport from endosomes to the trans‑Golgi network."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In early secretory compartments, scaffold molecules such as Scyl1 selectively link class II ARFs, notably ARF4, to specific COPI subcomplexes, thereby contributing to trafficking specificity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Moreover, ARF4 is essential for the targeted delivery of sensory receptors; during photoreceptor ciliary transport, ARF4 recruits adaptors like ASAP1 and helps organize a Rab GTPase cascade that ensures proper ciliary import of rhodopsin."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " ARF4 further contributes to the viral life cycle, as depletion of ARF4 (in conjunction with ARF5) disrupts early pre‑Golgi trafficking required for the secretion of dengue virus particles."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Collectively, these studies underline ARF4’s diverse roles in modulating Golgi dynamics, specialized trafficking pathways (including ciliary transport), and cellular responses to infection and oncogenic signals.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jan H Reiling, Andrew J Olive, Sumana Sanyal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A CREB3-ARF4 signalling pathway mediates the response to Golgi stress and susceptibility to pathogens."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb2865"}], "href": "https://doi.org/10.1038/ncb2865"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24185178"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24185178"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Breege V Howley, Laura A Link, Simon Grelet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A CREB3-regulated ER-Golgi trafficking signature promotes metastatic progression in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-017-0023-0"}], "href": "https://doi.org/10.1038/s41388-017-0023-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29249802"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29249802"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sung-Woo Kim, Masaaki Hayashi, Jeng-Fan Lo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ADP-ribosylation factor 4 small GTPase mediates epidermal growth factor receptor-dependent phospholipase D2 activation."}]}, {"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.M205819200"}], "href": "https://doi.org/10.1074/jbc.M205819200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12446727"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12446727"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Waka Nakai, Yumika Kondo, Akina Saitoh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ARF1 and ARF4 regulate recycling endosomal morphology and retrograde transport from endosomes to the Golgi apparatus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E13-04-0197"}], "href": "https://doi.org/10.1091/mbc.E13-04-0197"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23783033"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23783033"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jason N R Hamlin, Lena K Schroeder, Maryam Fotouhi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Scyl1 scaffolds class II Arfs to specific subcomplexes of coatomer through the γ-COP appendage domain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.136481"}], "href": "https://doi.org/10.1242/jcs.136481"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24481816"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24481816"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jing Wang, Dusanka Deretic "}, {"type": "b", "children": [{"type": "t", "text": "The Arf and Rab11 effector FIP3 acts synergistically with ASAP1 to direct Rabin8 in ciliary receptor targeting."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.162925"}], "href": "https://doi.org/10.1242/jcs.162925"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25673879"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25673879"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Mateusz Kudelko, Jean-Baptiste Brault, Kevin Kwok, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Class II ADP-ribosylation factors are required for efficient secretion of dengue viruses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.270579"}], "href": "https://doi.org/10.1074/jbc.M111.270579"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22105072"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22105072"}]}]}]}
Synonyms	ARF2
Proteins	ARF4_HUMAN
NCBI Gene ID	378
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ARF4 has 11,086 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 117 datasets.

Click the + buttons to view associations for ARF4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ARF4 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 ARF4 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 ARF4 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 ARF4 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 ARF4 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 ARF4 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 ARF4 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 ARF4 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 ARF4 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 ARF4 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 ARF4 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ARF4 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 ARF4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ARF4 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ARF4 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 ARF4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ARF4 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 ARF4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ARF4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing ARF4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with ARF4 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 ARF4 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 ARF4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ARF4 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ARF4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of ARF4 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 ARF4 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 ARF4 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 ARF4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ARF4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for ARF4 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at ARF4 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 ARF4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ARF4 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 ARF4 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 ARF4 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with ARF4 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 ARF4 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of ARF4 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 ARF4 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 ARF4 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.