RFX5 Gene

Name	regulatory factor X, 5 (influences HLA class II expression)
Description	A lack of MHC-II expression results in a severe immunodeficiency syndrome called MHC-II deficiency, or the bare lymphocyte syndrome (BLS; MIM 209920). At least 4 complementation groups have been identified in B-cell lines established from patients with BLS. The molecular defects in complementation groups B, C, and D all lead to a deficiency in RFX, a nuclear protein complex that binds to the X box of MHC-II promoters. The lack of RFX binding activity in complementation group C results from mutations in the RFX5 gene encoding the 75-kD subunit of RFX (Steimle et al., 1995). RFX5 is the fifth member of the growing family of DNA-binding proteins sharing a novel and highly characteristic DNA-binding domain called the RFX motif. Multiple alternatively spliced transcript variants have been found but the full-length natures of only two have been determined. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRFX5 is a critical transcription factor that plays a central role in the regulation of major histocompatibility complex class II (MHCII) genes. As an essential member of the heterotrimeric RFX complex—which also includes RFXAP and RFXB—RFX5 binds conserved X‐box sequences in MHCII promoters to initiate adaptive immune responses. Structural and functional analyses have revealed that RFX5 dimerizes and, together with defined nuclear localization signals, facilitates nuclear import of the complex. Mutations in RFX5 that impair its DNA binding lead to severe immunodeficiency syndromes, underscoring its indispensable role. In addition, specific post‐translational elements such as an AT-hook motif contribute to isotype‐specific fine-tuning of MHCII expression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond immune gene regulation, RFX5 also modulates extracellular matrix homeostasis by repressing collagen gene expression. In fibroblasts and vascular smooth muscle cells, RFX5 binds to the transcription start site of the collagen α2(I) (COL1A2) gene, thereby participating in interferon-γ–mediated repression of collagen synthesis. RFX5 forms part of a dynamic regulatory network in which it associates with class II transactivator (CIITA) as well as various deacetylases—including histone deacetylase 2 (HDAC2) and SIRT1—to balance MHCII activation and collagen suppression. This multifaceted control highlights the context-dependent functions of RFX5 in tissue remodeling and immune modulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_fs", "start_ref": "7", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging evidence further expands the functional repertoire of RFX5 into the realm of oncogenesis and higher-order chromatin organization. In hepatocellular carcinoma, aberrantly upregulated RFX5 directly binds to promoters—such as those of TPP1 and KDM4A—to drive gene expression that promotes cell cycle progression and tumor development. In addition, deletion studies indicate that RFX5 influences chromatin topology; its absence augments binding of architectural proteins and strengthens long-range chromatin interactions at clusters of genes (for example, the protocadherin α cluster), thereby modulating their expression. These findings demonstrate that RFX5 functions extend well beyond immune regulation to include critical roles in cancer progression and genome organization."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Pritam K Sengupta, John Fargo, Barbara D Smith "}, {"type": "b", "children": [{"type": "t", "text": "The RFX family interacts at the collagen (COL1A2) start site and represses transcription."}]}, {"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.M111712200"}], "href": "https://doi.org/10.1074/jbc.M111712200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11986307"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11986307"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Nada Nekrep, Nabila Jabrane-Ferrat, Hermann M Wolf, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutation in a winged-helix DNA-binding motif causes atypical bare lymphocyte syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni840"}], "href": "https://doi.org/10.1038/ni840"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12368908"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12368908"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yong Xu, Lin Wang, Giovanna Buttice, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interferon gamma repression of collagen (COL1A2) transcription is mediated by the RFX5 complex."}]}, {"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.M309003200"}], "href": "https://doi.org/10.1074/jbc.M309003200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12968017"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12968017"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Uma M Nagarajan, Alyssa B Long, Michelle T Harreman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A hierarchy of nuclear localization signals governs the import of the regulatory factor X complex subunits and MHC class II expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.173.1.410"}], "href": "https://doi.org/10.4049/jimmunol.173.1.410"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15210800"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15210800"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Kholiswa M Laird, LaTese L Briggs, Jeremy M Boss, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Solution structure of the heterotrimeric complex between the interaction domains of RFX5 and RFXAP from the RFX gene regulatory complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmb.2010.08.025"}], "href": "https://doi.org/10.1016/j.jmb.2010.08.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20732328"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20732328"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Phoebe Stavride, Panagiota Arampatzi, Joseph Papamatheakis "}, {"type": "b", "children": [{"type": "t", "text": "Differential regulation of MHCII genes by PRMT6, via an AT-hook motif of RFX5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Immunol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molimm.2013.05.235"}], "href": "https://doi.org/10.1016/j.molimm.2013.05.235"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23911394"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23911394"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yong Xu, Pritam K Sengupta, Edward Seto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulatory factor for X-box family proteins differentially interact with histone deacetylases to repress collagen alpha2(I) gene (COL1A2) expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M511724200"}], "href": "https://doi.org/10.1074/jbc.M511724200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16464847"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16464847"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yong Xu, Stephen R Farmer, Barbara D Smith "}, {"type": "b", "children": [{"type": "t", "text": "Peroxisome proliferator-activated receptor gamma interacts with CIITA x RFX5 complex to repress type I collagen gene expression."}]}, {"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.M703652200"}], "href": "https://doi.org/10.1074/jbc.M703652200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17611194"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17611194"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Xiaocen Kong, Mingming Fang, Ping Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HDAC2 deacetylates class II transactivator and suppresses its activity in macrophages and smooth muscle cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Cell Cardiol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yjmcc.2008.10.023"}], "href": "https://doi.org/10.1016/j.yjmcc.2008.10.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19041327"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19041327"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Jun Xia, Xiaoyan Wu, Yuyu Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SIRT1 deacetylates RFX5 and antagonizes repression of collagen type I (COL1A2) transcription in smooth muscle cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2012.10.043"}], "href": "https://doi.org/10.1016/j.bbrc.2012.10.043"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23079621"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23079621"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Yangjing Zhao, Xingwang Xie, Weijia Liao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The transcription factor RFX5 is a transcriptional activator of the TPP1 gene in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2016.5240"}], "href": "https://doi.org/10.3892/or.2016.5240"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27840983"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27840983"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Dong-Bo Chen, Xing-Wang Xie, Yang-Jing Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RFX5 promotes the progression of hepatocellular carcinoma through transcriptional activation of KDM4A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-020-71403-1"}], "href": "https://doi.org/10.1038/s41598-020-71403-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32883983"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32883983"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Na Wang, Zhi Lian Jia, Qiang Wu "}, {"type": "b", "children": [{"type": "t", "text": "RFX5 regulates gene expression of the Pcdhα cluster."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Yi Chuan (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.16288/j.yczz.20-184"}], "href": "https://doi.org/10.16288/j.yczz.20-184"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32952112"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32952112"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Lili Guo, Dingsheng Liu "}, {"type": "b", "children": [{"type": "t", "text": "Identification of RFX5 as prognostic biomarker and associated with immune infiltration in stomach adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Med Res (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s40001-022-00794-w"}], "href": "https://doi.org/10.1186/s40001-022-00794-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36045400"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36045400"}]}]}]}
Proteins	RFX5_HUMAN
NCBI Gene ID	5993
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

RFX5 has 7,520 functional associations with biological entities spanning 8 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) extracted from 121 datasets.

Click the + buttons to view associations for RFX5 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

RFX5 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 RFX5 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 RFX5 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 RFX5 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 RFX5 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 RFX5 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 RFX5 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 RFX5 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 RFX5 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 RFX5 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of RFX5 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 RFX5 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with RFX5 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with RFX5 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 RFX5 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of RFX5 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 RFX5 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 RFX5 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with RFX5 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of RFX5 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing RFX5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing RFX5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with RFX5 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 RFX5 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 RFX5 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with RFX5 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with RFX5 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with RFX5 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of RFX5 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 RFX5 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving RFX5 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving RFX5 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with RFX5 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 RFX5 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 RFX5 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with RFX5 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 RFX5 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 RFX5 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of RFX5 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 RFX5 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with RFX5 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.