RFXAP Gene

Name	regulatory factor X-associated protein
Description	Major histocompatibility (MHC) class II molecules are transmembrane proteins that have a central role in development and control of the immune system. The protein encoded by this gene, along with regulatory factor X-associated ankyrin-containing protein and regulatory factor-5, forms a complex that binds to the X box motif of certain MHC class II gene promoters and activates their transcription. Once bound to the promoter, this complex associates with the non-DNA-binding factor MHC class II transactivator, which controls the cell type specificity and inducibility of MHC class II gene expression. Mutations in this gene have been linked to bare lymphocyte syndrome type II, complementation group D. Transcript variants utilizing different polyA signals have been found for this gene. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRFXAP is an essential subunit of the heterotrimeric regulatory factor X (RFX) complex, which is required for the transcription of major histocompatibility complex class II (MHCII) genes that play a central role in adaptive immunity. RFXAP, together with RFX5 and RFXB, cooperates to bind conserved promoter elements and facilitate the expression of MHCII molecules. Genetic alterations or diminished RFXAP expression can lead to severe immune deficiencies such as bare lymphocyte syndrome, as evidenced by promoter mutations or aberrant transcript processing that impair MHCII expression in patient cells and lymphoma models"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n<br><br>\nAt the molecular level, RFXAP contributes not only through its role in the formation of the RFX complex but also via specific structural and trafficking signals. Studies have demonstrated that RFXAP contains domains necessary for its assembly with RFX5, helping overcome inhibitory flanking regions and enabling high‐affinity binding with RFXB once in the nucleus. Detailed biophysical and structural analyses, including NMR and calorimetry, revealed that RFXAP adopts a defined conformation when bound to the dimeric RFX5 “staple” structure, ensuring effective RFX complex formation and subsequent MHCII promoter activation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n<br><br>\nBeyond its classical immunological role, RFXAP has emerged as an important mediator in disease contexts such as cancer. In pancreatic cancer, tumor-derived exosomal miRNAs (e.g., miR-212-3p) downregulate RFXAP expression in dendritic cells, resulting in decreased MHCII expression and the induction of immune tolerance. Similarly, in diffuse large B cell lymphoma, mutations that truncate the C-terminal region of RFXAP lead to MHCII loss. In pancreatic adenocarcinoma, low RFXAP expression correlates with advanced tumor stage and poor prognosis, while its upregulation can modulate histone demethylation events (via targets such as KDM4A) that impair DNA repair, thereby enhancing the cytotoxic effects of agents like fisetin."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "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": 2, "children": [{"type": "t", "text": "Alyssa B Long, Angela M Ferguson, Parimal Majumder, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Conserved residues of the bare lymphocyte syndrome transcription factor RFXAP determine coordinate MHC class II expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Immunol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molimm.2005.03.008"}], "href": "https://doi.org/10.1016/j.molimm.2005.03.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16337482"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16337482"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Marja C J A van Eggermond, Ilhan Tezcan, Mirjam H M Heemskerk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptional silencing of RFXAP in MHC class II-deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Immunol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molimm.2008.01.026"}], "href": "https://doi.org/10.1016/j.molimm.2008.01.026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18336911"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18336911"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Colin W Garvie, Jeremy M Boss "}, {"type": "b", "children": [{"type": "t", "text": "Assembly of the RFX complex on the MHCII promoter: role of RFXAP and RFXB in relieving autoinhibition of RFX5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbagrm.2008.07.012"}], "href": "https://doi.org/10.1016/j.bbagrm.2008.07.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18723135"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18723135"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "LaTese Briggs, Kholiswa Laird, Jeremy M Boss, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Formation of the RFX gene regulatory complex induces folding of the interaction domain of RFXAP."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proteins (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/prot.22379"}], "href": "https://doi.org/10.1002/prot.22379"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19274739"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19274739"}]}, {"type": "r", "ref": 6, "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": 7, "children": [{"type": "t", "text": "Meghan Bushway, Kelly A Cycon, Kathleen Mulvaney, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Coordinate loss of MHC class II expression in the diffuse large B cell lymphoma cell line OCI-Ly2 is due to a novel mutation in RFX-AP."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunogenetics (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00251-009-0418-3"}], "href": "https://doi.org/10.1007/s00251-009-0418-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20024540"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20024540"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Guoping Ding, Liangjing Zhou, Yingming Qian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pancreatic cancer-derived exosomes transfer miRNAs to dendritic cells and inhibit RFXAP expression via miR-212-3p."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.4924"}], "href": "https://doi.org/10.18632/oncotarget.4924"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26337469"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26337469"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Guoping Ding, Xiaodong Xu, Dan Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fisetin inhibits proliferation of pancreatic adenocarcinoma by inducing DNA damage via RFXAP/KDM4A-dependent histone H3K36 demethylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-020-03019-2"}], "href": "https://doi.org/10.1038/s41419-020-03019-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33093461"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33093461"}]}]}]}
Proteins	RFXAP_HUMAN
NCBI Gene ID	5994
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

RFXAP has 4,888 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 112 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

RFXAP 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 RFXAP 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 RFXAP 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 RFXAP 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 RFXAP 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 RFXAP 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 RFXAP 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 RFXAP 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 RFXAP 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 RFXAP gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of RFXAP 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 RFXAP gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with RFXAP protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of RFXAP gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of RFXAP 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 RFXAP 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 RFXAP gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with RFXAP gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of RFXAP gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing RFXAP 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 RFXAP gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing RFXAP protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing RFXAP protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with RFXAP 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 RFXAP 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 RFXAP gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with RFXAP gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with RFXAP gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of RFXAP 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 RFXAP gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for RFXAP protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving RFXAP gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with RFXAP 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 RFXAP 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 RFXAP 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 RFXAP gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with RFXAP 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 RFXAP 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 RFXAP gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of RFXAP 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 RFXAP from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.