RFXANK Gene

HGNC Family	Ankyrin repeat domain containing (ANKRD)
Name	regulatory factor X-associated ankyrin-containing 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 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. This protein contains ankyrin repeats involved in protein-protein interactions. Mutations in this gene have been linked to bare lymphocyte syndrome type II, complementation group B. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2013]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRFXANK is a key component of the heterotrimeric regulatory factor‐X (RFX) complex that is essential for the transcriptional activation of major histocompatibility complex (MHC) class II genes. Acting together with RFX5 and RFXAP, RFXANK nucleates the formation of the MHC class II enhanceosome that is required for the expression of MHC class II antigens—crucial for antigen presentation to CD4⁺ T cells. Genetic studies have shown that autosomal‐recessive mutations in RFXANK, including recurrent 26‐bp deletions observed in North African patients, account for a significant proportion of MHC class II deficiency, a combined immunodeficiency disorder often leading to life‐threatening infections."}, {"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 its role in basic transcriptional activation, the ankyrin repeat domain of RFXANK is critical for the assembly of the RFX complex by mediating specific protein–protein interactions. Structure–function analyses have demonstrated that point mutations within the ankyrin repeats can disrupt binding to the other subunits, such as RFXAP, and compromise complex formation, even if the RFX complex is able to bind DNA in vitro. Moreover, RFXANK interacts with other regulatory proteins including HDAC4—which in turn is capable of modulating MHC class II expression—as well as partners like the paralogue ANKRA2 and molecules involved in non‐apoptotic signaling such as caspase‐2 and RFX7. These interactions underscore a multifaceted role for RFXANK in bridging the core transcriptional machinery with additional signaling and epigenetic regulatory pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn summary, RFXANK is indispensable for the proper formation and function of the MHC class II enhanceosome, acting primarily through its ankyrin repeat domain to coordinate the assembly of transcription factors and interact with regulatory proteins. Disruption of RFXANK function through genetic mutations not only impairs MHC class II expression leading to severe immunodeficiency, but also reveals its broader role in integrating transcriptional, epigenetic, and signaling pathways that are critical for immune regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "5"}, {"type": "fg_fs", "start_ref": "10", "end_ref": "12"}, {"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Wojciech Wiszniewski, Marie-Claude Fondaneche, Pascale Louise-Plence, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel mutations in the RFXANK gene: RFX complex containing in-vitro-generated RFXANK mutant binds the promoter without transactivating MHC II."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunogenetics (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00251-002-0521-1"}], "href": "https://doi.org/10.1007/s00251-002-0521-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12618906"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12618906"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Audrey H Wang, Serge Grégoire, Eleni Zika, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of the ankyrin repeat proteins ANKRA and RFXANK as novel partners of class IIa histone deacetylases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M500295200"}], "href": "https://doi.org/10.1074/jbc.M500295200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15964851"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15964851"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hamid Naamane, Ouafaa El Maataoui, Fatima Ailal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The 752delG26 mutation in the RFXANK gene associated with major histocompatibility complex class II deficiency: evidence for a founder effect in the Moroccan population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Pediatr (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00431-010-1179-6"}], "href": "https://doi.org/10.1007/s00431-010-1179-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20414676"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20414676"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Monia Ouederni, Quentin B Vincent, Pierre Frange, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Major histocompatibility complex class II expression deficiency caused by a RFXANK founder mutation: a survey of 35 patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2011-05-352716"}], "href": "https://doi.org/10.1182/blood-2011-05-352716"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21908431"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21908431"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Katherine Clarridge, David Leitenberg, Brett Loechelt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Major Histocompatibility Complex Class II Deficiency due to a Novel Mutation in RFXANK in a Child of Mexican Descent."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Immunol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10875-015-0219-4"}], "href": "https://doi.org/10.1007/s10875-015-0219-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26634365"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26634365"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Mohadese Sadat Mousavi Khorshidi, Yoann Seeleuthner, Zahra Chavoshzadeh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical, Immunological, and Genetic Findings in Iranian Patients with MHC-II Deficiency: Confirmation of c.162delG RFXANK Founder Mutation in the Iranian Population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Immunol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10875-023-01562-z"}], "href": "https://doi.org/10.1007/s10875-023-01562-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37584719"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37584719"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Michal Krawczyk, Krzysztof Masternak, Madeleine Zufferey, et al. "}, {"type": "b", "children": [{"type": "t", "text": "New functions of the major histocompatibility complex class II-specific transcription factor RFXANK revealed by a high-resolution mutagenesis study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.25.19.8607-8618.2005"}], "href": "https://doi.org/10.1128/MCB.25.19.8607-8618.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16166641"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16166641"}]}, {"type": "r", "ref": 8, "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": 9, "children": [{"type": "t", "text": "Lixia Yu, Qiuxia Lin, Jianhua Feng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of nephrin activation by c-mip through Csk-Cbp-Fyn axis plays a critical role in Angiotensin II-induced podocyte damage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2012.11.017"}], "href": "https://doi.org/10.1016/j.cellsig.2012.11.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23200848"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23200848"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Jeremy Forsberg, Xinge Li, Birce Akpinar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A caspase-2-RFXANK interaction and its implication for MHC class II expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-017-0144-y"}], "href": "https://doi.org/10.1038/s41419-017-0144-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29362422"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29362422"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Julie Oniszczuk, Kelhia Sendeyo, Cerina Chhuon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CMIP is a negative regulator of T cell signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Immunol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41423-019-0266-5"}], "href": "https://doi.org/10.1038/s41423-019-0266-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31395948"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31395948"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Jun Gao, Chao Xu "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis for the recognition of RFX7 by ANKRA2 and RFXANK."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2019.12.059"}], "href": "https://doi.org/10.1016/j.bbrc.2019.12.059"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31864703"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31864703"}]}]}]}
Synonyms	ANKRA1, BLS, F14150_1, RFX-B
Proteins	RFXK_HUMAN
NCBI Gene ID	8625
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

RFXANK has 5,765 functional associations with biological entities spanning 8 categories (molecular profile, organism, disease, phenotype or trait, functional term, phrase or reference, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 122 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

RFXANK 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 RFXANK 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 RFXANK 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 RFXANK 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 RFXANK 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 RFXANK 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 RFXANK 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 RFXANK 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 RFXANK 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 RFXANK 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 RFXANK 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 RFXANK gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with RFXANK protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with RFXANK 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 RFXANK gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of RFXANK 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 RFXANK 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 RFXANK gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with RFXANK gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing RFXANK 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 RFXANK gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing RFXANK protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing RFXANK protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing RFXANK protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing RFXANK protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with RFXANK 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 RFXANK 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 RFXANK gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with RFXANK gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with RFXANK gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with RFXANK gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with RFXANK 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 RFXANK 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 RFXANK gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving RFXANK gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving RFXANK gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with RFXANK 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 RFXANK 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 RFXANK 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 RFXANK gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with RFXANK gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.