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. ... See more...

Aliases for RFXANK Gene

Aliases for RFXANK Gene

  • Regulatory Factor X Associated Ankyrin Containing Protein 2 3 5
  • Regulatory Factor X Subunit B 2 3 4
  • DNA-Binding Protein RFXANK 2 3 4
  • ANKRA1 2 3 4
  • RFX-B 2 3 4
  • Ankyrin Repeat-Containing Regulatory Factor X-Associated Protein 2 3
  • Regulatory Factor X-Associated Ankyrin-Containing Protein 2 4
  • Ankyrin Repeat Family A Protein 1 3 4
  • RFX-Bdelta4 2 3
  • F14150_1 2 3
  • BLS 2 3
  • MGC138628 2
  • RFXANK 5
  • RFXB 4

External Ids for RFXANK Gene

Previous GeneCards Identifiers for RFXANK Gene

  • GC19P019797
  • GC19P019694
  • GC19P019148
  • GC19P019164
  • GC19P019303
  • GC19P018866

Summaries for RFXANK Gene

Entrez Gene Summary for RFXANK Gene

  • 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]

GeneCards Summary for RFXANK Gene

RFXANK (Regulatory Factor X Associated Ankyrin Containing Protein) is a Protein Coding gene. Diseases associated with RFXANK include Bare Lymphocyte Syndrome, Type Ii and Combined Immunodeficiency. Among its related pathways are Primary immunodeficiency and Allograft rejection. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and transcription coregulator activity. An important paralog of this gene is ANKRA2.

UniProtKB/Swiss-Prot Summary for RFXANK Gene

  • Activates transcription from class II MHC promoters. Activation requires the activity of the MHC class II transactivator/CIITA. May regulate other genes in the cell. RFX binds the X1 box of MHC-II promoters (PubMed:9806546, PubMed:10072068, PubMed:10725724). May also potentiate the activation of RAF1 (By similarity).
  • Isoform 2 is not involved in the positive regulation of MHC class II genes.

Gene Wiki entry for RFXANK Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for RFXANK Gene

Genomics for RFXANK Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for RFXANK Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around RFXANK on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for RFXANK

Top Transcription factor binding sites by QIAGEN in the RFXANK gene promoter:
  • AREB6
  • c-Ets-1
  • CREB
  • MIF-1
  • Roaz
  • SREBP-1a
  • SREBP-1b
  • SREBP-1c
  • SRF
  • SRF (504 AA)

Genomic Locations for RFXANK Gene

Latest Assembly
chr19:19,192,229-19,201,869
(GRCh38/hg38)
Size:
9,641 bases
Orientation:
Plus strand

Previous Assembly
chr19:19,303,067-19,312,675
(GRCh37/hg19 by Entrez Gene)
Size:
9,609 bases
Orientation:
Plus strand

chr19:19,303,008-19,312,678
(GRCh37/hg19 by Ensembl)
Size:
9,671 bases
Orientation:
Plus strand

Genomic View for RFXANK Gene

Genes around RFXANK on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RFXANK Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RFXANK Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RFXANK Gene

Proteins for RFXANK Gene

  • Protein details for RFXANK Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O14593-RFXK_HUMAN
    Recommended name:
    DNA-binding protein RFXANK
    Protein Accession:
    O14593
    Secondary Accessions:
    • O95839
    • Q24JQ1
    • Q6FGA8

    Protein attributes for RFXANK Gene

    Size:
    260 amino acids
    Molecular mass:
    28102 Da
    Quaternary structure:
    • Forms homodimers (By similarity). The RFX heterotetrameric complex consists of 2 molecules of RFX5 and one each of RFXAP and RFX-B/RFXANK; with each subunit representing a separate complementation group. Interacts (via ankyrin repeats) with RFX5 (via PxLPxI/L motif); the interaction is direct. RFX forms cooperative DNA binding complexes with X2BP and CBF/NF-Y. RFX associates with CIITA to form an active transcriptional complex (PubMed:20732328, PubMed:22649097). Interacts with RAF1 (By similarity). Interacts (via ankyrin repeats) with RFX7 (via PxLPxI/L motif) (PubMed:25752541).

    Three dimensional structures from OCA and Proteopedia for RFXANK Gene

    Alternative splice isoforms for RFXANK Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for RFXANK Gene

Post-translational modifications for RFXANK Gene

No data available for DME Specific Peptides for RFXANK Gene

Domains & Families for RFXANK Gene

Gene Families for RFXANK Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for RFXANK Gene

InterPro:
Blocks:
  • Ankyrin repeat signature
ProtoNet:

Suggested Antigen Peptide Sequences for RFXANK Gene

GenScript: Design optimal peptide antigens:
  • RFXANK protein (Q6IB23_HUMAN)
  • Regulatory factor X-associated ankyrin-containing protein (RFXK_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O14593

UniProtKB/Swiss-Prot:

RFXK_HUMAN :
  • Interacts with RAF1 via its C-terminal ankyrin repeat domain. The same domain also mediates its homodimerization (By similarity). The third ankyrin repeat is required for association with the two other RFX subunits; RFX5 and RFXAP. The three central ANK repeats mediate binding to the PxLPxI/L motif of RFX5 (PubMed:20732328, PubMed:22649097).
Domain:
  • Interacts with RAF1 via its C-terminal ankyrin repeat domain. The same domain also mediates its homodimerization (By similarity). The third ankyrin repeat is required for association with the two other RFX subunits; RFX5 and RFXAP. The three central ANK repeats mediate binding to the PxLPxI/L motif of RFX5 (PubMed:20732328, PubMed:22649097).
genes like me logo Genes that share domains with RFXANK: view

Function for RFXANK Gene

Molecular function for RFXANK Gene

UniProtKB/Swiss-Prot Function:
Activates transcription from class II MHC promoters. Activation requires the activity of the MHC class II transactivator/CIITA. May regulate other genes in the cell. RFX binds the X1 box of MHC-II promoters (PubMed:9806546, PubMed:10072068, PubMed:10725724). May also potentiate the activation of RAF1 (By similarity).
UniProtKB/Swiss-Prot Function:
Isoform 2 is not involved in the positive regulation of MHC class II genes.
GENATLAS Biochemistry:
transactivating DNA binding regulator,28kDa,component of the RFX complex,involved in MHC class II expression

Phenotypes From GWAS Catalog for RFXANK Gene

Gene Ontology (GO) - Molecular Function for RFXANK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000977 contributes_to RNA polymerase II regulatory region sequence-specific DNA binding IDA 9806546
GO:0001228 contributes_to DNA-binding transcription activator activity, RNA polymerase II-specific IDA 9806546
GO:0003677 DNA binding IEA --
GO:0005515 protein binding IEA --
GO:0042826 histone deacetylase binding IEA --
genes like me logo Genes that share ontologies with RFXANK: view
genes like me logo Genes that share phenotypes with RFXANK: view

Human Phenotype Ontology for RFXANK Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for RFXANK Gene

MGI Knock Outs for RFXANK:
  • Rfxank Rfxank<tm1b(EUCOMM)Hmgu>

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for RFXANK

Clone products for research

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for RFXANK Gene

Localization for RFXANK Gene

Subcellular locations from UniProtKB/Swiss-Prot for RFXANK Gene

Cytoplasm. Nucleus.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for RFXANK gene
Compartment Confidence
nucleus 5
cytosol 5
extracellular 4
plasma membrane 1
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for RFXANK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IBA 21873635
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol IDA --
GO:0045171 intercellular bridge IDA --
genes like me logo Genes that share ontologies with RFXANK: view

Pathways & Interactions for RFXANK Gene

genes like me logo Genes that share pathways with RFXANK: view

Pathways by source for RFXANK Gene

Gene Ontology (GO) - Biological Process for RFXANK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006357 regulation of transcription by RNA polymerase II IBA 21873635
GO:0007265 Ras protein signal transduction IEA --
GO:0010468 regulation of gene expression IBA 21873635
GO:0045944 positive regulation of transcription by RNA polymerase II IDA 9806546
genes like me logo Genes that share ontologies with RFXANK: view

No data available for SIGNOR curated interactions for RFXANK Gene

Drugs & Compounds for RFXANK Gene

No Compound Related Data Available

Transcripts for RFXANK Gene

mRNA/cDNA for RFXANK Gene

10 REFSEQ mRNAs :
15 NCBI additional mRNA sequence :
15 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for RFXANK

Clone products for research

Alternative Splicing Database (ASD) splice patterns (SP) for RFXANK Gene

ExUns: 1a · 1b · 1c · 1d ^ 2a · 2b · 2c · 2d ^ 3a · 3b ^ 4 ^ 5 ^ 6 ^ 7a · 7b ^ 8a · 8b ^ 9a · 9b ^ 10 ^ 11
SP1: - - - - -
SP2: - -
SP3: -
SP4: -
SP5: -
SP6: - -
SP7: - - - - - -
SP8:
SP9: - - -
SP10:
SP11:

Relevant External Links for RFXANK Gene

GeneLoc Exon Structure for
RFXANK

Expression for RFXANK Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for RFXANK Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for RFXANK Gene

This gene is overexpressed in Lymph node (57.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for RFXANK Gene



Protein tissue co-expression partners for RFXANK Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for RFXANK

SOURCE GeneReport for Unigene cluster for RFXANK Gene:

Hs.296776

mRNA Expression by UniProt/SwissProt for RFXANK Gene:

O14593-RFXK_HUMAN
Tissue specificity: Ubiquitous.

Evidence on tissue expression from TISSUES for RFXANK Gene

  • Blood(4.4)
  • Skin(2.5)
  • Lung(2.3)
  • Nervous system(2.2)
  • Lymph node(2.2)
  • Spleen(2.1)
  • Bone marrow(2)
  • Kidney(2)
  • Intestine(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for RFXANK Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • digestive
  • immune
  • integumentary
  • nervous
  • respiratory
  • urinary
Regions:
Head and neck:
  • brain
  • head
  • larynx
  • meninges
  • neck
  • pharynx
Thorax:
  • bronchus
  • lung
  • trachea
Abdomen:
  • biliary tract
  • gallbladder
  • intestine
  • kidney
  • large intestine
  • liver
  • pancreas
  • small intestine
Pelvis:
  • ureter
  • urethra
  • urinary bladder
Limb:
  • digit
  • finger
  • foot
  • hand
  • lower limb
  • nail
  • toe
  • upper limb
General:
  • blood
  • skin
  • white blood cell
genes like me logo Genes that share expression patterns with RFXANK: view

Primer products for research

No data available for mRNA differential expression in normal tissues for RFXANK Gene

Orthologs for RFXANK Gene

This gene was present in the common ancestor of animals.

Orthologs for RFXANK Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia RFXANK 30 31
  • 99.49 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia RFXANK 30 31
  • 86.41 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia RFXANK 30 31
  • 85.38 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Rfxank 30
  • 83.85 (n)
Mouse
(Mus musculus)
Mammalia Rfxank 30 17 31
  • 83.01 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia RFXANK 31
  • 82 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia RFXANK 31
  • 51 (a)
OneToOne
Chicken
(Gallus gallus)
Aves RFXANK 30 31
  • 79.03 (n)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia rfxank 30
  • 67.28 (n)
Str.7350 30
Zebrafish
(Danio rerio)
Actinopterygii rfxank 30 31
  • 65.21 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta CG5846 30 31
  • 49.07 (n)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP009822 30
  • 48.23 (n)
Species where no ortholog for RFXANK was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for RFXANK Gene

ENSEMBL:
Gene Tree for RFXANK (if available)
TreeFam:
Gene Tree for RFXANK (if available)
Aminode:
Evolutionary constrained regions (ECRs) for RFXANK: view image

Paralogs for RFXANK Gene

Paralogs for RFXANK Gene

(5) SIMAP similar genes for RFXANK Gene using alignment to 9 proteins:

  • RFXK_HUMAN
  • F5GY33_HUMAN
  • F5H7D2_HUMAN
  • H0YFU5_HUMAN
  • H0YFZ0_HUMAN
  • H0YGQ6_HUMAN
  • K7ENE6_HUMAN
  • Q24JQ1_HUMAN
  • Q6IB23_HUMAN
genes like me logo Genes that share paralogs with RFXANK: view

Variants for RFXANK Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for RFXANK Gene

SNP ID Clinical significance and condition Chr 19 pos Variation AA Info Type
835732 Uncertain Significance: Bare lymphocyte syndrome 2 19,196,966(+) G/T
NM_003721.4(RFXANK):c.191G>T (p.Gly64Val)
MISSENSE
844630 Uncertain Significance: Bare lymphocyte syndrome 2 19,197,032(+) C/T
NM_003721.4(RFXANK):c.257C>T (p.Pro86Leu)
MISSENSE
844671 Conflicting Interpretations: Bare lymphocyte syndrome 2 19,197,626(+) G/A
NM_003721.4(RFXANK):c.438+5G>A
INTRON
845010 Uncertain Significance: Bare lymphocyte syndrome 2 19,198,146(+) G/A
NM_003721.4(RFXANK):c.478G>A (p.Ala160Thr)
MISSENSE
845021 Uncertain Significance: Bare lymphocyte syndrome 2 19,197,206(+) G/A
NM_003721.4(RFXANK):c.292G>A (p.Ala98Thr)
MISSENSE_VARIANT,INTRON

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for RFXANK Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for RFXANK Gene

Variant ID Type Subtype PubMed ID
nsv1151217 CNV deletion 26484159
nsv833779 CNV loss 17160897

Variation tolerance for RFXANK Gene

Residual Variation Intolerance Score: 31.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.32; 63.03% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for RFXANK Gene

Human Gene Mutation Database (HGMD)
RFXANK
SNPedia medical, phenotypic, and genealogical associations of SNPs for
RFXANK

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for RFXANK Gene

Disorders for RFXANK Gene

MalaCards: The human disease database

(15) MalaCards diseases for RFXANK Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

Disorder Aliases PubMed IDs
bare lymphocyte syndrome, type ii
  • bls, type ii
combined immunodeficiency
  • combined t cell and b cell immunodeficiency
bjornstad syndrome
  • bjs
severe combined immunodeficiency
  • combined t and b cell inborn immunodeficiency
tarsal tunnel syndrome
  • neuropathy of the posterior tibial nerve and its branches
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

RFXK_HUMAN
  • Bare lymphocyte syndrome 2 (BLS2) [MIM:209920]: A severe combined immunodeficiency disease with early onset. It is characterized by a profound defect in constitutive and interferon-gamma induced MHC II expression, absence of cellular and humoral T-cell response to antigen challenge, hypogammaglobulinemia and impaired antibody production. The consequence include extreme susceptibility to viral, bacterial and fungal infections. {ECO:0000269 PubMed:10072068, ECO:0000269 PubMed:10725724, ECO:0000269 PubMed:22649097, ECO:0000269 PubMed:9806546}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for RFXANK

Genetic Association Database
(GAD)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with RFXANK: view

No data available for Genatlas for RFXANK Gene

Publications for RFXANK Gene

  1. A gene encoding a novel RFX-associated transactivator is mutated in the majority of MHC class II deficiency patients. (PMID: 9806546) Masternak K … Reith W (Nature genetics 1998) 2 3 4 23 74
  2. Novel mutations within the RFX-B gene and partial rescue of MHC and related genes through exogenous class II transactivator in RFX-B-deficient cells. (PMID: 10725724) Nagarajan UM … van den elsen PJ (Journal of immunology (Baltimore, Md. : 1950) 2000) 3 4 23
  3. Founder effect for a 26-bp deletion in the RFXANK gene in North African major histocompatibility complex class II-deficient patients belonging to complementation group B. (PMID: 10803838) Wiszniewski W … Lisowska-Grospierre B (Immunogenetics 2000) 3 23 74
  4. RFX-B is the gene responsible for the most common cause of the bare lymphocyte syndrome, an MHC class II immunodeficiency. (PMID: 10072068) Nagarajan UM … Boss JM (Immunity 1999) 2 3 4
  5. Ankyrin repeats of ANKRA2 recognize a PxLPxL motif on the 3M syndrome protein CCDC8. (PMID: 25752541) Nie J … Yang XJ (Structure (London, England : 1993) 2015) 3 4

Products for RFXANK Gene

Sources for RFXANK Gene