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FLASH GENE
Symbol RBFOX1 contributors: mct - updated : 20-12-2017
HGNC name RNA binding protein, fox-1 homolog (C. elegans) 1
HGNC id 18222
Location 16p13.3      Physical location : 6.069.131 - 7.763.340
Synonym name
  • ataxin 2-binding protein 1
  • hexaribonucleotide binding protein
  • Synonym symbol(s) SCA2BP1, FOX1, HRNBP1, A2BP1
    DNA
    TYPE functioning gene
    STRUCTURE 1694.21 kb     16 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    text
  • alternatively spliced in response to chronic depolarization of cells, resulting in the increased expression of the nuclear, splicing-active RBFOX1 isoform
  • while RBFOX1 functions as a splicing regulator in the nucleus, it is also alternatively spliced to produce cytoplasmic isoforms (PMID: 26687839)
  • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    13 - 4102 45 418 - 2009 19762510
    also called gamma
    13 splicing 4024 42.2 392 - 2009 19762510
  • also called alpha
  • lacking an in-frame segment in the 3' coding region
  • 14 splicing 4155 42.5 395 - 2009 19762510
  • also called beta
  • alternate exon in the 3' coding region
  • 16 splicing 4775 42.75 397 - 2009 19762510
    lacking an in-frame segment in the 3' region
    14 - 4007 - 397 - 2009 19762510
    15 - 4694 - 370 - 2009 19762510
    - - 1684 - 425 - 2009 19762510
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheartatrium    Homo sapiens
    Nervousbrainlimbic systemhippocampusdentate gyruspredominantly Homo sapiens
     nerve     Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal specific Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • RNA binding motifs
  • an RNP motif highly conserved among RNA-binding proteins
  • a hydrophobic PY nuclear localization consensus sequence recognized by Karyopherin beta 2 (
  • HOMOLOGY
    intraspecies homolog to RBFOX2, RBFOX3
    Homologene
    FAMILY
  • Fox (Feminizing gene on X) protein family
  • CATEGORY RNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,nucleus
    text
  • trans-Golgi network
  • transcripts missing exon 19 encode a nuclear isoform that progressively replaces the cytoplasmic A2BP1 isoform as cells are maintained depolarizing media
  • nuclear RBFOX1 rescued splicing changes, whereas cytoplasmic RBFOX1 rescued changes in mRNA levels
  • basic FUNCTION
  • potentially involved in RNA distribution and splicing
  • playing a role in mediating the neuronal pathway of calcitonin/calcitonin gene-related peptide alternative RNA processing
  • regulates alternative splicing of tissue-specific exons by binding to GCAUG elements
  • RBFOX1, RBFOX2 potent regulators of alternative splicing in the heart, skeletal muscle, and brain, repress calcitonin-specific splicing of the calcitonin/CGRP pre-mRNA
  • implicated in a variety of neurological diseases, and can counteract the effects of chronic depolarization on splicing
  • controls a secondary splicing response to cellular depolarization
  • directs a genetic program required in the prevention of neuronal hyperexcitation and seizures
  • unique role for RBFOX1 in regulating neuronal gene expression
  • RBFOX1 and RBFOX2 are not fully redundant in their neuronal functions
  • plays a unique role in the cellular response to overexcitation
  • is subsequently required with RBFOX2 to maintain mature neuronal physiology, specifically Purkinje cell pacemaking, through their shared control of sodium channel transcript splicing
  • is a neuron-specific splicing factor predicted to regulate neuronal splicing networks clinically implicated in neurodevelopmental disease, including autism spectrum disorder (ASD)
  • RBFOX1 function is likely also important for the correct regulation of a network of clinically relevant neuronal transcriptional programs in human neurodevelopment
  • neuronal splicing factor RBFOX1 regulates the alternative splicing of an extensive network of genes involved in neuronal differentiation and maintenance
  • is a key regulator of transcriptional and splicing programs in neural cells during development, and it is expressed in a neuronal module enriched for known autism susceptibility genes
  • RBFOX1 cooperates with MBNL1 to control splicing in muscle, including events altered in myotonic dystrophy type 1
  • regulates a network of alternative splicing (AS) events required to maintain multiple aspects of muscle physiology
  • new role for RBFOX1, RBFOX2 proteins in regulating myogenesis through activation of essential muscle-specific splicing events
  • RBFOX1 is a potent regulator of RNA splicing and is required for a conserved splicing process of transcription factor MEF2 family members that yields different MEF2 isoforms with differential effects on cardiac hypertrophic gene expression
  • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA binding
    small molecule
    protein
  • binds to the C-terminus of ataxin-2 and may contribute to the restricted pathology of spinocerebellar ataxia type 2 (SCA2)
  • RBFOX2, RBFOX1 specifically bind the RNA element UGCAUG, and regulate alternative splicing positively or negatively in a position-dependent manner
  • HNRNPH1, RALY, and TFG are proteins that specifically interact with the C-terminal domain of RBFOX1 and RBFOX2
  • HNRNPH1 and TFG modulate the splicing activity of RBFOX1/2, whereas RALY had no effect
  • WNK3, implicated in the control of neuronal excitability through actions on ion transport, binds RBFOX1 and inhibits its splicing activity in a kinase activity-dependent manner
  • RBFOX1 differentially binds neuronal relative to nonneuronal forms of WNK3
  • direct and specific RBFOX1 and RBFOX2 binding to MEF2D pre-mRNA
  • RBFOX1-mediated RNA splicing regulates cardiac hypertrophy and heart failure
  • RBFOX1 targets PUM1 mRNA for destabilization and translational silencing, thereby promoting germ cell development
  • nuclear RBFOX1 is a candidate master regulator that binds intronic UGCAUG elements to impact splicing efficiency of target alternative exons, many in transcripts for other splicing regulators
  • RBFOX1, RBFOX2, RBFOX3 regulates alternative pre-mRNA splicing in various tissues via direct binding to their RNA binding element
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    loss of RBFOX1 causes an increase in excitability of the neuronal population of the dentate gyrus, and seizures
    constitutional   deletion    
    in genetic generalised epilepsy (GGE)
    constitutional       loss of function
    haploinsufficiency causes severe neurodevelopmental phenotypes including autism spectrum disorder (ASD), intellectual disability, and epilepsy
    Susceptibility
  • to autism spectrum disorder
  • to rolandic epilepsy (RE)
  • to lower blood pressure
  • Variant & Polymorphism other
  • de novo copy number variant in autism spectrum disorder
  • a frameshift mutation (p.A233Vfs*74) and a hexanucleotide deletion (p.A299_A300del), associated to rolandic epilepsy
  • multiple rare, coding variants in RBFOX1 associated with reduced systolic blood pressure (SBP)
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    Rbfox1 downregulation and altered Capn3 splicing by Frg1 in a mouse model of Facioscapulohumeral muscular dystrophy (FSHD)