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FLASH GENE
Symbol IFNA1 contributors: mct/npt - updated : 03-04-2020
HGNC name interferon, alpha 1
HGNC id 5417
Location 9p21.3      Physical location : 21.440.439 - 21.441.315
Synonym name
  • interferon alpha-D
  • IFN-alpha 1b
    • Synonym symbol(s) IFNA@, IFL, IFN, IFNA13, IFN-ALPHA, MGC138207, MGC138505, MGC138507
    DNA
    TYPE functioning gene
    SPECIAL FEATURE component of a cluster
    STRUCTURE 0.87 kb     1 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    1 - 878 21 189 - 2019 3154279
  • IFNA1a
  • IFNalpha-1a and IFNalpha-1b, differ from each other in only 1 amino acid, at residue 114
  • IFNalpha-1a-mediated cell apoptosis is directly linked to intrinsic and endoplasmic reticulum (ER) stress-related apoptosis, but is independent of extrinsic apoptosis
    • - - - - - - 2019 3154279
  • IFNalpha-1a and IFNalpha-1b, differ from each other in only 1 amino acid, at residue 114
    		•
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoietic    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a 23 amino acids signal peptide (2,6 kDa)
    • isoforms Precursor an 166 amino acids mature peptide (19.1 kDa)
    HOMOLOGY
    interspecies homolog to C.elegans c47e12.9
    Homologene
    FAMILY
  • interferon alpha, beta and delta family
    • CATEGORY immunity/defense
    SUBCELLULAR LOCALIZATION extracellular
    basic FUNCTION
  • playing a critical role in antiviral and antitumor protection and immune regulation
  • involved in the pathogenesis of certain neurological disorders
  • key factor in autoimmune disease
  • may control uveitis by promoting induction of IL10-producing T-cells
  • amplifies human naive B cell TLR-9-mediated activation and Ig production
  • regulates the dynamic balance between human activated regulatory and effector T cells
  • plasmacytoid dendritic cells (pDCs) play an important role in IFNA1 production during varicella-zoster virus (VZV) infection through TLR9-dependent and -independent pathways
  • IFNA1 is a critical mediator of human systemic lupus erythematosus (SLE)
  • multifunctional cytokine important in the innate immune system, that may playing a major pathogenic role in the development of systemic lupus erythematosus
  • autocrine IFNG promotes naive CD8 T cell differentiation and synergizes with IFNA1 to stimulate strong function
  • is a key cytokine regulating the activity of numerous immune cells
  • has immunoregulatory functions in autoimmune inflammatory disease
  • production of IFNA1 plays likely a role in amplification of antiviral responses to control the spread of RNA viral infection in human hepatocytes
  • elevated plasmacytoid dendritic cells (pDCs) and increased IFNA1 production by these cells may play an important role in the Th1-mediated disease, T1Diabetes )
  • despite their use of the same receptor, IFNB1 and IFNA1 have unique and distinguishable biologic functions, with IFNB1 being mainly responsible for promoting viral persistence
  • is a key mediator of antiviral immune responses used to treat Hepatitis C infection
  • is a cytokine essential to a vast array of immunologic processes
  • IFNA1 impairs insulin production through the induction of endoplasmic reticulum stress as well as by impairing mitochondrial function
  • is a prompt and efficient orchestrator of host defense against nucleic acids but upon chronicity becomes a potent mediator of autoimmunity
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • STAT1(essential signaling molecule in many IFNA -regulated processes)
  • represents a fourth class of extracellular ligands for CR2 and interacts with the same domain as the other three ligands
  • IFNA1-induced the expression of IFIT3 and STAT1 in THP-1 cells, and this process was significantly antagonized by the specific inhibitors of both PRKCD and MAPK8
  • ADRB2 stimulation suppresses TLR9-dependent IFNA1 secretion in human peripheral blood mononuclear cells
  • ISG15 is a ubiquitin-like protein transcriptionally regulated by IFNA1 which shows antivirus and antitumor activities
  • ISG15 inhibits IFNA1-resistant liver cancer cell growth
  • IFNA1 can selectively inhibit cytokine-induced P-AKT1 as a potential mechanism to disrupt homeostasis of T lymphocytes
  • IFNA1 mediates inhibition of IL7- or IL2-induced T cell proliferation
  • close association between the increased proportion of CD180-negative B cells and the activation of IFNA1 signaling in SLE
  • ARID3A is important for IFNA1 expression and show a strong association between ARID3A expression and transcription of genes associated with lupus IFN signatures
  • IFNA1 may possess anti-cervical cancer capacity by activating cell apoptosis via the intrinsic mitochondrial pathway and CASP4-related ER stress-induced pathway
  • anti-viral role for STAT3 in the IFNA1 pathway
  • signaling via TLR7 leads to an upregulation of XBP1 and IFNA1-production
  • central role of XBP1 in TLR7-induced IFNA1 production
  • HIV protein, Vif, inhibits effective IFNA1 signalling via degradation of essential JAK/STAT pathway components
  • IFNA1-mediated deregulation of mitochondrial metabolism and impairment of autophagic degradation, leading to cytosolic accumulation of mtDNA that is sensed via stimulator of interferon genes (STING1) to promote induction of autoinflammatory Dendritic,cells
  • IFNA1 markedly induced IL6 expression in hepatocytes, especially in HBV replicating hepatocytes
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    IFNA1 signaling is highly activated in systemic lupus erythematosus (SLE) B cells and plays a vital role in the antibody response by B cell
    constitutional     --over  
    in neuromyelitis optica (NMO) patients, with higher frequency in NMO patients with acute relapse
    Susceptibility
  • to systemic lupus erythematosus (SLE)
  • to chronic hepatitis B virus infection
    • Variant & Polymorphism SNP
  • A allele of -1823G/A SNP within IFNA1 gene was significantly associated with an increased risk of chronic HBV infection as compared to healthy individuals
    • Candidate gene
    Marker
  • high serum IFNA1 is a heritable risk factor for SLE
    • Therapy target
    SystemTypeDisorderPubmed
    diabetetype 1 
    due to its central role in the early phases of beta cell death, targeting IFNA1 and its pathways in genetically predisposed individuals may represent a potential novel therapeutic strategy in the very early stages of T1D
    ANIMAL & CELL MODELS