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FLASH GENE
Symbol RUNX1 contributors: mct - updated : 28-09-2016
HGNC name runt-related transcription factor 1
HGNC id 10471
Corresponding disease
AML1 sporadic myeloid and lymphoid leukemias
FPDAML familial platelet disorder with propensity to myeloid malignancy
Location 21q22.12      Physical location : 36.160.098 - 36.421.595
Synonym name
  • core binding factor,runt domain alpha subunit 2 (acute myeloid leukemia 1)
  • tumor suppressor gene 21 A
  • aml1 oncogene
  • AML1-EVI-1 fusion protein
  • polyomavirus enhancer-binding protein 2 alpha B subunit
  • SL3/AKV core-binding factor alpha B subunit
  • Synonym symbol(s) AML1, PEBP2A2, CBFA2, AMLCR1, RUN1, EVI13, TSG21A, AML1-EVI-1, EVI-1
    DNA
    TYPE functioning gene
    STRUCTURE 261.50 kb     9 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    cytosine-phosphate-guanine/HTF
    text structure
  • very large CPG marks the proximal promoter and an additional at the 3'extremity
  • two distinct promoter regions
  • MAPPING cloned Y linked N status confirmed
    Map cen - GART ,CRYZL1 - D21S58 - D21S219 - D21S216 - IFNAR1 - KCNE1 - D21S65 - RUNX1 - D21S393 - D21S211 - D21S17 ,D21S136 - CBR1 - D21S167 - D21S55 - D21S60 - ERG - qter
    Text see SOD1
    Physical map
    C21orf4 21q22.1-q22.2 chromosome 21 open reading frame 4 RPS5L 21q22.11 ribosomal protein S5-like C21orf55 21q22.11 chromosome 21 open reading frame 55 GART 21q22.1 phosphoribosylglycinamide formyltransferase, phosphoribosylglycinamide synthetase, phosphoribosylaminoimidazole synthetase SON 21q22.1-q22.2 SON DNA binding protein DONSON 21q22.1 downstream neighbor of SON CRYZL1 21q22.1 crystallin, zeta (quinone reductase)-like 1 ITSN1 21q22.1-q22.2 intersectin 1 (SH3 domain protein) ATP5O 21q22.1-q22.2 ATP synthase, H+ transporting, mitochondrial F1 complex, O subunit (oligomycin sensitivity conferring protein) LOC388819 21 similar to GNGT1 protein MRPS6 21q21.3-q22.1 mitochondrial ribosomal protein S6 SLC5A3 21q22.1 solute carrier family 5 (inositol transporters), member 3 C21orf82 21q22.1 chromosome 21 open reading frame 82 KCNE2 21q22.12 potassium voltage-gated channel, Isk-related family, member 2 C21orf51 21q22.12 chromosome 21 open reading frame 51 LOC388820 21 hypothetical gene supported by BC049386 KCNE1 21q22.2 potassium voltage-gated channel, Isk-related family, member 1 DSCR1 21q22.1-q22.2 Down syndrome critical region gene 1 CLIC6 21q22.12 chloride intracellular channel 6 RUNX1 21q22.1-q22.3 runt-related transcription factor 1 (acute myeloid leukemia 1; AML1 oncogene) C21orf96 21q22.12 chromosome 21 open reading frame 96 RPL34P3 21q22.12 ribosomal protein L34 pseudogene 3 LOC266693 21q22.2 enhancer of zeste homolog 2 (Drosophila) pseudogene RPS20P1 21q22.12 ribosomal protein S20, pseudogene 1 PPP1R2P2 21q22.13 protein phosphatase 1, regulatory (inhibitor) subunit 2 pseudogene 2
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 2722 - 250 - 2010 20206228
  • isoform AML1a, or RUNX1A
  • expressed consistently throughout hematopoietic differentiation
  • - splicing 2722 - 228 - 2008 18687690
  • also called AML1dc
  • found in translocation t(8;21)
  • C-terminal deletion mutant of AML1b, which was originally identified in a patient with myelodysplastic syndrome
  • negatively suppressed transcriptional activity of wild-type AML1
  • 6 splicing polyA site initiation site 7274 - 453 localized to nuclear speckles (Wt and mutant) 2010 20206228
  • transcript lacking exon 6 (AML1b(Del179-242)) in ovarian cancer patients (Nanjundan (2007)
  • AML1b(Del179-242) have dramatically reduced transactivation potential with the plasminogen activator inhibitor-1 promoters (PMID: 17072347)
  • Wt inhibit the growth and migration of immortalized ovarian epithelial cells (PMID: 17072347)
  • expressed consistently throughout hematopoietic differentiation
  • 9 splicing polyA site initiation site 5967 - 480 more abundant in leukemia cells 2010 20206228
  • isoform AML1c, or RUNX1c
  • has a distinct role in hematopoietic stem cells (HSCs), only expressed at the time of emergence of definitive HSCs
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus   highly
    Nervousbrainhindbrain   
     spinal cord    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  predominantly Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte Homo sapiens
    Blood/Hematopoieticmature hematopoietic Homo sapiens
    Nervousneuron
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal alanine and glutamine stretches
  • a C terminal Runt domain, forming a DNA-binding motif with an Ig-like protein fold, related to the DNA-binding domain of TP53
  • a nuclear matrix localization signal (NLS)
  • a transactivation domain (AML1R) missing in AML1
  • a putative ATP binding site
  • a proline/serine/threonine rich region
  • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies homolog to Drosophila Runt pair rule-related transcription factor 1
    homolog to murine Runx1
    intraspecies homolog to RUNX2
    Homologene
    FAMILY
  • runt domain gene family
  • CATEGORY DNA associated , transcription factor , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    basic FUNCTION
  • involved in hematopoiesis and osteogenesis
  • regulating CD4 silencer function in thymocytes
  • required for maturation of megakaryocytes and differentiation of T and B cells
  • playing an important role in the development of hindbrain cholinergic branchiovisceral motor neurons and selected cranial sensory neurons
  • master regulator in the development of the hematopoietic system and leukemia
  • plays an important role in the maturation of megakaryocytes and platelet production
  • acting as a negative regulator of MPL expression in hematopoietic stem/progenitor cells which is opposite to its role in megakaryocytes
  • potential role of the STAT5B-RUNX interaction in lymphocyte development
  • can regulate the MPL promoter both positively and negatively by changing the binding partner according to cell types
  • common and critical regulator essential for proliferation of embryonic/adult hematopoietic stem cells and transformed leukemic cells
  • is essential in endothelial cells from haematopoietic progenitor and haematopoietic stem cells formation from the vasculature
  • inducing senescence-like growth arrest independently of replicative stress in primary fibroblasts
  • controls hematopoietic stem cell emergence and hair follicle stem cell (HFSC) activation and proliferation in adult skin
  • implicated in epithelial cell adhesion and migration and in regulation of paracrine epithelial-mesenchymal cross talk
  • required for the specification of definitive hematopoietic stem cells (HSC) in the developing embryo
  • by directly regulating the expression of SMAD6, RUNX1 sets up a functional rheostat to control its own activity
  • RUNX1 and RUNX3 play crucial roles in dorsal root ganglion neurogenesis
  • the function of RUNX1 is essential for neuroblastoma cell proliferation
  • important regulator of SERPINB13 and CTSK activity
  • negative regulator of SERPINB13 transcription
  • may influence cathepsin K activity in the bone marrow by altering SERPINB13 levels
  • role as a cytoplasmic attenuator of NFKB signaling
  • RUNX1 and RUNX3 are involved in the generation and function of highly suppressive IL17-producing T regulatory cells
  • like RUNX3, RUNX1 plays a pivotal role in the regulation of apoptosis in response to a wide variety of cellular pro-apoptotic stimuli such as DNA damage and TGFB1
  • CBFB and RUNX1 are critical for the establishment of definitive hematopoiesis and are implicated in leukemic transformation
  • RUNX1 and RUNX3 maintain genomic integrity in a transcriptional manner by regulating the transactivation of apoptotic genes following DNA damage via complex formation with TP53
  • CELLULAR PROCESS cell life, differentiation
    nucleotide, transcription
    cell organization/biogenesis
    PHYSIOLOGICAL PROCESS development
    text hematopoiesis in the fetal brain; control of cell proliferation
    PATHWAY
    metabolism
    signaling
    a component
  • complexing with ZNF220 (for role in cell differention)
  • INTERACTION
    DNA binding to the enhancer of T cell receptor genes
    RNA
    small molecule
    protein
  • CBFB
  • fusion protein RUNX1/RUNX1T1 up-regulating NTRK1 expression in CD34+ cells
  • target genes controlled by RUNX1 will have considerable importance in disease progression in both familial and sporadic leukemia as well as therapeutic implications
  • interaction between RUNX1 and EVI1 altering the ability of RUNX1 to bind to DNA and to regulate a reporter gene, whereas the expression of the isolated 8th zinc finger motif of EVI1 is sufficient to block the granulocyte colony-stimulating factor leading to cell death
  • RUNX1/RUNX1T1 interacts with SP1 (promotes leukemogenesis by blocking cell differentiation through inhibition of SP1 transactivity)
  • ALOX12 is a direct transcriptional target of RUNX1
  • interacting with STAT5B (inhibits the nuclear localization of RUNX proteins and retains them in the cytoplasm)
  • TAL1 interacts with RUNX1 and ETS1, and these transcription factors are critically required for TAL1 binding to genes that modulate T-cell differentiation
  • C16orf54 is a novel transcriptional target of RUNX1 at the onset of hematopoietic development that is extensively expressed within the hematopoietic system
  • cooperates with SPI1 to activate myeloid differentiation genes, such as macrophage and granulocyte macrophage colony-stimulating factor receptors (MCSFR and GMCSFR)
  • in conjunction with FLI1, GATA2, and TAL1, directly regulates the expression of SMAD6 in the aorta-gonad-mesonephros (AGM) region in the developing embryo
  • functional and coordinated role for RUNX1 and CEBPB transcription factors during activation of P2RX3 gene transcription
  • binds the SERPINB13 promoter in chromatin to repress its transcription
  • may negatively regulate cyclin A1 expression in hematopoietic cells
  • role of RUNX1 in mediating interactions between distal and proximal elements of the haematopoietic stem cell gene CD34
  • concerted action of the transcription factor RUNX1, together with the epigenetic repressor PCGF1, is necessary for terminal differentiation
  • PRMT1 interacts with RUNX1-RUNX1T1 to promote its transcriptional activation and progenitor cell proliferative potential
  • GFI1 and GFI1B are direct targets of RUNX1 and critical regulators of endothelial to hematopoietic transition (EHT)
  • RUNX1 and ELK1, two proteins with essential functions in hematopoiesis, regulate MECOM in acute myeloid leukemia
  • RUNX1 interacts with two novel protein partners, KDM1A and MYEF2, in erythroid cells
  • RUNX1 acts as a co-activator for TP53 in response to DNA damage
  • RUNX1 activates endogenous PF4 expression in megakaryocytic differentiation
  • MYSM1 directly associates with the GFI1 enhancer element and promotes its transcription through GATA2 and RUNX1 transactivation
  • critical role of direct ETS1•RUNX1 interaction in ETS1 activation
  • JMJD1C functions as a coactivator for RUNX1-RUNX1T1 and is required for its transcriptional program
  • MECOM promotes CKMT1A expression by repressing the myeloid differentiation regulator RUNX1
  • RUNX1 and RUNX3 also maintain genomic integrity in a non-transcriptional manner during interstand crosslink repair by promoting the recruitment of FANCD2 to sites of DNA damage
  • cell & other
    REGULATION
    activated by ZNF220
    arginine-methylation by PRMT1, the methylation abrogates SIN3A binding and potentiates the transcriptional activity of RUNX1
    inhibited by the complex ZNF220-CREBP
    repressed by RUNX3 (required to allow the cell proliferation and this provides an experimental system to investigate the mechanism of the different activities of RUNX1 and RUNX3 in these cells)
    ASSOCIATED DISORDERS
    corresponding disease(s) FPDAML , AML1 , DEL21Q2212
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    fused with FGA7 in t(4;21) (q31;q22) in T cell acute leukemia
    tumoral   LOH    
    in acute myeloid leukemia
    tumoral       gain of function
    in acute myeloid leukemia
    tumoral fusion      
    with CBFA2T1 in acute myeloid leukemia (AML1-ETO) with t(8;21)(q22;q22), often associated with prior therapy t(17;21)(q11.2;q22) and others myelodysplasia syndrome with t(3;21)(q26;q22), acute lymphoblastic leukemia with t(12;21)(p13;q22) only in childhood
    tumoral fusion      
    fusion with PRDM16 in a patient with acute myeloid leukemia showing t(1;21)(p36;q22)
    tumoral     --low  
    in acute megakaryoblastic leukemia of Down syndrome
    tumoral somatic mutation      
    in high-risk myelodysplastic syndrome
    tumoral fusion      
    AML1-ETO9a leads to rapid development of leukemia and results in the substantially earlier onset of AML because blocks myeloid cell differentiation at a more immature stage (arg-methyaltion sites are lost in the fusion protein and contribute to its dominant inhibitory activity
    tumoral fusion      
    with ZFPM2, in myelodysplasia
    tumoral   translocation    
    t(9;21)(q34;q22), in myeloproliferative syndrome with with a high risk of transformation to acute myeloid leukemia
    tumoral somatic mutation      
    deregulated alternative splicing of AML1b transcripts may potentially contribute to the pathophysiology of ovarian cancers
    tumoral fusion      
    LRP16 fusion partner involving t(11;21)(q13;q22) in monocytic leukemia
    tumoral fusion      
    with LPXN in an acute myeloid leukemia (AML) patient with t(11;21)(q12;q22)
    tumoral fusion      
    with AFF3, partner of MLL, in childhood T-cell acute lymphoblastic leukemia with t(2;21)(q11;q22)
    tumoral fusion      
    cryptic inversion of chromosomal region 21q21-22 leading to break and fusion of RUNX1 to USP16, in chronic myelomonocytic leukemia )
    constitutional     --over  
    of CHRNG, CHRND, NCAM1, RUNX1 associated with neuromuscular junction denervation in ageing
    tumoral     --over  
    with NFE2 in granulocytes of patients with polycythemia vera and other myeloproliferative neoplasms
    Susceptibility
  • to rheumatoid arthritis in association with SLC22A4
  • to psoriasis
  • role of RUNX1 haploinsufficiency in megakaryopoiesis and predisposition to AML
  • Variant & Polymorphism SNP SNP between SLC9AR1 and NAT9 leading to loss of RUNX1 binding site, associated with psoriasis
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    dasatinib could be a potent inhibitor for both activation loop and juxtamembrane domain mutants of KIT, thus opening therapeutic perspectives for dasatinib in the treatment of leukemias with activated KIT abnormalities.
    cancerhemopathy 
    NFKB signaling is one of the promising therapeutic targets of hematologic malignancies with RUNX1 abnormality
    ANIMAL & CELL MODELS