RUNX1

RUNX family transcription factor 1, the group of Runt-related transcription factors

Basic information

Region (hg38): 21:34787801-36004667

Previous symbols: [ "AML1", "CBFA2" ]

Links

ENSG00000159216NCBI:861OMIM:151385HGNC:10471Uniprot:Q01196AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • acute myeloid leukemia (Strong), mode of inheritance: AD
  • hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 (Strong), mode of inheritance: AD
  • hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 (Strong), mode of inheritance: AD
  • hereditary thrombocytopenia and hematologic cancer predisposition syndrome (Supportive), mode of inheritance: AD
  • hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 (Definitive), mode of inheritance: AD
  • hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 (Definitive), mode of inheritance: AD
  • hereditary thrombocytopenia and hematologic cancer predisposition syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Platelet disorder, familial, with associated myeloid malignancyADHematologic; OncologicIndividuals can have thrombocytopenia and bleeding episodes (eg, associated with surgical procedures), and awareness may allow preventive measures as well as prompt treatment; There is a reported increased risk of malignancy (such as acute myelogenous leukemia), and awareness may allow surveillance measures enabling early detection and management, which may be beneficial; BMT has been reportedHematologic; Oncologic10508512; 11830488; 18478040; 19357396; 19387465; 20846103; 22571758

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RUNX1 gene.

  • Hereditary_thrombocytopenia_and_hematologic_cancer_predisposition_syndrome (1398 variants)
  • Hereditary_thrombocytopenia_and_hematological_cancer_predisposition_syndrome_associated_with_RUNX1 (1262 variants)
  • Inborn_genetic_diseases (636 variants)
  • not_provided (218 variants)
  • Acute_myeloid_leukemia (127 variants)
  • RUNX1-related_disorder (53 variants)
  • not_specified (46 variants)
  • Hereditary_cancer-predisposing_syndrome (44 variants)
  • Thrombocytopenia (22 variants)
  • Abnormal_bleeding (12 variants)
  • Storage_pool_disease_of_platelets (2 variants)
  • Aggressive_systemic_mastocytosis (2 variants)
  • Abnormal_platelet_function (1 variants)
  • Castleman-Kojima_disease (1 variants)
  • Myelodysplasia (1 variants)
  • Inherited_bleeding_disorder,_platelet-type (1 variants)
  • Anaplastic_ependymoma (1 variants)
  • LEUKEMIA,_ACUTE_MYELOID,_M0_SUBTYPE (1 variants)
  • Clonal_Cytopenia_of_Undetermined_Significance (1 variants)
  • TRANSIENT_MYELOPROLIFERATIVE_DISORDER_OF_DOWN_SYNDROME (1 variants)
  • Pancytopenia (1 variants)
  • Atypical_chronic_myeloid_leukemia,_BCR-ABL1_negative (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RUNX1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001754.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
88
clinvar
254
clinvar
13
clinvar
355
missense
7
clinvar
33
clinvar
735
clinvar
24
clinvar
14
clinvar
813
nonsense
22
clinvar
11
clinvar
4
clinvar
37
start loss
2
2
frameshift
77
clinvar
51
clinvar
8
clinvar
136
splice donor/acceptor (+/-2bp)
8
clinvar
11
clinvar
10
clinvar
1
clinvar
30
Total 114 106 847 278 28

Highest pathogenic variant AF is 0.00000657212

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
RUNX1protein_codingprotein_codingENST00000300305 81216868
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.6540.346125741071257480.0000278
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.002183180.6850.00002013057
Missense in Polyphen70123.490.566861203
Synonymous2.561081480.7320.00001091026
Loss of Function3.42420.90.1920.00000118203

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.00005330.0000439
Middle Eastern0.000.00
South Asian0.00006710.0000653
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Forms the heterodimeric complex core-binding factor (CBF) with CBFB. RUNX members modulate the transcription of their target genes through recognizing the core consensus binding sequence 5'-TGTGGT-3', or very rarely, 5'-TGCGGT-3', within their regulatory regions via their runt domain, while CBFB is a non-DNA- binding regulatory subunit that allosterically enhances the sequence-specific DNA-binding capacity of RUNX. The heterodimers bind to the core site of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL3 and GM-CSF promoters (Probable). Essential for the development of normal hematopoiesis (PubMed:17431401). Acts synergistically with ELF4 to transactivate the IL-3 promoter and with ELF2 to transactivate the BLK promoter (PubMed:10207087, PubMed:14970218). Inhibits KAT6B-dependent transcriptional activation (By similarity). Involved in lineage commitment of immature T cell precursors. CBF complexes repress ZBTB7B transcription factor during cytotoxic (CD8+) T cell development. They bind to RUNX-binding sequence within the ZBTB7B locus acting as transcriptional silencer and allowing for cytotoxic T cell differentiation. CBF complexes binding to the transcriptional silencer is essential for recruitment of nuclear protein complexes that catalyze epigenetic modifications to establish epigenetic ZBTB7B silencing (By similarity). Controls the anergy and suppressive function of regulatory T-cells (Treg) by associating with FOXP3. Activates the expression of IL2 and IFNG and down-regulates the expression of TNFRSF18, IL2RA and CTLA4, in conventional T-cells (PubMed:17377532). Positively regulates the expression of RORC in T-helper 17 cells (By similarity). {ECO:0000250|UniProtKB:Q03347, ECO:0000269|PubMed:10207087, ECO:0000269|PubMed:11965546, ECO:0000269|PubMed:14970218, ECO:0000269|PubMed:17377532, ECO:0000269|PubMed:17431401, ECO:0000305}.; FUNCTION: Isoform AML-1L interferes with the transactivation activity of RUNX1. {ECO:0000269|PubMed:9199349}.;
Disease
DISEASE: Note=A chromosomal aberration involving RUNX1/AML1 is a cause of M2 type acute myeloid leukemia (AML-M2). Translocation t(8;21)(q22;q22) with RUNX1T1.; DISEASE: Note=A chromosomal aberration involving RUNX1/AML1 is a cause of therapy-related myelodysplastic syndrome (T-MDS). Translocation t(3;21)(q26;q22) with EAP or MECOM.; DISEASE: Note=A chromosomal aberration involving RUNX1/AML1 is a cause of chronic myelogenous leukemia (CML). Translocation t(3;21)(q26;q22) with EAP or MECOM.; DISEASE: Note=A chromosomal aberration involving RUNX1/AML1 is found in childhood acute lymphoblastic leukemia (ALL). Translocation t(12;21)(p13;q22) with TEL. The translocation fuses the 3'-end of TEL to the alternate 5'-exon of AML-1H.; DISEASE: Note=A chromosomal aberration involving RUNX1 is found in acute leukemia. Translocation t(11,21)(q13;q22) that forms a MACROD1-RUNX1 fusion protein.; DISEASE: Familial platelet disorder with associated myeloid malignancy (FPDMM) [MIM:601399]: Autosomal dominant disease characterized by qualitative and quantitative platelet defects, and propensity to develop acute myelogenous leukemia. {ECO:0000269|PubMed:10508512}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=A chromosomal aberration involving RUNX1/AML1 is found in therapy-related myeloid malignancies. Translocation t(16;21)(q24;q22) that forms a RUNX1-CBFA2T3 fusion protein.; DISEASE: Note=A chromosomal aberration involving RUNX1/AML1 is a cause of chronic myelomonocytic leukemia. Inversion inv(21)(q21;q22) with USP16.; DISEASE: Note=A chromosomal aberration involving RUNX1/AML1 is found in acute myeloid leukemia. Translocation t(20;21)(q11;q22) with CBFA2T2. {ECO:0000269|PubMed:20520637}.;
Pathway
Chronic myeloid leukemia - Homo sapiens (human);Tight junction - Homo sapiens (human);Acute myeloid leukemia - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Hematopoietic Stem Cell Differentiation;Dual hijack model of Vif in HIV infection;Transcriptional regulation by RUNX3;Signal Transduction;Gene expression (Transcription);RUNX3 regulates RUNX1-mediated transcription;RUNX3 regulates p14-ARF;Transcriptional regulation by RUNX3;RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known;Generic Transcription Pathway;RNA Polymerase II Transcription;RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function;RUNX1 regulates transcription of genes involved in BCR signaling;Transport of bile salts and organic acids, metal ions and amine compounds;SLC-mediated transmembrane transport;Transport of small molecules;Organic cation transport;Organic cation/anion/zwitterion transport;TGF_beta_Receptor;Signaling by Nuclear Receptors;Regulation of RUNX1 Expression and Activity;Estrogen-dependent gene expression;RUNX1 regulates transcription of genes involved in differentiation of HSCs;RUNX1 regulates transcription of genes involved in differentiation of myeloid cells;RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs);RUNX1 regulates transcription of genes involved in interleukin signaling;RUNX1 regulates estrogen receptor mediated transcription;RUNX1 regulates transcription of genes involved in WNT signaling;RUNX1 regulates expression of components of tight junctions;ESR-mediated signaling;RUNX1 regulates transcription of genes involved in differentiation of keratinocytes;Transcriptional regulation by RUNX1;Validated transcriptional targets of deltaNp63 isoforms;Regulation of nuclear SMAD2/3 signaling (Consensus)

Recessive Scores

pRec
0.725

Intolerance Scores

loftool
0.146
rvis_EVS
-0.23
rvis_percentile_EVS
37.11

Haploinsufficiency Scores

pHI
0.718
hipred
Y
hipred_score
0.831
ghis
0.535

Essentials

essential_gene_CRISPR
E
essential_gene_CRISPR2
N
essential_gene_gene_trap
K
gene_indispensability_pred
E
gene_indispensability_score
0.858

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Runx1
Phenotype
nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype; skeleton phenotype; embryo phenotype; liver/biliary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); endocrine/exocrine gland phenotype; neoplasm; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan);

Zebrafish Information Network

Gene name
runx1
Affected structure
neutrophil progenitor cell
Phenotype tag
abnormal
Phenotype quality
decreased amount

Gene ontology

Biological process
negative regulation of transcription by RNA polymerase II;regulation of cytokine-mediated signaling pathway;negative regulation of gene expression;hemopoiesis;regulation of Wnt signaling pathway;neuron differentiation;positive regulation of granulocyte differentiation;positive regulation of interleukin-2 production;regulation of intracellular estrogen receptor signaling pathway;negative regulation of CD4-positive, alpha-beta T cell differentiation;positive regulation of CD8-positive, alpha-beta T cell differentiation;regulation of regulatory T cell differentiation;regulation of keratinocyte differentiation;regulation of myeloid cell differentiation;regulation of megakaryocyte differentiation;positive regulation of angiogenesis;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;peripheral nervous system neuron development;regulation of B cell receptor signaling pathway;hematopoietic stem cell proliferation;regulation of hematopoietic stem cell differentiation;regulation of bicellular tight junction assembly
Cellular component
nucleus;nucleoplasm;cytosol;core-binding factor complex;intracellular membrane-bounded organelle
Molecular function
RNA polymerase II regulatory region sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;protein binding;ATP binding;transcription regulatory region DNA binding