RUNX1
RUNX family transcription factor 1, the group of Runt-related transcription factors
Basic information
Region (hg38): 21:34787800-36004667
Previous symbols: [ "AML1", "CBFA2" ]
Links
Phenotypes
GenCC
Source:
- 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:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Platelet disorder, familial, with associated myeloid malignancy | AD | Hematologic; Oncologic | Individuals 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 reported | Hematologic; Oncologic | 10508512; 11830488; 18478040; 19357396; 19387465; 20846103; 22571758 |
ClinVar
This is a list of variants' phenotypes submitted to
- Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 (1200 variants)
- Hereditary thrombocytopenia and hematologic cancer predisposition syndrome (304 variants)
- not provided (161 variants)
- Acute myeloid leukemia (71 variants)
- not specified (47 variants)
- Hereditary cancer-predisposing syndrome (44 variants)
- RUNX1-related condition (17 variants)
- Thrombocytopenia (11 variants)
- Inborn genetic diseases (11 variants)
- Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1;Acute myeloid leukemia (10 variants)
- Abnormal bleeding;Thrombocytopenia (8 variants)
- Acute myeloid leukemia;Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 (4 variants)
- Thrombocytopenia;Abnormal bleeding (3 variants)
- Storage pool disease of platelets (2 variants)
- Transient myeloproliferative disorder of Down syndrome (1 variants)
- Anaplastic ependymoma (1 variants)
- Atypical chronic myeloid leukemia, BCR-ABL1 negative (1 variants)
- Myelodysplasia (1 variants)
- Abnormal platelet function (1 variants)
- Clonal Cytopenia of Undetermined Significance (1 variants)
- Castleman-Kojima disease (1 variants)
- Inherited bleeding disorder, platelet-type (1 variants)
- Pancytopenia (1 variants)
- Leukemia, acute myeloid, m0 subtype (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.
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.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 35 | 209 | 12 | 257 | ||
| missense | 23 | 551 | 12 | 12 | 603 | |
| nonsense | 13 | 28 | ||||
| start loss | 2 | |||||
| frameshift | 50 | 27 | 12 | 90 | ||
| inframe indel | 19 | 20 | ||||
| splice donor/acceptor (+/-2bp) | 17 | |||||
| splice region ? | 1 | 29 | 24 | 1 | 55 | |
| non coding ? | 69 | 104 | 75 | 249 | ||
| Total | 74 | 66 | 700 | 326 | 100 |
Highest pathogenic variant AF is 0.00000658
Variants in RUNX1
This is a list of pathogenic ClinVar variants found in the RUNX1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 21-34787885-G-A | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 • Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | Benign (May 13, 2020) | ||
| 21-34787897-C-A | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 • Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | Benign (May 13, 2020) | ||
| 21-34787947-C-G | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 • Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | Likely benign (May 26, 2021) | ||
| 21-34787988-G-C | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | Uncertain significance (Jan 13, 2018) | ||
| 21-34787995-G-A | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 • Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | Benign (May 13, 2020) | ||
| 21-34788103-A-G | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | Benign (Jan 13, 2020) | ||
| 21-34788132-G-A | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | Uncertain significance (Jan 12, 2018) | ||
| 21-34788158-C-T | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 • Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | Benign (May 13, 2020) | ||
| 21-34788191-C-T | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | Uncertain significance (Jan 13, 2018) | ||
| 21-34788414-T-A | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 • Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | Benign (May 13, 2020) | ||
| 21-34788493-G-A | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | Uncertain significance (Jan 13, 2018) | ||
| 21-34788497-C-T | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | Uncertain significance (Jan 13, 2018) | ||
| 21-34788516-T-C | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 • Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | Benign (May 13, 2020) | ||
| 21-34788547-C-G | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | Uncertain significance (Jan 13, 2018) | ||
| 21-34788553-C-T | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 • Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | Uncertain significance (Jun 23, 2022) | ||
| 21-34788555-A-C | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | Uncertain significance (Jan 13, 2018) | ||
| 21-34788561-T-C | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | Benign (Jan 13, 2020) | ||
| 21-34788578-G-A | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | Uncertain significance (Jan 15, 2018) | ||
| 21-34788608-A-C | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 • Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | Likely benign (Jun 30, 2022) | ||
| 21-34788691-T-C | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 • Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | Likely benign (Jul 08, 2022) | ||
| 21-34788718-T-C | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | Uncertain significance (Jan 12, 2018) | ||
| 21-34788755-T-C | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | Benign (Jan 13, 2020) | ||
| 21-34788790-T-A | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | Benign (Jan 13, 2020) | ||
| 21-34788838-A-G | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 • Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | Uncertain significance (Nov 13, 2023) | ||
| 21-34788854-C-A | Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | Uncertain significance (Jan 13, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| RUNX1 | protein_coding | protein_coding | ENST00000300305 | 8 | 1216868 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.654 | 0.346 | 125741 | 0 | 7 | 125748 | 0.0000278 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.00 | 218 | 318 | 0.685 | 0.0000201 | 3057 |
| Missense in Polyphen | 70 | 123.49 | 0.56686 | 1203 | ||
| Synonymous | 2.56 | 108 | 148 | 0.732 | 0.0000109 | 1026 |
| Loss of Function | 3.42 | 4 | 20.9 | 0.192 | 0.00000118 | 203 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000533 | 0.0000439 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000671 | 0.0000653 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- 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
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
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