RUNX1 (RUNX family transcription factor 1)

Gene

• Entrez ID: 861
• Gene name: RUNX family transcription factor 1
• Gene symbol: RUNX1
• Synonyms: AML1, AML1-EVI-1, AMLCR1, CBF2alpha, CBFA2, EVI-1, PEBP2aB, PEBP2alpha
• Chromosome: 21
• Chromosome location: 21q22.12
• Summary: Core binding factor (CBF) is a heterodimeric transcription factor that binds to the core element of many enhancers and promoters. The protein encoded by this gene represents the alpha subunit of CBF and is thought to be involved in the development of normal hematopoiesis. Chromosomal translocations involving this gene are well-documented and have been associated with several types of leukemia. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs74315450	C>T	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs121912498	T>C	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs121912499	G>A,C,T	Pathogenic, likely-pathogenic, likely-benign	Non coding transcript variant, coding sequence variant, stop gained, synonymous variant, genic downstream transcript variant
rs121912500	G>T	Pathogenic, likely-benign	Missense variant, non coding transcript variant, coding sequence variant
rs150042294	C>T	Likely-benign, conflicting-interpretations-of-pathogenicity	Intron variant, missense variant, non coding transcript variant, coding sequence variant
rs561166961	C>A	Likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant, non coding transcript variant
rs761390141	C>A,G,T	Conflicting-interpretations-of-pathogenicity	3 prime UTR variant, genic downstream transcript variant
rs769628054	G>A	Conflicting-interpretations-of-pathogenicity	Synonymous variant, downstream transcript variant, genic downstream transcript variant, coding sequence variant
rs1057519748	G>A	Pathogenic, likely-pathogenic	Coding sequence variant, stop gained, non coding transcript variant
rs1060502579	C>G,T	Pathogenic, likely-pathogenic	Splice donor variant
rs1555884790	->CG	Pathogenic, likely-pathogenic	Downstream transcript variant, frameshift variant, genic downstream transcript variant, coding sequence variant
rs1555889984	C>A	Pathogenic	Intron variant, non coding transcript variant, stop gained, coding sequence variant
rs1555899735	A>T	Uncertain-significance, likely-pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs1555899813	->CC	Pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant
rs1569001972	->AGCCGCCCACCATGGAGAACTGGTAGGAGCCGGCCGAGGCGCCGTAGTACAGGTGGTAGGAGGG	Likely-pathogenic	Downstream transcript variant, frameshift variant, genic downstream transcript variant, coding sequence variant
rs1569002077	->CCGA	Likely-pathogenic	Downstream transcript variant, frameshift variant, genic downstream transcript variant, coding sequence variant
rs1569002159	->GAGC	Likely-pathogenic	Downstream transcript variant, frameshift variant, genic downstream transcript variant, coding sequence variant
rs1569002296	G>T	Likely-pathogenic	Downstream transcript variant, stop gained, genic downstream transcript variant, coding sequence variant
rs1569002881	G>A	Likely-pathogenic	Stop gained, non coding transcript variant, genic downstream transcript variant, coding sequence variant
rs1569008655	G>A	Pathogenic, likely-pathogenic	Stop gained, non coding transcript variant, genic downstream transcript variant, coding sequence variant
rs1569009004	G>-	Likely-pathogenic	Frameshift variant, non coding transcript variant, genic downstream transcript variant, coding sequence variant
rs1569037127	G>-	Likely-pathogenic	Intron variant, frameshift variant, non coding transcript variant, coding sequence variant
rs1569061762	C>T	Pathogenic, likely-pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs1569061768	G>A	Pathogenic, likely-pathogenic	Non coding transcript variant, stop gained, coding sequence variant
rs1569061786	T>A,G	Uncertain-significance, likely-pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs1569061831	G>C	Pathogenic	Non coding transcript variant, stop gained, coding sequence variant
rs1569084032	G>-	Likely-pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant
rs1569084082	C>G	Pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs1569084106	C>T	Likely-pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs1569084116	T>G	Uncertain-significance, likely-pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs1569084170	G>-	Pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant
rs1569084388	CC>-	Likely-pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant
rs1569084451	CGCCGCTCCTCAGCTTGCCGGCCAGGGCAGCGCCGGCGTCCGGGGCGCCCAGC>-	Likely-pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant
rs1569084530	->GGCGTCCGGGGCGCCCAGCGGCAACGCC	Pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant
rs1569084646	G>-	Likely-pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant
rs1601333051	C>-	Likely-pathogenic	Downstream transcript variant, frameshift variant, genic downstream transcript variant, coding sequence variant
rs1601415426	G>A	Likely-pathogenic	Intron variant, non coding transcript variant, stop gained, coding sequence variant
rs1601470652	A>T	Likely-pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs1601528621	G>T	Likely-pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs1601528701	GAGCAGAGGAA>CAGCGGAAGGAG	Pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT000107	hsa-miR-27a-3p	HITS-CLIP	23313552
MIRT003741	hsa-miR-17-5p	Luciferase reporter assay, Reporter assay, qRT-PCR, Western blot	17589498
MIRT003742	hsa-miR-20a-5p	Luciferase reporter assay, qRT-PCR, Western blot	17589498
MIRT003743	hsa-miR-106a-5p	Luciferase reporter assay, qRT-PCR, Western blot	17589498
MIRT038069	hsa-miR-423-5p	CLASH	23622248
MIRT053591	hsa-miR-675-5p	Luciferase reporter assay, qRT-PCR, Western blot	24388988
MIRT053591	hsa-miR-675-5p	qRT-PCR, Western blot	26931432
MIRT203374	hsa-miR-8485	HITS-CLIP	23824327
MIRT203374	hsa-miR-8485	HITS-CLIP	23313552
MIRT203374	hsa-miR-8485	HITS-CLIP	27418678
MIRT438218	hsa-miR-221-3p	qRT-PCR, Western blot	24329418
MIRT534539	hsa-miR-7111-3p	PAR-CLIP	22012620
MIRT534540	hsa-miR-4792	PAR-CLIP	22012620
MIRT534541	hsa-miR-6721-5p	PAR-CLIP	22012620
MIRT534542	hsa-miR-6860	PAR-CLIP	22012620
MIRT534543	hsa-miR-612	PAR-CLIP	22012620
MIRT534544	hsa-miR-5189-5p	PAR-CLIP	22012620
MIRT534545	hsa-miR-3187-5p	PAR-CLIP	22012620
MIRT534546	hsa-miR-1285-3p	PAR-CLIP	22012620
MIRT534547	hsa-miR-939-3p	PAR-CLIP	22012620
MIRT534548	hsa-miR-6769b-3p	PAR-CLIP	22012620
MIRT534549	hsa-miR-4723-3p	PAR-CLIP	22012620
MIRT534550	hsa-miR-3183	PAR-CLIP	22012620
MIRT534551	hsa-miR-6791-5p	PAR-CLIP	22012620
MIRT534552	hsa-miR-4292	PAR-CLIP	22012620
MIRT534553	hsa-miR-4308	PAR-CLIP	22012620
MIRT534554	hsa-miR-4762-5p	PAR-CLIP	22012620
MIRT534555	hsa-miR-605-5p	PAR-CLIP	22012620
MIRT534556	hsa-miR-551b-5p	PAR-CLIP	22012620
MIRT534556	hsa-miR-551b-5p	HITS-CLIP	23313552
MIRT569539	hsa-miR-4417	PAR-CLIP	20371350
MIRT569540	hsa-miR-4467	PAR-CLIP	20371350
MIRT569541	hsa-miR-6853-5p	PAR-CLIP	20371350
MIRT569542	hsa-miR-8072	PAR-CLIP	20371350
MIRT569543	hsa-miR-4530	PAR-CLIP	20371350
MIRT569544	hsa-miR-3960	PAR-CLIP	20371350
MIRT569545	hsa-miR-922	PAR-CLIP	20371350
MIRT612533	hsa-miR-4789-3p	HITS-CLIP	23824327
MIRT612533	hsa-miR-4789-3p	HITS-CLIP	23313552
MIRT612533	hsa-miR-4789-3p	HITS-CLIP	27418678
MIRT622381	hsa-miR-335-3p	HITS-CLIP	23824327
MIRT622381	hsa-miR-335-3p	HITS-CLIP	27418678
MIRT622382	hsa-miR-5096	HITS-CLIP	23824327
MIRT622382	hsa-miR-5096	HITS-CLIP	27418678
MIRT622383	hsa-miR-377-3p	HITS-CLIP	23824327
MIRT622383	hsa-miR-377-3p	HITS-CLIP	27418678
MIRT699881	hsa-miR-6885-3p	HITS-CLIP	23313552
MIRT699882	hsa-miR-4446-5p	HITS-CLIP	23313552
MIRT699883	hsa-miR-7152-5p	HITS-CLIP	23313552
MIRT699884	hsa-miR-5006-3p	HITS-CLIP	23313552
MIRT699885	hsa-miR-4755-5p	HITS-CLIP	23313552
MIRT699886	hsa-miR-3180-5p	HITS-CLIP	23313552
MIRT699887	hsa-miR-4639-5p	HITS-CLIP	23313552
MIRT699888	hsa-miR-4497	HITS-CLIP	23313552
MIRT699889	hsa-miR-642a-5p	HITS-CLIP	23313552
MIRT699890	hsa-miR-513a-5p	HITS-CLIP	23313552
MIRT699891	hsa-miR-3160-5p	HITS-CLIP	23313552
MIRT699892	hsa-miR-1266-3p	HITS-CLIP	23313552
MIRT699893	hsa-miR-4667-3p	HITS-CLIP	23313552
MIRT699894	hsa-miR-1470	HITS-CLIP	23313552
MIRT699895	hsa-miR-7157-5p	HITS-CLIP	23313552
MIRT699896	hsa-miR-4310	HITS-CLIP	23313552
MIRT699897	hsa-miR-141-5p	HITS-CLIP	23313552
MIRT699898	hsa-miR-2115-3p	HITS-CLIP	23313552
MIRT699899	hsa-miR-1179	HITS-CLIP	23313552
MIRT699900	hsa-miR-27b-3p	HITS-CLIP	23313552
MIRT699900	hsa-miR-27b-3p	Luciferase reporter assay	26870610
MIRT699901	hsa-miR-128-3p	HITS-CLIP	23313552
MIRT699902	hsa-miR-216a-3p	HITS-CLIP	23313552
MIRT699903	hsa-miR-3681-3p	HITS-CLIP	23313552
MIRT731126	hsa-miR-18a-5p	Luciferase reporter assay, qRT-PCR, Western blot,	25452107
MIRT732121	hsa-miR-215-5p	Immunohistochemistry, Luciferase reporter assay, qRT-PCR, Western blot	26716895
MIRT733692	hsa-miR-9-5p	Luciferase reporter assay	26091714
MIRT734125	hsa-miR-101-3p	Luciferase reporter assay, qRT-PCR, Western blot	26628987
MIRT734389	hsa-miR-144-5p	Luciferase reporter assay, qRT-PCR, Western blot	26030000
MIRT734590	hsa-miR-181a-5p	Luciferase reporter assay	26580398
MIRT734686	hsa-miR-378a-3p	Luciferase reporter assay, qRT-PCR, Western blot, Microarray	26749280

Transcription factors

Transcription factor	Regulation	Reference
CBFB	Unknown	24648201
GATA1	Unknown	16628190
HLF	Repression	11486032
L3MBTL1	Repression	18474616
PITX1	Repression	21425961
RUNX3	Repression	19403666
RUNX3	Unknown	15688019
TLE3	Repression	19403666
TOP2B	Activation	24327541

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	ISS
GO:0000785	Component	Chromatin	ISA
GO:0000976	Function	Transcription regulatory region sequence-specific DNA binding	IDA	21873977
GO:0000977	Function	RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA	9199349
GO:0000977	Function	RNA polymerase II transcription regulatory region sequence-specific DNA binding	IMP	9199349
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA	21873635
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA	17377532
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA	21873635
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IDA	9199349
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IMP	9199349
GO:0001503	Process	Ossification	IBA	21873635
GO:0001959	Process	Regulation of cytokine-mediated signaling pathway	TAS
GO:0002062	Process	Chondrocyte differentiation	IBA	21873635
GO:0005515	Function	Protein binding	IPI	2845103, 10207087, 11965546, 14970218, 16917507, 17377532, 17431401, 18280240, 19497860, 21179004, 21873977, 22253733, 25241761, 25283809, 25678665, 28533407, 29391048
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IDA	7862156
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA	21873635
GO:0010629	Process	Negative regulation of gene expression	TAS
GO:0010755	Process	Regulation of plasminogen activation	ISS
GO:0016513	Component	Core-binding factor complex	TAS	18258917
GO:0030097	Process	Hemopoiesis	IBA	21873635
GO:0030097	Process	Hemopoiesis	IDA	21873977
GO:0030111	Process	Regulation of Wnt signaling pathway	TAS
GO:0030182	Process	Neuron differentiation	IBA	21873635
GO:0030854	Process	Positive regulation of granulocyte differentiation	IMP	9199349
GO:0032743	Process	Positive regulation of interleukin-2 production	IMP	17377532
GO:0032967	Process	Positive regulation of collagen biosynthetic process	ISS
GO:0033146	Process	Regulation of intracellular estrogen receptor signaling pathway	TAS
GO:0043231	Component	Intracellular membrane-bounded organelle	IDA
GO:0043371	Process	Negative regulation of CD4-positive, alpha-beta T cell differentiation	ISS
GO:0043378	Process	Positive regulation of CD8-positive, alpha-beta T cell differentiation	ISS
GO:0045589	Process	Regulation of regulatory T cell differentiation	TAS
GO:0045595	Process	Regulation of cell differentiation	IBA	21873635
GO:0045616	Process	Regulation of keratinocyte differentiation	TAS
GO:0045637	Process	Regulation of myeloid cell differentiation	TAS
GO:0045652	Process	Regulation of megakaryocyte differentiation	TAS
GO:0045766	Process	Positive regulation of angiogenesis	ISS
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IDA	10207087, 14970218
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	9199349, 10207087, 14970218, 21873977
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IMP	9199349, 20972335
GO:0048935	Process	Peripheral nervous system neuron development	TAS	20096094
GO:0050855	Process	Regulation of B cell receptor signaling pathway	TAS
GO:0060043	Process	Regulation of cardiac muscle cell proliferation	ISS
GO:0061026	Process	Cardiac muscle tissue regeneration	ISS
GO:0071425	Process	Hematopoietic stem cell proliferation	TAS	21873977
GO:1902036	Process	Regulation of hematopoietic stem cell differentiation	TAS
GO:1903055	Process	Positive regulation of extracellular matrix organization	ISS
GO:1905203	Process	Regulation of connective tissue replacement	ISS
GO:2000810	Process	Regulation of bicellular tight junction assembly	TAS

Other IDs

• MIM: 151385
• HGNC: 10471
• e!Ensembl: ENSG00000159216

Protein

• UniProt ID: Q01196
• Protein name: Runt-related transcription factor 1 (Acute myeloid leukemia 1 protein) (Core-binding factor subunit alpha-2) (CBF-alpha-2) (Oncogene AML-1) (Polyomavirus enhancer-binding protein 2 alpha B subunit) (PEA2-alpha B) (PEBP2-alpha B) (SL3-3 enhancer factor 1 alpha B subunit) (SL3/AKV core-binding factor alpha B subunit)
• Protein 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). ; Isoform AML-1G shows higher binding activities for target genes and binds TCR-beta-E2 and RAG-1 target site with threefold higher affinity than other isoforms. It is less effective in the context of neutrophil terminal differentiation. ; Isoform AML-1L interferes with the transactivation activity of RUNX1.
• PDB: 1CMO, 1CO1, 1E50, 1H9D, 1LJM
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00853	Runt	51 → 180	Runt domain	Domain
  PF08504	RunxI	362 → 453	Runx inhibition domain	Family

• Sequence:

  MRIPVDASTSRRFTPPSTALSPGKMSEALPLGAPDAGAALAGKLRSGDRSMVEVLADHPG
  ELVRTDSPNFLCSVLPTHWRCNKTLPIAFKVVALGDVPDGTLVTVMAGNDENYSAELRNA
  TAAMKNQVARFNDLRFVGRSGRGKSFTLTITVFTNPPQVATYHRAIKITVDGPREPRRHR
  QKLDDQTKPGSLSFSERLSELEQLRRTAMRVSPHHPAPTPNPRASLNHSTAFNPQPQSQM
  QDTRQIQPSPPWSYDQSYQYLGSIASPSVHPATPISPGRASGMTTLSAELSSRLSTAPDL
  TAFSDPRQFPALPSISDPRMHYPGAFTYSPTPVTSGIGIGMSAMGSATRYHTYLPPPYPG
  SSQAQGGPFQASSPSYHLYYGASAGSYQFSMVGGERSPPRILPPCTNASTGSALLNPSLP
  NQSDVVEAEGSHSNSPTNMAPSARLEEAVWRPY

• Sequence length: 453