RUNX3

RUNX family transcription factor 3, the group of Runt-related transcription factors|MicroRNA protein coding host genes

Basic information

Region (hg38): 1:24899510-24965121

Previous symbols: [ "CBFA3" ]

Links

ENSG00000020633 ∙ NCBI:864 ∙ OMIM:600210 ∙ HGNC:10473 ∙ Uniprot:Q13761 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RUNX3 gene.

• Inborn genetic diseases (12 variants)
• not provided (4 variants)
• not specified (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RUNX3 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					2	2
missense			10	2	1	13
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding				1	2	3
Total	0	0	10	3	5

Variants in RUNX3

This is a list of pathogenic ClinVar variants found in the RUNX3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-24902171-G-A		not specified	Uncertain significance (Sep 14, 2022)
1-24902222-C-T		not specified	Uncertain significance (Jan 16, 2024)
1-24902223-C-T		not specified	Uncertain significance (Sep 16, 2021)
1-24902248-G-A			Benign (Dec 31, 2018)
1-24902256-C-T		not specified	Uncertain significance (Jun 24, 2022)
1-24902276-G-C		not specified	Uncertain significance (Dec 14, 2023)
1-24902456-T-C		not specified	Uncertain significance (Jun 13, 2023)
1-24902486-G-A		not specified	Uncertain significance (Jan 23, 2024)
1-24902510-G-A		not specified	Uncertain significance (Dec 15, 2022)
1-24902528-C-T		not specified	Uncertain significance (Jul 13, 2022)
1-24902580-G-C		not specified	Uncertain significance (Jul 12, 2022)
1-24902585-C-T		not specified	Uncertain significance (Jan 23, 2024)
1-24902601-T-C		not specified	Likely benign (May 24, 2023)
1-24902636-G-A		not specified	Uncertain significance (Aug 28, 2023)
1-24907249-C-T			Likely benign (Oct 10, 2018)
1-24907333-G-A		not specified	Uncertain significance (Dec 26, 2023)
1-24919265-G-A		not specified	Likely benign (Oct 31, 2023)
1-24927697-C-T		not specified	Uncertain significance (Oct 12, 2022)
1-24927713-G-A			Benign (Jul 16, 2018)
1-24927826-C-T		not specified	Benign (Jan 24, 2024)
1-24929666-C-A		not specified	Uncertain significance (Apr 17, 2023)
1-24929745-C-A		not specified	Uncertain significance (Jan 23, 2024)
1-24929769-C-A		not specified	Uncertain significance (Jan 02, 2024)
1-24929817-G-T		not specified	Likely benign (Apr 07, 2023)
1-24929953-G-A		not specified	Benign (Jan 24, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RUNX3	protein_coding	protein_coding	ENST00000399916	6	65611

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.843	0.157	125697	0	2	125699	0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.69	155	282	0.549	0.0000187	2742
Missense in Polyphen		46	116.2	0.39587		1066
Synonymous	-0.307	133	129	1.03	0.00000956	898
Loss of Function	3.09	2	14.9	0.135	9.32e-7	140

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000919	0.00000880
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

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 (By similarity). May be involved in the control of cellular proliferation and/or differentiation. In association with ZFHX3, upregulates CDKN1A promoter activity following TGF-beta stimulation (PubMed:20599712). 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). {ECO:0000250|UniProtKB:Q64131, ECO:0000269|PubMed:20599712}.
• Pathway: Th1 and Th2 cell differentiation - Homo sapiens (human);TYROBP Causal Network;Endochondral Ossification;TGF-beta Receptor Signaling;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Regulation of RUNX3 expression and activity;RUNX3 regulates CDKN1A transcription;RUNX3 regulates NOTCH signaling;RUNX3 Regulates Immune Response and Cell Migration;Signaling by WNT;Signal Transduction;Gene expression (Transcription);RUNX3 regulates WNT signaling;RUNX3 regulates YAP1-mediated transcription;RUNX3 regulates RUNX1-mediated transcription;RUNX3 regulates p14-ARF;RUNX3 regulates BCL2L11 (BIM) transcription;Transcriptional regulation by RUNX3;Generic Transcription Pathway;RNA Polymerase II Transcription;TGF_beta_Receptor;Binding of TCF/LEF:CTNNB1 to target gene promoters;Formation of the beta-catenin:TCF transactivating complex;TCF dependent signaling in response to WNT;Regulation of nuclear SMAD2/3 signaling (Consensus)

Recessive Scores

• pRec: 0.528

Intolerance Scores

• loftool: 0.0512
• rvis_EVS: -0.27
• rvis_percentile_EVS: 34.32

Haploinsufficiency Scores

• pHI: 0.480
• hipred: Y
• hipred_score: 0.851
• ghis: 0.619

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.894

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Runx3
• Phenotype: digestive/alimentary phenotype; limbs/digits/tail 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); skeleton phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; growth/size/body region phenotype; hematopoietic system 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); 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); craniofacial phenotype; muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: runx3
• Affected structure: neurocranium
• Phenotype tag: abnormal
• Phenotype quality: aplastic

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;chondrocyte differentiation;regulation of transcription, DNA-templated;transcription by RNA polymerase II;protein phosphorylation;hemopoiesis;neuron differentiation;negative regulation of CD4-positive, alpha-beta T cell differentiation;positive regulation of CD8-positive, alpha-beta T cell differentiation;negative regulation of cell cycle;positive regulation of transcription, DNA-templated;peripheral nervous system neuron development;negative regulation of epithelial cell proliferation;response to transforming growth factor beta
• Cellular component: nuclear chromatin;nucleus;nucleoplasm;nucleolus;cytoplasm;cytosol;core-binding factor complex;intracellular membrane-bounded organelle
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription factor activity;protein binding;ATP binding