RUNX3
Basic information
Region (hg38): 1:24899510-24965121
Previous symbols: [ "CBFA3" ]
Links
Phenotypes
GenCC
Source:
ClinVar
This is a list of variants' phenotypes submitted to
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 | 3 | |||||
missense | 17 | 20 | ||||
nonsense | 0 | |||||
start loss | 0 | |||||
frameshift | 0 | |||||
inframe indel | 0 | |||||
splice donor/acceptor (+/-2bp) | 0 | |||||
splice region | 1 | 1 | ||||
non coding | 3 | |||||
Total | 0 | 0 | 17 | 4 | 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) | ||
1-24902196-C-T | not specified | Uncertain significance (Apr 17, 2024) | ||
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) | |||
1-24907315-C-A | not specified | Uncertain significance (Mar 15, 2024) | ||
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) |
GnomAD
Source:
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:
- 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