RUNX3 Gene: Runt-Related Transcription Factor 3
A key tumor suppressor and developmental regulator in gastric, colorectal, and breast cancers
Gene Information Card
| Symbol | RUNX3 |
|---|---|
| Full Name | RUNX family transcription factor 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 1p36.11 |
| NCBI Gene ID | 864 ncbi.nlm.nih.gov/gene/864 |
| Ensembl ID | ENSG00000078399 |
| UniProt ID | Q13761 |
| OMIM ID | 600210 |
| HGNC ID | 10473 |
| Aliases | AML2, CBFA3, PEBP2aC |
Description
RUNX3 encodes a member of the runt domain-containing family of transcription factors. It acts as a tumor suppressor by regulating cell proliferation, apoptosis, and differentiation, particularly in the gastrointestinal epithelium. RUNX3 is frequently silenced by promoter hypermethylation or inactivated by mutations in various cancers, including gastric, colorectal, and breast cancers. It also plays critical roles in neurogenesis and thymopoiesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Gastric cancer | Loss of RUNX3 expression via promoter hypermethylation or mutation leads to reduced TGF-beta-mediated growth inhibition and increased cell survival. | Multiple studies; ClinVar; COSMIC |
| Colorectal cancer | RUNX3 inactivation contributes to Wnt pathway dysregulation and epithelial-mesenchymal transition, promoting tumor progression. | COSMIC; PubMed |
| Breast cancer | Reduced RUNX3 expression correlates with poor prognosis and increased metastasis, partly through altered CDH1 (E-cadherin) regulation. | ClinVar; PubMed |
| Lung cancer | Hypermethylation of RUNX3 promoter is frequent, leading to loss of tumor suppressor function and enhanced proliferation. | COSMIC; PubMed |
| Hepatocellular carcinoma | RUNX3 downregulation is associated with aggressive tumor features and poor survival, affecting TGF-beta signaling. | PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Stomach | 12.3 | Medium |
| Colon | 8.7 | Low |
| Breast | 5.2 | Low |
| Lung | 4.1 | Low |
| Brain | 2.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MKN-45 (gastric cancer) | 3.2 | Reduced expression due to methylation |
| HCT116 (colorectal cancer) | 5.8 | Moderate expression |
| MCF7 (breast cancer) | 2.1 | Low expression |
| A549 (lung cancer) | 1.5 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.472C>T (p.Arg158*) | Nonsense | Rare (<1%) | Truncated protein, loss of function |
| c.430G>A (p.Gly144Ser) | Missense | Rare (<1%) | Impaired DNA binding |
| c.511A>G (p.Thr171Ala) | Missense | Rare (<1%) | Reduced transactivation activity |
| Promoter hypermethylation | Epigenetic | Frequent in gastric cancer (up to 60%) | Silencing of gene expression |
Mutation functional classification
Loss of Function (LOF)
Most RUNX3 mutations are loss-of-function, leading to reduced tumor suppressor activity.
Gain of Function (GOF)
No gain-of-function mutations reported; RUNX3 acts as a tumor suppressor.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with wild-type RUNX3 function.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • protein dimerization activity | • regulation of transcription by RNA polymerase II |
| • cell differentiation | • apoptotic process |
| • negative regulation of cell population proliferation | • epithelial to mesenchymal transition |
Pathways
• TGF-beta signaling pathway
• Wnt signaling pathway
• p53 signaling pathway
• Gastric cancer pathway
• Colorectal cancer pathway
Protein Summary
RUNX3 is a 415-amino acid protein containing a conserved runt domain that mediates DNA binding and heterodimerization with CBFB. It functions as a transcription factor that regulates target genes involved in cell cycle arrest, apoptosis, and differentiation. In the absence of RUNX3, cells escape growth control, leading to tumorigenesis. The protein is predominantly nuclear and is essential for the development of the gastrointestinal tract and immune system.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RUNX3 Knockout HEK293 Cell Line | EDJ-KQ3513 | Human | 864 | Details Get a Quote |
| RUNX3 Knockout A-549 Cell Line | EDJ-KQ26655 | Human | 864 | Details Get a Quote |
| RUNX3 Knockout HCT 116 Cell Line | EDJ-KQ26657 | Human | 864 | Details Get a Quote |
| RUNX3 Knockout HeLa Cell Line | EDJ-KQ26658 | Human | 864 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
