RUNX1T1 Gene: RUNX1 Partner Transcriptional Co-Repressor 1
Comprehensive biomedical resource for RUNX1T1 (ETO, MTG8) – gene function, expression, mutations, and disease associations in leukemia and cancer.
Gene Information Card
| Symbol | RUNX1T1 |
|---|---|
| Full Name | RUNX1 Partner Transcriptional Co-Repressor 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 8q21.3 |
| NCBI Gene ID | 862 ncbi.nlm.nih.gov/gene/862 |
| Ensembl ID | ENSG00000179111 |
| UniProt ID | Q06455 |
| OMIM ID | 133435 |
| HGNC ID | 10471 |
| Aliases | ETO, MTG8, ZMYND2, CBFA2T1 |
Description
RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1), also known as ETO or MTG8, encodes a transcriptional co-repressor that interacts with RUNX1 (AML1) to regulate gene expression during hematopoiesis. The gene is frequently involved in the t(8;21)(q22;q22) translocation in acute myeloid leukemia (AML), producing the RUNX1-RUNX1T1 (AML1-ETO) fusion protein that disrupts normal differentiation and promotes leukemogenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute Myeloid Leukemia (AML) with t(8;21)(q22;q22) | RUNX1-RUNX1T1 fusion protein acts as a dominant-negative repressor of RUNX1 target genes, blocking hematopoietic differentiation and promoting proliferation. | Strong: recurrent cytogenetic abnormality in ~10-15% of AML cases; validated in multiple studies (NCBI, OMIM, COSMIC). |
| Myelodysplastic Syndromes (MDS) | Rare RUNX1T1 rearrangements or fusion transcripts may contribute to dysplastic hematopoiesis. | Limited: case reports and small cohort studies (ClinVar, COSMIC). |
| Acute Lymphoblastic Leukemia (ALL) | Rarely, t(8;21) involving RUNX1T1 is reported in B-ALL, leading to similar fusion-mediated transcriptional dysregulation. | Weak: isolated cases (COSMIC, literature). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 12.5 | Medium |
| Whole Blood | 8.3 | Low |
| Spleen | 6.1 | Low |
| Brain (Cerebellum) | 4.2 | Low |
| Heart | 3.8 | Low |
| Lung | 2.9 | Not detected |
| Liver | 1.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Kasumi-1 (AML with t(8;21)) | High | Endogenous RUNX1-RUNX1T1 fusion expressed; used as model for AML1-ETO studies. |
| SKNO-1 (AML with t(8;21)) | High | Another t(8;21) cell line expressing RUNX1-RUNX1T1 fusion. |
| HEK293 (embryonic kidney) | Low | Basal expression of wild-type RUNX1T1. |
| K562 (CML) | Not detected | No RUNX1T1 expression; negative control. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| t(8;21)(q22;q22) | Translocation | ~10-15% of AML | Creates RUNX1-RUNX1T1 fusion; dominant-negative transcriptional repressor. |
| c.1129C>T (p.Arg377*) | Nonsense | <0.1% | Premature stop; potential loss of function. |
| c.1462G>A (p.Gly488Arg) | Missense | <0.1% | Unknown significance; reported in COSMIC. |
| c.1742_1743insA (p.Glu581Glufs*12) | Frameshift | <0.1% | Predicted loss of function. |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg377*, p.Glu581Glufs*12) are predicted to cause loss of function by truncating the protein, impairing co-repressor activity.
Gain of Function (GOF)
The t(8;21) translocation produces a RUNX1-RUNX1T1 fusion that gains a dominant repressor function, aberrantly silencing RUNX1 target genes.
Dominant Negative (DN)
RUNX1-RUNX1T1 fusion acts as a dominant-negative inhibitor of wild-type RUNX1, blocking normal hematopoietic differentiation.
View complete mutation data：
Gene Ontology (GO)
Pathways
• RUNX1-RUNX1T1 fusion targets – KEGG hsa05221 (Acute myeloid leukemia)
• Transcriptional misregulation in cancer – KEGG hsa05202
• Notch signaling pathway – Reactome R-HSA-157118
• HDAC-mediated deacetylation – Reactome R-HSA-3214815
Protein Summary
RUNX1T1 (ETO) is a 604-amino acid nuclear protein containing four Nervy homology domains (NHR1-4) that mediate interactions with transcriptional co-repressors (e.g., HDACs, NCOR, SIN3A). It functions as a transcriptional co-repressor by recruiting histone deacetylase complexes to RUNX1-bound promoters, silencing genes required for hematopoietic differentiation. The t(8;21) fusion protein retains the NHR2 and NHR4 domains, enabling oligomerization and aberrant repression of RUNX1 targets, a key driver of AML.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RUNX1T1 Knockout HEK293 Cell Line | EDJ-KQ3204 | Human | 862 | Details Get a Quote |
| RUNX1T1 Knockout HeLa Cell Line | EDJ-KQ52794 | Human | 862 | Details Get a Quote |
| RUNX1T1 Knockout A-549 Cell Line | EDJ-KQ61265 | Human | 862 | Details Get a Quote |
| RUNX1T1 Knockout HCT 116 Cell Line | EDJ-KQ69760 | Human | 862 | Details Get a Quote |
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