RUNX1T1

Chr 8

RUNX1 partner transcriptional co-repressor 1

Also known as: AML1-MTG8, AML1T1, CBFA2T1, CDR, ETO, MTG8, ZMYND2

NCBI Gene: 862 ENSG00000079102 UniProt: Q06455

The protein encoded by this gene is a transcriptional corepressor that facilitates gene silencing by recruiting histone-modifying enzymes and other corepressor complexes to DNA-binding transcription factors. RUNX1T1 is highly constrained against loss-of-function variants and is best known for its involvement in the t(8;21) translocation associated with acute myeloid leukemia, though germline mutations causing Mendelian disease have not been well-established in pediatric populations. The gene plays important roles in hematopoietic differentiation and adipogenesis regulation.

Summary from RefSeq, UniProt

Research Assistant →

Active trials

Pubs (1 yr)

P/LP submissions

P/LP missense

0.31

LOEUF· LoF intol.

LOF

Mechanism· predicted

Clinical Summary— RUNX1T1

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

36 unique Pathogenic / Likely Pathogenic· 79 VUS of 142 total submissions

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Clinical Trials

9 active or recruiting trials — potential therapeutic options may be available

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint

0.31LOEUF

pLI 0.978

Z-score 4.33

OE 0.14 (0.07–0.31)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint

2.17Z-score

OE missense 0.68 (0.62–0.76)

255 obs / 372.8 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios

LoF OE0.14 (0.07–0.31)

0≤0.351.4

Missense OE0.68 (0.62–0.76)

0≤0.61.4

Synonymous OE1.01

0≤1.21.6

LoF obs/exp: 4 / 29.3Missense obs/exp: 255 / 372.8Syn Z: -0.09

0.3097th %ile

GOF

0.3193th %ile

LOF

0.86top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.31

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

142 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35

Likely Pathogenic1

VUS79

Likely Benign9

Benign7

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	34	0	35
Likely Pathogenic	0	1	0	0	1
VUS	5	66	8	0	79
Likely Benign	0	1	2	6	9
Benign	0	0	1	6	7
Total	6	68	45	12	131

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RUNX1T1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Acute Myeloid LeukemiaAdult Acute Megakaryoblastic LeukemiaAdult Acute Monoblastic Leukemia

Azacitidine and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

ACTIVE NOT RECRUITING

NCT00658814Phase PHASE2National Cancer Institute (NCI)Started 2008-12-01

AzacitidineGemtuzumab Ozogamicin

Relapsed Adult AML

Study Investigating the Safety of CD19 CAR-T Cells in Relapsed/Refractory AML Expressing CD19

RECRUITING

NCT06649227Phase PHASE1University Hospital, LilleStarted 2025-07-10

CAR-T cell therapy

Previously Untreated Relapsed Refractory Acute Myeloid Leukemia

Study of Biomarker-Based Treatment of Acute Myeloid Leukemia

RECRUITING

NCT03013998Phase PHASE1, PHASE2Beat AML, LLCStarted 2016-11

Samalizumab (BAML-16-001-S1)BI 836858 (BAML-16-001-S2)Laboratory Biomarker Analysis

C-KIT Mutation

A Study of c-Kit Mutation as MRD in Acute Myeloid Leukemia

RECRUITING

NCT06116318Institute of Hematology & Blood Diseases Hospital, ChinaStarted 2023-11-01

AMLRUNX1-RUNX1T1 Fusion Protein Expression

Standard-dose vs Intermediate-dose Cytarabine Induction in the Treatment of Acute Myeloid Leukemia With RUNX1-RUNX1T1

RECRUITING

NCT06744504Phase PHASE3Institute of Hematology & Blood Diseases Hospital, ChinaStarted 2025-01-10

cytarabinedaunorubicinidarubicin

AML (Acute Myelogenous Leukemia)

Avapritinib Combined With Azacitidine and Venetoclax in the Treatment of Relapsed AML After Allo-HSCT

RECRUITING

NCT06783790Phase PHASE2Institute of Hematology & Blood Diseases Hospital, ChinaStarted 2025-01-20

Avapritinib, azacitidine, Venetoclax

Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1

Fludarabine Phosphate, Cytarabine, Filgrastim-sndz, Gemtuzumab Ozogamicin, and Idarubicin Hydrochloride in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

RECRUITING

NCT00801489Phase PHASE2M.D. Anderson Cancer CenterStarted 2007-04-04

CytarabineDecitabineFilgrastim-sndz

AML, ChildhoodAcute Myeloid Leukemia

Clinical Study of Induction Therapy Options Based on Molecular Subtyping and MRD in Children and Adolescents With AML

RECRUITING

NCT06221683Phase PHASE2Children's Hospital of Soochow UniversityStarted 2024-01-01

HomoharringtonineCytarabineEtoposide

Acute Myeloid Leukemia With T(8;21)(Q22;Q22)Acute Myeloid Leukemia With T(16;16)(P13;Q22)KIT Gene Mutation

A New Treatment of Newly Diagnosed KIT Mutation CBF-Acute Myeloid Leukemia

RECRUITING

NCT07028073Phase PHASE1, PHASE2The First Affiliated Hospital of Soochow UniversityStarted 2025-05-15