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 OMIM: 133435

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the myeloid translocation gene family which interact with DNA-bound transcription factors and recruit a range of corepressors to facilitate transcriptional repression. The t(8;21)(q22;q22) translocation is one of the most frequent karyotypic abnormalities in acute myeloid leukemia. The translocation produces a chimeric gene made up of the 5'-region of the runt-related transcription factor 1 gene fused to the 3'-region of this gene. The chimeric protein is thought to associate with the nuclear corepressor/histone deacetylase complex to block hematopoietic differentiation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2010]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

120

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.31

LOEUF· LoF intol.

LOF

Mechanism· predicted

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 OE?0.14 (0.07–0.31)

0≤0.351.4

Missense OE?0.68 (0.62–0.76)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

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

Background carrier burden — how many people carry a rare variant somewhere in RUNX1T1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

788 rare PASS variants

Rare truncating (LoF)

1 in 3,100

65 rare PASS variants

Rare synonymous (reference)

1 in 110

393 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RUNX1T1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 140	1 in 3,200
South Asian	~43k	1 in 89	1 in 5,000
Remaining (unassigned)	~30k	1 in 120	1 in 3,700
European (Finnish)	~27k	1 in 230	≈ 1 in 6,400
Admixed American	~22k	1 in 100	1 in 1,400
African / African American	~21k	1 in 82	≈ 1 in 4,300
East Asian	~20k	1 in 91	1 in 970
Ashkenazi Jewish	~13k	1 in 700	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 90	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 9 of 11 coding exons well covered in gnomAD exomes; exons 5, 8 marginal. Genomes: all 11.? see exons ↓

ClinVar

No ClinVar data available.

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

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

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

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

Clinical Literature

Open Research Assistant →

Landmark / reviewRecent case evidence

Full-Text Mentions

NLP-detected gene mentions in article bodies · via PubTator3

PubTator3

RUNX1T1 function in cell fate

Hu N et al.·Stem Cell Res Ther

2022