RUNX1

Chr 21ADSomatic

RUNX family transcription factor 1

Also known as: AML1, AML1-EVI-1, AMLCR1, CBF2alpha, CBFA2, EVI-1, PEBP2aB, PEBP2alpha

NCBI Gene: 861ENSG00000159216UniProt: Q01196

Core binding factor (CBF) is a heterodimeric transcription factor that binds to the core element of many enhancers and promoters. The protein encoded by this gene represents the alpha subunit of CBF and is thought to be involved in the development of normal hematopoiesis. Chromosomal translocations involving this gene are well-documented and have been associated with several types of leukemia. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Leukemia, acute myeloidMIM #601626
ADSomatic
Platelet disorder, familial, with associated myeloid malignancyMIM #601399
AD
UniProtFamilial platelet disorder with associated myeloid malignancy
590
ClinVar variants
95
Pathogenic / LP
0.65
pLI score
9
Active trials
Clinical Summary— RUNX1
🧬
Gene-Disease Validity (ClinGen)
hereditary thrombocytopenia and hematologic cancer predisposition syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.65) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
95 Pathogenic / Likely Pathogenic· 350 VUS of 590 total submissions
💊
Clinical Trials
9 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.44LOEUF
pLI 0.654
Z-score 3.42
OE 0.19 (0.09–0.44)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.00Z-score
OE missense 0.68 (0.61–0.77)
218 obs / 318.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.19 (0.09–0.44)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.68 (0.61–0.77)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.73
0≤1.21.6
LoF obs/exp: 4 / 20.9Missense obs/exp: 218 / 318.4Syn Z: 2.56

ClinVar Variant Classifications

590 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic58
Likely Pathogenic37
VUS350
Likely Benign142
Benign3
58
Pathogenic
37
Likely Pathogenic
350
VUS
142
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
37
0
21
0
58
Likely Pathogenic
24
10
3
0
37
VUS
13
278
31
28
350
Likely Benign
0
4
43
95
142
Benign
0
1
1
1
3
Total7429399124590

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

View in ClinVar →

Protein Context — Lollipop Plot

RUNX1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

RUNX1-related platelet disorder, familial, with associated myeloid malignancy

definitive
ADLoss Of FunctionAbsent Gene Product
Cancer
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Leukemia, acute myeloid

MIM #601626

Molecular basis of disorder known

Autosomal dominantSomatic mutation

Platelet disorder, familial, with associated myeloid malignancy

MIM #601399

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — RUNX1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Severe congenital neutropenias.
Skokowa J et al.·Nat Rev Dis Primers
2017Review
Mapping human haematopoietic stem cells from haemogenic endothelium to birth.
Calvanese V et al.·Nature
2022
Combination of RUNX1 inhibitor and gemcitabine mitigates chemo-resistance in pancreatic ductal adenocarcinoma by modulating BiP/PERK/eIF2α-axis-mediated endoplasmic reticulum stress.
She C et al.·J Exp Clin Cancer Res
2023
A causal mechanism for childhood acute lymphoblastic leukaemia.
Greaves M·Nat Rev Cancer
2018Review
RUNX1 and cancer.
Lin TC·Biochim Biophys Acta Rev Cancer
2022Review
Methyl-CpG-binding 2 K271 lactylation-mediated M2 macrophage polarization inhibits atherosclerosis.
Chen L et al.·Theranostics
2024
Hyperglycemia Induces Trained Immunity in Macrophages and Their Precursors and Promotes Atherosclerosis.
Edgar L et al.·Circulation
2021
Integrating clinical features and genetic lesions in the risk assessment of patients with chronic myelomonocytic leukemia.
Elena C et al.·Blood
2016Cohort
Hematopoietic Transcription Factor RUNX1 is Essential for Promoting Macrophage-Myofibroblast Transition in Non-Small-Cell Lung Carcinoma.
Tang PC et al.·Adv Sci (Weinh)
2024
RUNX1-ETO Leukemia.
Lin S et al.·Adv Exp Med Biol
2017Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
A genetic architect of opioid responses: Microglial Runx1.
Dong D et al.·Neuron
2026
Differential Prognosis and Transplant Strategies in CBF-AML With RUNX1::RUNX1T1 Versus CBFβ::MYH11 Fusions.
Huang J et al.·Am J Hematol
2026
Nomogram-based prediction models for clinical outcomes in pediatric RUNX1::RUNX1T1-positive acute myeloid leukemia: a retrospective analysis from AML-CAMS serial trials.
Chen X et al.·Front Oncol
2026🔓 Open AccessFunctional
RUNX1 is a mediator of fibrotic activation and epigenetic memory in lung fibroblasts.
Gilbert RM et al.·Am J Respir Cell Mol Biol
2026
Comprehensive multi-omics analysis reveals RUNX1's prognostic value, immune associations, and MUC13-Mediated mechanistic role in hepatocellular carcinoma pathogenesis.
ALMatrafi TA.·Biochem Biophys Rep
2026🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Chronic Myeloid Leukemia, Chronic PhaseWithdrawal;Drug

Efficacy and Safety of TKIs' Withdrawal After a Two-step Dose Reduction in Patients with Chronic Myeloid Leukemia

ACTIVE NOT RECRUITING
NCT04147533Phase PHASE2Masaryk UniversityStarted 2020-06-16
Imatinib withdrawalDasatinibNilotinib
Acute Myeloid LeukemiaRecurrent Acute Myeloid LeukemiaRefractory Acute Myeloid Leukemia

Entrectinib in Combination With ASTX727 for the Treatment of Relapsed/Refractory TP53 Mutated Acute Myeloid Leukemia

ACTIVE NOT RECRUITING
NCT05396859Phase PHASE1OHSU Knight Cancer InstituteStarted 2022-10-28
Decitabine and CedazuridineEntrectinibLaboratory Biomarker Analysis
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

IDH Targeted/Non- Targeted vs Non-targeted/IDH-targeted Approaches in the Treatment of Newly Diagnosed IDH Mutated AML Patients Not Candidates for Intensive Induction Therapy (I- DATA Study)

RECRUITING
NCT05401097Phase PHASE2Alice MimsStarted 2022-09-13
AzacitidineBiopsyEnasidenib
Inherited Hematological DiseasesRare DiseasesFPDMM

Longitudinal Studies of Patient With FPDMM

RECRUITING
NCT03854318National Human Genome Research Institute (NHGRI)Started 2019-03-28
Bone Marrow Failure DisordersVEXAS SyndromeHemoglobinurea, Paroxysmal

Molecular and Clinical Analysis of Bone Marrow Failure: A Secondary Research Study

ENROLLING BY INVITATION
NCT07102849National Heart, Lung, and Blood Institute (NHLBI)Started 2025-09-09
Polycythemia VeraEssential ThrombocythaemiaMyelofibrosis

Prevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History

NOT YET RECRUITING
NCT06923670Phase NAFondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2025-05-21
NGS testingNGS analysis for mutations in genes involved in familial predisposition to hematological malignancies
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
Group A (FIT): Avapritinib + IA regimenGroup B (UNFIT): Avapritinib + VA regimen
Inherited Bone Marrow Failure SyndromeFamilial Platelet Disorder With Predisposition to Myeloid Malignancies

Imatinib to Increase RUNX1 Activity in Participants With Germline RUNX1 Deficiency

RECRUITING
NCT06090669Phase PHASE1National Cancer Institute (NCI)Started 2023-12-19
imatinibTruSight Oncology

External Resources

Links to major genomics databases and tools