CBFA2T3

Chr 16

CBFA2/RUNX1 partner transcriptional co-repressor 3

Also known as: ETO2, MTG16, MTGR2, RUNX1T3, ZMYND4

NCBI Gene: 863 ENSG00000129993 UniProt: O75081 OMIM: 603870

The protein encoded by this gene functions as a transcriptional corepressor that facilitates gene silencing by recruiting other corepressors and histone-modifying enzymes to DNA-binding transcription factors. Mutations in CBFA2T3 cause autosomal dominant neurodevelopmental disorders with intellectual disability, autism spectrum disorder, and variable features including seizures and behavioral abnormalities. This gene is moderately constrained against loss-of-function mutations, and the associated conditions primarily affect the central nervous system with onset in early childhood.

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(16;21)(q24;q22) translocation is one of the less common 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. This gene is also a putative breast tumor suppressor. Alternative splicing results in transcript variants. [provided by RefSeq, Nov 2010]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.50

Clinical Summary— CBFA2T3

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.

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ClinVar Variants

133 VUS of 154 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.50LOEUF

pLI 0.048

Z-score 3.60

OE 0.28 (0.16–0.50)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.16Z-score

OE missense 0.98 (0.90–1.06)

428 obs / 437.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.28 (0.16–0.50)

0≤0.351.4

Missense OE?0.98 (0.90–1.06)

0≤0.61.4

Synonymous OE?1.30

0≤1.21.6

LoF obs/exp: 8 / 28.9Missense obs/exp: 428 / 437.1Syn Z: -3.40

This gene — mechanism propensity

0.6357th %ile

GOF

0.5464th %ile

LOF

0.55top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

154 submitted variants in ClinVar

ClinVar

Classification Summary

VUS133

Likely Benign9

Benign1

133

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	132	1	0	133
Likely Benign	6	1	2	9
Benign	0	0	1	1
Total	138	2	3	143

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

View in ClinVar →

70 pathogenic / likely-pathogenic (of 98) ClinVar copy-number / structural variants overlap CBFA2T3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →