CBFA2T2

protein-coding

CBFA2/RUNX1 partner transcriptional co-repressor 2, the group of Zinc fingers MYND-type

Gene summary

In acute myeloid leukemia, especially in the M2 subtype, the t(8;21)(q22;q22) translocation is one of the most frequent karyotypic abnormalities. The translocation produces a chimeric gene made up of the 5'-region of the RUNX1 (AML1) gene fused to the 3'-region of the CBFA2T1 (MTG8) gene. The chimeric protein is thought to associate with the nuclear corepressor/histone deacetylase complex to block hematopoietic differentiation. The protein encoded by this gene binds to the AML1-MTG8 complex and may be important in promoting leukemogenesis. Several transcript variants are thought to exist for this gene, but the full-length natures of only three have been described. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001032999.3

Inheritance

—

ClinVar variants

U:65B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr20:33,490,075-33,650,036

External References & Databases

Ensembl (ENSG00000078699)

Transcript & Mutation Effects

hg38 • Region Span ~160.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CBFA2T2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 66

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001032999.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar			2
missense			60 clinvar	3 clinvar		63
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	65	3	0	68

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001032999.3	RefSeq	NP_001028171.1	11	MANE Select
ENST00000342704.11	Ensembl	ENSP00000345810.6	11	MANE Select
NM_001039709.2	RefSeq	NP_001034798.1	10	Standard
NM_005093.4	RefSeq	NP_005084.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of transcription by RNA polymerase II
positive regulation of neuron projection development
negative regulation of neuron projection development
negative regulation of Notch signaling pathway
negative regulation of transcription, DNA-templated

Molecular Function

DNA-binding transcription factor activity
transcription corepressor activity
protein binding
metal ion binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000346541
Coding exons: 11
Length: 159962
Individuals with no LoFs: 125743
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 125746
p: 0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.48	235	369	0.637	0.0000221	3935
Missense (PolyPhen)		56	117.06	0.47837		1203
Synonymous	0.196	136	139	0.979	0.00000857	1223
Loss of Function	4.51	3	29.4	0.102	0.00000157	321

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional corepressor which facilitates transcriptional repression via its association with DNA-binding transcription factors and recruitment of other corepressors and histone-modifying enzymes (PubMed:12559562, PubMed:15203199). Via association with PRDM14 is involved in regulation of embryonic stem cell (ESC) pluripotency (PubMed:27281218). Involved in primordial germ cell (PCG) formation. Stabilizes PRDM14 and OCT4 on chromatin in a homooligomerization-dependent manner (By similarity). Can repress the expression of MMP7 in a ZBTB33- dependent manner (PubMed:23251453). May function as a complex with the chimeric protein RUNX1/AML1-CBFA2T1/MTG8 (AML1-MTG8/ETO fusion protein) which is produced in acute myeloid leukemia with the chromosomal translocation t(8;21). May thus be involved in the repression of AML1-dependent transcription and the induction of G- CSF/CSF3-dependent cell growth. May be a tumor suppressor gene candidate involved in myeloid tumors with the deletion of the 20q11 region. Through heteromerization with CBFA2T3/MTG16 may be involved in regulation of the proliferation and the differentiation of erythroid progenitors by repressing the expression of TAL1 target genes (By similarity). Required for the maintenance of the secretory cell lineage in the small intestine. Can inhibit Notch signaling probably by association with RBPJ and may be involved in GFI1-mediated Paneth cell differentiation (By similarity). {ECO:0000250|UniProtKB:O70374, ECO:0000269|PubMed:23251453, ECO:0000303|PubMed:12559562, ECO:0000303|PubMed:15203199}.;
Disease: DISEASE: Note=A chromosomal aberration involving CBFA2T2 is found in childhood precursor B-cell acute lymphoblastic leukemia (pre-B ALL). Translocation t(9;20)(p13;q11) with PAX5. {ECO:0000269|PubMed:26115422}.; DISEASE: Note=A chromosomal aberration involving CBFA2T2 is found in acute myeloid leukemia. Translocation t(20;21)(q11;q22) with RUNX1/AML1. {ECO:0000269|PubMed:20520637}.;

Recessive Scores

pRec: 0.277

Intolerance Scores

LoFtool: 0.432
RVIS EVS: -0.36
RVIS percentile EVS: 29.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.981

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium