GeneBe

CBFA2T3

protein-coding

CBFA2/RUNX1 partner transcriptional co-repressor 3, the group of Zinc fingers MYND-type|A-kinase anchoring proteins

Gene summary

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]

MANE transcript

NM_005187.6

Inheritance

—

ClinVar variants

U:136B:9

Top phenotype

Autism

gnomAD constraint

pLI —, LoF o/e 0.28

Max pathogenic AF

—

Genomic locus

chr16:88,874,858-88,977,207

External References & Databases

Ensembl (ENSG00000129993)NCBI Gene (863)OMIM (603870)HGNC:1537GenCCUniProt (O75081)AlphaFoldClinVar (CBFA2T3)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~102.3 kb
Loading mutation effect viewer...

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 CBFA2T3 variants in ClinVar

3 Conditions Cataloged
not specifiedTotal: 136
not providedTotal: 6
AutismTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005187.6. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
2
clinvar
1
clinvar
 4
missense
134
clinvar
6
clinvar
 140
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total0013681145
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_005187.6RefSeqNP_005178.412MANE Select
ENST00000268679.9EnsemblENSP00000268679.412MANE Select
NM_175931.3RefSeqNP_787127.110Standard
ENST00000327483.9EnsemblENSP00000332122.510Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
cbfa2t3Danio rerio

Structure: nucleate erythrocyte

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Hematopoietic Stem Cell Differentiation
  • ErbB4 signaling events

Biological Process

  • response to hypoxia
  • cell population proliferation
  • negative regulation of cell population proliferation
  • granulocyte differentiation
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process

Molecular Function

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

Cellular Component

  • Golgi membrane
  • nucleus
  • nucleoplasm
  • nucleolus

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000268679
Coding exons
12
Length
102347
Individuals with no LoFs
125448
Homozygous LoFs
0
Heterozygous LoFs
8
Defined
125456
p
0.0000319
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.1554284370.9790.00003184110
Missense (PolyPhen)93119.590.777651101
Synonymous-3.402642021.300.00001621378
Loss of Function3.60828.90.2770.00000165298

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish0.000100.000099rare
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000290.000026rare
South Asian0.000110.000098rare
Other00.0absent

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). Can repress the expression of MMP7 in a ZBTB33-dependent manner (PubMed:23251453). Reduces the protein levels and stability of the transcriptinal regulator HIF1A; interacts with EGLN1 and promotes the HIF1A prolyl hydroxylation-dependent ubiquitination and proteasomal degradation pathway (PubMed:25974097). Contributes to inhibition of glycolysis and stimulation of mitochondrial respiration by down-regulating the expression of glycolytic genes including PFKFB3, PFKFB4, PDK1, PFKP, LDHA and HK1 which are direct targets of HIF1A (PubMed:23840896, PubMed:25974097). Regulates the proliferation and the differentiation of erythroid progenitors by repressing the expression of TAL1 target genes (By similarity). Plays a role in granulocyte differentiation (PubMed:15231665). {ECO:0000250|UniProtKB:O54972, ECO:0000269|PubMed:12183414, ECO:0000269|PubMed:15231665, ECO:0000269|PubMed:16966434, ECO:0000269|PubMed:23251453, ECO:0000269|PubMed:23840896, ECO:0000269|PubMed:25974097, ECO:0000303|PubMed:12559562, ECO:0000303|PubMed:15203199}.;
Disease
DISEASE: Note=A chromosomal aberration involving CBFA2T3 is found in therapy-related myeloid malignancies. Translocation t(16;21)(q24;q22) that forms a RUNX1-CBFA2T3 fusion protein. {ECO:0000269|PubMed:10995019, ECO:0000269|PubMed:11224496, ECO:0000269|PubMed:9596646}.;

Recessive Scores

pRec
0.181

Intolerance Scores

LoFtool
0.281
RVIS EVS
-1.02
RVIS percentile EVS
8.14

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
S
Essential (gene trap)
K
Indispensability pred.
E
Indispensability score
0.985

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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