CBFA2T3

Summary

CBFA2T3 (CBFA2/RUNX1 partner transcriptional co-repressor 3, HGNC:1537) is a protein-coding gene on chromosome 16q24.3, encoding Transcriptional corepressor CBFA2T3 (O75081). Transcriptional corepressor which facilitates transcriptional repression via its association with DNA-binding transcription factors and recruitment of other corepressors and histone-modifying enzymes.

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.

Source: NCBI Gene 863 — RefSeq curated summary.

At a glance

• GWAS associations: 23
• Clinical variants (ClinVar): 158 total — 3 pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_005187

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1537
Approved symbol	CBFA2T3
Name	CBFA2/RUNX1 partner transcriptional co-repressor 3
Location	16q24.3
Locus type	gene with protein product
Status	Approved
Aliases	MTGR2, ZMYND4, MTG16, RUNX1T3, ETO2
Ensembl gene	ENSG00000129993
Ensembl biotype	protein_coding
OMIM	603870
Entrez	863

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000268679, ENST00000327483, ENST00000562719, ENST00000563640, ENST00000563856, ENST00000563920, ENST00000564416, ENST00000566868, ENST00000569443, ENST00000569464, ENST00000570046

RefSeq mRNA: 2 — MANE Select: NM_005187 NM_005187, NM_175931

CCDS: CCDS10972, CCDS10973

Canonical transcript exons

ENST00000268679 — 12 exons

Exon	Start	End
ENSE00000946068	88891882	88891971
ENSE00001305140	88898078	88898152
ENSE00001825844	88874858	88877275
ENSE00002222897	88881291	88881489
ENSE00002229748	88885046	88885269
ENSE00002240324	88882676	88882761
ENSE00002255220	88885961	88886142
ENSE00002619134	88976657	88977207
ENSE00003464121	88879270	88879460
ENSE00003516637	88901504	88901656
ENSE00003596355	88880720	88880788
ENSE00003785867	88892244	88892485

Expression profiles

Bgee: expression breadth ubiquitous, 197 present calls, max score 94.09.

FANTOM5 (CAGE): breadth broad, TPM avg 9.4048 / max 504.1870, expressed in 727 samples.

FANTOM5 promoters (19 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158592	3.3969	562
158604	1.6597	156
158606	1.0823	167
158605	1.0165	177
158603	0.7390	108
158607	0.5191	114
158598	0.2061	109
158601	0.1739	55
158593	0.1525	85
158595	0.1009	34

Top tissues by expression

279 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
endometrium epithelium	UBERON:0004811	94.09	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.32	gold quality
cerebellar hemisphere	UBERON:0002245	92.64	gold quality
cerebellar cortex	UBERON:0002129	92.47	gold quality
thymus	UBERON:0002370	91.77	gold quality
cerebellum	UBERON:0002037	90.93	gold quality
apex of heart	UBERON:0002098	89.53	gold quality
monocyte	CL:0000576	89.21	gold quality
mononuclear cell	CL:0000842	88.64	gold quality
leukocyte	CL:0000738	88.46	gold quality
granulocyte	CL:0000094	88.34	gold quality
body of pancreas	UBERON:0001150	87.82	gold quality
spleen	UBERON:0002106	86.33	gold quality
right lung	UBERON:0002167	86.07	gold quality
paraflocculus	UBERON:0005351	84.59	gold quality
bone marrow cell	CL:0002092	84.56	gold quality
tendon of biceps brachii	UBERON:0008188	83.66	silver quality
blood	UBERON:0000178	83.41	gold quality
Brodmann (1909) area 10	UBERON:0013541	83.00	gold quality
heart left ventricle	UBERON:0002084	82.84	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.51	gold quality
cardiac ventricle	UBERON:0002082	82.24	gold quality
secondary oocyte	CL:0000655	81.66	gold quality
upper lobe of left lung	UBERON:0008952	81.66	gold quality
pancreas	UBERON:0001264	81.39	gold quality
upper lobe of lung	UBERON:0008948	81.27	gold quality
cortical plate	UBERON:0005343	81.09	gold quality
gastrocnemius	UBERON:0001388	80.86	gold quality
muscle of leg	UBERON:0001383	80.46	gold quality
endothelial cell	CL:0000115	80.20	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	7.36
E-ANND-3	yes	6.22
E-CURD-112	no	3.65

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
EPB42
TCF12	Unknown
ZNF652	Repression

Upstream regulators (CollecTRI, top): GATA1, RUNX1, SPI1, TAL1, TCF12, ZBTB33, ZBTB38, ZBTB4

miRNA regulators (miRDB)

203 targeting CBFA2T3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784

Literature-anchored findings (GeneRIF, showing 31)

• In the first pediatric leukemia case in whom AML1-MTG16 was identified, the breakpoint of MTG16 was determined, and suggested as a possible characteristic of secondary leukemia. (PMID:11999578)
• CBFA2T3 (MTG16) is a putative breast tumor suppressor gene from the breast cancer loss of heterozygosity region at 16q24.3. (PMID:12183414)
• The transcriptional repression of growth factor independent-1 (GFI-1), a previously characterized ETO effector zinc finger protein, was shown to be enhanced by CBFA2T1, but to a lesser extent by CBFA2T2 and CBFA2T3. (PMID:16966434)
• CBFA2T3 interacts with ZNF652 to repress HEB expression, and in addition CBFA2T3 interacts with the HEB protein to inhibit its activator function. (PMID:18456661)
• ETO family member-mediated oligomerization and repression can be distinct events and that interaction between ETO family members and hSIN3B or N-CoR may not necessarily strengthen transcriptional repression. (PMID:18586123)
• RUNX1-MTG16 fusion gene in acute myeloblastic leukemia with t(16/21)(q24’q22) is reported. (PMID:18656694)
• Both wild type MTGs and chimeric AML1-MTG proteins display in vitro RNA-binding properties (PMID:18950503)
• Data show that ZNF651 is a ZNF652 paralogue that shares a common DNA binding sequence with ZNF652 and represses target gene expression through the formation of a CBFA2T3-ZNF651 corepressor complex. (PMID:20116376)
• Study provides the first evidence that MTG16b is a dual AKAP capable of binding plexins. (PMID:20138877)
• Alternative NLI complexes mediate gamma-globin transcription or silencing through long-range locus control region interactions involving an intergenic site of noncoding RNA transcription and that ETO2 is critical to this process. (PMID:22010104)
• Our data indicate that the CBFA2T3/ACSF3 locus is a novel recurrent oncogenic target of immunoglobulin heavy chain translocations, which might contribute to the pathogenesis of pediatric GC-derived B-cell lymphoma. (PMID:22420028)
• An evolutionary conserved GATA binding site is critical in transcriptional regulation of the MTG16 promoter. (PMID:22443175)
• Data indicate taht ETO2/CBFA2T3 regulates GATA-1 target genes critical for erythroid differentiation, and the decrease of ETO2 levels during erythroid differentiation would contribute to the activation of these targets. (PMID:23127762)
• Identification of a cryptic chromosome 16 inversion (inv(16)(p13.3q24.3)) in 27% of pediatric acute megakaryoblastic leukemia cases, which encodes a CBFA2T3-GLIS2 fusion protein. (PMID:23153540)
• presence of MTG16 in this complex, and its contributions to transcriptional repression both required Kaiso binding to its binding site on DNA, establishing MTG16-Kaiso binding as functionally relevant in Kaiso-dependent transcriptional repression (PMID:23251453)
• Expression of MTG16 reduced glycolytic metabolism while mitochondrial respiration and formation of reactive oxygen species increased. (PMID:23840896)
• Findings are unprecedented and indicate that the DHH-RHEBL1 fusion transcript is a novel recurrent feature in the changing landscape of CBFA2T3-GLIS2-positive childhood AML. (PMID:24127550)
• study defined eight additional recurrently mutated genes in SMZL; these genes are CREBBP, CBFA2T3, AMOTL1, FAT4, FBXO11, PLA2G4D, TRRAP and USH2A. (PMID:24349473)
• MTG16 co-repressor promotes degradation of HIF1alpha in lymphoblasts. (PMID:25974097)
• ETO2 and IRF2BP2 interacting with the NCOR1/SMRT co-repressor complex, suppresses the expression of erythroid genes until erythroid differentiation. (PMID:26593974)
• The here presented transcriptomic subgroup-based approach unified the gene expression profiles of RUNX1-CBFA2T3 and RUNX1-RUNX1T1 acute myeloid leukemia. (PMID:26968532)
• Clinical courses of pediatric patients with AMKL harboring the CBFA2T3-GLIS2 fusion gene are poor due to resistance to chemotherapies and SCT. New treatment strategies are necessary. (PMID:27094503)
• Analysis of chromatin immunoprecipitation sequencing data sets for MTGR1 and MTG16 targets indicated that MTGR1 can regulate Wnt and Notch signaling. (PMID:27270437)
• CBFA2T3 expression is regulated by Med19 in breast cancer cells. (PMID:27572702)
• specific interference with ETO2-GLIS2 oligomerization reverses the transcriptional activation at enhancers and promotes megakaryocytic differentiation, providing a relevant interface to target in this poor-prognosis pediatric leukemia. (PMID:28292442)
• Kaiso modifies MTG16-driven inflammation and tumorigenesis; this suggests that Kaiso deregulation contributes to MTG16-dependent colitis and Colitis-associated carcinoma phenotypes. (PMID:30858547)
• CBFA2T3 is functional in t(8;21) acute myeloid leukemia cells, a possible RUNX1-RUNX1T1-mediated direct interference of CBFA2T3 corepressor function may be compensated by a higher threshold level of CBFA2T3 expression that is needed to drive the relapse of t(8;21) acute myeloid leukemia. (PMID:31040112)
• These findings suggest rs13333659 in CBFA2T3 as a risk locus to modulate the decline rate of cerebrospinal fluid amyloid-beta42 peptide preceding the onset of clinical symptoms (PMID:31370031)
• The transcriptional corepressor CBFA2T3 inhibits all-trans-retinoic acid-induced myeloid gene expression and differentiation in acute myeloid leukemia. (PMID:32434928)
• Embryonic erythropoiesis and hemoglobin switching require transcriptional repressor ETO2 to modulate chromatin organization. (PMID:32960220)
• CNS erythroblastic sarcoma: a potential emerging pediatric tumor type characterized by NFIA::RUNX1T1/3 fusions. (PMID:38243303)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cbfa2t3	ENSDARG00000079012
mus_musculus	Cbfa2t3	ENSMUSG00000006362
rattus_norvegicus	Cbfa2t3	ENSRNOG00000014723
drosophila_melanogaster	nvy	FBGN0005636

Paralogs (2): CBFA2T2 (ENSG00000078699), RUNX1T1 (ENSG00000079102)

Protein

Protein identifiers

Transcriptional corepressor CBFA2T3 — O75081 (reviewed: O75081)

Alternative names: MTG8-related protein 2, Myeloid translocation gene on chromosome 16 protein, Zinc finger MYND domain-containing protein 4

All UniProt accessions (8): O75081, H3BMZ0, H3BNH2, H3BNI7, H3BR72, H3BSI4, H3BU07, J3QRB1

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional corepressor which facilitates transcriptional repression via its association with DNA-binding transcription factors and recruitment of other corepressors and histone-modifying enzymes. Can repress the expression of MMP7 in a ZBTB33-dependent manner. 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. 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. Regulates the proliferation and the differentiation of erythroid progenitors by repressing the expression of TAL1 target genes. Plays a role in granulocyte differentiation. Isoform 2 functions as an A-kinase-anchoring protein.

Subunit / interactions. Homooligomer. Homotetramerization is mediated by nervy homology region 2 (NRH2). Can interact with RUNX1T1 and CBFA2T2; heterotetramerization between members of the CBFA2T family is proposed. Component of a TAL-1 complex composed at least of CBFA2T3, LDB1, TAL1 and TCF3. Interacts with ERBB4, HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, NCOR1, NCOR2, and ZNF652. According to PubMed:12242670, may not interact with HDAC6. Interacts with PLXNA1, PLXNA3 and PRKAR1A. Isoform 2 interacts with PRKAR2A, PDE7A and probably PDE4A. Interacts with ZBTB4, ZBTB38 and ZBTB33. Interacts with HIF1A and EGLN1. Interacts with the AML1-MTG8/ETO fusion protein. Interacts with ZNF652.

Subcellular location. Nucleus. Nucleolus Nucleus. Nucleoplasm. Golgi apparatus membrane.

Tissue specificity. Widely expressed with higher expression in heart, pancreas, skeletal muscle, spleen, thymus and peripheral blood leukocytes. Expressed in hematopoietic cells (at protein level).

Disease relevance. 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.

Domain organisation. Nervy homology region 2 (NHR2) mediates homo- and possibly heterotypic oligomerization by forming a four-helix bundle tetrameric structure.

Induction. Down-regulated by all-trans retinoic acid (ATRA).

Similarity. Belongs to the CBFA2T family.

Isoforms (4)

UniProt ID	Names	Canonical?
O75081-1	1, CBFA2T3A, MTG16a	yes
O75081-2	2, CBFA2T3B, MTG16b
O75081-4	3, MTG16c
O75081-5	4, MTG16HEL

RefSeq proteins (2): NP_005178, NP_787127 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002893	Znf_MYND	Domain
IPR003894	TAFH_NHR1	Domain
IPR013289	CBFA2T1/2/3	Family
IPR013292	CBFA2T3	Family
IPR014896	NHR2	Domain
IPR037249	TAFH/NHR1_dom_sf	Homologous_superfamily

Pfam: PF01753, PF07531, PF08788

UniProt features (61 total): region of interest 12, compositionally biased region 8, binding site 8, modified residue 6, sequence conflict 6, splice variant 5, sequence variant 4, site 2, turn 2, strand 2, chain 1, domain 1, coiled-coil region 1, zinc finger region 1, mutagenesis site 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9DE2	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75081-F1	62.26	0.26

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 51–52 (breakpoint for translocation to form type-1 runx1-cbfa2t3 fusion protein); 127–128 (breakpoint for translocation to form type-2 runx1-cbfa2t3 fusion protein)

Ligand- & substrate-binding residues (8): 556; 559; 567; 570; 576; 580; 588; 592

Post-translational modifications (6): 457, 459, 479, 637, 641, 650

Mutagenesis-validated functional residues (1):

Position	Phenotype
494	loss of interaction with prkar2a.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 351 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GOBP_MYELOID_CELL_DIFFERENTIATION, GSE45365_NK_CELL_VS_CD8A_DC_DN, RNGTGGGC_UNKNOWN, RRAGTTGT_UNKNOWN, ACTACCT_MIR196A_MIR196B, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GCANCTGNY_MYOD_Q6, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, AP4_Q6

GO Biological Process (11): negative regulation of transcription by RNA polymerase II (GO:0000122), response to hypoxia (GO:0001666), DNA-templated transcription (GO:0006351), negative regulation of cell population proliferation (GO:0008285), granulocyte differentiation (GO:0030851), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), negative regulation of glycolytic process (GO:0045820), negative regulation of DNA-templated transcription (GO:0045892), regulation of aerobic respiration (GO:1903715), regulation of DNA-templated transcription (GO:0006355), cell differentiation (GO:0030154)

GO Molecular Function (4): transcription corepressor activity (GO:0003714), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (6): Golgi membrane (GO:0000139), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), Golgi apparatus (GO:0005794), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of DNA-templated transcription	2
DNA-templated transcription	2
intracellular membrane-bounded organelle	2
nuclear lumen	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
response to stress	1
response to decreased oxygen levels	1
gene expression	1
RNA biosynthetic process	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
myeloid leukocyte differentiation	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
positive regulation of proteasomal protein catabolic process	1
positive regulation of ubiquitin-dependent protein catabolic process	1
glycolytic process	1
regulation of glycolytic process	1
negative regulation of purine nucleotide catabolic process	1
negative regulation of carbohydrate metabolic process	1
negative regulation of ATP metabolic process	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
aerobic respiration	1
regulation of cellular respiration	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cellular developmental process	1
transcription coregulator activity	1
transition metal ion binding	1
binding	1
cation binding	1
Golgi apparatus	1
bounding membrane of organelle	1
intracellular membraneless organelle	1
cytoplasm	1
endomembrane system	1

Protein interactions and networks

STRING

1938 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CBFA2T3	LDB1	Q86U70	982
CBFA2T3	LDB2	O43679	981
CBFA2T3	RUNX1	Q01196	955
CBFA2T3	GATA1	P15976	946
CBFA2T3	TAL1	P17542	886
CBFA2T3	GLIS2	Q9BZE0	797
CBFA2T3	LYL1	P12980	775
CBFA2T3	HDAC1	Q13547	768
CBFA2T3	SPI1	P17947	760
CBFA2T3	ZNF652	Q9Y2D9	758
CBFA2T3	TCF3	P15883	757
CBFA2T3	CBFB	Q13951	754
CBFA2T3	LMO2	P25791	740
CBFA2T3	NCOR1	O75376	680
CBFA2T3	ZBTB47	Q9UFB7	662

IntAct

33 interactions, top by confidence:

A	B	Type	Score
PRDM14	CBFA2T2	psi-mi:“MI:0914”(association)	0.860
TAL1	KDM1A	psi-mi:“MI:0914”(association)	0.560
CBFA2T2	CBFA2T3	psi-mi:“MI:0914”(association)	0.530
CBFA2T3	CBFA2T2	psi-mi:“MI:0914”(association)	0.530
TCF4	CBFA2T3	psi-mi:“MI:0914”(association)	0.530
PLXNA3	CBFA2T3	psi-mi:“MI:0915”(physical association)	0.520
CBFA2T3	ZNF652	psi-mi:“MI:0915”(physical association)	0.510
CBFA2T3	ZBTB47	psi-mi:“MI:0915”(physical association)	0.400
Prkar1a	CBFA2T3	psi-mi:“MI:0915”(physical association)	0.400
ATN1	CBFA2T3	psi-mi:“MI:0915”(physical association)	0.370
CBFA2T3	CHRM4	psi-mi:“MI:0915”(physical association)	0.370
MATN2	CBFA2T3	psi-mi:“MI:0915”(physical association)	0.370
SEC24A	CBFA2T3	psi-mi:“MI:0915”(physical association)	0.370
CBFA2T3	GMEB2	psi-mi:“MI:0915”(physical association)	0.370
TCF4	TRIM24	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
TRIM33	CBFA2T2	psi-mi:“MI:0914”(association)	0.350
SYCE3	CBFA2T3	psi-mi:“MI:0914”(association)	0.350
EXOSC5	CNOT1	psi-mi:“MI:2364”(proximity)	0.270
ILF3	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
NONO	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
PPIL4	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
QKI	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
ZC3H11A	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
ZRANB2	SBNO1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (121): CBFA2T3 (Affinity Capture-MS), TAL1 (Affinity Capture-MS), CBFA2T3 (Affinity Capture-MS), CBFA2T3 (Affinity Capture-MS), CBFA2T3 (Reconstituted Complex), HIF1A (Reconstituted Complex), HIF1A (Affinity Capture-Western), CBFA2T3 (Affinity Capture-Western), PDK1 (Co-localization), PFKFB3 (Co-localization), PFKFB4 (Co-localization), LDHA (Co-localization), HK1 (Co-localization), PFKM (Co-localization), EGLN1 (Affinity Capture-Western)

ESM2 similar proteins: A0A087WPF7, A0A0R4IBL7, O09000, O54972, O70305, O75081, O75376, P15806, P15881, P15884, P15923, P21677, P30985, P51514, P98180, Q05AQ8, Q14157, Q14687, Q1LY51, Q2VPM4, Q3U3C9, Q4KKX4, Q4VCS5, Q566L4, Q5F3B1, Q5SFM8, Q5T6F2, Q60722, Q60974, Q61286, Q62655, Q6DIH5, Q7ZWN6, Q7ZXS3, Q80X50, Q86YP4, Q8BZ47, Q8CHY6, Q8IXK0, Q8VHG2

Diamond homologs: O00268, O43439, O54972, O70374, O75081, O75398, O77562, O88450, P47825, Q06455, Q5F3B1, Q61909, Q9IAB2, Q9Z1T5, O88873, P23497, P58929, Q13342, Q3KRF1, Q8BVK9, Q921C6, Q9H930, Q9HB58, Q9UKD1, Q24180

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CBFA2T3	“down-regulates activity”	ZNF652	binding
CBFA2T3	“form complex”	CBFA2T3/ZNF651	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

158 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	134
Likely benign	9
Benign	1

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
3243662	NC_000016.9:g.(?88851289)(89383486_?)del	Pathogenic
998057	inv(16)(p13.3q24.3)	Pathogenic
998058	t(16;16)(p13.3;q24.3)	Pathogenic

SpliceAI

3674 predictions. Top by Δscore:

Variant	Effect	Δscore
16:88879264:CCCTA:C	donor_loss	1.0000
16:88879265:CCTA:C	donor_loss	1.0000
16:88879266:CTACC:C	donor_loss	1.0000
16:88879267:TAC:T	donor_loss	1.0000
16:88879268:A:AC	donor_gain	1.0000
16:88879269:C:CC	donor_gain	1.0000
16:88879269:C:G	donor_loss	1.0000
16:88879269:CCTCG:C	donor_gain	1.0000
16:88879283:T:TA	donor_gain	1.0000
16:88879456:CTCTT:C	acceptor_gain	1.0000
16:88879458:CTT:C	acceptor_gain	1.0000
16:88879458:CTTCT:C	acceptor_loss	1.0000
16:88879459:TT:T	acceptor_gain	1.0000
16:88879460:TC:T	acceptor_loss	1.0000
16:88879461:C:CC	acceptor_gain	1.0000
16:88879462:T:A	acceptor_loss	1.0000
16:88880718:A:AC	donor_gain	1.0000
16:88880718:ACCAG:A	donor_gain	1.0000
16:88880719:C:CC	donor_gain	1.0000
16:88880719:CCAGC:C	donor_gain	1.0000
16:88880726:T:TA	donor_gain	1.0000
16:88880786:CGT:C	acceptor_gain	1.0000
16:88881287:GCAC:G	donor_loss	1.0000
16:88881288:CACC:C	donor_loss	1.0000
16:88881289:ACCTA:A	donor_loss	1.0000
16:88881290:C:G	donor_loss	1.0000
16:88881290:CCTAG:C	donor_gain	1.0000
16:88881294:G:C	donor_gain	1.0000
16:88881305:TCGGG:T	donor_gain	1.0000
16:88881490:C:CA	acceptor_loss	1.0000

AlphaMissense

4225 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:88877183:C:A	W585C	1.000
16:88877183:C:G	W585C	1.000
16:88877184:C:G	W585S	1.000
16:88877185:A:G	W585R	1.000
16:88877185:A:T	W585R	1.000
16:88877198:G:C	C580W	1.000
16:88877199:C:A	C580F	1.000
16:88877199:C:G	C580S	1.000
16:88877199:C:T	C580Y	1.000
16:88877200:A:G	C580R	1.000
16:88877200:A:T	C580S	1.000
16:88877210:G:C	C576W	1.000
16:88877211:C:A	C576F	1.000
16:88877211:C:G	C576S	1.000
16:88877211:C:T	C576Y	1.000
16:88877212:A:G	C576R	1.000
16:88877212:A:T	C576S	1.000
16:88877214:T:C	Y575C	1.000
16:88877215:A:C	Y575D	1.000
16:88877215:A:G	Y575H	1.000
16:88877229:C:G	C570S	1.000
16:88877229:C:T	C570Y	1.000
16:88877230:A:G	C570R	1.000
16:88877230:A:T	C570S	1.000
16:88877237:G:C	C567W	1.000
16:88877238:C:G	C567S	1.000
16:88877238:C:T	C567Y	1.000
16:88877239:A:G	C567R	1.000
16:88877239:A:T	C567S	1.000
16:88877261:G:C	C559W	1.000

dbSNP variants (sampled 300 via entrez): RS1000007589 (16:88945147 A>G), RS1000010322 (16:88944171 A>T), RS1000013028 (16:88919061 C>T), RS1000061063 (16:88971854 C>T), RS1000069587 (16:88896520 G>A,T), RS1000106783 (16:88874374 A>T), RS1000109844 (16:88874425 C>T), RS1000110087 (16:88916753 C>A,G), RS1000122824 (16:88886776 G>A), RS1000126516 (16:88922274 T>C), RS1000139924 (16:88895993 G>A), RS1000166964 (16:88878076 C>G,T), RS1000173061 (16:88930869 G>A), RS1000181458 (16:88939964 C>CGTCCG), RS1000181784 (16:88929189 T>G)

Disease associations

OMIM: gene MIM:603870 | disease phenotypes: MIM:209850

GenCC curated gene-disease

Mondo (2): autism (MONDO:0005260), acute megakaryoblastic leukemia without down syndrome (MONDO:0018004)

Orphanet (1): Acute megakaryoblastic leukemia in children without Down syndrome (Orphanet:329469)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST002228_6	Social autistic-like traits	8.000000e-06
GCST003479_9	Hair color	1.000000e-07
GCST004599_111	Mean platelet volume	5.000000e-11
GCST004630_208	Mean corpuscular hemoglobin	2.000000e-12
GCST004785_4	Vitiligo	5.000000e-08
GCST006986_21	Red vs. brown/black hair color	1.000000e-30
GCST007436_8	Carotid intima media thickness	6.000000e-09
GCST008476_17	Emphysema annual change measurement in smokers (percent low attenuation area)	4.000000e-07
GCST008476_9	Emphysema annual change measurement in smokers (percent low attenuation area)	5.000000e-06
GCST008642_1	Annualised percent change of cerebrospinal fluid AB1-42 levels	2.000000e-09
GCST009597_124	Multiple sclerosis	1.000000e-06
GCST009921_6	Carotid intima media thickness (mean)	4.000000e-09
GCST010083_109	Hemoglobin levels	1.000000e-09
GCST011065_5	Levodopa-induced dyskinesia in levodopa treated Parkinson’s disease	1.000000e-06
GCST90002387_17	Immature fraction of reticulocytes	4.000000e-13
GCST90002389_213	Lymphocyte percentage of white cells	2.000000e-11
GCST90002390_100	Mean corpuscular hemoglobin	1.000000e-25
GCST90002390_99	Mean corpuscular hemoglobin	7.000000e-11
GCST90002392_518	Mean corpuscular volume	6.000000e-18
GCST90002395_231	Mean platelet volume	1.000000e-18
GCST90002396_601	Mean reticulocyte volume	8.000000e-15
GCST90002398_257	Neutrophil count	7.000000e-12
GCST90002404_346	Red cell distribution width	2.000000e-12

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0005426	autism spectrum disorder symptom
EFO:0004527	mean corpuscular hemoglobin
EFO:0003924	hair color
EFO:0007626	emphysema imaging measurement
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0004509	hemoglobin measurement
EFO:0010747	response to levodopa
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0010701	mean reticulocyte volume
EFO:0004833	neutrophil count
EFO:0009188	Red cell distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	4
bisphenol A	decreases expression, increases expression, affects methylation, affects cotreatment, decreases methylation	2
Tobacco Smoke Pollution	affects expression, decreases methylation	2
Genistein	increases expression	2
triphenyl phosphate	affects expression	1
pirinixic acid	increases activity, affects binding, decreases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
pentanal	increases expression	1
abrine	increases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation, increases methylation	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects methylation	1
Cadmium	increases expression	1
Diethylstilbestrol	increases expression	1
Estradiol	increases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment, decreases expression	1
Methapyrilene	increases methylation	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, decreases expression	1
Rotenone	increases expression	1
Tretinoin	decreases expression	1
Valproic Acid	affects expression	1
Zearalenone	increases expression	1
Aflatoxin B1	affects methylation	1

Cellosaurus cell lines

18 cell lines: 15 cancer cell line, 2 induced pluripotent stem cell, 1 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0559	TF-1	Cancer cell line	Male
CVCL_2106	M-07e	Cancer cell line	Female
CVCL_3607	TF-1.CN5a.1	Cancer cell line	Male
CVCL_3608	TF-1a	Cancer cell line	Male
CVCL_5607	WSU-AML	Cancer cell line
CVCL_8059	TF-1 D2	Cancer cell line	Male
CVCL_8060	TF-1 D8	Cancer cell line	Male
CVCL_A4BL	TF-1 IDH2 p.R140Q-Luc2	Cancer cell line	Male
CVCL_A4BP	TF-1-Luc2	Cancer cell line	Male
CVCL_J294	TF-1 BCR/ABL	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms