TAL1

Summary

TAL1 (TAL bHLH transcription factor 1, erythroid differentiation factor, HGNC:11556) is a protein-coding gene on chromosome 1p33, encoding T-cell acute lymphocytic leukemia protein 1 (P17542). Implicated in the genesis of hemopoietic malignancies.

Enables several functions, including E-box binding activity; RNA polymerase II-specific DNA-binding transcription factor binding activity; and histone deacetylase binding activity. Involved in several processes, including myeloid cell differentiation; positive regulation of cellular component organization; and positive regulation of erythrocyte differentiation. Located in chromatin and nucleoplasm. Part of transcription regulator complex. Implicated in acute lymphoblastic leukemia.

Source: NCBI Gene 6886 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 64 total
• Phenotypes (HPO): 3
• Cancer driver (intOGen): ambiguous (mixed evidence) across 1 cancer types
• Transcription factor: yes — 106 downstream targets (CollecTRI)
• MANE Select transcript: NM_001290403

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11556
Approved symbol	TAL1
Name	TAL bHLH transcription factor 1, erythroid differentiation factor
Location	1p33
Locus type	gene with protein product
Status	Approved
Aliases	SCL, bHLHa17
Ensembl gene	ENSG00000162367
Ensembl biotype	protein_coding
OMIM	187040
Entrez	6886

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000294339, ENST00000371884, ENST00000459729, ENST00000465912, ENST00000481091, ENST00000691006, ENST00000859820, ENST00000859821

RefSeq mRNA: 6 — MANE Select: NM_001290403 NM_001287347, NM_001290403, NM_001290404, NM_001290405, NM_001290406, NM_003189

CCDS: CCDS547

Canonical transcript exons

ENST00000691006 — 5 exons

Exon	Start	End
ENSE00001064461	47225443	47225889
ENSE00001131020	47224004	47224098
ENSE00001456379	47229196	47229351
ENSE00001823382	47232167	47232225
ENSE00003938481	47216291	47220174

Expression profiles

Bgee: expression breadth ubiquitous, 200 present calls, max score 97.74.

FANTOM5 (CAGE): breadth broad, TPM avg 4.5639 / max 394.3598, expressed in 417 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12219	1.3676	255
12227	0.9657	160
12224	0.8780	276
12228	0.3698	55
12222	0.3285	131
12225	0.1424	68
12226	0.1159	55
12223	0.1105	64
12220	0.1045	46
12229	0.0771	24

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trabecular bone tissue	UBERON:0002483	97.74	gold quality
monocyte	CL:0000576	93.22	gold quality
mononuclear cell	CL:0000842	92.51	gold quality
leukocyte	CL:0000738	91.61	gold quality
bone marrow	UBERON:0002371	89.66	gold quality
right lung	UBERON:0002167	88.68	gold quality
endothelial cell	CL:0000115	88.63	gold quality
blood	UBERON:0000178	87.33	gold quality
upper lobe of left lung	UBERON:0008952	85.77	gold quality
bone marrow cell	CL:0002092	85.30	gold quality
upper lobe of lung	UBERON:0008948	84.97	gold quality
buccal mucosa cell	CL:0002336	82.92	silver quality
omental fat pad	UBERON:0010414	81.48	gold quality
peritoneum	UBERON:0002358	81.42	gold quality
adipose tissue of abdominal region	UBERON:0007808	81.02	gold quality
colonic epithelium	UBERON:0000397	80.86	gold quality
apex of heart	UBERON:0002098	80.65	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	80.13	silver quality
spleen	UBERON:0002106	79.97	gold quality
granulocyte	CL:0000094	79.79	gold quality
lung	UBERON:0002048	79.15	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.76	gold quality
subcutaneous adipose tissue	UBERON:0002190	78.68	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.93	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	77.57	gold quality
left lobe of thyroid gland	UBERON:0001120	77.47	gold quality
right lobe of thyroid gland	UBERON:0001119	77.42	gold quality
adipose tissue	UBERON:0001013	77.31	gold quality
lower lobe of lung	UBERON:0008949	77.13	gold quality
connective tissue	UBERON:0002384	77.09	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-75367	yes	464.54
E-CURD-112	yes	55.28
E-ANND-3	yes	7.45
E-HCAD-9	yes	5.43
E-MTAB-6678	no	3.56
E-MTAB-6142	no	0.61

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

106 targets.

Target	Regulation
ADCY3
ALDH1A2	Activation
ANGPT2	Unknown
ARVCF
BRF1	Unknown
C3AR1	Unknown
CA1
CBFA2T3
CBX5
CCND1	Activation
CD34	Repression
CD4	Repression
CD7
CD74
CDH13	Unknown
CDH23	Unknown
CDH5
CDKN2A
CDKN2B
CEL
CHST11	Unknown
CNTN2
CSNK2A1
CWC27
DCSTAMP
DLST
DMP1
DOCK9	Unknown
DSC3
ELMO1	Unknown

JASPAR motifs

Motif	Name	Family
MA0091.1	TAL1::TCF3	Tal-related::E2A
MA0091.2	TAL1::TCF3	Tal-related::E2A
MA0140.2	GATA1::TAL1	C4-GATA-related::Tal-related
MA0140.3	GATA1::TAL1	C4-GATA-related::Tal-related

JASPAR matrix evidence (PMIDs): PMID:8289805, PMID:20566737

Upstream regulators (CollecTRI, top): ARID5B, CDX2, FLI1, GATA1, GATA2, GATA3, GATA4, ID1, LYL1, MAF, MAZ, NKX3-1, SP1, SP3, SPI1, TAL1, TCF12, TCF3, ZFAT

miRNA regulators (miRDB)

143 targeting TAL1, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394

Literature-anchored findings (GeneRIF, showing 40)

• role of hypoxia in stimulating phosphorylation, ubiquitination, and proteasomal breakdown in endothelial cells (PMID:11904294)
• SCL locus can rescue knockout scl(-/-) mice (PMID:12010791)
• Ectopic expression of human TAL-1 protein in Ly-6E.1-htal-1 transgenic mice induces defects in B- and T-lymphoid differentiation, but did not cause leukemia. (PMID:12091340)
• regulates c-kit expression in hematopoietic cells through functional interaction with Sp1 (PMID:12239153)
• is a survival factor for erythroid cells (PMID:12867998)
• These results indicate that TAL1 can affect both T cell proliferation and differentiation. (PMID:14651981)
• Enforced expression of a TAL1 protein deleted of its DNA-binding domain mimicked most TAL1 effects except for the LTC-IC enhancement, the down-regulation of the CD34 surface marker, and the GPA(+) cell production (PMID:14715640)
• TAL-1 modulates the angiogenic response of endothelial cells by stimulating cell morphogenesis and by influencing their behavior in migration. (PMID:14970264)
• Possible role for SCL in renal vasculogenesis. Undifferentiated mesenchymal cells expressing SCL during early nephrogenesis might represent putative progenitors that can simultaneously give rise to kidney, blood, and endothelium. (PMID:15086455)
• Tal1/SCL binding to pericentromeric DNA represses transcription (PMID:15677454)
• Results show striking coexpression of SCL and its immediate downstream neighbor, MAP17, suggesting that they share regulatory elements. (PMID:15923636)
• TAL1 expression level regulates immature human hematopoietic cell self-renewal and this regulation requires TAL1 DNA-binding activity (PMID:15961517)
• PU.1, in addition to its positive role in TAL-1 expression in early hematopoietic progenitors, may also act as a mediator of TAL-1 silencing in some hematopoietic lineages (PMID:16298389)
• TAL1 may act as a bifunctional transcriptional regulator (activator and repressor) at the top of a complex regulatory network that disrupts normal T-cell homeostasis and contributes to leukemogenesis. (PMID:16621969)
• Scl acts up-stream of NF-E2 expression to control megakaryocyte development and platelet release in settings of thrombopoietic stress (PMID:16763211)
• TAL1 modulates NFKB1 expression and an NF-kappaB-dependent transcriptional program in a subset of human T-cell leukemia cells. (PMID:16778171)
• Using lentiviral delivery of TAL1-directed shRNA in human hematopoietic cells showed that decreased expression of TAL1 induced major disorders at different levels of adult hematopoietic cell development (PMID:16849639)
• Conditional activation of the SCL transgene under control of ubiquitously expressed SCL interrupting locus (SIL) transgenic regulatory elements impairs normal T-cell development. (PMID:17460775)
• CD3epsilon-mediated signal transduction pathway is essential for this transformation process (PMID:17507663)
• the SCL-LMO2 interaction couples protein stabilization with higher order protein complex assembly, thus providing a powerful means of modulating the stoichiometry and spatiotemporal activity of SCL complexes (PMID:17878155)
• characterize the assembly of a five-component complex containing TAL1, LMO2, Ldb1, E12, and DNA. The bHLH domains of TAL1 and E12 alone primarily formed helical homodimers, but together formed heterodimers, to which LMO2 bound with high affinity (PMID:17910069)
• Operation of cullin-based ubiquitin ligase complexes and potential means by which Notch and Tal1/SCL regulate eukaryotic development. (PMID:17962192)
• LMO2, TAL1, Ttg-1, and SIL support levels of V(D)J recombination above background levels in cell culture and are also cleaved by the RAG proteins, while Hox11 and SCL are nicked but not cleaved efficiently in vitro (PMID:18187418)
• Data definitively delineate the human myeloid progenitors that are regulated by TAL1. (PMID:18436863)
• TAL-1 deletion is associated with T-cell acute lymphoblastic leukemia. (PMID:18439091)
• analysis of cross talk between the human T-cell leukemia virus type 1 Tax transactivator and the oncogenic bHLH transcription factor TAL1 (PMID:18495761)
• different mechanisms of SCL’s action predominate depending on the developmental/cellular context (PMID:18550854)
• The intracellular concentration of TAL1 is regulated by TGF-beta, which triggers its polyubiquitylation & degradation by the proteasome. This is mediated by AKT1, which phosphorylates TAL1 at threonine 90. (PMID:19406989)
• LSD1 may negatively regulate TAL1-mediated transcription and suggest that the dynamic regulation of TAL1-associated LSD1/HDAC1 (PMID:19497860)
• TAL-1, a basic-helix-loop-helix transcription factor, plays a key role in the formation and functioning of both blood and endothelial systems. Review. (PMID:19527627)
• observations support a model in which Tax and TAL1 by repressing hTERT would initially favor genomic instability, whereas expression of factors such as HBZ allows at a later stage an increase in hTERT production and consequently in telomerase activity (PMID:19587703)
• Generated high-level hematopoietic chimeras using donor cells from mice transgenic for the stem cell leukaemia 3’ enhancer human placental alkaline phosphatase reporter construct to demonstrate vascular contribution potential of fetal liver cells. (PMID:19785037)
• Tal1 expression activated UBE2H expression, whereas Tal1 knock-down reduced UBE2H expression and ubiquitin transfer activity. (PMID:20028976)
• Data open up several areas for further investigation and adds new layers of complexity to our understanding of the regulation of SCL expression. (PMID:20140202)
• in human TAL1-expressing T-ALL cell lines, TAL1 directly activates NKX3.1 (PMID:20855495)
• TAL1 interacts with RUNX1 and ETS1, and that these transcription factors are critically required for TAL1 binding to genes that modulate T-cell differentiation. (PMID:21179004)
• The association between single nucleotide polymorphisms (SNPs) of the TAL1 gene, one of the candidate genes of leukemia and schizophrenia, is reported. (PMID:21407147)
• regulation of adult hematopoiesis through TIF1gamma-mediated transcriptional repression of TAL1 and PU.1 target genes. (PMID:21474105)
• The genome-wide binding sites for the SCL in primary human megakaryocytes to identify the essential regulator of complex mammalian differentiation processes. (PMID:21571218)
• results indicate that the HDACi-mediated apoptotic program in T-ALL cells is partially dependent on their capacity to downregulate TAL1 and provide support for the therapeutic use of HDACi in T-ALL (PMID:21647153)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tal1	ENSDARG00000019930
mus_musculus	Tal1	ENSMUSG00000028717
rattus_norvegicus	Tal1	ENSRNOG00000025051

Paralogs (4): LYL1 (ENSG00000104903), NHLH1 (ENSG00000171786), NHLH2 (ENSG00000177551), TAL2 (ENSG00000186051)

Protein

Protein identifiers

T-cell acute lymphocytic leukemia protein 1 — P17542 (reviewed: P17542)

Alternative names: Class A basic helix-loop-helix protein 17, Stem cell protein, T-cell leukemia/lymphoma protein 5

All UniProt accessions (1): P17542

UniProt curated annotations — full annotation on UniProt →

Function. Implicated in the genesis of hemopoietic malignancies. It may play an important role in hemopoietic differentiation. Serves as a positive regulator of erythroid differentiation.

Subunit / interactions. Efficient DNA binding requires dimerization with another bHLH protein. Forms heterodimers with TCF3. Binds to the LIM domain containing protein LMO2 and to DRG1. Can assemble in a complex with LDB1 and LMO2. Component of a TAL-1 complex composed at least of CBFA2T3, LDB1, TAL1 and TCF3. Interacts with SBNO2; this interaction inhibits TAL1 occupancy of the DCSTAMP promoter, leading to the activation of the DCSTAMP promoter by the transcription factor MITF.

Subcellular location. Nucleus.

Tissue specificity. Leukemic stem cell.

Post-translational modifications. Phosphorylated on serine residues. Phosphorylation of Ser-122 is strongly stimulated by hypoxia. Ubiquitinated; subsequent to hypoxia-dependent phosphorylation of Ser-122, ubiquitination targets the protein for rapid degradation via the ubiquitin system. This process may be characteristic for microvascular endothelial cells, since it could not be observed in large vessel endothelial cells.

Disease relevance. A chromosomal aberration involving TAL1 may be a cause of some T-cell acute lymphoblastic leukemias (T-ALL). Translocation t(1;14)(p32;q11) with T-cell receptor alpha chain (TCRA) genes.

Domain organisation. The helix-loop-helix domain is necessary and sufficient for the interaction with DRG1.

Isoforms (3)

UniProt ID	Names	Canonical?
P17542-1	PP42-TAL1	yes
P17542-2	PP39-TAL1
P17542-3	PP22-TAL1

RefSeq proteins (6): NP_001274276, NP_001277332, NP_001277333, NP_001277334, NP_001277335, NP_003180 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011598	bHLH_dom	Domain
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily
IPR040238	TAL-like	Family

Pfam: PF00010

UniProt features (16 total): compositionally biased region 4, modified residue 3, region of interest 3, splice variant 2, helix 2, chain 1, domain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2YPA	X-RAY DIFFRACTION	2.8
2YPB	X-RAY DIFFRACTION	2.87

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17542-F1	62.19	0.22

Functional residue map

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

Post-translational modifications (3): 122, 172, 12

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-8939236	RUNX1 regulates transcription of genes involved in differentiation of HSCs
R-HSA-9616222	Transcriptional regulation of granulopoiesis
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-1266738	Developmental Biology
R-HSA-212436	Generic Transcription Pathway
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8878171	Transcriptional regulation by RUNX1

MSigDB gene sets: 394 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_CHROMOSOME_ORGANIZATION, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_EMBRYONIC_HEMOPOIESIS, BENPORATH_ES_WITH_H3K27ME3, GOBP_POSITIVE_REGULATION_OF_ERYTHROCYTE_DIFFERENTIATION, GOBP_BEHAVIOR, GNF2_PRDX2, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_MYELOID_CELL_DEVELOPMENT, MODULE_255, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER, LFA1_Q6, TTTGTAG_MIR520D

GO Biological Process (34): negative regulation of transcription by RNA polymerase II (GO:0000122), angiogenesis (GO:0001525), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), locomotory behavior (GO:0007626), spinal cord association neuron differentiation (GO:0021527), hemopoiesis (GO:0030097), erythrocyte differentiation (GO:0030218), megakaryocyte differentiation (GO:0030219), platelet formation (GO:0030220), basophil differentiation (GO:0030221), positive regulation of protein-containing complex assembly (GO:0031334), embryonic hemopoiesis (GO:0035162), megakaryocyte development (GO:0035855), regulation of cell population proliferation (GO:0042127), erythrocyte maturation (GO:0043249), cell fate commitment (GO:0045165), positive regulation of erythrocyte differentiation (GO:0045648), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of mitotic cell cycle (GO:0045931), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of cell division (GO:0051781), astrocyte fate commitment (GO:0060018), definitive hemopoiesis (GO:0060216), hemangioblast cell differentiation (GO:0060217), hematopoietic stem cell differentiation (GO:0060218), regulation of mast cell differentiation (GO:0060375), regulation of somatic stem cell population maintenance (GO:1904672), positive regulation of chromatin organization (GO:1905269), central nervous system neuron differentiation (GO:0021953), myeloid cell differentiation (GO:0030099), cell differentiation (GO:0030154), regulation of myeloid cell differentiation (GO:0045637), generation of neurons (GO:0048699)

GO Molecular Function (12): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), chromatin binding (GO:0003682), DNA-binding transcription factor activity (GO:0003700), enzyme binding (GO:0019899), histone deacetylase binding (GO:0042826), protein dimerization activity (GO:0046983), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), E-box binding (GO:0070888), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Transcriptional regulation by RUNX1	1
Developmental Biology	1
Dengue Virus Infection	1
RNA Polymerase II Transcription	1
Gene expression (Transcription)	1
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	3
myeloid cell differentiation	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
anatomical structure formation involved in morphogenesis	2
DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
binding	2
protein binding	2
cellular anatomical structure	2
negative regulation of DNA-templated transcription	1
blood vessel morphogenesis	1
behavior	1
cell differentiation in spinal cord	1
dorsal spinal cord development	1
central nervous system neuron differentiation	1
cell development	1
erythrocyte homeostasis	1
platelet morphogenesis	1
granulocyte differentiation	1
regulation of protein-containing complex assembly	1
positive regulation of cellular component biogenesis	1
positive regulation of cellular component organization	1
protein-containing complex assembly	1
hemopoiesis	1
embryonic organ development	1
megakaryocyte differentiation	1
myeloid cell development	1
cell population proliferation	1
regulation of cellular process	1
cell maturation	1
erythrocyte development	1
cell differentiation	1
cellular developmental process	1
erythrocyte differentiation	1
positive regulation of myeloid cell differentiation	1
regulation of erythrocyte differentiation	1
positive regulation of RNA biosynthetic process	1
mitotic cell cycle	1
regulation of mitotic cell cycle	1

Protein interactions and networks

STRING

2102 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAL1	LMO2	P25791	999
TAL1	GATA1	P15976	998
TAL1	GATA2	P23769	997
TAL1	TCF3	P15883	996
TAL1	LDB2	O43679	995
TAL1	LDB1	Q86U70	995
TAL1	RUNX1	Q01196	968
TAL1	GATA3	P23771	938
TAL1	KLF1	Q13351	901
TAL1	TCF12	Q99081	900
TAL1	CBFA2T3	O75081	886
TAL1	LMO1	P25800	876
TAL1	GFI1B	Q5VTD9	872
TAL1	TLX1	P31314	860
TAL1	TLX3	O43711	824

IntAct

39 interactions, top by confidence:

A	B	Type	Score
TCF3	TAL1	psi-mi:“MI:0915”(physical association)	0.880
TAL1	TCF3	psi-mi:“MI:0915”(physical association)	0.880
TCF12	TAL1	psi-mi:“MI:0915”(physical association)	0.830
TCF4	TAL1	psi-mi:“MI:0915”(physical association)	0.690
TAL1	TCF4	psi-mi:“MI:0914”(association)	0.690
TAL1	RUNX1	psi-mi:“MI:0915”(physical association)	0.620
TAL1	KDM1A	psi-mi:“MI:0914”(association)	0.560
HDAC1	KDM1A	psi-mi:“MI:0915”(physical association)	0.560
KDM1A	TAL1	psi-mi:“MI:0915”(physical association)	0.560
TAL1	Lmo2	psi-mi:“MI:0407”(direct interaction)	0.530
TAL1	Lmo2	psi-mi:“MI:0915”(physical association)	0.530
TAL1	ETS1	psi-mi:“MI:0914”(association)	0.500
ETS1	TAL1	psi-mi:“MI:0915”(physical association)	0.500
TRIM33	TAL1	psi-mi:“MI:0914”(association)	0.460
TAL1	CDK9	psi-mi:“MI:0914”(association)	0.460
CDK9	TAL1	psi-mi:“MI:0914”(association)	0.460
TAL1	MYB	psi-mi:“MI:0915”(physical association)	0.400
CRK	TAL1	psi-mi:“MI:0915”(physical association)	0.400
NPNT	TAL1	psi-mi:“MI:0915”(physical association)	0.400
TAL1	DRG1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (168): EP300 (Reconstituted Complex), LMO2 (Two-hybrid), NCAPG2 (Two-hybrid), TAL1 (Affinity Capture-MS), TAL1 (Affinity Capture-MS), EP300 (Affinity Capture-Western), EP300 (Reconstituted Complex), TAL1 (Reconstituted Complex), TAL1 (Reconstituted Complex), TAL1 (Affinity Capture-Western), TAL1 (Affinity Capture-Western), TAL1 (Two-hybrid), TCF4 (Reconstituted Complex), TAL1 (Affinity Capture-Western), TCF3 (Affinity Capture-MS)

ESM2 similar proteins: A0A2Z4LIS9, A6QPM6, A7X8B3, A7X8B5, A7X8B7, A7X8C4, A7X8C7, A7X8C9, A7XW16, A7XW20, A7XW25, O08664, O15054, O43151, O70218, O89113, P09066, P14652, P17542, P19419, P19622, P22091, P23683, P49640, P70061, P78412, P82976, P97503, Q00587, Q04890, Q05916, Q05917, Q12950, Q15270, Q17QW1, Q3U133, Q5JPB2, Q5NCY0, Q6ZW13, Q80WY3

Diamond homologs: A8E5T6, B6VQA1, O13125, O13126, O16867, O35437, O42202, O42606, O43680, O57598, O60682, O73615, O73823, O88940, O93507, O96004, O96642, P13903, P17542, P22091, P24899, P26687, P46581, P48985, P48987, P57100, P57101, P57102, P59101, P61295, P61296, P70661, P79765, P79782, P97831, P97832, Q02575, Q02576, Q02577, Q0VCE2

SIGNOR signaling

23 interactions.

A	Effect	B	Mechanism
MAP2K1	down-regulates	TAL1	phosphorylation
MAPK3	down-regulates	TAL1	phosphorylation
AKT	down-regulates	TAL1	phosphorylation
PRKACA	up-regulates	TAL1	phosphorylation
PRKACA	down-regulates	TAL1	phosphorylation
TAL1	“up-regulates quantity by expression”	ANGPT2	“transcriptional regulation”
MEK1/2	down-regulates	TAL1	phosphorylation
AKT1	down-regulates	TAL1	phosphorylation
TAL1	“up-regulates quantity by expression”	ERG	“transcriptional regulation”
TAL1	“up-regulates quantity by expression”	MEF2C	“transcriptional regulation”
SPI1	“down-regulates activity”	TAL1	binding
ARID5B	“up-regulates quantity by expression”	TAL1	“transcriptional regulation”
TAL1	“up-regulates quantity by expression”	FUBP1	“transcriptional regulation”
ZC3H12A	“up-regulates quantity”	TAL1	“post transcriptional regulation”
TAL1	“down-regulates quantity by destabilization”	TSG101	polyubiquitination
LMO1	up-regulates	TAL1	binding
LMO2	up-regulates	TAL1	binding
GATA1	“up-regulates quantity by expression”	TAL1	“transcriptional regulation”
TAL1	“up-regulates activity”	Megakaryocyte_differentiation
TAL1	“up-regulates activity”	Erythrocyte_differentiation
STUB1	“down-regulates quantity by destabilization”	TAL1	ubiquitination
TAL1	“up-regulates quantity by expression”	UBE2H	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 23 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RUNX1 regulates transcription of genes involved in differentiation of HSCs	5	26.4×	2e-04
Estrogen-dependent gene expression	5	21.0×	2e-04

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: ambiguous (mixed evidence) across 1 cancer types — HCC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	7
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

1158 predictions. Top by Δscore:

Variant	Effect	Δscore
1:47219970:T:TA	donor_gain	1.0000
1:47219973:T:TA	donor_gain	1.0000
1:47219976:T:TA	donor_gain	1.0000
1:47220016:T:TA	donor_gain	1.0000
1:47220174:CCTG:C	acceptor_loss	1.0000
1:47220175:C:CC	acceptor_gain	1.0000
1:47220176:T:A	acceptor_loss	1.0000
1:47223999:CTCA:C	donor_loss	1.0000
1:47224000:TCAC:T	donor_loss	1.0000
1:47224001:CACCA:C	donor_loss	1.0000
1:47224002:ACC:A	donor_loss	1.0000
1:47224003:C:G	donor_loss	1.0000
1:47224095:CCCG:C	acceptor_gain	1.0000
1:47224096:CCGC:C	acceptor_gain	1.0000
1:47219691:T:TA	donor_gain	0.9900
1:47219936:AGGGT:A	donor_gain	0.9900
1:47219940:T:TA	donor_gain	0.9900
1:47220013:A:AC	donor_gain	0.9900
1:47220014:C:CC	donor_gain	0.9900
1:47220170:GGGAC:G	acceptor_gain	0.9900
1:47220171:GGAC:G	acceptor_gain	0.9900
1:47220172:GAC:G	acceptor_gain	0.9900
1:47220182:T:C	acceptor_gain	0.9900
1:47220182:T:TC	acceptor_gain	0.9900
1:47223997:GACTC:G	donor_loss	0.9900
1:47223998:ACT:A	donor_loss	0.9900
1:47224002:A:AC	donor_gain	0.9900
1:47224003:C:CC	donor_gain	0.9900
1:47224003:CCAT:C	donor_gain	0.9900
1:47224094:ACCCG:A	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000051743 (1:47229029 A>C), RS1000285429 (1:47216411 C>A,T), RS1000346723 (1:47222290 G>A), RS1000718576 (1:47217591 C>T), RS1000947154 (1:47223946 C>G,T), RS1001058533 (1:47230477 G>A), RS1001108203 (1:47220607 T>G), RS1001132004 (1:47230181 A>G), RS1001170790 (1:47233990 C>T), RS1001360112 (1:47224206 C>T), RS1001620838 (1:47220656 T>A), RS1001623454 (1:47233672 C>G,T), RS1001864846 (1:47233179 TGAA>T), RS1001893520 (1:47234316 T>G), RS1002029354 (1:47220968 C>T)

Disease associations

OMIM: gene MIM:187040 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0001442	Typified by somatic mosaicism
HP:0006721	Acute lymphoblastic leukemia
HP:0010982	Polygenic inheritance

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST002595_12	Clozapine-induced agranulocytosis	2.000000e-06
GCST002783_253	Body mass index	2.000000e-08
GCST002783_432	Body mass index	9.000000e-08
GCST004602_9	Mean corpuscular volume	2.000000e-25
GCST010988_532	Adult body size	1.000000e-14
GCST90002390_2	Mean corpuscular hemoglobin	5.000000e-10
GCST90002392_164	Mean corpuscular volume	3.000000e-44
GCST90002392_165	Mean corpuscular volume	6.000000e-11
GCST90002396_130	Mean reticulocyte volume	5.000000e-104
GCST90002397_630	Mean spheric corpuscular volume	7.000000e-73
GCST90002404_465	Red cell distribution width	3.000000e-13

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
kojic acid	decreases expression	1
arsenite	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
MK-8776	decreases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Amphotericin B	increases expression	1
Arbutin	decreases expression	1
Arsenic	affects expression	1
Benzo(a)pyrene	affects methylation	1
Triclosan	decreases expression	1
Valproic Acid	affects expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1
Copper Sulfate	increases expression	1
Sirolimus	affects activity, decreases reaction	1
Nanotubes, Carbon	decreases expression	1

Cellosaurus cell lines

17 cell lines: 8 cancer cell line, 5 embryonic stem cell, 2 induced pluripotent stem cell, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1667	RPMI-8402	Cancer cell line	Female
CVCL_1859	CCRF-HSB-2	Cancer cell line	Male
CVCL_1Y12	HSB2/GS	Cancer cell line	Male
CVCL_2878	CPT-K5	Cancer cell line	Female
CVCL_A0DR	HSB.2-A7-D2	Cancer cell line	Male
CVCL_A0DS	HSB.2-A7-D9	Cancer cell line	Male
CVCL_A0DT	HSB.2-C5-B2	Cancer cell line	Male
CVCL_A6Z9	SEES3-1V human TAL1, clone1	Embryonic stem cell	Male
CVCL_A7A0	SEES3-1V human TAL1, clone2	Embryonic stem cell	Male
CVCL_A7A1	SEES3-1V human TAL1, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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