TCF3

Summary

TCF3 (transcription factor 3, HGNC:11633) is a protein-coding gene on chromosome 19p13.3, encoding Transcription factor E2-alpha (P15923). Transcriptional regulator involved in the initiation of neuronal differentiation and mesenchymal to epithelial transition.

This gene encodes a member of the E protein (class I) family of helix-loop-helix transcription factors. E proteins activate transcription by binding to regulatory E-box sequences on target genes as heterodimers or homodimers, and are inhibited by heterodimerization with inhibitor of DNA-binding (class IV) helix-loop-helix proteins. E proteins play a critical role in lymphopoiesis, and the encoded protein is required for B and T lymphocyte development. Deletion of this gene or diminished activity of the encoded protein may play a role in lymphoid malignancies. This gene is also involved in several chromosomal translocations that are associated with lymphoid malignancies including pre-B-cell acute lymphoblastic leukemia (t(1;19), with PBX1), childhood leukemia (t(19;19), with TFPT) and acute leukemia (t(12;19), with ZNF384). Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the short arm of chromosome 9.

Source: NCBI Gene 6929 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal agammaglobulinemia (Definitive, ClinGen) — +2 more curated relationships
• Clinical variants (ClinVar): 1,209 total — 22 pathogenic, 13 likely-pathogenic
• Phenotypes (HPO): 54
• Transcription factor: yes — 386 downstream targets (CollecTRI)
• MANE Select transcript: NM_003200

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11633
Approved symbol	TCF3
Name	transcription factor 3
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	E2A, ITF1, MGC129647, MGC129648, bHLHb21, VDIR, E47, p75
Ensembl gene	ENSG00000071564
Ensembl biotype	protein_coding
OMIM	147141
Entrez	6929

Gene structure

Transcript identifiers

Ensembl transcripts: 38 — 30 protein_coding, 5 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000262965, ENST00000395423, ENST00000453954, ENST00000585731, ENST00000585855, ENST00000586164, ENST00000586318, ENST00000586410, ENST00000587235, ENST00000587425, ENST00000588136, ENST00000590436, ENST00000590605, ENST00000590684, ENST00000592395, ENST00000592628, ENST00000593064, ENST00000610756, ENST00000651991, ENST00000705032, ENST00000705033, ENST00000863491, ENST00000863492, ENST00000863493, ENST00000931963, ENST00000931964, ENST00000931965, ENST00000931966, ENST00000931967, ENST00000931968, ENST00000931969, ENST00000931970, ENST00000931971, ENST00000931972, ENST00000931973, ENST00000931974, ENST00000931975, ENST00000948466

RefSeq mRNA: 4 — MANE Select: NM_003200 NM_001136139, NM_001351778, NM_001351779, NM_003200

CCDS: CCDS12074, CCDS45899

Canonical transcript exons

ENST00000262965 — 19 exons

Exon	Start	End
ENSE00000336287	1632332	1632405
ENSE00000651461	1646355	1646427
ENSE00000651464	1632038	1632116
ENSE00000651466	1625576	1625708
ENSE00000651469	1622313	1622415
ENSE00000651472	1621838	1621970
ENSE00000651474	1620968	1621046
ENSE00000651478	1615686	1615821
ENSE00000651479	1615285	1615520
ENSE00000873563	1619316	1619474
ENSE00001151915	1619780	1619853
ENSE00001151926	1621133	1621191
ENSE00001151931	1622054	1622223
ENSE00001151938	1623951	1624000
ENSE00001151945	1627359	1627426
ENSE00001376842	1650177	1650287
ENSE00002701060	1619111	1619234
ENSE00003738996	1609292	1611849
ENSE00003899108	1652300	1652615

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.0185 / max 87.2661, expressed in 1457 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178058	44.5688	1811
178057	4.4746	1414
178056	0.2269	110
178054	0.2191	83
178053	0.0979	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	98.75	gold quality
ventricular zone	UBERON:0003053	98.74	gold quality
embryo	UBERON:0000922	97.97	gold quality
right testis	UBERON:0004534	96.86	gold quality
left testis	UBERON:0004533	96.83	gold quality
pancreatic ductal cell	CL:0002079	96.78	gold quality
testis	UBERON:0000473	96.26	gold quality
lymph node	UBERON:0000029	96.14	gold quality
bone marrow cell	CL:0002092	95.43	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.21	gold quality
vermiform appendix	UBERON:0001154	95.19	gold quality
stromal cell of endometrium	CL:0002255	95.16	gold quality
spleen	UBERON:0002106	95.07	gold quality
trabecular bone tissue	UBERON:0002483	94.07	gold quality
bone marrow	UBERON:0002371	93.94	gold quality
cervix squamous epithelium	UBERON:0006922	93.94	gold quality
caecum	UBERON:0001153	93.88	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.87	gold quality
buccal mucosa cell	CL:0002336	93.69	gold quality
epithelial cell of pancreas	CL:0000083	93.66	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.61	gold quality
granulocyte	CL:0000094	93.54	gold quality
mucosa of transverse colon	UBERON:0004991	93.21	gold quality
small intestine	UBERON:0002108	93.10	gold quality
parotid gland	UBERON:0001831	93.07	gold quality
cortical plate	UBERON:0005343	92.97	gold quality
blood	UBERON:0000178	92.81	gold quality
hair follicle	UBERON:0002073	92.81	gold quality
right ovary	UBERON:0002118	92.81	gold quality
thymus	UBERON:0002370	92.79	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	37.59
E-MTAB-9067	yes	15.65
E-ANND-3	yes	12.21
E-GEOD-93593	yes	6.90
E-MTAB-9801	yes	3.84

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

386 targets.

Target	Regulation
ABCB1
ABCB11
ABCC3
ABL1
ACAN
ACHE
ACOT11
ACSL4
ACTA2
ADAM2
ADAMTS5
ADIPOQ
ADORA1
ADORA3
ADRA1D
AFP
AGR2
AHR
AICDA	Unknown
AKT1
ALB
ALDH3A1
ALOX15
ALX3
ANKRD2
APOC3
APOE
APP
AQP1
AR

JASPAR motifs

Motif	Name	Family
MA0091.1	TAL1::TCF3	Tal-related::E2A
MA0091.2	TAL1::TCF3	Tal-related::E2A
MA0522.2	TCF3	E2A
MA0522.3	TCF3	E2A
MA0522.4	TCF3	E2A

JASPAR matrix evidence (PMIDs): PMID:8289805, PMID:10594029

Upstream regulators (CollecTRI, top): AHR, BHLHE41, DBP, E4F1, ESR1, FHL2, FIGLA, FOS, GFI1, ID1, ID2, ID3, IRF6, JUN, JUND, LDB1, LEF1, LMX1B, MYC, NFKB, NR0B2, PARP1, PROX1, SP1, SP3, TCF12, TCF23, TCF3, TFDP1, TWIST1, UTF1

miRNA regulators (miRDB)

92 targeting TCF3, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-374C-5P	99.80	72.06	2910

Literature-anchored findings (GeneRIF, showing 40)

• Functional collaboration between E47 and early B cell factor enables direct targeting of the surrogate light chain VpreB promoter for trans-activation during B cell development. (PMID:11994467)
• E2A, along with histone acetyltransferases, regulates B cell development (PMID:12435739)
• Evidence pertaining to leukemogenesis by the well-characterized E2A-fusion proteins E2A-PBX1 and E2A-HLF is reviewed and mechanistic implications are considered. (PMID:12700034)
• E2a-Pbx1 and Bmi-1 are likely to play a role in the pathogenesis of human lymphoid leukemias through downregulation of the INK4A-ARF gene (PMID:14536079)
• basic helix-loop-helix (bHLH) transcription factors, the E2A proteins (E47, E12 and E2/5), activated the human SHP promoter (PMID:14627819)
• E2A-HLF induces annexin II by substituting for cytokines that activate downstream pathways of Ras (PMID:15070701)
• E47 is involved in the regulation of p16(INK4a) transcription in cellular senescence (PMID:15138269)
• in B cells, E47 and PU.1/IRF-4 interact with the E-box motifs and the EICE, respectively, and act synergistically in the activation of CIITA-PIII (PMID:15242870)
• Ca2+ signaling can inhibit the transcriptional activities of E12 and E47 through direct binding of Ca2+/calmodulin to the basic sequence of E-proteins (PMID:15280352)
• E2A is a positive regulator for one set of genes and a negative regulator for another set of genes in developing B lymphocytes (PMID:15310760)
• study identifes E proteins(HEB, E2A) as AML1-ETO targets whose dysregulation may be important for t(8;21) leukemogenesis, as well as an E protein silencing mechanism that is distinct from that associated with differentiation-inhibitory proteins (PMID:15333839)
• dHAND/E-protein (E2A, ME2, and ALF1) heterodimers have distinct DNA binding specificities (PMID:15351717)
• E2A-PBX1 interacts directly with the KIX domain of CBP/p300 in the induction of proliferation in primary hematopoietic cells (PMID:15507449)
• FHL2 interacts with Hand1 via the bHLH domain and is able to repress Hand1/E12 heterodimer-induced transcription (PMID:15509787)
• A reporter assay with the p21 promoter demonstrated that Snail inhibited expression of p21 induced by E2A. (PMID:15555546)
• E12 and E47 modulate both MyoD and Id1 degradation and may have implications for the physiological regulation of muscle (PMID:16007194)
• the SREBP-1c.BETA2.E47 complex is in a DNA looping structure which is required for efficient recruitment of CREB-binding protein/p300 (PMID:16055439)
• The E2A-HLF-mediated over-expression of ABCB1 may play a role in the clinical phenotype of ALLs with a t(17;19), suggesting pharmacologic modulation of ABCB1 activity as a rational therapeutic strategy for this chemotherapy resistant subtype of ALL. (PMID:16206189)
• The patients with immunophenotype of Pre-B-acute lymphoblastic leukemia were found to carry: E2A/PBX1 and E2A/HLF. (PMID:16215946)
• Notch1 is an important “second hit” for the transformation of E2A deficient T cell lymphomas. (PMID:16449526)
• activin A enhances PAX4 expression by enhanced transactivation of E47/E12 proteins and might result in a cumulative transactivation of the promoter (PMID:16546275)
• Global gene expression analysis in neuroblastoma cells engineered to acutely express the E protein E47 and Id2, showed that p57Kip2 is a target of E47. (PMID:16705184)
• Targeted-E2A-PBX1 inhibition leads to reduced expression of the EB-1 and Wnt16b genes; aberrant expression of these genes may be a key step in leukemogenesis in t(1;19)-positive pre-B leukemia. (PMID:16769578)
• E47 coordinately regulates the expression of genes involved in cell survival, cell cycle progression, lipid metabolism, stress response, and lymphoid maturation. (PMID:16782810)
• role of the E2A gene products in the progression of CsA-induced Epithelial-mesenchymal transition and provide novel insights into CsA-induced renal fibrosis. (PMID:16814783)
• In childhood acute lymphoblastic leukemia and hypercalcemia, translocation was observed in E2A-HLF fusion protein. (PMID:17183364)
• E2A proteins prevent lymphoma cell expansion, at least in part through regulation of Gfi1b and modulation of Gata3 expression. (PMID:17272506)
• Involvement of the TCF3 gene in 19p13 rearrangements and in identifying novel and cryptic TCF3 translocations and also acts as a tumor suppressor gene in b-cell precursor acute lymphoblastic leukemia. (PMID:17311319)
• results obtained with activated CD19(+) B cells show that the expression of transcription factor E2A, activation-induced cytidine deaminase, and Iggamma1 circle transcripts progressively decrease with age (PMID:18390709)
• The prevalence of the E2A-PBX1 fusion gene is one of the highest that has been described thus far in childhood acute lymphoblastic leukemia. (PMID:18455790)
• E2A and Na/K-ATPase beta1 subunit expression in epithelial cells are regulated by interactions between these proteins. (PMID:18727914)
• hCASK regulation of cell growth might involve p21 expression, and that the bHLH (basic helix-loop-helix) transcription factor E2A probably participates in hCASK regulation of p21 expression (PMID:19125693)
• multiple inhibitory mechanisms can be suppressed and myogenic differentiation can be induced in the RD rhabdomyosarcomas by increasing the abundance of MyoD:E-protein heterodimers (PMID:19299559)
• Mixed lineage kinase phosphorylates transcription factor E47 and inhibits TrkB expression to link neuronal death and survival pathways (PMID:19801649)
• Ca(2+) down-regulates SLC and CD19 gene expression upon pre-BCR activation through inhibition of E2A by Ca(2+)/calmodulin. (PMID:20022378)
• Suppressed TCF3 gene expression is associated with cigarette smoking. (PMID:20217071)
• E2A-HLF promotes cell survival of t(17;19)- acute lymphoblastic leukemia cells by aberrantly up-regulating LMO2 expression (PMID:20519628)
• Aberrant E2A expression is a diagnostic feature of a subtype of gastric MALT lymphoma with weaker plasmacytoid infiltrates and stronger miR-223 expression. (PMID:20802470)
• CD38 upregulation was primarily conditioned by the presence of E2A and then by the G allele (PMID:21212793)
• Data show that miR-495 expression was directly modulated by transcription factor E12/E47, and promotes oncogenesis via downregulation of E-cadherin and REDD1. (PMID:21258409)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	tcf3a	ENSDARG00000005915
danio_rerio	tcf3b	ENSDARG00000099999
mus_musculus	Tcf3	ENSMUSG00000020167
rattus_norvegicus	Tcf3	ENSRNOG00000051499
drosophila_melanogaster	da	FBGN0267821
caenorhabditis_elegans	hlh-2	WBGENE00001949

Paralogs (2): TCF12 (ENSG00000140262), TCF4 (ENSG00000196628)

Protein

Protein identifiers

Transcription factor E2-alpha — P15923 (reviewed: P15923)

Alternative names: Class B basic helix-loop-helix protein 21, Immunoglobulin enhancer-binding factor E12/E47, Immunoglobulin transcription factor 1, Kappa-E2-binding factor, Transcription factor 3, Transcription factor ITF-1

All UniProt accessions (15): P15923, A0A0A0MTS0, A0A494C1R3, A0A994J7B2, K7EJN4, K7EK65, K7EKB9, K7ELF3, K7EMM4, K7ENH8, K7ENI0, K7EPH6, K7EPS2, K7ERZ7, X6REB3

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional regulator involved in the initiation of neuronal differentiation and mesenchymal to epithelial transition. Heterodimers between TCF3 and tissue-specific basic helix-loop-helix (bHLH) proteins play major roles in determining tissue-specific cell fate during embryogenesis, like muscle or early B-cell differentiation. Together with TCF15, required for the mesenchymal to epithelial transition. Dimers bind DNA on E-box motifs: 5’-CANNTG-3’. Binds to the kappa-E2 site in the kappa immunoglobulin gene enhancer. Binds to IEB1 and IEB2, which are short DNA sequences in the insulin gene transcription control region. Facilitates ATOH7 binding to DNA at the consensus sequence 5’-CAGGTG-3’, and positively regulates transcriptional activity.

Subunit / interactions. Homodimer. Heterodimer; efficient DNA binding requires dimerization with another bHLH protein. Forms a heterodimer with ASH1, TWIST1 and TWIST2. Forms a heterodimer with MYOG; heterodimerization enhances MYOG DNA-binding and transcriptional activities. Forms a heterodimer with NEUROD1; the heterodimer is inhibited in presence of ID2, but not NR0B2, to E-box element. Forms a heterodimer with TCF15; the heterodimer binds E-box element. Forms a heterodimer with ATOH8; repress transcription of TCF3 and TCF3/NEUROG3 dimer-induced transactivation of E box-dependent promoters. Component of a nuclear TAL-1 complex composed at least of CBFA2T3, LDB1, TAL1 and TCF3. Interacts with NEUROD2, PTF1A and TGFB1I1. Interacts with EP300 and UBE2I. Interacts with BHLHA9. Interacts with ASB2; the interaction is mediated by SKP2 and targets TCF3 for Notch-induced proteasomal degradation. Forms a heterodimer with ATOH7; required for ATOH7 DNA-binding. Interacts with RALGAPA1 and FIGLA.

Subcellular location. Nucleus.

Post-translational modifications. Phosphorylated following NGF stimulation. Undergoes Notch-induced ubiquitination and subsequent proteasomal degradation which is mediated by ASB1 or ASB2, the substrate-recognition components of probable ECS E3 ubiquitin-protein ligase complexes.

Disease relevance. Chromosomal aberrations involving TCF3 are cause of forms of pre-B-cell acute lymphoblastic leukemia (B-ALL). Translocation t(1;19)(q23;p13.3) with PBX1. TCF3-PBX1 transforms cells by constitutively activating transcription of genes regulated by PBX1 or by other members of the PBX protein family. Translocation t(17;19)(q22;p13.3) with HLF. Inversion inv(19)(p13;q13) with TFPT. Agammaglobulinemia 8A, autosomal dominant (AGM8A) [MIM:616941] A form of agammaglobulinemia, a primary immunodeficiency characterized by profoundly low or absent serum antibodies and low or absent circulating B-cells due to an early block of B-cell development. Affected individuals develop severe infections in the first years of life. The disease is caused by variants affecting the gene represented in this entry. Agammaglobulinemia 8B, autosomal recessive (AGM8B) [MIM:619824] A form of agammaglobulinemia, a primary immunodeficiency characterized by profoundly low or absent serum antibodies and low or absent circulating B-cells due to an early block of B-cell development. AGM8B is characterized by onset of recurrent infections in early childhood. AGM8B patients may show dysmorphic facies and subtle abnormalities of other immune cells, such as T cells. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.

Miscellaneous. The bHLH domain encompassing amino acids 546 to 599 is sufficient to mediate DNA-binding and homodimerization. Combined mutagenesis of Phe-566 and Leu-569 to Asp-566 and Glu-569, mutagenesis of Lys-585 to Ala-585 or combined mutagenesis of Ile-588 and Leu-589 to Asp-588 and Glu-589 prevents DNA-binding and homodimerization. Mutagenesis of Arg-548 to Lys-548, combined mutagenesis of Arg-547 and Arg-548 to Gly-547 and Gly-548, mutagenesis of Arg-556 to Lys-556, mutagenesis of Arg-558 to Lys-558, or combined mutagenesis of Arg-556 and Arg-558 to Gly-556 and Gly-558, alter DNA-binding but not dimerization.

Isoforms (3)

UniProt ID	Names	Canonical?
P15923-1	E12, PAN-2	yes
P15923-2	E47, PAN-1
P15923-3	3

RefSeq proteins (4): NP_001129611, NP_001338707, NP_001338708, NP_003191* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011598	bHLH_dom	Domain
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily
IPR051098	NeuroDiff_E-box_TFs	Family

Pfam: PF00010

UniProt features (47 total): compositionally biased region 8, region of interest 8, modified residue 8, sequence variant 6, sequence conflict 4, splice variant 3, helix 3, short sequence motif 2, cross-link 2, chain 1, domain 1, site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
3U5V	X-RAY DIFFRACTION	1.7
6MGN	X-RAY DIFFRACTION	1.9
2YPA	X-RAY DIFFRACTION	2.8
2YPB	X-RAY DIFFRACTION	2.87
2MH0	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P15923-F1	52.42	0.13

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 (1): 483–484 (breakpoint for translocation to form tcf3-pbx1 oncogene)

Post-translational modifications (10): 134, 139, 355, 359, 371, 379, 529, 498, 625, 531

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-525793	Myogenesis
R-HSA-8939236	RUNX1 regulates transcription of genes involved in differentiation of HSCs
R-HSA-9764725	Negative Regulation of CDH1 Gene Transcription
R-HSA-9839394	TGFBR3 expression
R-HSA-9943411	CHD1 and CHD2 subfamily
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
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
R-HSA-9006936	Signaling by TGFB family members
R-HSA-9839373	Signaling by TGFBR3

MSigDB gene sets: 493 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_B_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_B_CELL_PROLIFERATION, GOBP_NEUROGENESIS, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN, GOBP_POSITIVE_REGULATION_OF_B_CELL_PROLIFERATION, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, PUJANA_CHEK2_PCC_NETWORK, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION

GO Biological Process (15): negative regulation of transcription by RNA polymerase II (GO:0000122), B cell lineage commitment (GO:0002326), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), nervous system development (GO:0007399), B cell differentiation (GO:0030183), positive regulation of B cell proliferation (GO:0030890), immunoglobulin V(D)J recombination (GO:0033152), positive regulation of neuron differentiation (GO:0045666), positive regulation of cell cycle (GO:0045787), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), obsolete positive regulation of DNA-binding transcription factor activity (GO:0051091), regulation of G1/S transition of mitotic cell cycle (GO:2000045), cell differentiation (GO:0030154)

GO Molecular Function (18): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), cis-regulatory region sequence-specific DNA binding (GO:0000987), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), mitogen-activated protein kinase kinase kinase binding (GO:0031435), protein homodimerization activity (GO:0042803), bHLH transcription factor binding (GO:0043425), protein heterodimerization activity (GO:0046982), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), vitamin D response element binding (GO:0070644), E-box binding (GO:0070888), DNA-binding transcription factor binding (GO:0140297), transcription cis-regulatory region binding (GO:0000976), protein binding (GO:0005515), protein dimerization activity (GO:0046983)

GO Cellular Component (8): chromatin (GO:0000785), euchromatin (GO:0000791), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), cytoplasm (GO:0005737), protein-containing complex (GO:0032991), RNA polymerase II transcription regulator complex (GO:0090575)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Developmental Biology	1
Transcriptional regulation by RUNX1	1
Regulation of CDH1 Gene Transcription	1
Signaling by TGFBR3	1
CHD chromatin remodelers	1
RNA Polymerase II Transcription	1
Gene expression (Transcription)	1
Generic Transcription Pathway	1
Signal Transduction	1
Signaling by TGFB family members	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	4
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
regulation of DNA-templated transcription	3
cellular anatomical structure	3
DNA-templated transcription	2
chromatin	2
transcription cis-regulatory region binding	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
protein dimerization activity	2
DNA-binding transcription factor binding	2
RNA polymerase II cis-regulatory region sequence-specific DNA binding	2
negative regulation of DNA-templated transcription	1
B cell differentiation	1
cell fate commitment	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
system development	1
lymphocyte differentiation	1
B cell activation	1
regulation of B cell proliferation	1
B cell proliferation	1
positive regulation of lymphocyte proliferation	1
positive regulation of B cell activation	1
somatic recombination of immunoglobulin gene segments	1
V(D)J recombination	1
neuron differentiation	1
positive regulation of cell differentiation	1
regulation of neuron differentiation	1
cell cycle	1
positive regulation of cellular process	1
regulation of cell cycle	1
positive regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
G1/S transition of mitotic cell cycle	1
regulation of mitotic cell cycle phase transition	1
regulation of cell cycle G1/S phase transition	1
cellular developmental process	1
cis-regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

98 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
RUVBL1	ZNHIT1	psi-mi:“MI:0914”(association)	0.860
RUVBL2	ZNHIT1	psi-mi:“MI:0914”(association)	0.810
ID2	TCF4	psi-mi:“MI:0914”(association)	0.800
TAL1	TCF4	psi-mi:“MI:0914”(association)	0.690
ID2	TCF3	psi-mi:“MI:0915”(physical association)	0.670
TAL2	TCF4	psi-mi:“MI:0914”(association)	0.670
HAND2	TCF4	psi-mi:“MI:0914”(association)	0.670
NEUROG3	GXYLT2	psi-mi:“MI:0914”(association)	0.640
ASCL1	TCF3	psi-mi:“MI:0915”(physical association)	0.630
TCF3	ASCL1	psi-mi:“MI:0915”(physical association)	0.630
TCF3	ID3	psi-mi:“MI:0915”(physical association)	0.560
TCF3	TCAF1	psi-mi:“MI:0915”(physical association)	0.560
TCAF1	TCF3	psi-mi:“MI:0915”(physical association)	0.560
TAL1	KDM1A	psi-mi:“MI:0914”(association)	0.560
NHLH2	AP3B1	psi-mi:“MI:0914”(association)	0.530
FKBP9	CASC3	psi-mi:“MI:0914”(association)	0.530
TCF4	CBFA2T3	psi-mi:“MI:0914”(association)	0.530
COLGALT2	COL1A1	psi-mi:“MI:0914”(association)	0.530
MYOG	TCF4	psi-mi:“MI:0914”(association)	0.530
NEUROD1	TCF4	psi-mi:“MI:0914”(association)	0.530

BioGRID (359): TCF3 (Two-hybrid), FAM115A (Two-hybrid), TCF3 (Affinity Capture-Western), CREBBP (Reconstituted Complex), KAT2B (Reconstituted Complex), TCF3 (Reconstituted Complex), TCF3 (Reconstituted Complex), CREBBP (Two-hybrid), CREBBP (Reconstituted Complex), CREBBP (Reconstituted Complex), TCF3 (Biochemical Activity), TCF3 (Biochemical Activity), TCF3 (Protein-peptide), TCF3 (Reconstituted Complex), TCF3 (Affinity Capture-MS)

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: A0A0R4IBL7, G5EEG9, P11420, P15806, P15881, P15884, P15923, P21677, P30985, P51514, P98180, Q01978, Q28772, Q60420, Q60722, Q61286, Q62655, Q90683, Q91605, Q99081

SIGNOR signaling

30 interactions.

A	Effect	B	Mechanism
CSNK1E	up-regulates	TCF3	phosphorylation
MAPK11	up-regulates	TCF3	phosphorylation
MAPK14	“up-regulates activity”	TCF3	phosphorylation
MAP3K10	down-regulates	TCF3	phosphorylation
RANBP17	up-regulates	TCF3	binding
MAPKAPK2	up-regulates	TCF3	phosphorylation
TCF3	“up-regulates quantity by expression”	NOTCH1	“transcriptional regulation”
TCF3	“up-regulates activity”	MYOD1	binding
MSC	“down-regulates activity”	TCF3	binding
TCF3	“up-regulates quantity by expression”	CDKN1A	“transcriptional regulation”
TCF3	“down-regulates quantity by repression”	BBC3	“transcriptional regulation”
TCF3	“down-regulates quantity by repression”	CR2	“transcriptional regulation”
PAK5	“up-regulates activity”	TCF3	phosphorylation
TCF3	“down-regulates quantity by repression”	CDH1	“transcriptional regulation”
HIPK2	“down-regulates activity”	TCF3	phosphorylation
DTX1	down-regulates	TCF3
NOTCH1	down-regulates	TCF3	binding
NOTCH2	down-regulates	TCF3	binding
ID1	“down-regulates activity”	TCF3	binding
ID3	“down-regulates activity”	TCF3	binding
ID2	“down-regulates activity”	TCF3	binding
TCF3	“form complex”	MYOD/E12E47	binding
MAPK3	“down-regulates quantity by destabilization”	TCF3	phosphorylation
MAPK1	“down-regulates quantity by destabilization”	TCF3	phosphorylation
Gbeta	“down-regulates quantity by destabilization”	TCF3	phosphorylation
ERK1/2	“down-regulates quantity by destabilization”	TCF3	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 77 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
TGFBR3 expression	6	53.7×	4e-07
Myogenesis	5	37.3×	3e-05
Signaling by TGFBR3	5	36.1×	3e-05
NGF-stimulated transcription	5	28.0×	9e-05
Gastrulation	5	25.4×	1e-04
Transcriptional regulation by RUNX2	5	24.9×	1e-04
TCF dependent signaling in response to WNT	6	13.8×	3e-04
Signaling by WNT	6	13.2×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
developmental process	6	55.4×	3e-07
negative regulation of osteoblast differentiation	6	24.3×	3e-05
positive regulation of epithelial to mesenchymal transition	5	21.8×	3e-04
positive regulation of neuron differentiation	6	16.3×	2e-04
muscle organ development	6	13.7×	3e-04
Notch signaling pathway	5	9.7×	5e-03
osteoblast differentiation	5	8.3×	1e-02
transcription by RNA polymerase II	7	6.8×	3e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

1209 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	22
Likely pathogenic	13
Uncertain significance	565
Likely benign	500
Benign	47

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1405740	NM_003200.5(TCF3):c.1331dup (p.Gly445fs)	Pathogenic
1450388	NM_003200.5(TCF3):c.1459C>T (p.Arg487Ter)	Pathogenic
1454718	NM_003200.5(TCF3):c.136G>T (p.Gly46Ter)	Pathogenic
1676601	NM_003200.5(TCF3):c.808C>T (p.Gln270Ter)	Pathogenic
1676602	TCF3, EX5-11 DEL	Pathogenic
2020729	NM_003200.5(TCF3):c.1169_1170insAA (p.Ser391fs)	Pathogenic
2029431	NM_003200.5(TCF3):c.310G>T (p.Glu104Ter)	Pathogenic
2073832	NM_003200.5(TCF3):c.670del (p.Ser224fs)	Pathogenic
225870	NM_001136139.4(TCF3):c.1663G>A (p.Glu555Lys)	Pathogenic
2420906	NM_003200.5(TCF3):c.961C>T (p.Arg321Ter)	Pathogenic
2422486	NC_000019.9:g.(?1206913)(1650247_?)del	Pathogenic
2700730	NM_003200.5(TCF3):c.1178_1181del (p.Ile393fs)	Pathogenic
2715547	NM_003200.5(TCF3):c.759_760del (p.Ser253fs)	Pathogenic
2859583	NM_003200.5(TCF3):c.1359dup (p.Gly454fs)	Pathogenic
2869183	NM_003200.5(TCF3):c.692dup (p.Gln233fs)	Pathogenic
3359020	NM_003200.5(TCF3):c.1913C>G (p.Ser638Ter)	Pathogenic
3377280	NM_003200.5(TCF3):c.604del (p.Ser202fs)	Pathogenic
3778414	NM_003200.5(TCF3):c.1081C>T (p.Gln361Ter)	Pathogenic
4774069	NM_003200.5(TCF3):c.1573dup (p.Arg525fs)	Pathogenic
4798196	NM_003200.5(TCF3):c.295G>T (p.Gly99Ter)	Pathogenic
4810505	NM_003200.5(TCF3):c.130C>T (p.Gln44Ter)	Pathogenic
982676	NM_003200.5(TCF3):c.1338_1360del (p.Ser446fs)	Pathogenic
2018154	NM_003200.5(TCF3):c.367-1G>T	Likely pathogenic
2029712	NM_003200.5(TCF3):c.1094-2A>T	Likely pathogenic
2129140	NM_003200.5(TCF3):c.550-1G>C	Likely pathogenic
2184750	NM_003200.5(TCF3):c.219+1G>C	Likely pathogenic
2799628	NM_003200.5(TCF3):c.1168-2A>G	Likely pathogenic
3255617	NM_001136139.4(TCF3):c.1643_1649dup (p.Asn551fs)	Likely pathogenic
3662484	NM_003200.5(TCF3):c.653-2A>G	Likely pathogenic
3728233	NM_003200.5(TCF3):c.1167+1G>A	Likely pathogenic

SpliceAI

4364 predictions. Top by Δscore:

Variant	Effect	Δscore
19:1619105:GCTT:G	donor_loss	1.0000
19:1619106:CTTA:C	donor_loss	1.0000
19:1619108:TA:T	donor_loss	1.0000
19:1619109:A:AC	donor_gain	1.0000
19:1619109:A:AT	donor_loss	1.0000
19:1619110:C:CC	donor_gain	1.0000
19:1619110:CCA:C	donor_gain	1.0000
19:1619230:CCAAC:C	acceptor_gain	1.0000
19:1619231:CAACC:C	acceptor_gain	1.0000
19:1619232:AACCT:A	acceptor_loss	1.0000
19:1619233:AC:A	acceptor_gain	1.0000
19:1619234:CC:C	acceptor_gain	1.0000
19:1619235:CTGC:C	acceptor_loss	1.0000
19:1619236:T:G	acceptor_loss	1.0000
19:1619242:C:CT	acceptor_gain	1.0000
19:1619470:CTCTG:C	acceptor_gain	1.0000
19:1619472:CTG:C	acceptor_gain	1.0000
19:1619473:TG:T	acceptor_gain	1.0000
19:1619474:GCTG:G	acceptor_loss	1.0000
19:1619475:C:CC	acceptor_gain	1.0000
19:1619476:T:G	acceptor_loss	1.0000
19:1619775:CTCA:C	donor_loss	1.0000
19:1619776:TCA:T	donor_loss	1.0000
19:1619777:CACC:C	donor_loss	1.0000
19:1619778:A:AC	donor_gain	1.0000
19:1619778:ACCAG:A	donor_loss	1.0000
19:1619779:C:A	donor_loss	1.0000
19:1619779:C:CC	donor_gain	1.0000
19:1619779:CCAGG:C	donor_gain	1.0000
19:1619852:TC:T	acceptor_gain	1.0000

AlphaMissense

4195 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:1611830:T:A	K614N	1.000
19:1611830:T:G	K614N	1.000
19:1611842:G:C	N610K	1.000
19:1611842:G:T	N610K	1.000
19:1611844:T:C	N610D	1.000
19:1611846:C:G	R609P	1.000
19:1615287:C:G	R607P	1.000
19:1615298:C:A	E603D	1.000
19:1615298:C:G	E603D	1.000
19:1615299:T:A	E603V	1.000
19:1615300:C:T	E603K	1.000
19:1615302:A:G	L602S	1.000
19:1615308:A:G	L600P	1.000
19:1615311:A:C	I599S	1.000
19:1615311:A:G	I599T	1.000
19:1615311:A:T	I599N	1.000
19:1615314:A:T	V598D	1.000
19:1615320:A:T	V596D	1.000
19:1615323:G:T	A595D	1.000
19:1615324:C:G	A595P	1.000
19:1615326:T:G	Q594P	1.000
19:1615332:A:C	L592R	1.000
19:1615332:A:G	L592P	1.000
19:1615332:A:T	L592Q	1.000
19:1615341:A:G	L589P	1.000
19:1615341:A:T	L589Q	1.000
19:1615343:T:A	K588N	1.000
19:1615343:T:G	K588N	1.000
19:1615344:T:A	K588I	1.000
19:1615345:T:C	K588E	1.000

dbSNP variants (sampled 300 via entrez): RS1000002388 (19:1629272 G>A), RS1000038362 (19:1610153 C>A,T), RS1000054026 (19:1651216 C>A,T), RS1000063337 (19:1622447 C>A,T), RS1000092749 (19:1635422 C>G), RS1000232187 (19:1624635 C>G,T), RS1000255203 (19:1631553 G>A,C), RS1000304629 (19:1631381 G>A), RS1000321962 (19:1651414 A>G), RS1000342890 (19:1648468 G>A), RS1000347106 (19:1621636 C>CA,CAA), RS1000400833 (19:1652987 G>A), RS1000431872 (19:1652839 G>A), RS1000486983 (19:1627242 G>A,C,T), RS1000540403 (19:1645339 G>A,C,T)

Disease associations

OMIM: gene MIM:147141 | disease phenotypes: MIM:616941, MIM:619824, MIM:300352, MIM:618718, MIM:254500

GenCC curated gene-disease

Disease	Classification	Inheritance
agammaglobulinemia 8, autosomal dominant	Strong	Autosomal dominant
agammaglobulinemia 8b, autosomal recessive	Moderate	Autosomal recessive
autosomal agammaglobulinemia	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
autosomal agammaglobulinemia	Definitive	SD

Mondo (8): agammaglobulinemia 8, autosomal dominant (MONDO:0014840), agammaglobulinemia 8b, autosomal recessive (MONDO:0859234), myeloproliferative neoplasm, unclassifiable (MONDO:0019452), cerebral creatine deficiency syndrome (MONDO:0000456), neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotonia (MONDO:0032878), Castleman-Kojima disease (MONDO:0018702), plasma cell myeloma (MONDO:0009693), autosomal agammaglobulinemia (MONDO:0011096)

Orphanet (5): Chronic myeloproliferative disease, unclassifiable (Orphanet:86830), Creatine deficiency syndrome (Orphanet:79172), TAFRO syndrome (Orphanet:457077), Multiple myeloma (Orphanet:29073), AL amyloidosis (Orphanet:85443)

HPO phenotypes

54 total (30 of 54 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000246	Sinusitis
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000377	Abnormal pinna morphology
HP:0000389	Chronic otitis media
HP:0000396	Overfolded helix
HP:0000403	Recurrent otitis media
HP:0000509	Conjunctivitis
HP:0000988	Skin rash
HP:0001287	Meningitis
HP:0001369	Arthritis
HP:0001508	Failure to thrive
HP:0001581	Recurrent skin infections
HP:0001744	Splenomegaly
HP:0001875	Decreased total neutrophil count
HP:0001876	Pancytopenia
HP:0001903	Anemia
HP:0001944	Dehydration
HP:0001945	Fever
HP:0002014	Diarrhea
HP:0002024	Malabsorption
HP:0002028	Chronic diarrhea
HP:0002110	Bronchiectasis
HP:0002205	Recurrent respiratory infections
HP:0002719	Recurrent infections
HP:0002720	Decreased circulating IgA concentration

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D009101	Multiple Myeloma	C04.557.595.500; C14.907.454.460; C15.378.147.780.650; C15.378.463.515.460; C20.683.515.845; C20.683.780.650
C538056	Agammaglobulinemia, non-Bruton type (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

55 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases methylation, affects cotreatment	8
Benzo(a)pyrene	affects activity, decreases expression, increases methylation	4
trichostatin A	decreases expression, affects cotreatment	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
bisphenol A	decreases expression, decreases methylation	2
cobaltous chloride	decreases expression, increases expression	2
Arsenic	affects cotreatment, decreases expression, increases abundance, increases expression, affects methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Plant Extracts	affects cotreatment, decreases expression	2
tert-Butylhydroperoxide	decreases expression	2
FR900359	decreases phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
4-hydroxy-2-nonenal	decreases expression	1
periodate-oxidized adenosine	affects expression	1
coumarin	decreases phosphorylation	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
MK-8776	increases expression	1
(+)-JQ1 compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Vorinostat	decreases expression	1

Cellosaurus cell lines

33 cell lines: 28 cancer cell line, 3 embryonic stem cell, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0079	697	Cancer cell line	Male
CVCL_0089	MHH-CALL-3	Cancer cell line	Female
CVCL_0590	Kasumi-2	Cancer cell line	Male
CVCL_1242	HAL-01	Cancer cell line	Female
CVCL_1851	RCH-ACV	Cancer cell line	Female
CVCL_9247	THP-4	Cancer cell line	Male
CVCL_A079	YAMN-90R	Cancer cell line	Male
CVCL_A080	YAMN-92	Cancer cell line	Male
CVCL_A082	YCUB-2	Cancer cell line	Male
CVCL_A087	YCUB-6	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00104104	PHASE4	COMPLETED	A Multiple Myeloma Trial in Patients With Bone Metastases
NCT00211211	PHASE4	COMPLETED	FREE Study - Fracture Reduction Evaluation
NCT00242528	PHASE4	WITHDRAWN	Open-label Study, to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Bone Lesions Secondary to Multiple Myeloma.
NCT00257114	PHASE4	COMPLETED	Evaluation of VELCADE Given as Retreatment to Multiple Myeloma Patients for Efficacy, Safety and Tolerability
NCT00352703	PHASE4	COMPLETED	PROMPT - Palifermin in Reduction of Oral Mucositis in PBSC Transplantation
NCT00361140	PHASE4	COMPLETED	Busulfan Safety/Efficacy as Conditioning Prior to Hematopoietic Cell Transplantation (HCT)
NCT00622505	PHASE4	COMPLETED	Zoledronic Acid Treatment (Every 4 or 12 Weeks) to Prevent Skeletal Complications in Advanced Multiple Myeloma Participants
NCT00652041	PHASE4	COMPLETED	Bortezomib/Adriamycine/Melfalan/Prednisone (VAMP)/Thalidomide/Cyclophosphamide/Dexamethasone (TaCyDex) or Bortezomib/Melfalan/Prednisone (V-MP)/TaCyDex) in Refractary or Relapsed Multiple Myeloma
NCT00733538	PHASE4	COMPLETED	Stage I Multiple Myeloma Treatment
NCT01087008	PHASE4	COMPLETED	Zoledronic Acid in Patients With Multiple Myeloma and Asymptomatic Biochemical Relapse
NCT01249690	PHASE4	UNKNOWN	Efficacy Study of PAD and TAD in Newly Diagnosed Multiple Myeloma
NCT01410929	PHASE4	WITHDRAWN	Evaluation of Vertebral Compression Fracture Fixation With RF Kyphoplasty in Patients With Multiple Myeloma
NCT01731886	PHASE4	COMPLETED	Lenalidomide and Dexamethasone With/Without Stem Cell Transplant in Patients With Multiple Myeloma
NCT01868828	PHASE4	UNKNOWN	A Study of PAD Versus Velcade, Cyclophosphamide and Dexamethasone (VCD) Treatment in Subjects With Multiple Myeloma
NCT02268890	PHASE4	COMPLETED	A Pharmacokinetic Study of Bortezomib in Taiwanese Participants With Multiple Myeloma
NCT02286830	PHASE4	COMPLETED	Prolonged Protection From Bone Disease in Multiple Myeloma
NCT02559154	PHASE4	UNKNOWN	Modified Bortezomib-based Combination Therapy for Multiple Myeloma
NCT02577783	PHASE4	UNKNOWN	PDD vs PAD to Treat Initially Diagnosed MM
NCT02773550	PHASE4	TERMINATED	Treatment With a Scheme With Low Doses of Bortezomib / Melphalan / Prednisone (MPV) in Patients With Multiple Myeloma
NCT02958969	PHASE4	COMPLETED	Apixaban for Primary Prevention of Venous Thromboembolism in Patients With Multiple Myeloma
NCT03173092	PHASE4	TERMINATED	A Study of Ixazomib (NINLARO®) in Combination With Lenalidomide and Dexamethasone (IRD) for the Treatment of Participants With Multiple Myeloma (MM)
NCT03619252	PHASE4	COMPLETED	Pneumococcal Vaccination of Multiple Myeloma Patients on Novel Agents
NCT03768960	PHASE4	COMPLETED	A Study of DARZALEX (Daratumumab) In Indian Participants With Relapsed and Refractory Multiple Myeloma, Whose Prior Therapy Included a Proteasome Inhibitor and an Immunomodulatory Agent
NCT03829371	PHASE4	ACTIVE_NOT_RECRUITING	STUDY COMPARING TWO STANDARD TREATMENTS IN AUTOLOGOUS STEM CELL TRANSPLANTATION INELIGIBLE POPULATION AFFECTED BY MULTIPLE MYELOMA
NCT03908138	PHASE4	UNKNOWN	RDD Versus VDD in Newly Diagnosed Patients With Multiple Myeloma
NCT04217967	PHASE4	COMPLETED	Ixazomib, Lenalidomide, and Combination for Maintenance in NDMM Patients
NCT04952766	PHASE4	COMPLETED	Study Evaluating SARS-CoV-2 (COVID-19) Humoral Response After BNT162b2 Vaccine in Immunocompromised Adults Compared to Healthy Adults
NCT04989140	PHASE4	UNKNOWN	Study of Pomalidomide, Oral Dexamethasone and Ixazomib in Patients With Relapsed MM Who Have Received Lenalidomide
NCT05183139	PHASE4	WITHDRAWN	A Multicenter In-class Transition Study of Ixazomib Combined With Pomalidomide and Dexamethasone or With Lenalidomide and Dexamethasone in Adults With Relapsed/Refractory Multiple Myeloma
NCT05201781	PHASE4	RECRUITING	A Long-term Study for Participants Previously Treated With Ciltacabtagene Autoleucel
NCT05429515	PHASE4	NOT_YET_RECRUITING	Effect of HFR-SUPRA in the Treatment of Multiple Myeloma-related Acute Kidney Injury
NCT05511428	PHASE4	COMPLETED	Home Based Daratumumab Administration for Patients With Multiple Myeloma
NCT05545202	PHASE4	UNKNOWN	A Randomized, Comparative, Double-blind Trial of Pentaisomaltose and Dimethyl Sulphoxide for Cryoprotection of Hematopoietic Stem Cells in Subjects With Multiple Myeloma or Malignant Lymphoma With a Need for Autologous Transplantation
NCT05555329	PHASE4	COMPLETED	Alternative Dosing Scheme of Pomalidomide 4 mg Every Other Day Versus Pomalidomide 2 mg and 4 mg Every Day; the POMAlternative Study
NCT05722405	PHASE4	RECRUITING	Ixazomib Plus Low-dose Lenalidomide Versus Ixazomib Alone for Maintenance Treatment of High Risk Multiple Myeloma
NCT05855122	PHASE4	UNKNOWN	Safety and ASCT-related Symptom Burden Optimization of Tocilizumab in ASCT Following HD Melphalan Conditioning for Multiple Myeloma Patients
NCT05944783	PHASE4	NOT_YET_RECRUITING	Bioequivalence Studies of Dasatinib 100 Mg
NCT06057402	PHASE4	RECRUITING	Elranatamab Post Trial Access Study for Participants With Multiple Myeloma (MM)
NCT06251076	PHASE4	RECRUITING	Plan Development for Giving Teclistamab in the Outpatient Setting