Details for: TCL1B

Gene ID: 9623

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: TCL1B

Ensembl ID: ENSG00000213231

Description: TCL1 family AKT coactivator B

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • immature B cell CL0000816
    CSI 12.36
    rCSI 9.19%
    PRS 98.22
  • small pre-B-II cell CL0000954
    CSI 11.61
    rCSI 11.17%
    PRS 98.19
  • precursor B cell CL0000817
    CSI 6.06
    rCSI 5.31%
    PRS 97.43
  • pro-B cell CL0000826
    CSI 5.45
    rCSI 4.51%
    PRS 96.26
  • placental villous trophoblast CL2000060
    CSI 3.57
    rCSI 5.51%
    PRS 94.1
  • syncytiotrophoblast cell CL0000525
    CSI 1.67
    rCSI 4.8%
    PRS 95.15
  • large pre-B-II cell CL0000957
    CSI 1.08
    rCSI 3.08%
    PRS 94.56

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [TCL1B](/details-gene/9623) (TCL1 family AKT coactivator B) is a protein-coding gene located on chromosome 14q32.13. It is a member of the T-cell leukemia/lymphoma 1 (TCL1) family of proto-oncogenes. Functionally, [TCL1B](/details-gene/9623) acts as a coactivator for the AKT serine/threonine kinase, a central node in signaling pathways that regulate cell growth, proliferation, and survival ([Link](https://doi.org/10.1016/s1097-2765(00)00039-3), [Link](https://doi.org/10.1074/jbc.m107069200)). Expression data indicates that **Overall**, [TCL1B](/details-gene/9623) is a highly significant marker for early stages of B-lymphocyte development, with its highest significance observed in [immature B cell](/details-cell/CL0000816)s and [small pre-B-II cell](/details-cell/CL0000954)s. This specific expression pattern, combined with its role in AKT activation, suggests it is a critical regulator of B-cell maturation and has been implicated in T-cell malignancies ([Link](https://doi.org/10.1073/pnas.96.6.2949)). ## Cellular Roles and Expression Landscape The expression profile of [TCL1B](/details-gene/9623) strongly points to a specialized role in the hematopoietic system, particularly during B-cell lymphopoiesis. **Overall**, the gene exhibits its highest significance in B-lymphoid precursors, underscoring its role in establishing the identity and function of these cells. The top-ranking cell types include: * [immature B cell](/details-cell/CL0000816) (CSI: 12.36) * [small pre-B-II cell](/details-cell/CL0000954) (CSI: 11.61) * [precursor B cell](/details-cell/CL0000817) (CSI: 6.06) * [pro-B cell](/details-cell/CL0000826) (CSI: 5.45) This pattern suggests that [TCL1B](/details-gene/9623) is a key molecular player during the transition from pro-B to immature B-cell stages, a period characterized by intense selection, proliferation, and differentiation. The high CSI values in these cells indicate that its expression is not only abundant but also highly specific to this developmental window. Interestingly, [TCL1B](/details-gene/9623) also shows notable significance in specific non-hematopoietic cells, such as [placental villous trophoblast](/details-cell/CL2000060) (CSI: 3.57) and [syncytiotrophoblast cell](/details-cell/CL0000525) (CSI: 1.67). This suggests a secondary role for the gene, potentially related to proliferation and survival signaling during placental development, though its impact appears less pronounced than in the B-cell lineage. ## Pathways and Molecular Function The function of [TCL1B](/details-gene/9623) is intrinsically linked to intracellular signaling cascades. Gene Ontology annotations highlight its involvement in '[Intracellular signal transduction](/details-go/GO:0035556)' and its molecular capacity for '[Protein binding](/details-go/GO:0005515)' and '[Protein kinase binding](/details-go/GO:0019901)'. Specifically, [TCL1B](/details-gene/9623) is characterized by its '[Protein serine/threonine kinase activator activity](/details-go/GO:0043539)'. This is consistent with extensive research demonstrating that the TCL1 family proteins, including [TCL1B](/details-gene/9623), function as coactivators for the AKT kinase ([Link](https://doi.org/10.1016/s1097-2765(00)00039-3)). By binding to and enhancing AKT activity, [TCL1B](/details-gene/9623) potentiates a critical pathway that promotes cell survival and blocks apoptosis. This function is highly relevant in the context of developing B-cells, where AKT signaling is essential for mediating signals from the pre-B-cell receptor and B-cell receptor to ensure proper maturation and survival. ## Research Directions The specific expression of [TCL1B](/details-gene/9623) in lymphoid precursors and its function as a pro-survival AKT coactivator raise important questions about its role in both normal development and oncogenesis. Its chromosomal location at 14q32.1 is a known hotspot for translocations in T-cell malignancies ([Link](https://doi.org/10.1073/pnas.96.6.2949)), providing a direct link to cancer. ### Proposed Hypotheses 1. **Role in B-cell Malignancy:** Given its high expression during B-cell development and its pro-survival function, aberrant or sustained expression of [TCL1B](/details-gene/9623) in mature B-cells may act as a driver for B-cell lymphomas by providing a persistent anti-apoptotic signal through AKT hyperactivation. 2. **Function in Placental Development:** The expression of [TCL1B](/details-gene/9623) in trophoblasts suggests it may be required for normal placental function. It is hypothesized that [TCL1B](/details-gene/9623)-mediated AKT activation is crucial for trophoblast proliferation, invasion, and survival during gestation. ### Experimental Approach To test the hypothesis regarding its role in B-cell malignancy, a conditional transgenic mouse model could be developed. Specifically, a mouse strain with a LoxP-STOP-LoxP cassette followed by the [TCL1B](/details-gene/9623) coding sequence knocked into a safe harbor locus (e.g., Rosa26) could be crossed with a CD19-CreERT2 line. This would allow for tamoxifen-inducible, B-cell-specific expression of [TCL1B](/details-gene/9623) in adult mice. Following induction, peripheral blood and lymphoid organs could be monitored via flow cytometry for signs of abnormal B-cell expansion, and mice could be aged to assess the incidence and latency of B-cell lymphoma development. ### Therapeutic Potential As a proto-oncogene that promotes cell survival by enhancing AKT signaling, [TCL1B](/details-gene/9623) represents a compelling therapeutic target for cancers characterized by its overexpression. Its restricted expression pattern, primarily in lymphoid precursors, suggests that targeting it may have a favorable therapeutic window with limited toxicity to other tissues. The therapeutic strategy would focus on **inhibition**. Developing small molecule inhibitors or peptidomimetics designed to disrupt the protein-protein interaction between [TCL1B](/details-gene/9623) and AKT could selectively block its pro-survival function in malignant cells, potentially inducing apoptosis and sensitizing them to conventional chemotherapy.

Genular Protein ID: 3727730563

Symbol: TCL1B_HUMAN

Name: T-cell leukemia/lymphoma protein 1B

UniProtKB Accession Codes:

O95988 A6NEK7 Q6IAR7 Q9UBQ4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 10 Ensembl 1 ExpressionAtlas 1 GO 3 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SIGNOR 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 10344735

Title: Identification of the TCL1/MTCP1-like 1 (TML1) gene from the region next to the TCL1 locus.

PubMed ID: 10344735

PubMed ID: 10077617

Title: Abnormalities at 14q32.1 in T cell malignancies involve two oncogenes.

PubMed ID: 10077617

DOI: 10.1073/pnas.96.6.2949

PubMed ID: 12508121

Title: The DNA sequence and analysis of human chromosome 14.

PubMed ID: 12508121

DOI: 10.1038/nature01348

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 10983986

Title: The protooncogene TCL1 is an Akt kinase coactivator.

PubMed ID: 10983986

DOI: 10.1016/s1097-2765(00)00039-3

PubMed ID: 11707444

Title: Differential regulation of Akt kinase isoforms by the members of the TCL1 oncogene family.

PubMed ID: 11707444

DOI: 10.1074/jbc.m107069200

Sequence Information:

  • Length: 128
  • Mass: 14846
  • Checksum: 6BA2CF3F40F78B4D
  • Sequence:
    • MASEASVRLG VPPGRLWIQR PGIYEDEEGR TWVTVVVRFN PSRREWARAS QGSRYEPSIT 
VHLWQMAVHT RELLSSGQMP FSQLPAVWQL YPGRKYRAAD SSFWEIADHG QIDSMEQLVL 
TYQPERKD