Details for: BCL2L2

Gene ID: 599

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: BCL2L2

Ensembl ID: ENSG00000129473

Description: BCL2 like 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • goblet cell CL0000160
    CSI 3.27
    rCSI 3.09%
    PRS 96.4
  • ionocyte CL0005006
    CSI 2.83
    rCSI 3.03%
    PRS 97.93
  • rod bipolar cell CL0000751
    CSI 2.75
    rCSI 4.95%
    PRS 94.9
  • retina horizontal cell CL0000745
    CSI 2.59
    rCSI 3.95%
    PRS 95.8
  • ciliated epithelial cell CL0000067
    CSI 2.58
    rCSI 2.27%
    PRS 93.4
  • multi-ciliated epithelial cell CL0005012
    CSI 2.54
    rCSI 2.53%
    PRS 94.81
  • ciliated cell CL0000064
    CSI 2.5
    rCSI 4.05%
    PRS 93.91
  • retinal ganglion cell CL0000740
    CSI 2.45
    rCSI 5.41%
    PRS 92.49
  • retinal cone cell CL0000573
    CSI 2.12
    rCSI 3.41%
    PRS 93.47
  • type B pancreatic cell CL0000169
    CSI 2.1
    rCSI 4.65%
    PRS 97.19
  • club cell CL0000158
    CSI 2.05
    rCSI 3%
    PRS 96.16
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.84
    rCSI 3.26%
    PRS 92.4
  • vascular associated smooth muscle cell CL0000359
    CSI 1.7
    rCSI 5.51%
    PRS 97.26

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 [BCL2L2](/details-gene/599), or B-cell lymphoma 2-like 2, is a protein-coding gene located on chromosome 14q11.2. As a member of the BCL-2 family of proteins, it is a key regulator of apoptosis. The encoded protein, Bcl-w, primarily functions as a pro-survival factor by inhibiting the intrinsic apoptotic pathway at the mitochondrial outer membrane. Its expression is particularly significant in a diverse array of specialized cell types, including secretory [goblet cell](/details-cell/CL0000160)s, various neuronal cells of the retina, and ciliated epithelial cells. This expression pattern suggests a critical role in maintaining the viability of terminally differentiated or high-stress cells that are essential for sensory function and tissue barrier integrity. Its clinical association is noted under OMIM entry [601931](https://omim.org/entry/601931). ## Cellular Roles and Expression Landscape The expression profile of [BCL2L2](/details-gene/599) highlights its importance in maintaining the integrity of specific, functionally specialized cell populations. **Overall**, the gene shows the highest significance in cells associated with mucosal surfaces, the nervous system, and endocrine function. Its top marker status in [goblet cell](/details-cell/CL0000160)s (CSI: 3.27), [ciliated epithelial cell](/details-cell/CL0000067)s (CSI: 2.58), and [club cell](/details-cell/CL0000158)s (CSI: 2.05) suggests a crucial pro-survival role in maintaining the cellular machinery of respiratory and gastrointestinal tracts. This is consistent with research identifying its tissue expression and subcellular localization ([Link](https://doi.org/10.1038/sj.cdd.4400835)). Furthermore, [BCL2L2](/details-gene/599) is a significant factor in the retina, with high CSI scores in [rod bipolar cell](/details-cell/CL0000751)s (CSI: 2.75), [retina horizontal cell](/details-cell/CL0000745)s (CSI: 2.59), [retinal ganglion cell](/details-cell/CL0000740)s (CSI: 2.45), and [retinal cone cell](/details-cell/CL0000573)s (CSI: 2.12). This concentrated expression points to a vital function in preventing apoptosis in these non-regenerating, high-metabolic-demand neuronal cells, which are critical for vision. The gene also appears important for specialized cells like [ionocyte](/details-cell/CL0005006)s (CSI: 2.83) and pancreatic [type B pancreatic cell](/details-cell/CL0000169)s (CSI: 2.10), suggesting it protects cells involved in ion transport and hormone secretion from metabolic or environmental stress. The collective data portrays [BCL2L2](/details-gene/599) not as a ubiquitous housekeeping gene but as a specialized survival factor essential for the longevity and function of specific, often irreplaceable, cell types. ## Pathways and Molecular Function [BCL2L2](/details-gene/599) is centrally involved in the regulation of apoptosis. Its molecular function is primarily characterized by its anti-apoptotic activity, as annotated by Gene Ontology terms such as [negative regulation of apoptotic process](/details-cell/GO0043066) ([GO:0043066](https://www.ebi.ac.uk/QuickGO/term/GO:0043066)). It is a core component of the [Bcl-2 family protein complex](/details-cell/GO0097136) ([GO:0097136](https://www.ebi.ac.uk/QuickGO/term/GO:0097136)) and localizes to the [mitochondrial outer membrane](/details-cell/GO0005741) ([GO:0005741](https://www.ebi.ac.uk/QuickGO/term/GO:0005741)). The primary mechanism of its pro-survival function involves the [negative regulation of release of cytochrome c from mitochondria](/details-cell/GO0090201) ([GO:0090201](https://www.ebi.ac.uk/QuickGO/term/GO:0090201)) and the [negative regulation of mitochondrial membrane permeability](/details-cell/GO0035795) ([GO:0035795](https://www.ebi.ac.uk/QuickGO/term/GO:0035795)). By sequestering pro-apoptotic BH3-only proteins, [BCL2L2](/details-gene/599) prevents the activation of BAX and BAK, thereby blocking mitochondrial outer membrane permeabilization and the subsequent cascade of caspase activation ([Link](https://doi.org/10.1083/jcb.200302144)). While primarily anti-apoptotic, its annotation for [positive regulation of apoptotic process](/details-cell/GO0043065) ([GO:0043065](https://www.ebi.ac.uk/QuickGO/term/GO:0043065)) hints at the contextual complexity of Bcl-2 family interactions. The gene is also implicated in specific developmental processes like [spermatogenesis](/details-cell/GO0007283) ([GO:0007283](https://www.ebi.ac.uk/QuickGO/term/GO:0007283)) and cellular responses to stimuli such as [amyloid-beta](/details-cell/GO1904646) ([GO:1904646](https://www.ebi.ac.uk/QuickGO/term/GO:1904646)) and [ischemia](/details-cell/GO0002931) ([GO:0002931](https://www.ebi.ac.uk/QuickGO/term/GO:0002931)), underscoring its role as a stress-response survival factor. ## Research Directions The specific expression pattern and anti-apoptotic function of [BCL2L2](/details-gene/599) suggest several avenues for future research, particularly in the context of degenerative diseases and cancer. **Testable Hypotheses:** 1. **Role in Retinal Degeneration:** Given its high significance in multiple retinal cell types, downregulation of [BCL2L2](/details-gene/599) may be a key event in the pathogenesis of diseases like age-related macular degeneration or retinitis pigmentosa, by sensitizing photoreceptors and retinal ganglion cells to stress-induced apoptosis. 2. **Contribution to Diabetes:** The specific high expression of [BCL2L2](/details-gene/599) in [type B pancreatic cell](/details-cell/CL0000169)s suggests that its activity is crucial for protecting these cells from glucotoxicity and inflammatory cytokines. Impaired [BCL2L2](/details-gene/599) function could be a contributing factor to beta-cell loss in both type 1 and type 2 diabetes. 3. **Involvement in Chronic Respiratory Disease:** In diseases like chronic obstructive pulmonary disease (COPD) or asthma, characterized by damage to the airway epithelium, dysregulation of [BCL2L2](/details-gene/599) in [ciliated epithelial cell](/details-cell/CL0000067)s and [goblet cell](/details-cell/CL0000160)s could impair tissue repair and accelerate the loss of barrier function. **Proposed Experiment:** To test the hypothesis that [BCL2L2](/details-gene/599) has a protective role in retinal degeneration, a gene therapy approach could be employed in a mouse model. An adeno-associated virus (AAV) vector engineered to overexpress [BCL2L2](/details-gene/599) could be delivered via intravitreal injection to a mouse model of light-induced retinal damage or a genetic model such as the *rd10* mouse. The therapeutic effect would be quantified by measuring retinal function via electroretinography (ERG), assessing photoreceptor survival through histological analysis of outer nuclear layer thickness, and quantifying apoptosis using TUNEL assays. This experiment would directly test whether enhancing [BCL2L2](/details-gene/599) function can mitigate retinal cell death. **Therapeutic Potential:** [BCL2L2](/details-gene/599) presents a dual therapeutic potential. In diseases characterized by excessive apoptosis, such as neurodegenerative and retinal diseases, it is a promising target for **activation**. Therapeutic strategies could include gene therapy to restore its expression or the development of small-molecule stabilizers that enhance its anti-apoptotic function. Conversely, in cancers that overexpress [BCL2L2](/details-gene/599) to evade apoptosis, it represents a valid target for **inhibition**. The development of specific BH3-mimetic drugs that selectively bind to and inactivate the Bcl-w protein could offer a targeted therapeutic option, analogous to existing inhibitors of other Bcl-2 family members.

Genular Protein ID: 2524631309

Symbol: B2CL2_HUMAN

Name: Bcl-2-like protein 2

UniProtKB Accession Codes:

Q92843 A8K0F4 Q2M3U0 Q5U0H4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CPTC 1 CTD 1 ChEMBL 1 ComplexPortal 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 DrugCentral 1 EMBL 10 Ensembl 7 EvolutionaryTrace 1 ExpressionAtlas 1 GO 20 Gene3D 1 GeneCards 2 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GuidetoPHARMACOLOGY 1 HGNC 2 HOGENOM 1 HPA 2 InParanoid 1 IntAct 1 InterPro 9 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 2 OrthoDB 1 PANTHER 2 PDB 5 PDBsum 5 PRINTS 2 PROSITE 5 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 RefSeq 2 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TCDB 1 TreeFam 2 UCSC 1 VEuPathDB 2 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8761287

Title: Bcl-w, a novel member of the Bcl-2 family, promotes cell survival.

PubMed ID: 8761287

PubMed ID: 9039502

Title: Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain.

PubMed ID: 9039502

DOI: 10.1093/dnares/3.5.321

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

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: 11423909

Title: Tissue expression and subcellular localization of the pro-survival molecule Bcl-w.

PubMed ID: 11423909

DOI: 10.1038/sj.cdd.4400835

PubMed ID: 12952938

Title: Proapoptotic BH3-only proteins trigger membrane integration of prosurvival Bcl-w and neutralize its activity.

PubMed ID: 12952938

DOI: 10.1083/jcb.200302144

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19413330

Title: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.

PubMed ID: 19413330

DOI: 10.1021/ac9004309

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 24129315

Title: Immunoaffinity enrichment and mass spectrometry analysis of protein methylation.

PubMed ID: 24129315

DOI: 10.1074/mcp.o113.027870

PubMed ID: 12660157

Title: The structure of Bcl-w reveals a role for the C-terminal residues in modulating biological activity.

PubMed ID: 12660157

DOI: 10.1093/emboj/cdg144

PubMed ID: 12651847

Title: Solution structure of human BCL-w: modulation of ligand binding by the C-terminal helix.

PubMed ID: 12651847

DOI: 10.1074/jbc.m301798200

Sequence Information:

  • Length: 193
  • Mass: 20746
  • Checksum: 3542243A532B1762
  • Sequence:
    • MATPASAPDT RALVADFVGY KLRQKGYVCG AGPGEGPAAD PLHQAMRAAG DEFETRFRRT 
FSDLAAQLHV TPGSAQQRFT QVSDELFQGG PNWGRLVAFF VFGAALCAES VNKEMEPLVG 
QVQEWMVAYL ETQLADWIHS SGGWAEFTAL YGDGALEEAR RLREGNWASV RTVLTGAVAL 
GALVTVGAFF ASK