BCL2L13

BCL2L13 Gene — BCL2 Like 13 (Bcl-Rambo)

Pathway Diagram

```mermaid
flowchart TD
BCL2L13["BCL2L13<br/>Mitochondrial<br/>Anti-apoptotic Protein"]

%% Mitochondrial regulation partners
DNM1L["DNM1L<br/>Mitochondrial<br/>Fission Protein"]
OPTN["OPTN<br/>Autophagy<br/>Receptor"]
SQSTM1["SQSTM1/p62<br/>Autophagy<br/>Adapter"]
CALCOCO2["CALCOCO2/NDP52<br/>Selective<br/>Autophagy"]

%% Cellular stress response
CAT["CAT<br/>Catalase<br/>Antioxidant"]
CANX["CANX<br/>ER Chaperone<br/>Calnexin"]
G3BP1["G3BP1<br/>Stress Granule<br/>Assembly"]

%% Neurological diseases - pathological
Alzheimer["Alzheimer's<br/>Disease"]
Parkinson["Parkinson's<br/>Disease"]
ALS["Amyotrophic<br/>Lateral Sclerosis"]
FTD["Frontotemporal<br/>Dementia"]
MS["Multiple<br/>Sclerosis"]

%% Biological processes
Aging["Cellular<br/>Aging"]
Ischemia["Ischemic<br/>Damage"]
MitoFunction["Mitochondrial<br/>Dysfunction"]
Autophagy["Mitophagy/<br/>Autophagy"]

%% Interactions
BCL2L13 -->|"regulates"| DNM1L
BCL2L13 -->|"interacts"| OPTN
BCL2L13 -->|"interacts"| SQSTM1
BCL2L13 -->|"interacts"| CALCOCO2
BCL2L13 -->|"interacts"| CAT
BCL2L13 -->|"interacts"| CANX
BCL2L13 -->|"interacts"| G3BP1

%% Pathway connections
DNM1L -->|"promotes"| MitoFunction
OPTN -->|"mediates"| Autophagy
SQSTM1 -->|"facilitates"| Autophagy
CALCOCO2 -->|"promotes"| Autophagy
CAT -->|"reduces"| MitoFunction

%% Disease connections
BCL2L13 -->|"inhibits"| Aging
BCL2L13

BCL2L13 Gene — BCL2 Like 13 (Bcl-Rambo)

Pathway Diagram

Introduction

Bcl2L13 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-gene"> [@zhang2020]
<table> [@liu2021]
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">BCL2L13</th></tr> [@gao2022]
<tr><td><strong>Gene Symbol</strong></td><td>BCL2L13</td></tr> [@wang2021]
<tr><td><strong>Full Name</strong></td><td>BCL2 Like 13</td></tr>
<tr><td><strong>Alternative Names</strong></td><td>Bcl-Rambo, BCL-Rambo</td></tr>
<tr><td><strong>Chromosomal Location</strong></td><td>22q11.21</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[23765](https://www.ncbi.nlm.nih.gov/gene/23765)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q9HAW5](https://www.uniprot.org/uniprot/Q9HAW5)</td></tr>
<tr><td><strong>Protein Type</strong></td><td>Mitochondrial Outer Membrane Protein</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>~32 kDa</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/ad" style="color:#ef9a9a">AD</a>, <a href="/wiki/ali" style="color:#ef9a9a">ALI</a>, <a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">413 edges</a></td>
</tr>
</table>
</div>

Overview

BCL2L13 (also known as Bcl-Rambo) is a member of the BCL-2 protein family localized primarily to the mitochondrial outer membrane. Unlike anti-apoptotic BCL-2 proteins, BCL2L13 exhibits unique pro-apoptotic and mitophagy-regulating functions. It plays important roles in mitochondrial quality control, [apoptosis](/entities/apoptosis) regulation, and has been implicated in neurodegenerative diseases.

Function and Mechanism

Mitochondrial Apoptosis Regulation

BCL2L13 has complex functions in apoptosis:

• Pro-apoptotic activity: BCL2L13 can induce mitochondrial outer membrane permeabilization (MOMP)
• BH3-only protein: Contains a BH3 domain that can interact with anti-apoptotic BCL-2 proteins
• Sequestration: Can sequester pro-apoptotic proteins like BAX and BAK
• Voltage-dependent anion channel (VDAC): Interacts with VDAC1 to regulate mitochondrial permeability

Mitophagy Regulation

BCL2L13 is a key player in mitophagy:

• PINK1-Parkin-independent mitophagy: BCL2L13 can mediate mitophagy without Parkin
• BCL2L13-Atg32 axis: Functional homolog of yeast Atg32 in mammals
• Mitochondrial quality control: Targets damaged mitochondria for lysosomal degradation
• [Reactive oxygen species](/entities/reactive-oxygen-species) (ROS): Regulates ROS-induced mitophagy

Mitochondrial Dynamics

BCL2L13 influences mitochondrial morphology:

• Fusion/fission balance: Affects mitochondrial fission rates
• Cristae remodeling: Modulates inner membrane cristae structure
• Energy metabolism: Impacts mitochondrial respiratory function

Role in Neurodegenerative Diseases

Alzheimer's Disease

• Mitochondrial dysfunction: BCL2L13 dysregulation contributes to AD-associated mitochondrial defects
• [Amyloid-beta](/proteins/amyloid-beta) toxicity: Modulates Aβ-induced mitochondrial apoptosis
• [Tau](/proteins/tau) pathology: May be affected by tau-mediated mitochondrial damage
• Therapeutic potential: BCL2L13 activators could enhance mitophagy in AD

Parkinson's Disease

• Mitophagy in PD: Critical for clearing damaged dopaminergic mitochondria
• [LRRK2](/entities/lrrk2) connection: Interacts with LRRK2 pathogenic mutations
• PINK1/Parkin pathway: Modulates both PINK1-dependent and independent mitophagy
• Dopaminergic neuron survival: Essential for maintaining dopaminergic neuron health

Amyotrophic Lateral Sclerosis

• Mitochondrial quality control: Impaired mitophagy contributes to motor neuron degeneration
• [C9orf72](/entities/c9orf72) interactions: May cooperate with C9orf72 in mitochondrial homeostasis
• [TDP-43](/mechanisms/tdp-43-proteinopathy) pathology: BCL2L13 dysfunction exacerbates TDP-43-induced toxicity
• Energy crisis: Contributes to the bioenergetic deficit in ALS

Other Neurodegenerative Conditions

• Huntington's Disease: BCL2L13-mediated mitophagy helps clear mutant [huntingtin](/proteins/huntingtin)-affected mitochondria
• Prion diseases: Mitochondrial dysfunction involves BCL2L13 dysregulation
• Multiple system atrophy: May contribute to oligodendrocyte mitochondrial defects
• Friedreich's ataxia: Frataxin deficiency affects BCL2L13 function

Therapeutic Implications

| Approach | Mechanism | Status |
|----------|-----------|--------|
| BCL2L13 agonists | Enhance mitophagy to clear damaged mitochondria | Preclinical |
| Small molecule modulators | Stabilize BCL2L13 for neuroprotection | Research |
| Gene therapy | Overexpress BCL2L13 in target [neurons](/entities/neurons) | Preclinical |
| Combination with [mTOR](/mechanisms/mtor-signaling-pathway) inhibitors | Boost mitophagy capacity | Research |

Interactions

• BCL-2 family: BCL2, BCL-XL, MCL1 (antagonists)
• Apoptosis regulators: BAX, BAK, BOK
• Mitochondrial proteins: VDAC1, TOM complex
• [Autophagy](/entities/autophagy) machinery: LC3, Atg proteins

Background

The study of Bcl2L13 has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

Cross-References

• [BCL2L13 Protein](/proteins/bcl2l13-protein)
• [Mitophagy in Parkinson's Disease](/mechanisms/mitophagy-parkinsons-disease)
• [Mitochondrial Dynamics in Neurodegeneration](/mechanisms/mitochondrial-dynamics-neurodegeneration)
• [Apoptosis in Neurodegenerative Disease](/mechanisms/apoptosis-neurodegeneration)

External Links

• [NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/) - Gene database
• [UniProt](https://www.uniprot.org/) - Protein database

References

Pathway Diagram

The following diagram shows the key molecular relationships involving BCL2L13 discovered through SciDEX knowledge graph analysis:

Disease Associations

Source: Open Targets Platform (opentargets.org)

| Disease | Association Score | Disease ID |
|--------|-------------------|------------|
| sign or symptom | 0.2937 | EFO_0003765 |
| Phenotypic abnormality | 0.2937 | HP_0000118 |
| placenta praevia | 0.2924 | EFO_0007442 |
| neurodegenerative disease | 0.2907 | EFO_0005772 |
| pneumonitis | 0.2240 | EFO_1001991 |

Expression Profile

Sources: [GTEx Portal v10](https://gtexportal.org/home/gene/bcl2l13) | [Allen Brain Atlas](https://www.brain-map.org/)

GTEx Tissue Expression (median TPM)

| Rank | Tissue | Median TPM |
|------|--------|------------|
| 1 | Muscle Skeletal | 38.54 |
| 2 | Adrenal Gland | 24.30 |
| 3 | Cells Cultured fibroblasts | 23.45 |
| 4 | Esophagus Muscularis | 23.35 |
| 5 | Adipose Subcutaneous | 22.16 |
| 6 | Skin Sun Exposed Lower leg | 19.70 |
| 7 | Bladder | 19.69 |
| 8 | Pituitary | 19.66 |
| 9 | Cells EBV-transformed lymphocytes | 18.55 |
| 10 | Esophagus Gastroesophageal Junction | 18.36 |
| 11 | Colon Sigmoid | 18.19 |
| 12 | Skin Not Sun Exposed Suprapubic | 17.78 |
| 13 | Breast Mammary Tissue | 17.66 |
| 14 | Nerve Tibial | 17.12 |
| 15 | Adipose Visceral Omentum | 16.82 |

Brain-Region Expression:

| Region | Median TPM |
|--------|------------|
| Brain Cerebellar Hemisphere | 15.08 |