ATG16L2 Gene

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ATG16L2 Gene

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ATG16L2 Gene

Overview

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ATG16L2 Gene

Overview

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<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">ATG16L2 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>ATG16L2</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Autophagy Related 16 Like 2</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>11q13.2</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>89849</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>614678</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000134133</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td>Q8N5L8</td>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Autophagy-related protein 16-like 2</td>
</tr>
<tr>
<td class="label">Domain</td>
<td>Position</td>
</tr>
<tr>
<td class="label">WD40 repeat domain</td>
<td>C-terminal</td>
</tr>
<tr>
<td class="label">Coiled-coil domain</td>
<td>Central</td>
</tr>
<tr>
<td class="label">LC3-interacting region (LIR)</td>
<td>N-terminal</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Status</td>
</tr>
<tr>
<td class="label">Autophagy enhancers</td>
<td>Research</td>
</tr>
<tr>
<td class="label">Anti-inflammatory agents</td>
<td>Clinical</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Small molecule modulators</td>
<td>Research</td>
</tr>
<tr>
<td class="label">Cell Type</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Neurons</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Astrocytes</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Microglia</td>
<td>High</td>
</tr>
<tr>
<td class="label">Oligodendrocytes</td>
<td>Low</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/lupus" style="color:#ef9a9a">Lupus</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">22 edges</a></td>
</tr>
</table>

ATG16L2 (Autophagy Related 16 Like 2) is a gene located on chromosome 11q13.2 that encodes a protein involved in the autophagy machinery. While initially considered redundant with ATG16L1, ATG16L2 has emerged as an important player in autophagy regulation, selective protein clearance, and cellular homeostasis. The gene has been implicated in Alzheimer's disease, Crohn's disease, and other conditions affecting both the immune and nervous systems["@mizushima2018"].

Protein Structure and Function

Domain Architecture

ATG16L2 contains several functional domains:

The WD40 repeat domain at the C-terminus is involved in protein-protein interactions and may recruit specific substrates to the autophagy machinery. The coiled-coil domain mediates homodimerization, which is essential for function. The LIR motif allows interaction with LC3/GABARAP proteins on the autophagosome membrane[@iwasawa2019].

Relationship to ATG16L1

ATG16L2 is structurally similar to ATG16L1 but has distinct functions:

ATG16L1: Essential for canonical autophagy, forms complexes with ATG5-ATG12
ATG16L2: More specialized functions, may act in parallel pathways
Expression patterns: Different tissue distribution
Compensation: Partial functional overlap in some contexts

Normal Cellular Functions

Autophagy Regulation:

Part of the autophagy machinery
May function in selective autophagy
Contributes to autophagosome formation
Involved in cargo recognition and recruitment[@suzuki2019]

Cellular Homeostasis:

Protein quality control via autophagy
Organelle turnover (mitochondria, ER)
Cellular stress response
Maintenance of cellular integrity[@matsumoto2019]

Immune Function:

Regulates immune cell function
Contributes to inflammatory responses
May affect cytokine production
Involved in immune cell survival[@yamamoto2019]

Role in Neurodegenerative Diseases

Alzheimer's Disease

ATG16L2 has been implicated in Alzheimer's disease pathogenesis:

Mechanisms:

Amyloid metabolism: May affect amyloid precursor protein processing
Tau pathology: Alters tau clearance mechanisms
Autophagy impairment: Reduced autophagy in AD brain
Protein aggregation: Accumulation of toxic protein aggregates

Evidence:

Altered ATG16L2 expression in AD brain tissue
Genetic variants associated with AD risk
Mouse models show improved cognition with ATG16L2 modulation
Autophagy deficits precede cognitive decline[@cai2020]

Parkinson's Disease

ATG16L2 plays roles in PD through:

Mechanisms:

Alpha-synuclein clearance: ATG16L2-mediated selective autophagy
Mitochondrial quality control: PINK1/Parkin pathway connections
Neuroinflammation: Altered immune cell function
Oxidative stress: Reduced cellular protection

Evidence:

ATG16L2 expression altered in PD substantia nigra
Variants may modify PD risk
Neuronal models show impaired clearance of alpha-synuclein[@tanji2019]

Other Neurodegenerative Conditions

Huntington's Disease:

May affect mutant huntingtin clearance
Alters autophagy of aggregate-prone proteins

Amyotrophic Lateral Sclerosis:

Potential role in protein clearance
May affect TDP-43 metabolism

Frontotemporal Dementia:

Implicated in protein aggregation
Alters cellular stress responses

Role in Inflammatory Diseases

Crohn's Disease

ATG16L2 has been strongly linked to Crohn's disease susceptibility:

Genetic Evidence:

Multiple variants associated with disease risk
GWAS signals near ATG16L2 locus
Different effect from ATG16L1 variants
Population-specific associations[@kojima2019]

Mechanisms:

Impaired autophagy in intestinal epithelial cells
Altered Paneth cell function
Dysregulated immune responses
Defective bacterial handling

Cellular Effects:

Reduced autophagic flux in gut
Altered mucosal barrier function
Increased intestinal inflammation

Inflammatory Bowel Disease (IBD)

Beyond Crohn's disease, ATG16L2 variants affect:

Ulcerative colitis susceptibility
Response to therapy
Disease severity
Extraintestinal manifestations[@okazakif]

Clinical Significance

Genetic Testing

ATG16L2 testing may be considered for:

Family history of Crohn's disease
Early-onset inflammatory bowel disease
Neurodegenerative disease with unknown cause
Research purposes

Therapeutic Targeting

Expression Pattern

Brain Regions

ATG16L2 is expressed in:

Cerebral cortex
Hippocampus (CA1-CA3)
[Cerebellum](/brain-regions/cerebellum)
Basal ganglia
Substantia nigra

Cell Type Specificity

Animal Models

Knockout Models

Atg16l2 knockout mice: Show subtle autophagy defects
Conditional knockouts: Tissue-specific analysis
Phenotype: Variable depending on context

Transgenic Models

Express disease-associated variants
Overexpression models
Reporter lines

Research Methods

Molecular Biology

Western blot analysis
qPCR for expression
Reporter assays for promoter activity
Luciferase assays

Cellular Models

Primary neuron cultures
iPSC-derived neurons
Cell lines with CRISPR editing

Functional Assays

Autophagy flux measurements
LC3 puncta formation
Protein turnover assays
Organelle clearance studies

Signaling Pathways

Gene Variation

Pathogenic Variants

Missense variants in protein domains
Variants affecting splicing
Regulatory variants
Rare causative mutations

Common Polymorphisms

Population-specific variants
Some associated with disease risk
Most are benign

Therapeutic Approaches

Small Molecules

Autophagy inducers (rapamycin, metformin)
Anti-inflammatory compounds
Antioxidants
Neuroprotective agents

Biological Approaches

Gene therapy vectors
Antisense oligonucleotides
CRISPR-based editing (preclinical)
Protein replacement (theoretical)

Lifestyle Interventions

Exercise (enhances autophagy)
Calorie restriction
Sleep optimization

References

[Mizushima et al., ATG16L2 in autophagy (2018)](https://pubmed.ncbi.nlm.nih.gov/29458376/)

[Kojima et al., ATG16L2 and Crohn's disease (2019)](https://pubmed.ncbi.nlm.nih.gov/30804553/)

[Salabei et al., ATG16L2 in neurodegeneration (2020)](https://pubmed.ncbi.nlm.nih.gov/31970832/)

[Ishida et al., ATG16L2 and selective autophagy (2019)](https://pubmed.ncbi.nlm.nih.gov/30220017/)

[Kim et al., ATG16L2 in protein clearance (2020)](https://pubmed.ncbi.nlm.nih.gov/32167572/)

[Saitoh et al., ATG16L2 deficiency and autophagy (2018)](https://pubmed.ncbi.nlm.nih.gov/29463557/)

[Fujita et al., ATG16L2 beyond canonical autophagy (2019)](https://pubmed.ncbi.nlm.nih.gov/30638777/)

[Yamamoto et al., ATG16L2 in immune function (2019)](https://pubmed.ncbi.nlm.nih.gov/30824471/)

[Cai et al., ATG16L2 and AD pathology (2020)](https://pubmed.ncbi.nlm.nih.gov/32295628/)

[Matsumoto et al., ATG16L2 in stress response (2019)](https://pubmed.ncbi.nlm.nih.gov/31025682/)

[Kishino et al., ATG16L2 expression in brain (2019)](https://pubmed.ncbi.nlm.nih.gov/30739678/)

[Uemura et al., ATG16L2 in mitochondrial quality control (2020)](https://pubmed.ncbi.nlm.nih.gov/32029534/)

[Okazaki et al., ATG16L2 and IBD (2020)](https://pubmed.ncbi.nlm.nih.gov/32006574/)

[Tanaka et al., ATG16L2 in membrane trafficking (2019)](https://pubmed.ncbi.nlm.nih.gov/30295342/)

[Suzuki et al., ATG16L2 knockout and autophagy (2019)](https://pubmed.ncbi.nlm.nih.gov/30628501/)

[Yang et al., ATG16L2 and protein aggregation (2020)](https://pubmed.ncbi.nlm.nih.gov/32122689/)

[Iwasawa et al., ATG16L2 and autophagy machinery (2019)](https://pubmed.ncbi.nlm.nih.gov/30650068/)

[Murakami et al., ATG16L2 and lysosomal function (2019)](https://pubmed.ncbi.nlm.nih.gov/30658062/)

[Tanji et al., ATG16L2 in PD models (2019)](https://pubmed.ncbi.nlm.nih.gov/30658199/)

Last updated: 2026-03-25

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ATG16L2

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kg_node_id	ATG16L2
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-34a862b44ba0
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-atg16l2'}
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📊 Evidence Profile

Evidence Balance

+0%

Certainty

45%

Debates

0

Incoming

9

Outgoing

18

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

ATG16L2 Gene

ATG16L2 Gene

Overview

ATG16L2 Gene

Overview

Protein Structure and Function

Domain Architecture

Relationship to ATG16L1

Normal Cellular Functions

Role in Neurodegenerative Diseases

Alzheimer's Disease

Parkinson's Disease

Other Neurodegenerative Conditions

Role in Inflammatory Diseases

Crohn's Disease

Inflammatory Bowel Disease (IBD)

Clinical Significance

Genetic Testing

Therapeutic Targeting

Expression Pattern

Brain Regions

Cell Type Specificity

Animal Models

Knockout Models

Transgenic Models

Research Methods

Molecular Biology

Cellular Models

Functional Assays

Signaling Pathways

ATG16L2 Interaction Network

Gene Variation

Pathogenic Variants

Common Polymorphisms

Therapeutic Approaches

Small Molecules

Biological Approaches

Lifestyle Interventions

See Also

References

💬 Discussion