ATG16L2 Gene
Overview
flowchart TD
ATG16L2["ATG16L2"] -->|"associated with"| Lupus["Lupus"]
ATG16L2["ATG16L2"] -->|"associated with"| BECN1["BECN1"]
ATG16L2["ATG16L2"] -->|"associated with"| ATG5["ATG5"]
ATG16L2["ATG16L2"] -->|"associated with"| CDKN1B["CDKN1B"]
ATG16L2["ATG16L2"] -->|"associated with"| ATG7["ATG7"]
ATG16L2["ATG16L2"] -->|"associated with"| RUBCN["RUBCN"]
ATG16L2["ATG16L2"] -->|"associated with"| CYBB["CYBB"]
ATG16L2["ATG16L2"] -->|"associated with"| LRRK2["LRRK2"]
ATG16L2["ATG16L2"] -->|"associated with"| LC3["LC3"]
ATG16L2["ATG16L2"] -->|"associated with"| MAP1LC3B["MAP1LC3B"]
ATG16L2["ATG16L2"] -->|"associated with"| DRAM1["DRAM1"]
ATG16L2["ATG16L2"] -->|"associated with"| MTORC1["MTORC1"]
ATG16L2["ATG16L2"] -->|"associated with"| PHAGOCYTOSIS["PHAGOCYTOSIS"]
ATG16L2["ATG16L2"] -->|"associated with"| AUTOPHAGY["AUTOPHAGY"]
style ATG16L2 fill:#4fc3f7,stroke:#333,color:#000
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ATG16L2 Gene
Overview
Mermaid diagram (expand to render)
<table class="infobox infobox-gene">Gene Symbol </td>Full Name </td>Chromosomal Location </td>NCBI Gene ID </td>OMIM </td>Ensembl ID </td>UniProt </td>Protein Name </td>WD40 repeat domain </td>Coiled-coil domain </td>LC3-interacting region (LIR) </td>
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-ATG12ATG16L2: More specialized functions, may act in parallel pathwaysExpression patterns: Different tissue distributionCompensation: Partial functional overlap in some contextsNormal 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 processingTau pathology: Alters tau clearance mechanismsAutophagy impairment: Reduced autophagy in AD brainProtein aggregation: Accumulation of toxic protein aggregatesEvidence:
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 autophagyMitochondrial quality control: PINK1/Parkin pathway connectionsNeuroinflammation: Altered immune cell functionOxidative stress: Reduced cellular protectionEvidence:
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 defectsConditional knockouts: Tissue-specific analysisPhenotype: Variable depending on contextTransgenic 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
ATG16L2 Interaction Network ATG16L2
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
See Also
[ATG16L2 Protein](/proteins/atg16l2-protein)
[Autophagy Pathway](/mechanisms/autophagy)
[Alzheimer's Disease](/diseases/alzheimers-disease)
[Parkinson's Disease](/diseases/parkinsons-disease)
[Crohn's Disease](/diseases/crohns-disease)
[Protein Aggregation](/mechanisms/protein-aggregation)
[Selective Autophagy](/mechanisms/selective-autophagy)
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 Show full description