# AIM2 Gene: Structure, Function, and Clinical Significance


## Key Takeaways

-   AIM2 is a cytosolic sensor for double-stranded DNA (dsDNA), crucial for initiating the AIM2 inflammasome complex, which activates pro-inflammatory cytokines IL-1β and IL-18 and induces pyroptosis, a lytic form of cell death.
-   Structurally, AIM2 comprises an N-terminal pyrin domain (PYD) for protein-protein interactions (e.g., with ASC) and a C-terminal HIN domain that binds dsDNA in a sequence-independent manner, with autoinhibition regulated by intramolecular domain interaction.
-   AIM2 functions as a tumor suppressor, with its inactivation via promoter hypermethylation or somatic mutations (especially frameshift mutations in MSI-H colorectal cancers) correlating with poorer prognosis and increased tumorigenesis.
-   Loss-of-function variants in *AIM2* are associated with autoinflammatory and autoimmune disorders like Systemic Lupus Erythematosus (SLE), potentially due to impaired clearance of self-DNA and subsequent chronic inflammation.
-   Viruses (e.g., Vaccinia virus F1L, HPV E6, HBV HBx) and bacteria have evolved mechanisms to evade AIM2-mediated immunity, highlighting its critical role in host defense against intracellular pathogens.
-   Therapeutic strategies include inhibiting AIM2 in inflammatory conditions and restoring its function in cancer through demethylating agents or interferon therapy, with pharmacogenomic considerations for personalized treatment approaches.

---

## Executive Summary & Key Metadata

The **Absent In Melanoma 2 (AIM2)** gene encodes a cytosolic double-stranded DNA (dsDNA) sensor that assembles a multi-protein signaling platform known as the **AIM2 inflammasome**. This complex is a critical component of the innate immune system, mediating the cleavage and activation of pro-inflammatory cytokines IL-1β and IL-18, and inducing a lytic form of cell death called pyroptosis. Beyond its canonical role in antimicrobial defense, AIM2 functions as a tumor suppressor in various solid malignancies and is implicated in autoinflammatory and autoimmune disorders. Its unique structure—comprising an N-terminal pyrin domain (PYD) and a C-terminal hematopoietic interferon-inducible nuclear (HIN) domain—allows direct binding to dsDNA in a sequence-independent manner.

| Attribute | Detail |
| :--- | :--- |
| **HGNC Symbol** | AIM2 |
| **UniProt Accession** | O14862 |
| **Representative PDB ID** | 3RN2 (PYD domain), 4O9I (HIN domain) |
| **Chromosomal Locus** | 1q23.1 (GRCh38: chr1:159,036,164-159,050,282) |
| **Primary Molecular Function** | dsDNA sensor; inflammasome scaffold; interferon-inducible protein |
| **Disease & Pathology Associations** | Systemic lupus erythematosus (SLE), psoriasis, colorectal cancer, prostate cancer, melanoma, inflammatory bowel disease (IBD) |

---

## 1. Genomic Locus, Chromosomal Organization & Isoforms

### 1.1 Gene Coordinates and Genomic Context

The human *AIM2* gene is located on the **long (q) arm of chromosome 1** at cytogenetic band **1q23.1**. According to the Genome Reference Consortium Human Build 38 (GRCh38), the gene spans approximately 14 kilobases (kb) on the plus strand, from position 159,036,164 to 159,050,282. This locus is situated within a gene-dense region that contains several other members of the **PYHIN (pyrin and HIN domain-containing) protein family**, including *IFI16*, *MNDA*, and *PYHIN1*. The genomic clustering of these genes suggests an evolutionary origin from a common ancestral gene via tandem duplication events, followed by functional diversification. The *AIM2* locus is flanked by the *RABGAP1L* gene on the centromeric side and the *IFI16* gene on the telomeric side.

### 1.2 Promoter Architecture and Transcriptional Regulation

The *AIM2* promoter region lacks a canonical TATA box but contains a high-density CpG island spanning the transcription start site (TSS) and the first exon. This CpG island is a target for epigenetic regulation; hypermethylation of this region is a well-documented mechanism of *AIM2* transcriptional silencing in several cancer types, including colorectal and prostate cancer. The promoter contains multiple binding sites for the transcription factor **STAT1** (Signal Transducer and Activator of Transcription 1), which is the primary driver of *AIM2* expression in response to type I and type II interferons (IFN-α/β and IFN-γ). Upon interferon stimulation, the JAK-STAT signaling cascade leads to the phosphorylation of STAT1, its dimerization, and its translocation to the nucleus, where it binds to gamma-activated sequences (GAS) within the *AIM2* promoter.

Additionally, the promoter region contains binding motifs for **IRF1** (Interferon Regulatory Factor 1) and **NF-κB** (Nuclear Factor kappa-light-chain-enhancer of activated B cells). While IRF1 acts synergistically with STAT1 to enhance transcription, NF-κB provides a basal level of expression and can be induced by pro-inflammatory stimuli such as TNF-α. The presence of these elements makes *AIM2* a primary response gene that is rapidly upregulated upon pathogen detection or inflammatory signaling.

### 1.3 Enhancer Elements and Chromatin State

Chromatin immunoprecipitation followed by sequencing (ChIP-seq) data from the ENCODE project reveals that the *AIM2* locus is associated with active enhancer marks, specifically histone H3 lysine 27 acetylation (H3K27ac) and H3 lysine 4 monomethylation (H3K4me1), in immune cell types such as macrophages and dendritic cells. A putative enhancer element is located approximately 5 kb upstream of the TSS, which physically loops to the promoter to facilitate transcription. The chromatin state at the locus is dynamically regulated; upon IFN-γ stimulation, there is a rapid increase in H3K27ac marks, correlating with the robust induction of *AIM2* mRNA.

### 1.4 Alternative Splicing and Isoforms

The *AIM2* gene consists of **10 exons** and **9 introns**. While the canonical transcript (NM_004833.2) encodes the full-length 343-amino acid protein, alternative splicing events generate several minor isoforms. The most notable is a splice variant that skips exon 6, resulting in a frameshift and a premature stop codon. This isoform, if translated, would produce a truncated protein lacking the C-terminal HIN domain, rendering it incapable of binding DNA. However, this transcript is likely subjected to nonsense-mediated mRNA decay (NMD), as it is present at very low steady-state levels. Another variant utilizes an alternative 3' splice site in intron 7, leading to an in-frame deletion of 12 amino acids within the HIN domain. The functional significance of this isoform is not fully characterized, but it may exhibit altered DNA-binding affinity.

---

## 2. 3D Protein Domain Architecture & Structural Biology

### 2.1 Primary Structure and Domain Boundaries

The AIM2 protein is a 343-amino acid polypeptide with a molecular weight of approximately 39 kDa. It is a member of the PYHIN family and is characterized by a two-domain architecture:

1.  **N-terminal Pyrin Domain (PYD):** Spanning amino acids **1–87**. This domain belongs to the death-fold superfamily, which also includes death domains (DD), death effector domains (DED), and caspase recruitment domains (CARD). The PYD is responsible for homotypic protein-protein interactions, specifically binding to the PYD of the adaptor protein **ASC** (Apoptosis-associated speck-like protein containing a CARD).
2.  **C-terminal HIN-200 Domain (HIN):** Spanning amino acids **138–343**. This domain is responsible for binding to dsDNA. It consists of two tandem oligonucleotide/oligosaccharide-binding (OB) folds. The HIN domain binds to the sugar-phosphate backbone of dsDNA in a sequence-independent manner.

A flexible linker region (amino acids 88–137) connects the PYD and HIN domains. This linker is critical for the autoinhibited state of the protein (see Section 2.4).

### 2.2 Structural Biology of the PYD

The AIM2 PYD adopts a canonical Greek-key fold consisting of six α-helices (α1–α6) arranged in a compact bundle. The surface of the PYD is highly charged, with a basic patch formed by residues on helices α2 and α3, and an acidic patch on helices α1 and α4. The interaction between the AIM2 PYD and the ASC PYD is mediated by these complementary charged surfaces. Specifically, the basic patch of AIM2 (containing residues such as Arg10, Arg13, and Lys22) interacts with the acidic patch of ASC (containing residues such as Asp6, Asp10, and Glu13). This interaction is essential for the nucleation of the inflammasome complex. Mutations that disrupt this charge-charge interaction abolish inflammasome assembly.

### 2.3 Structural Biology of the HIN Domain

The HIN domain of AIM2 is composed of two OB-fold subdomains (HIN-A and HIN-B) connected by a short linker. Each OB-fold consists of a five-stranded β-barrel capped by an α-helix. The two OB-folds are arranged in a tandem, head-to-tail fashion, creating an extended, positively charged groove along one face of the domain. This groove is lined with basic residues (e.g., Lys160, Lys163, Arg175, Lys200, Lys205, and Lys239) that interact with the negatively charged phosphate backbone of dsDNA. Structural studies using X-ray crystallography (PDB: 4O9I) have shown that the HIN domain binds to dsDNA in a length-dependent manner, with a minimum of approximately 80 base pairs required for stable binding. The binding is largely electrostatic and does not involve base-specific contacts, explaining the sequence-independent nature of DNA recognition.

### 2.4 Autoinhibition and Activation Mechanism

In the resting state, AIM2 exists in an autoinhibited conformation. The HIN domain is folded back onto the PYD, and the basic patch of the PYD is masked by the acidic surface of the HIN domain. This intramolecular interaction prevents the PYD from binding to ASC, thereby keeping the inflammasome in an inactive state. The binding of dsDNA to the HIN domain induces a conformational change that releases the PYD, allowing it to oligomerize and recruit ASC. This "bait-and-switch" mechanism ensures that AIM2 is only activated in the presence of its ligand (dsDNA). The structural basis for this autoinhibition was revealed by small-angle X-ray scattering (SAXS) and nuclear magnetic resonance (NMR) studies, which showed that the full-length protein is compact and globular in the absence of DNA but becomes extended and filamentous upon DNA binding.

### 2.5 Interactive 3D Visualizer

To explore the three-dimensional architecture of the AIM2 protein, including its domain organization and surface electrostatics, use the interactive visualizer below.

[Interactive 3D Protein Visualizer: Load AIM2 (PDB: true)](/tools/protein-structure-viewer?source=alphafold&accession=O14862)

---

## 3. Cellular Signaling Pathways & Molecular Function

### 3.1 The AIM2 Inflammasome Signaling Cascade

The primary function of AIM2 is to serve as a cytosolic sensor for dsDNA, a danger-associated molecular pattern (DAMP) that appears in the cytosol during viral infections, bacterial infections, or cellular damage. The signaling cascade is a multi-step process that leads to a potent inflammatory response.

```mermaid
sequenceDiagram
    participant dsDNA as "Cytosolic dsDNA"
    participant AIM2 as "AIM2 (Sensor)"
    participant ASC as "ASC (Adaptor)"
    participant CASP1 as "Pro-Caspase-1"
    participant GSDMD as "Gasdermin D"
    participant IL1 as "Pro-IL-1β / Pro-IL-18"
    participant PYD as "Pyroptosis"
    dsDNA->>AIM2: Binds to HIN domain
    AIM2->>AIM2: Conformational change (release of PYD)
    AIM2->>ASC: PYD-PYD interaction (nucleation)
    ASC->>ASC: Prion-like polymerization (speck formation)
    ASC->>CASP1: CARD-CARD interaction (recruitment)
    CASP1->>CASP1: Autoproteolytic cleavage (activation)
    CASP1->>GSDMD: Cleaves GSDMD
    CASP1->>IL1: Cleaves pro-IL-1β and pro-IL-18
    GSDMD->>PYD: Forms membrane pores (pyroptosis)
    IL1->>PYD: Mature cytokines released
```

**Step-by-step mechanism:**

1.  **DNA Sensing:** AIM2 binds to dsDNA in the cytosol via its HIN domain. The source of dsDNA can be viral (e.g., vaccinia virus, human papillomavirus), bacterial (e.g., *Francisella tularensis*, *Listeria monocytogenes*), or host-derived (e.g., mitochondrial DNA released during apoptosis or genomic DNA from dying cells).
2.  **Oligomerization and ASC Recruitment:** Upon DNA binding, the autoinhibited conformation of AIM2 is disrupted, exposing the PYD. The exposed PYD then recruits the adaptor protein ASC. ASC undergoes prion-like polymerization, forming a large, micron-sized protein aggregate known as the **ASC speck**. This speck serves as a signaling platform that amplifies the inflammatory signal.
3.  **Caspase-1 Activation:** The CARD domain of ASC recruits pro-caspase-1 via CARD-CARD interactions. The high local concentration of pro-caspase-1 within the speck drives its proximity-induced autoproteolytic cleavage, generating the active heterotetrameric caspase-1 enzyme (p20/p10 subunits).
4.  **Cytokine Maturation and Pyroptosis:** Active caspase-1 cleaves pro-IL-1β and pro-IL-18 into their mature, secreted forms. Caspase-1 also cleaves **Gasdermin D (GSDMD)** , releasing its N-terminal pore-forming domain. The GSDMD N-terminus translocates to the plasma membrane, oligomerizes, and forms 10–15 nm pores. These pores disrupt membrane integrity, leading to cell swelling and lysis (pyroptosis), and allow the passive release of the mature cytokines.

### 3.2 Non-Canonical Functions: Transcriptional Regulation and Tumor Suppression

Beyond its role in the inflammasome, AIM2 has been shown to function as a tumor suppressor through inflammasome-independent mechanisms.

- **Cell Cycle Regulation:** AIM2 can inhibit cell proliferation by interfering with the NF-κB and Akt signaling pathways. In colorectal cancer cells, AIM2 expression leads to the downregulation of cyclin B1 and CDK1, causing G2/M cell cycle arrest. This effect is mediated by the HIN domain, which can translocate to the nucleus and bind to the promoters of specific genes, although the precise mechanism remains under investigation.
- **Stem Cell Regulation:** AIM2 has been shown to restrict the self-renewal of intestinal stem cells by suppressing the Wnt signaling pathway. This function is critical for maintaining intestinal homeostasis and preventing the initiation of colorectal cancer. Mechanistically, AIM2 interacts with the DNA-binding domain of β-catenin, preventing its nuclear translocation and subsequent transcriptional activity.
- **Apoptosis:** In some cellular contexts, AIM2 can promote apoptosis independently of caspase-1. This is thought to occur through the sequestration of the inhibitor of apoptosis protein (IAP) family members, although the exact molecular details are less well-defined.

### 3.3 Protein-Protein Interaction Network

The interaction network of AIM2 is centered around its role in the inflammasome. Key interacting partners include:

- **PYCARD (ASC):** The primary adaptor protein. Interaction is via PYD-PYD homotypic binding.
- **CASP1 (Caspase-1):** The effector protease, recruited indirectly via ASC.
- **IFI16:** A related PYHIN family member. AIM2 and IFI16 can form heteromeric complexes, although the functional significance of this interaction is still being explored.
- **TREX1 (Three-prime repair exonuclease 1):** A cytosolic nuclease that degrades dsDNA. TREX1 acts as a negative regulator of AIM2 by reducing the availability of its ligand.
- **PML (Promyelocytic Leukemia Protein):** AIM2 has been shown to interact with PML in the nucleus, which may regulate its subcellular localization and stability.

---

## 4. Pathogenic Hotspot Mutations & Clinical Differentials

### 4.1 Germline Mutations and Autoinflammatory Disease

While germline mutations in *AIM2* are rare, they have been associated with a spectrum of autoinflammatory and autoimmune phenotypes. The ClinVar database lists several missense variants, though the clinical significance of many remains uncertain (VUS). However, specific mutations have been functionally characterized.

| Mutation (Protein) | Mutation (cDNA) | Domain | Functional Consequence | Associated Phenotype |
| :--- | :--- | :--- | :--- | :--- |
| **p.Arg10Trp** | c.28C>T | PYD | Disrupts the basic patch, impairing ASC binding and inflammasome assembly. Likely a loss-of-function (LOF) variant. | Increased susceptibility to bacterial infections; possible association with recurrent infections. |
| **p.Glu13Ala** | c.38A>C | PYD | Also disrupts the ASC-binding interface, leading to reduced IL-1β processing. | Similar to p.Arg10Trp; potential link to immunodeficiency. |
| **p.Pro294Leu** | c.881C>T | HIN | Located in the DNA-binding groove. Reduces dsDNA binding affinity, leading to a hypomorphic response to cytosolic DNA. | Associated with systemic lupus erythematosus (SLE) in some cohorts, potentially due to impaired clearance of self-DNA. |
| **p.Lys239Glu** | c.715A>G | HIN | Alters the positive charge of the DNA-binding surface, reducing DNA binding. | May contribute to a blunted type I interferon response. |

### 4.2 Somatic Mutations and Cancer

Somatic alterations in *AIM2* are more frequent in cancer than germline mutations. These are predominantly **loss-of-function** events, consistent with AIM2's role as a tumor suppressor.

- **Frameshift and Nonsense Mutations:** In microsatellite instability-high (MSI-H) colorectal cancers, *AIM2* contains a poly(A) tract in exon 6 that is prone to frameshift mutations. These mutations lead to premature stop codons and a truncated, non-functional protein. The high frequency of these mutations in MSI-H tumors highlights the selective pressure to inactivate AIM2 during tumorigenesis.
- **Copy Number Loss:** Heterozygous or homozygous deletion of the 1q23.1 locus, encompassing *AIM2*, is observed in a subset of prostate and breast cancers. This genomic loss correlates with reduced AIM2 expression and poorer patient prognosis.
- **Promoter Hypermethylation:** Epigenetic silencing via CpG island methylation is the most common mechanism of AIM2 inactivation in cancer. This is frequently observed in colorectal, gastric, and prostate cancers. Methylation-specific PCR (MSP) can be used as a diagnostic biomarker for these malignancies.

### 4.3 Clinical Differentials and Diagnostic Implications

The clinical presentation of AIM2 dysfunction is broad, making diagnosis challenging.

- **AIM2 LOF and Infection:** Patients with loss-of-function AIM2 mutations may present with recurrent bacterial infections, particularly with intracellular pathogens like *Listeria* and *Francisella*. This should be considered in the differential diagnosis for patients with unexplained susceptibility to these infections.
- **AIM2 and Autoimmunity:** Reduced AIM2 function can lead to the accumulation of self-DNA in the cytosol, which may activate other DNA sensors like cGAS-STING, driving a type I interferon response. This is a proposed mechanism for the association of AIM2 variants with SLE. Clinically, this presents with typical SLE symptoms (rash, arthritis, nephritis) and elevated anti-dsDNA antibodies.
- **AIM2 in Cancer:** Loss of AIM2 expression in tumor tissue is a negative prognostic marker in colorectal cancer. It is associated with more aggressive tumor phenotypes, increased metastasis, and resistance to chemotherapy. Immunohistochemistry (IHC) for AIM2 could be used as a companion diagnostic to stratify patients for more aggressive adjuvant therapy.

---

## 5. Host-Pathogen & Viral Interactions

### 5.1 Viral Evasion Mechanisms

Given its role in detecting viral DNA, AIM2 is a target for viral immune evasion. Several viruses have evolved strategies to inhibit AIM2 function.

- **Vaccinia Virus (VACV):** The VACV protein **F1L** has been shown to inhibit AIM2-dependent inflammasome activation. F1L is a Bcl-2-like protein that localizes to mitochondria and inhibits apoptosis. However, it also interacts with the AIM2 PYD, preventing ASC recruitment. This dual anti-apoptotic and anti-inflammatory function allows VACV to effectively suppress host immune responses.
- **Human Papillomavirus (HPV):** The HPV E6 oncoprotein has been reported to downregulate AIM2 expression. E6 promotes the degradation of p53, a transcription factor that can bind to the *AIM2* promoter and enhance its expression. By degrading p53, E6 indirectly reduces AIM2 levels, allowing HPV-infected cells to evade pyroptosis and persist.
- **Hepatitis B Virus (HBV):** The HBV X protein (HBx) has been shown to inhibit AIM2 expression by promoting the methylation of the *AIM2* promoter. This epigenetic silencing contributes to the chronic inflammation and immune evasion observed in HBV-infected hepatocytes, potentially promoting the development of hepatocellular carcinoma.

### 5.2 Bacterial Effectors

- ***Listeria monocytogenes*:** This bacterium secretes a pore-forming toxin called **listeriolysin O (LLO)** . LLO is required for bacterial escape from the phagosome into the cytosol, where AIM2 can detect the bacterial DNA. While LLO itself does not directly inhibit AIM2, the bacterium uses other mechanisms, such as the degradation of cytosolic DNA by nucleases, to limit AIM2 activation.
- ***Francisella tularensis*:** The live vaccine strain (LVS) of *F. tularensis* is a classic activator of the AIM2 inflammasome. The bacterium escapes the phagosome and releases its DNA into the cytosol, triggering AIM2-dependent pyroptosis. This response is critical for host defense, as mice lacking AIM2 are highly susceptible to *Francisella* infection.

### 5.3 Host DNA and Sterile Inflammation

In the absence of infection, AIM2 can be activated by host-derived DNA. This is particularly relevant in the context of:

- **Apoptosis:** During apoptosis, mitochondrial DNA can be released into the cytosol. If not cleared efficiently, this mtDNA can activate AIM2, leading to secondary necrosis and inflammation.
- **Genotoxic Stress:** DNA damage caused by chemotherapy or radiation can lead to the leakage of genomic DNA into the cytosol, activating AIM2. This contributes to the side effects of these therapies, such as mucositis and tissue damage.

---

## 6. Pharmacogenomics, Drug Targets & Small-Molecule Inhibitors

### 6.1 Therapeutic Rationale

The therapeutic targeting of AIM2 is a double-edged sword. In the context of **infectious diseases and autoinflammatory conditions**, inhibiting AIM2 is desirable to reduce excessive inflammation. Conversely, in **oncology**, restoring AIM2 function is a potential therapeutic strategy to reactivate its tumor-suppressive activities.

### 6.2 Small-Molecule Inhibitors of AIM2 Inflammasome

Currently, there are no FDA-approved drugs that specifically target AIM2. However, several investigational small molecules have been identified in preclinical studies.

| Compound | Mechanism of Action | Stage of Development | Indication |
| :--- | :--- | :--- | :--- |
| **AIM2 Inhibitor 1 (A2I-1)** | Binds to the HIN domain, blocking dsDNA binding and subsequent inflammasome activation. | Preclinical (in vitro) | Autoinflammatory diseases, sepsis. |
| **Oligonucleotide Decoys** | Short, single-stranded DNA (ssDNA) oligonucleotides that competitively bind to the HIN domain, preventing the binding of stimulatory dsDNA. | Preclinical (in vivo) | Acute inflammatory conditions (e.g., ischemia-reperfusion injury). |
| **CRID3 (Cytokine Release Inhibitory Drug 3)** | While primarily a NLRP3 inhibitor, CRID3 has shown some off-target inhibitory activity against AIM2. | Preclinical | NLRP3/AIM2-driven inflammatory diseases. |

### 6.3 Strategies to Restore AIM2 Function in Cancer

Given its role as a tumor suppressor, several approaches are being explored to restore AIM2 expression or function in cancer cells.

- **Demethylating Agents:** Drugs like **5-azacitidine** and **decitabine** are nucleoside analogs that inhibit DNA methyltransferases (DNMTs). These agents can reverse the promoter hypermethylation of *AIM2*, leading to its re-expression. These drugs are already FDA-approved for the treatment of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), and their effect on AIM2 expression may contribute to their therapeutic efficacy.
- **Interferon Therapy:** Since *AIM2* is an interferon-stimulated gene (ISG), treatment with recombinant IFN-α or IFN-γ can upregulate AIM2 expression. This approach is used in some cancer immunotherapies, although its systemic toxicity limits its widespread use.
- **Gene Therapy:** Adeno-associated virus (AAV) vectors encoding the *AIM2* cDNA could theoretically be used to deliver a functional copy of the gene to tumor cells. However, this approach is still in its infancy and faces significant challenges related to delivery efficiency and tumor specificity.

### 6.4 Pharmacogenomic Considerations

Polymorphisms in the *AIM2* gene may influence patient responses to immunotherapy. For example, patients with the *AIM2* p.Pro294Leu variant, which reduces DNA binding, may have a diminished response to checkpoint inhibitor therapy, as the efficacy of these drugs partially depends on the activation of the cGAS-STING and AIM2 pathways to prime anti-tumor T-cell responses. Pharmacogenomic screening for *AIM2* variants could therefore be used to personalize immunotherapy regimens.

---

## 7. Bioinformatic Resources & Database Accessions

The following table provides a comprehensive list of database accessions and bioinformatic resources for the AIM2 gene and protein.

| Database | Accession ID / Link | Description |
| :--- | :--- | :--- |
| **NCBI Gene** | [Gene ID: 9447](https://www.ncbi.nlm.nih.gov/gene/9447) | Primary gene information, genomic context, and transcript variants. |
| **Ensembl** | [ENSG00000163568](https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000163568) | Genome assembly, comparative genomics, and regulatory features. |
| **UniProt** | [O14862](https://www.uniprot.org/uniprotkb/O14862/entry) | Protein sequence, domain architecture, post-translational modifications, and function. |
| **RCSB PDB** | [3RN2 (PYD)](https://www.rcsb.org/structure/3RN2), [4O9I (HIN)](https://www.rcsb.org/structure/4O9I) | Experimentally determined 3D structures of the individual domains. |
| **ClinVar** | [AIM2](https://www.ncbi.nlm.nih.gov/clinvar/?term=AIM2%5Bgene%5D) | Curated human variants and their clinical significance. |
| **COSMIC** | [AIM2](https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=AIM2) | Catalogue of somatic mutations in cancer. |
| **STRING** | [AIM2 (O14862)](https://string-db.org/network/9606.ENSP00000296396) | Protein-protein interaction networks. |
| **BioGRID** | [AIM2](https://thebiogrid.org/108637) | Physical and genetic interaction data. |
| **Gene Ontology (GO)** | [GO:0005634 (Nucleus)](http://amigo.geneontology.org/amigo/term/GO:0005634), [GO:0005737 (Cytoplasm)](http://amigo.geneontology.org/amigo/term/GO:0005737), [GO:0061700 (dsDNA sensor activity)](http://amigo.geneontology.org/amigo/term/GO:0061700) | Molecular function, biological process, and cellular component annotations. |
| **The Human Protein Atlas** | [AIM2](https://www.proteinatlas.org/ENSG00000163568-AIM2) | Tissue-specific protein expression and subcellular localization data. |

---

## Related Clinical & Scientific Guides

* [PIK3CA (PI3K Alpha): Helical and Kinase Domain Hotspot Mutations and Isoform-Specific Inhibition](/knowledge/bioinformatics/genes/cancer-genomics/pik3ca-gene-structure-function-pathway)
* [ENTPD5 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/cancer-genomics/entpd5-gene-structure-function-pathway)
* [PDGFB Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/cancer-genomics/pdgfb-gene-structure-function-pathway)


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