AIM2

protein-coding

absent in melanoma 2, the group of Pyrin domain containing|Pyrin and HIN domain family

Gene summary

AIM2 is a member of the IFI20X /IFI16 family. It plays a putative role in tumorigenic reversion and may control cell proliferation. Interferon-gamma induces expression of AIM2. [provided by RefSeq, Jul 2008]

MANE transcript

NM_004833.3

Inheritance

—

ClinVar variants

U:38B:9

Top phenotype

AIM2-related disorder

gnomAD constraint

pLI —, LoF o/e 1.04

Max pathogenic AF

—

Genomic locus

chr1:159,056,129-159,187,843

External References & Databases

Ensembl (ENSG00000163568)

Transcript & Mutation Effects

hg38 • Region Span ~131.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AIM2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 41

not providedTotal: 5

AIM2-related disorderTotal: 2

Hereditary breast ovarian cancer syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004833.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous					3 clinvar	3
missense			37 clinvar	5 clinvar		42
nonsense						0
start loss						0
frameshift					1 clinvar	1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	38	5	4	47

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004833.3	RefSeq	NP_004824.1	5	MANE Select
ENST00000368130.9	Ensembl	ENSP00000357112.4	5	MANE Select
NM_001348247.2	RefSeq	NP_001335176.1	4	Standard
ENST00000368129.3	Ensembl	ENSP00000357111.3	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cytosolic DNA-sensing pathway - Homo sapiens (human)
NOD-like receptor signaling pathway - Homo sapiens (human)
Nucleotide-binding Oligomerization Domain (NOD) pathway
Inflammasomes
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways

Biological Process

activation of innate immune response
positive regulation of defense response to virus by host
apoptotic process
inflammatory response
immune response

Molecular Function

double-stranded DNA binding
protein binding
identical protein binding

Cellular Component

nucleoplasm
cytoplasm
mitochondrion
cytosol
AIM2 inflammasome complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000368130
Coding exons: 5
Length: 84613
Individuals with no LoFs: 125681
Homozygous LoFs: 0
Heterozygous LoFs: 66
Defined: 125747
p: 0.000262

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.601	165	188	0.877	0.00000979	2275
Missense (PolyPhen)		21	35.606	0.58979		501
Synonymous	0.115	68	69.2	0.982	0.00000382	646
Loss of Function	-0.143	13	12.5	1.04	5.85e-7	169

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00087	0.00087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.00019	0.00019	rare
South Asian	0.00047	0.00046	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in innate immune response by recognizing cytosolic double-stranded DNA and inducing caspase-1-activating inflammasome formation in macrophages. Upon binding to DNA is thought to undergo oligomerization and to associate with PYCARD initiating the recruitment of caspase-1 precusrsor and processing of interleukin-1 beta and interleukin-18. Detects cytosolic dsDNA of viral and bacterial origin in a non-sequence-specific manner. Can also trigger PYCARD-dependent, caspase-1-independent cell death that involves caspase-8 (By similarity). Tumor suppressor which may act by repressing NF-kappa-B transcriptional activity. {ECO:0000250, ECO:0000269|PubMed:16432157, ECO:0000269|PubMed:17726700, ECO:0000269|PubMed:19158675, ECO:0000269|PubMed:19158676, ECO:0000269|PubMed:19158679, ECO:0000269|PubMed:20566831}.;

Recessive Scores

pRec: 0.0929

Intolerance Scores

LoFtool: 0.853
RVIS EVS: 0.04
RVIS percentile EVS: 56.92

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.889

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium