AIM2

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

Basic information

Region (hg38): 1:159061598-159187843

Links

ENSG00000163568 ∙ NCBI:9447 ∙ OMIM:604578 ∙ HGNC:357 ∙ Uniprot:O14862 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AIM2 gene.

• Inborn genetic diseases (14 variants)
• not provided (5 variants)
• Hereditary breast ovarian cancer syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AIM2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					3	3
missense			13	1		14
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	13	1	3

Variants in AIM2

This is a list of pathogenic ClinVar variants found in the AIM2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-159062694-A-C		Hereditary breast ovarian cancer syndrome • AIM2-related disorder	Conflicting classifications of pathogenicity (Dec 18, 2020)
1-159062696-GT-G		AIM2-related disorder	Benign (Feb 12, 2021)
1-159063541-A-T		not specified	Uncertain significance (Jul 17, 2023)
1-159063559-C-T		not specified	Uncertain significance (Jan 11, 2023)
1-159063587-T-C		not specified	Uncertain significance (Aug 04, 2023)
1-159063596-C-T		not specified	Uncertain significance (Dec 08, 2023)
1-159063602-T-C		not specified	Likely benign (Feb 11, 2022)
1-159065931-A-G			Benign (Jan 22, 2018)
1-159065966-T-C		not specified	Uncertain significance (Oct 20, 2021)
1-159065976-C-A			Benign (Aug 08, 2018)
1-159066037-G-A		not specified	Uncertain significance (Jun 18, 2021)
1-159066094-C-A		not specified	Uncertain significance (Apr 06, 2023)
1-159066145-T-C		not specified	Uncertain significance (Jul 10, 2023)
1-159066175-T-C		not specified	Uncertain significance (May 23, 2023)
1-159066178-G-A		not specified	Uncertain significance (May 16, 2023)
1-159066193-T-C		not specified	Uncertain significance (Jun 07, 2023)
1-159066287-C-T		not specified	Uncertain significance (May 03, 2023)
1-159068562-T-A			Benign (Aug 08, 2018)
1-159068615-C-A		not specified	Uncertain significance (Apr 19, 2023)
1-159073251-C-T			Benign (Jul 06, 2018)
1-159073337-T-C		not specified	Uncertain significance (Mar 11, 2024)
1-159073364-T-C		not specified	Uncertain significance (Sep 26, 2022)
1-159171815-G-A		Inborn genetic diseases	Uncertain significance (Dec 26, 2023)
1-159171838-A-C		Inborn genetic diseases	Uncertain significance (Feb 28, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AIM2	protein_coding	protein_coding	ENST00000368130	5	84613

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.19e-9	0.0760	125681	0	66	125747	0.000262

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.601	165	188	0.877	0.00000979	2275
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000869	0.000869
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000194	0.000193
Middle Eastern	0.00	0.00
South Asian	0.000467	0.000457
Other	0.00	0.00

dbNSFP

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}.
• Pathway: 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;Innate Immune System;Immune System;The AIM2 inflammasome (Consensus)

Recessive Scores

• pRec: 0.0929

Intolerance Scores

• loftool: 0.853
• rvis_EVS: 0.04
• rvis_percentile_EVS: 56.92

Haploinsufficiency Scores

• pHI: 0.0693
• hipred: N
• hipred_score: 0.112
• ghis: 0.451

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.889

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Aim2
• Phenotype: hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); immune system phenotype; skeleton phenotype; homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: activation of innate immune response;positive regulation of defense response to virus by host;apoptotic process;inflammatory response;immune response;negative regulation of NF-kappaB transcription factor activity;positive regulation of protein oligomerization;positive regulation of interleukin-1 beta production;tumor necrosis factor-mediated signaling pathway;cellular response to interferon-beta;cellular response to drug;innate immune response;interleukin-1 beta secretion;positive regulation of interleukin-1 beta secretion;positive regulation of NF-kappaB transcription factor activity;pyroptosis;positive regulation of cysteine-type endopeptidase activity
• Cellular component: nucleoplasm;cytoplasm;mitochondrion;cytosol;AIM2 inflammasome complex
• Molecular function: double-stranded DNA binding;protein binding;identical protein binding