IRGM

immunity related GTPase M

Basic information

Region (hg38): 5:150846520-150900736

Previous symbols: [ "IRGM1" ]

Links

ENSG00000237693 ∙ NCBI:345611 ∙ OMIM:608212 ∙ HGNC:29597 ∙ Uniprot:A1A4Y4 ∙ 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 IRGM gene.

• Inborn genetic diseases (33 variants)
• not provided (5 variants)
• not specified (1 variants)
• Inflammatory bowel disease 19 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IRGM 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				1	1	2
missense			12	2		14
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			18	1	4	23
Total	0	0	30	4	5

Variants in IRGM

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

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

Position	Type	Phenotype	Significance	ClinVar
5-150848136-A-C		not specified	Uncertain significance (Sep 16, 2021)
5-150848149-C-T		not specified	Uncertain significance (Dec 27, 2023)
5-150848207-A-G		not specified	Uncertain significance (Sep 16, 2021)
5-150848235-A-G		not specified	Likely benign (Sep 16, 2021)
5-150848275-G-A		not specified	Uncertain significance (Feb 13, 2023)
5-150848356-A-G		not specified	Uncertain significance (Oct 26, 2021)
5-150848397-C-T		not specified	Uncertain significance (Mar 23, 2022)
5-150848398-C-T		not specified	Uncertain significance (Jan 23, 2023)
5-150848408-G-A		IRGM-related disorder	Likely benign (May 01, 2022)
5-150848422-C-T		not specified	Uncertain significance (Feb 27, 2024)
5-150848436-C-T		Inflammatory bowel disease 19 • not specified	Benign (Apr 04, 2024)
5-150848457-C-T		not specified	Uncertain significance (Sep 14, 2022)
5-150848502-C-G		not specified	Uncertain significance (Jan 03, 2024)
5-150848502-C-T		not specified	Uncertain significance (Jul 16, 2021)
5-150848511-C-T		not specified	Uncertain significance (Apr 07, 2023)
5-150848517-A-G		not specified	Uncertain significance (Mar 28, 2023)
5-150848520-A-G			Uncertain significance (-)
5-150848587-G-A		not specified	Uncertain significance (Jan 10, 2023)
5-150848653-G-A		not specified	Likely benign (Jan 18, 2022)
5-150879654-T-C		IRGM-related disorder	Likely benign (Dec 01, 2022)
5-150895582-C-T		not specified	Uncertain significance (Dec 13, 2021)
5-150895617-C-T		not specified	Uncertain significance (Dec 31, 2023)
5-150895664-T-G		not specified	Uncertain significance (May 09, 2022)
5-150895692-G-A		not specified	Uncertain significance (Mar 25, 2022)
5-150895753-T-G		not specified	Uncertain significance (Dec 17, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IRGM	protein_coding	protein_coding	ENST00000522154	1	54214

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.414	84	95.4	0.881	0.00000447	1190
Missense in Polyphen		17	20.312	0.83695		294
Synonymous	0.132	34	35.0	0.972	0.00000156	361
Loss of Function

LoF frequencies by population

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

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Putative GTPase which is required for clearance of acute protozoan and bacterial infections. Functions in innate immune response probably through regulation of autophagy. May regulate proinflammatory cytokine production and prevent endotoxemia upon infection. May also play a role in macrophages adhesion and motility (By similarity). {ECO:0000250, ECO:0000269|PubMed:16888103}.
• Disease: DISEASE: Inflammatory bowel disease 19 (IBD19) [MIM:612278]: A chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology. It is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease may affect any part of the gastrointestinal tract from the mouth to the anus, but most frequently it involves the terminal ileum and colon. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. Both diseases include extraintestinal inflammation of the skin, eyes, or joints. {ECO:0000269|PubMed:17554261, ECO:0000269|PubMed:19174780, ECO:0000269|PubMed:21278745}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Toxoplasmosis - Homo sapiens (human) (Consensus)

Intolerance Scores

• rvis_EVS: 0.57
• rvis_percentile_EVS: 81.78

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.165

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Irgm2

Gene ontology

• Biological process: autophagosome assembly;positive regulation of protein phosphorylation;defense response;inflammatory response;positive regulation of autophagy;positive regulation of peptidyl-threonine phosphorylation;protein destabilization;positive regulation of peptidyl-serine phosphorylation;cellular response to interferon-beta;defense response to bacterium;regulation of protein complex assembly;innate immune response;protein stabilization;defense response to Gram-negative bacterium;positive regulation of interferon-gamma-mediated signaling pathway;regulation of protein complex stability;protein lipidation involved in autophagosome assembly;CAMKK-AMPK signaling cascade;nucleotide-binding oligomerization domain containing 2 signaling pathway;cellular response to lipopolysaccharide;positive regulation of protein serine/threonine kinase activity;autophagy of host cells involved in interaction with symbiont;cellular response to virus;positive regulation of autophagosome maturation
• Cellular component: Golgi membrane;autophagosome membrane;phagocytic cup;mitochondrion;endoplasmic reticulum membrane;Golgi apparatus;cytosol;phagocytic vesicle membrane;cell projection
• Molecular function: GTPase activity;protein binding;GTP binding;protein kinase binding;protein serine/threonine kinase activator activity;CARD domain binding;BH3 domain binding