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Tbio Immunity-related GTPase family M protein

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).

This gene encodes a member of the p47 immunity-related GTPase family. The encoded protein may play a role in the innate immune response by regulating autophagy formation in response to intracellular pathogens. Polymorphisms that affect the normal expression of this gene are associated with a susceptibility to Crohn's disease and tuberculosis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2016]

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Property Summary

NCBI Gene PubMed Count 67
Grant Count 74
R01 Count 46
Funding $8,124,769.68
PubMed Score 97.23
PubTator Score 80.35

Knowledge Summary

Patent

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TINX Plot

  Disease Relevance (8)

Disease Z-score Confidence
Crohn's disease 304 5.993 3.0
ulcerative colitis 2,087 4.545 2.3
tuberculosis 1,557 3.336 1.7
Crohn Disease 97
Inflammatory Bowel Disease 19 1
Inflammatory Bowel Diseases 87
Inflammatory bowel disease 142 2.0
MYCOBACTERIUM TUBERCULOSIS, SUSCEPTIBILI... 12 

Expression

Synonym

Accession A1A4Y4 B3VEX0
Symbols IFI1
IRGM1
LRG47
LRG-47

Gene

IRGM

 Grant Application (74)

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 GO Function (2)

 GO Component (6)

 GO Process (5)

 Compartment GO Term (50)

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 GWAS Trait (3)

Pathway (1)

 UniProt Keyword (15)

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Gene RIF (73)

PMID Text
26786655 IRGM functional polymorphisms and haplotypes in promoter were associated with the susceptibility to pulmonary tuberculosis in Chinese Hubei Han population.
26066377 The study confirms IRGM rs13361189 and rs4958847 polymorphisms to be important for Crohn's disease susceptibility and phenotype modulation, in accordance with previous findings.
25944217 In Korean children, IRGM rs1000113 and IRGM rs72553867 exhibited associations with early-onset Crohn Disease as risk loci and defense loci, respectively.
25891078 Data indicate that immunity-related GTPase family M (IRGM) plays a direct role in organizing the core autophagy machinery to endow it with antimicrobial and anti-inflammatory functions.
25891078 IRGM assembles core autophagy machinery (Beclin 1, Ulk1, ATG16L1) and connects it with innate immunity sensors (NOD2) through formation of protein complex assemblies.
25891078 RGM directly organizes the core autophagy machinery and links it with antimicrobial and anti-inflammatory functions. IRGM interacts with ULK1 and Beclin 1 promoting their co-assembly into autophagy initiation complexes. All three Crohn's disease risk factors, IRGM, NOD2 and ATG16L1, form a complex. NOD2 enhances K63-polyubiquitination of IRGM, promoting IRGM assembly with core autophagy regulators.
25853521 Expression of viral protein 2C enhanced IRGM promoter activation, thereby increasing IRGM expression and inducing autophagy.
25707354 Our findings suggest that expression of IRGM is dysregulated in gastric cancer and that the molecule may affect progression of the disease.
25619828 these data reveal an Irgm1-dependent mechanism that promotes the tumorigenesis of melanoma via dual regulation of apoptosis and Bif-1-dependent autophagy
25526194 The IRGM rs13361189 polymorphism is promising as a biomarker for early diagnosis of Crohn's disease. However, the IRGM rs10065172 and rs4958847 polymorphisms may not be the major determinants of Crohn's disease risk.
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AA Sequence 

MEAMNVEKASADGNLPEVISNIKETLKIVSRTPVNITMAGDSGNGMSTFISALRNTGHEGKASPPTELVK      1 - 70
ATQRCASYFSSHFSNVVLWDLPGTGSATTTLENYLMEMQFNRYDFIMVASAQFSMNHVMLAKTAEDMGKK     71 - 140
FYIVWTKLDMDLSTGALPEVQLLQIRENVLENLQKERVCEY                                 141 - 181
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Text Mined References (69)

PMID Year Title
26786655 2016 IRGM gene polymorphisms and haplotypes associate with susceptibility of pulmonary tuberculosis in Chinese Hubei Han population.
26066377 2015 Autophagy and inflammatory bowel disease: Association between variants of the autophagy-related IRGM gene and susceptibility to Crohn's disease.
25944217 2015 Genetic Polymorphisms in Autophagy-Associated Genes in Korean Children With Early-Onset Crohn Disease.
25891078 2015 IRGM governs the core autophagy machinery to conduct antimicrobial defense.
25853521 2015 Coxsackievirus A16 elicits incomplete autophagy involving the mTOR and ERK pathways.
25707354 2015 Elevated expression of immunity-related GTPase family M in gastric cancer.
25619828 2015 IFNg-induced Irgm1 promotes tumorigenesis of melanoma via dual regulation of apoptosis and Bif-1-dependent autophagy.
25526194 2014 Correlation between IRGM genetic polymorphisms and Crohn's disease risk: a meta-analysis of case-control studies.
25191865 2014 Association of IRGM gene mutations with inflammatory bowel disease in the Indian population.
24859836 2014 Functional IRGM polymorphism is associated with language impairment in glioma and upregulates cytokine expressions.
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