IRGM
protein-codingimmunity related GTPase M
Gene summary
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]
- IRGM1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~54.2 kbGenCC 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 IRGM variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001145805.2. 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 | 1 | 1 | ||||
| missense | 37 | 3 | 40 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 37 | 4 | 0 | 41 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001139277.1 | 1 | MANE Select | |
| Ensembl | ENSP00000428220.1 | 1 | MANE Select | |
| RefSeq | NP_001333486.1 | 3 | Standard | |
| Ensembl | ENSP00000429819.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Toxoplasmosis - Homo sapiens (human)
Biological Process
- autophagosome assembly
- positive regulation of protein phosphorylation
- defense response
- inflammatory response
- positive regulation of autophagy
Molecular Function
- GTPase activity
- protein binding
- GTP binding
- protein kinase binding
- protein serine/threonine kinase activator activity
Cellular Component
- Golgi membrane
- autophagosome membrane
- phagocytic cup
- mitochondrion
- endoplasmic reticulum membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000522154
- Coding exons
- 1
- Length
- 54214
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.414 | 84 | 95.4 | 0.881 | 0.00000447 | 1190 |
| Missense (PolyPhen) | 17 | 20.312 | 0.83695 | 294 | ||
| Synonymous | 0.132 | 34 | 35.0 | 0.972 | 0.00000156 | 361 |
| Loss of Function |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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.;
Intolerance Scores
- RVIS EVS
- 0.57
- RVIS percentile EVS
- 81.78
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.165
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |