ITGAM
protein-codingintegrin subunit alpha M, the group of CD molecules|Integrin alpha subunits|Complement system regulators and receptors
Gene summary
This gene encodes the integrin alpha M chain. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This I-domain containing alpha integrin combines with the beta 2 chain (ITGB2) to form a leukocyte-specific integrin referred to as macrophage receptor 1 ('Mac-1'), or inactivated-C3b (iC3b) receptor 3 ('CR3'). The alpha M beta 2 integrin is important in the adherence of neutrophils and monocytes to stimulated endothelium, and also in the phagocytosis of complement coated particles. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]
- CR3A
- CD11B
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~72.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0007915
Submitter: Orphanet
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ITGAM variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000632.4. 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 | 13 | 225 | 8 | 246 | ||
| missense | 536 | 14 | 6 | 556 | ||
| nonsense | 11 | 11 | ||||
| start loss | 0 | |||||
| frameshift | 20 | 20 | ||||
| splice donor/acceptor (+/-2bp) | 12 | 12 | ||||
| Total | 0 | 0 | 592 | 239 | 14 | 845 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000623.2 | 30 | MANE Select | |
| Ensembl | ENSP00000441691.3 | 30 | MANE Select | |
| RefSeq | NP_001139280.1 | 30 | Standard | |
| Ensembl | ENSP00000461850.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Complement and coagulation cascades - Homo sapiens (human)
- Cell adhesion molecules (CAMs) - Homo sapiens (human)
- Pertussis - Homo sapiens (human)
- Legionellosis - Homo sapiens (human)
- Acute myeloid leukemia - Homo sapiens (human)
Biological Process
- microglial cell activation
- phagocytosis, engulfment
- cell adhesion
- integrin-mediated signaling pathway
- ectodermal cell differentiation
Molecular Function
- amyloid-beta binding
- complement component C3b binding
- protein binding
- heat shock protein binding
- metal ion binding
Cellular Component
- extracellular space
- plasma membrane
- integrin complex
- external side of plasma membrane
- cell surface
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000544665
- Coding exons
- 30
- Length
- 72903
- Individuals with no LoFs
- 125406
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 152
- Defined
- 125558
- p
- 0.000605
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.42 | 582 | 687 | 0.847 | 0.0000410 | 7488 |
| Missense (PolyPhen) | 207 | 273.92 | 0.75568 | 3135 | ||
| Synonymous | 1.04 | 262 | 284 | 0.922 | 0.0000179 | 2287 |
| Loss of Function | 3.87 | 28 | 60.5 | 0.463 | 0.00000305 | 677 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00047 | 0.00044 | rare |
| Latino/Admixed American | 0.00017 | 0.00017 | rare |
| Ashkenazi Jewish | 0.0043 | 0.0041 | notable |
| East Asian | 0.00040 | 0.00038 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00063 | 0.00063 | rare |
| South Asian | 0.00057 | 0.00056 | rare |
| Other | 0.00050 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Integrin ITGAM/ITGB2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles. It is identical with CR-3, the receptor for the iC3b fragment of the third complement component. It probably recognizes the R-G-D peptide in C3b. Integrin ITGAM/ITGB2 is also a receptor for fibrinogen, factor X and ICAM1. It recognizes P1 and P2 peptides of fibrinogen gamma chain. Regulates neutrophil migration (PubMed:28807980). In association with beta subunit ITGB2/CD18, required for CD177-PRTN3-mediated activation of TNF primed neutrophils (PubMed:21193407). May regulate phagocytosis-induced apoptosis in extravasated neutrophils (By similarity). May play a role in mast cell development (By similarity). {ECO:0000250|UniProtKB:P05555, ECO:0000269|PubMed:21193407, ECO:0000269|PubMed:28807980, ECO:0000305}.;
- Disease
- DISEASE: Systemic lupus erythematosus 6 (SLEB6) [MIM:609939]: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. {ECO:0000269|PubMed:18204446, ECO:0000269|PubMed:18204448}. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry.;
Intolerance Scores
- LoFtool
- 0.543
- RVIS EVS
- -0.59
- RVIS percentile EVS
- 18.28
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.562
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |