ITGB2
integrin subunit beta 2, the group of CD molecules|Complement system regulators and receptors|Integrin beta subunits
Basic information
Region (hg38): 21:44885952-44931989
Previous symbols: [ "CD18", "MFI7" ]
Links
Phenotypes
GenCC
Source:
- leukocyte adhesion deficiency 1 (Definitive), mode of inheritance: AR
- leukocyte adhesion deficiency 1 (Strong), mode of inheritance: AR
- leukocyte adhesion deficiency 1 (Supportive), mode of inheritance: AR
- leukocyte adhesion deficiency 1 (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Leukocyte adhesion deficiency, type I | AR | Allergy/Immunology/Infectious | Individuals frequently first present with umbilical cord stump infection, and are prone to recurrent and severe bacterial infections, such that antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; BMT has been described as effective | Allergy/Immunology/Infectious | 52003; 86829; 7310581; 7259263; 6718115; 6096477; 3703627; 2877234; 3510003; 2880869; 3234429; 3279017; 1972597; 7902162; 17244687; 19864007; 20351460; 20549317 |
ClinVar
This is a list of variants' phenotypes submitted to
- Leukocyte adhesion deficiency 1 (645 variants)
- not provided (77 variants)
- Inborn genetic diseases (38 variants)
- not specified (22 variants)
- ITGB2-related condition (3 variants)
- Leukocyte adhesion deficiency (3 variants)
- Leukocyte adhesion deficiency 3 (2 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ITGB2 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 | 144 | 15 | 168 | |||
| missense | 255 | 277 | ||||
| nonsense | 12 | |||||
| start loss | 0 | |||||
| frameshift | 12 | 16 | ||||
| inframe indel | 1 | |||||
| splice donor/acceptor (+/-2bp) | 7 | |||||
| splice region ? | 22 | 20 | 2 | 44 | ||
| non coding ? | 11 | 68 | 57 | 138 | ||
| Total | 27 | 20 | 277 | 220 | 75 |
Highest pathogenic variant AF is 0.0000197
Variants in ITGB2
This is a list of pathogenic ClinVar variants found in the ITGB2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 21-44885965-G-A | Leukocyte adhesion deficiency 1 | Uncertain significance (Jan 13, 2018) | ||
| 21-44885998-C-A | Leukocyte adhesion deficiency 1 | Benign (Apr 27, 2017) | ||
| 21-44886018-AT-A | Leukocyte adhesion deficiency | Likely benign (Jun 14, 2016) | ||
| 21-44886079-T-C | Leukocyte adhesion deficiency 1 | Likely benign (Jan 13, 2018) | ||
| 21-44886143-CCCT-C | Leukocyte adhesion deficiency | Uncertain significance (Jun 14, 2016) | ||
| 21-44886197-C-G | Leukocyte adhesion deficiency 1 | Benign (Jan 12, 2018) | ||
| 21-44886198-G-A | Leukocyte adhesion deficiency 1 | Uncertain significance (Jan 12, 2018) | ||
| 21-44886200-C-A | Leukocyte adhesion deficiency 1 | Uncertain significance (Jan 12, 2018) | ||
| 21-44886201-G-A | Leukocyte adhesion deficiency 1 | Likely benign (Jan 13, 2018) | ||
| 21-44886220-G-A | Leukocyte adhesion deficiency 1 | Uncertain significance (Jan 13, 2018) | ||
| 21-44886223-G-A | Leukocyte adhesion deficiency 1 | Uncertain significance (Jan 12, 2018) | ||
| 21-44886223-G-T | Leukocyte adhesion deficiency 1 | Benign (Jan 02, 2024) | ||
| 21-44886246-C-T | Leukocyte adhesion deficiency 1 | Benign (Jan 13, 2018) | ||
| 21-44886247-G-A | Leukocyte adhesion deficiency 1 | Benign (Jan 13, 2018) | ||
| 21-44886308-T-TCGGC | Leukocyte adhesion deficiency | Uncertain significance (Jun 14, 2016) | ||
| 21-44886330-A-G | Leukocyte adhesion deficiency 1 | Likely benign (Apr 27, 2017) | ||
| 21-44886368-C-T | Leukocyte adhesion deficiency 1 | Uncertain significance (Jan 13, 2018) | ||
| 21-44886376-C-G | Leukocyte adhesion deficiency 1 | Uncertain significance (Jun 30, 2022) | ||
| 21-44886383-C-G | Leukocyte adhesion deficiency 1 • Inborn genetic diseases | Uncertain significance (Nov 03, 2023) | ||
| 21-44886386-G-A | Likely benign (Dec 13, 2018) | |||
| 21-44886393-A-C | Leukocyte adhesion deficiency 1 | Uncertain significance (Aug 17, 2023) | ||
| 21-44886395-G-A | Leukocyte adhesion deficiency 1 | Conflicting classifications of pathogenicity (Dec 17, 2023) | ||
| 21-44886398-C-T | Leukocyte adhesion deficiency 1 | Likely benign (Dec 25, 2023) | ||
| 21-44886401-C-G | Leukocyte adhesion deficiency 1 | Likely benign (Nov 04, 2022) | ||
| 21-44886401-C-T | Leukocyte adhesion deficiency 1 | Likely benign (Aug 05, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ITGB2 | protein_coding | protein_coding | ENST00000397850 | 15 | 46037 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 5.08e-15 | 0.519 | 125675 | 0 | 73 | 125748 | 0.000290 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.770 | 446 | 494 | 0.903 | 0.0000363 | 5033 |
| Missense in Polyphen | 137 | 199.56 | 0.6865 | 2118 | ||
| Synonymous | -1.83 | 259 | 224 | 1.16 | 0.0000188 | 1510 |
| Loss of Function | 1.60 | 28 | 38.8 | 0.722 | 0.00000205 | 413 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000728 | 0.000724 |
| Ashkenazi Jewish | 0.0000993 | 0.0000992 |
| East Asian | 0.000326 | 0.000326 |
| Finnish | 0.000466 | 0.000462 |
| European (Non-Finnish) | 0.000274 | 0.000273 |
| Middle Eastern | 0.000326 | 0.000326 |
| South Asian | 0.000163 | 0.000163 |
| Other | 0.000654 | 0.000652 |
dbNSFP
Source:
- Function
- FUNCTION: Integrin ITGAL/ITGB2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. Integrins ITGAM/ITGB2 and ITGAX/ITGB2 are receptors for the iC3b fragment of the third complement component and for fibrinogen. Integrin ITGAX/ITGB2 recognizes the sequence G-P-R in fibrinogen alpha-chain. Integrin ITGAM/ITGB2 recognizes P1 and P2 peptides of fibrinogen gamma chain. Integrin ITGAM/ITGB2 is also a receptor for factor X. Integrin ITGAD/ITGB2 is a receptor for ICAM3 and VCAM1. Contributes to natural killer cell cytotoxicity (PubMed:15356110). Involved in leukocyte adhesion and transmigration of leukocytes including T-cells and neutrophils (PubMed:11812992, PubMed:28807980). Triggers neutrophil transmigration during lung injury through PTK2B/PYK2-mediated activation (PubMed:18587400). Integrin ITGAL/ITGB2 in association with ICAM3, contributes to apoptotic neutrophil phagocytosis by macrophages (PubMed:23775590). In association with alpha subunit ITGAM/CD11b, required for CD177-PRTN3-mediated activation of TNF primed neutrophils (PubMed:21193407). {ECO:0000269|PubMed:11812992, ECO:0000269|PubMed:15356110, ECO:0000269|PubMed:18587400, ECO:0000269|PubMed:21193407, ECO:0000269|PubMed:23775590, ECO:0000269|PubMed:28807980}.;
- Disease
- DISEASE: Leukocyte adhesion deficiency 1 (LAD1) [MIM:116920]: LAD1 patients have recurrent bacterial infections and their leukocytes are deficient in a wide range of adhesion-dependent functions. {ECO:0000269|PubMed:1346613, ECO:0000269|PubMed:1347532, ECO:0000269|PubMed:1352501, ECO:0000269|PubMed:1590804, ECO:0000269|PubMed:1694220, ECO:0000269|PubMed:1968911, ECO:0000269|PubMed:20529581, ECO:0000269|PubMed:20549317, ECO:0000269|PubMed:7509236, ECO:0000269|PubMed:7686755, ECO:0000269|PubMed:9884339}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Complement and coagulation cascades - Homo sapiens (human);Cell adhesion molecules (CAMs) - Homo sapiens (human);Pertussis - Homo sapiens (human);Legionellosis - Homo sapiens (human);Viral myocarditis - Homo sapiens (human);Phagosome - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Malaria - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Staphylococcus aureus infection - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Natural killer cell mediated cytotoxicity - Homo sapiens (human);Leishmaniasis - Homo sapiens (human);Rheumatoid arthritis - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);Integrin-mediated Cell Adhesion;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Microglia Pathogen Phagocytosis Pathway;TYROBP Causal Network;Interleukin-4 and 13 signaling;Fibrin Complement Receptor 3 Signaling Pathway;Neutrophil degranulation;Integrin cell surface interactions;Toll-Like Receptors Cascades;Extracellular matrix organization;Innate Immune System;Immune System;Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell;Adaptive Immune System;Integrin;Cell surface interactions at the vascular wall;Hemostasis;Toll Like Receptor 4 (TLR4) Cascade;amb2 Integrin signaling;HIF-1-alpha transcription factor network;Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling;Beta2 integrin cell surface interactions
(Consensus)
Recessive Scores
- pRec
- 0.531
Intolerance Scores
- loftool
- 0.0333
- rvis_EVS
- -1.03
- rvis_percentile_EVS
- 7.86
Haploinsufficiency Scores
- pHI
- 0.244
- hipred
- Y
- hipred_score
- 0.599
- ghis
- 0.567
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.760
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Itgb2
- Phenotype
- vision/eye phenotype; skeleton phenotype; immune system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); normal phenotype; homeostasis/metabolism phenotype; cellular phenotype;
Gene ontology
- Biological process
- microglial cell activation;leukocyte migration involved in inflammatory response;phagocytosis, engulfment;apoptotic process;inflammatory response;cell adhesion;leukocyte cell-cell adhesion;cell-matrix adhesion;integrin-mediated signaling pathway;cell-cell signaling;aging;regulation of cell shape;cell migration;cytokine-mediated signaling pathway;natural killer cell activation;extracellular matrix organization;neutrophil chemotaxis;receptor internalization;positive regulation of superoxide anion generation;cell adhesion mediated by integrin;heterotypic cell-cell adhesion;toll-like receptor 4 signaling pathway;endodermal cell differentiation;receptor clustering;neutrophil degranulation;positive regulation of neutrophil degranulation;endothelial cell migration;cellular extravasation;positive regulation of nitric oxide biosynthetic process;positive regulation of angiogenesis;negative regulation of dopamine metabolic process;regulation of peptidyl-tyrosine phosphorylation;regulation of immune response;leukocyte migration;positive regulation of NF-kappaB transcription factor activity;cellular response to low-density lipoprotein particle stimulus;positive regulation of protein targeting to membrane;amyloid-beta clearance;cell-cell adhesion;cell-cell adhesion via plasma-membrane adhesion molecules;positive regulation of neuron death;positive regulation of microglial cell activation;neutrophil migration;positive regulation of prostaglandin-E synthase activity
- Cellular component
- plasma membrane;focal adhesion;integrin complex;external side of plasma membrane;cell surface;membrane;integrin alphaL-beta2 complex;integrin alphaM-beta2 complex;specific granule membrane;receptor complex;plasma membrane raft;extracellular exosome;tertiary granule membrane;cytoplasmic region;ficolin-1-rich granule membrane;extracellular vesicle
- Molecular function
- amyloid-beta binding;complement component C3b binding;integrin binding;protein binding;protein kinase binding;ICAM-3 receptor activity;heat shock protein binding;metal ion binding;protein heterodimerization activity;cell adhesion molecule binding