ITGB2

integrin subunit beta 2, the group of CD molecules|Complement system regulators and receptors|Integrin beta subunits

Basic information

Region (hg38): 21:44885953-44931989

Previous symbols: [ "CD18", "MFI7" ]

Links

ENSG00000160255 ∙ NCBI:3689 ∙ OMIM:600065 ∙ HGNC:6155 ∙ Uniprot:P05107 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the ITGB2 gene.

• Leukocyte adhesion deficiency 1 (29 variants)
• not provided (6 variants)
• ITGB2-related disorder (1 variants)
• Inborn genetic diseases (1 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			8	167	15	190
missense	4	7	262	9	2	284
nonsense	8	5				13
start loss						0
frameshift	17	4				21
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1	6	1			8
splice region			20	26	2	48
non coding	2		11	84	57	154
Total	32	22	283	260	74

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 (Sep 22, 2024)
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: gnomAD

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: dbNSFP

• 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