GeneBe

ITGB2

protein-coding

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

Gene summary

This gene encodes an integrin beta chain, which combines with multiple different alpha chains to form different integrin heterodimers. Integrins are integral cell-surface proteins that participate in cell adhesion as well as cell-surface mediated signalling. The encoded protein plays an important role in immune response and defects in this gene cause leukocyte adhesion deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

Previous symbols:
  • CD18
  • MFI7

MANE transcript

NM_000211.5

Inheritance

AR

ClinVar variants

P:87U:329B:277

Top phenotype

Leukocyte adhesion deficiency, type I

gnomAD constraint

pLI —, LoF o/e 0.72

Max pathogenic AF

—

Genomic locus

chr21:44,885,953-44,931,989

External References & Databases

Ensembl (ENSG00000160255)NCBI Gene (3689)OMIM (600065)HGNC:6155GenCCUniProt (P05107)AlphaFoldClinVar (ITGB2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~46.0 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

leukocyte adhesion deficiency 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0007293

Submitter: PanelApp Australia

leukocyte adhesion deficiency 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0007293

Submitter: Labcorp Genetics (formerly Invitae)

leukocyte adhesion deficiency 1DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0007293

Submitter: Ambry Genetics

leukocyte adhesion deficiency 1SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0007293

Submitter: Orphanet

leukocyte adhesion deficiency 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0007293

Submitter: Laboratory for Molecular Medicine

This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.

Clinical Genomic Database (CGD)

Leukocyte adhesion deficiency, type IAR

Manifestation: Allergy/Immunology/Infectious

Intervention: Allergy/Immunology/Infectious

Rationale: 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

Refs: 52003; 86829; 7310581; 7259263; 6718115; 6096477; 3703627; 2877234; 3510003; 2880869; 3234429; 3279017; 1972597; 7902162; 17244687; 19864007; 20351460; 20549317Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ITGB2 variants in ClinVar

6 Conditions Cataloged
Leukocyte adhesion deficiency 1Total: 790
Inborn genetic diseasesTotal: 112
not providedTotal: 108
not specifiedTotal: 104
ITGB2-related disorderTotal: 37
Leukocyte adhesion deficiency 3Total: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000211.5. 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.

EffectPLPVUSLBBSum
synonymous
19
clinvar
250
clinvar
3
clinvar
 272
missense
9
clinvar
10
clinvar
305
clinvar
22
clinvar
2
clinvar
 348
nonsense
12
clinvar
6
clinvar
 18
start loss
1
clinvar
1
clinvar
 2
frameshift
27
clinvar
7
clinvar
 34
splice donor/acceptor (+/-2bp)
4
clinvar
10
clinvar
5
clinvar
 19
Total53343292725693

Highest pathogenic variant AF is 0.000113999085

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 64 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000211.5RefSeqNP_000202.315MANE Select
ENST00000652462.1EnsemblENSP00000498780.115MANE Select
NM_001127491.3RefSeqNP_001120963.215Standard
NM_001303238.2RefSeqNP_001290167.113Standard

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)
  • Viral myocarditis - Homo sapiens (human)

Biological Process

  • microglial cell activation
  • leukocyte migration involved in inflammatory response
  • phagocytosis, engulfment
  • apoptotic process
  • inflammatory response

Molecular Function

  • amyloid-beta binding
  • complement component C3b binding
  • integrin binding
  • protein binding
  • protein kinase binding

Cellular Component

  • plasma membrane
  • focal adhesion
  • integrin complex
  • external side of plasma membrane
  • cell surface

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000397850
Coding exons
15
Length
46037
Individuals with no LoFs
125675
Homozygous LoFs
0
Heterozygous LoFs
73
Defined
125748
p
0.000290
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.7704464940.9030.00003635033
Missense (PolyPhen)137199.560.68652118
Synonymous-1.832592241.160.00001881510
Loss of Function1.602838.80.7220.00000205413

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000500.00049rare
Latino/Admixed American0.000230.00023rare
Ashkenazi Jewish0.0000990.000099rare
East Asian0.000330.00033rare
Finnish0.000470.00046rare
European (Non-Finnish)0.000270.00027rare
South Asian0.000160.00016rare
Other0.000650.00065rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.531

Intolerance Scores

LoFtool
0.0333
RVIS EVS
-1.03
RVIS percentile EVS
7.86

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.760

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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