ITGB2

Chr 21AR

integrin subunit beta 2

Also known as: CD18, LAD, LCAMB, LFA-1, MAC-1, MF17, MFI7

NCBI Gene: 3689ENSG00000160255UniProt: P05107

The ITGB2 protein forms integrin heterodimers that function as cell surface receptors mediating leukocyte adhesion, transmigration, and immune cell interactions with various ligands including ICAM proteins and complement fragments. Mutations cause leukocyte adhesion deficiency, an autosomal recessive primary immunodeficiency affecting the immune system's ability to mount effective responses to infections. The gene is highly intolerant to loss-of-function variants, reflecting its critical role in immune function.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Leukocyte adhesion deficiencyMIM #116920
AR
1
Active trials
134
Pubs (1 yr)
69
P/LP submissions
2%
P/LP missense
0.99
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— ITGB2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
62 unique Pathogenic / Likely Pathogenic· 153 VUS of 500 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.99LOEUF
pLI 0.000
Z-score 1.60
OE 0.72 (0.53–0.99)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.77Z-score
OE missense 0.90 (0.83–0.98)
446 obs / 494.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.72 (0.53–0.99)
0≤0.351.4
Missense OE0.90 (0.83–0.98)
0≤0.61.4
Synonymous OE1.16
0≤1.21.6
LoF obs/exp: 28 / 38.8Missense obs/exp: 446 / 494.2Syn Z: -1.83
DN
0.6840th %ile
GOF
0.6931th %ile
LOF
0.2968th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic49
Likely Pathogenic13
VUS153
Likely Benign255
Benign6
Conflicting3
49
Pathogenic
13
Likely Pathogenic
153
VUS
255
Likely Benign
6
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
16
1
32
0
49
Likely Pathogenic
9
0
4
0
13
VUS
1
138
12
2
153
Likely Benign
0
0
123
132
255
Benign
0
0
5
1
6
Conflicting
—3
Total26139176135479

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ITGB2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Identification and validation of immune and oxidative stress-related diagnostic markers for diabetic nephropathy by WGCNA and machine learning.
Xu M et al.·Front Immunol
2023
Single-cell transcriptomic analyses reveal distinct immune cell contributions to epithelial barrier dysfunction in checkpoint inhibitor colitis.
Thomas MF et al.·Nat Med
2024
Exploring the shared molecular mechanisms between systemic lupus erythematosus and primary Sjögren's syndrome based on integrated bioinformatics and single-cell RNA-seq analysis.
Cui Y et al.·Front Immunol
2023Functional
ITGB2-mediated metabolic switch in CAFs promotes OSCC proliferation by oxidation of NADH in mitochondrial oxidative phosphorylation system.
Zhang X et al.·Theranostics
2020
Targeting the tumor cell-intrinsic ITGB2 axis inhibits melanoma progression.
Rasbach E et al.·Mol Cancer
2025
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
The ITGB2-COPS3-SOX2 Axis and SOX2 Liquid-Liquid Phase Separation: Dual Mechanisms Governing Osteosarcoma Stemness.
Guo L et al.·Adv Sci (Weinh)
2026Functional
Shexiang Tongxin dropping pills attenuate cardiac remodeling in myocardial infarction rats by inhibiting Glycolysis via ITGB2 methylation.
Xu X et al.·Cytotechnology
2026Functional
Primed mesenchymal stem cells attenuate schistosomiasis fibrosis by enhancing macrophage subset switching and efferocytosis via Itgb2-Rac1 axis.
Lei J et al.·Cell Death Discov
2026Open Access
Cord blood natural killer cell-derived extracellular vesicles inhibit Zika virus infectivity through ITGB2/perforin-mediated envelope disruption in vitro and in vivo.
Cheng C et al.·Bioact Mater
2026Open Access
Myo1f regulates monocyte adhesion and contributes to atherosclerosis via MRTFA-dependent ITGB2 expression.
Lv Y et al.·Redox Biol
2026Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients