Leukocyte adhesion deficiency 1

Summary

Leukocyte adhesion deficiency 1 (MONDO:0007293) is a disease caused by ITGB2 (GenCC Definitive), with 1 cohort gene and 9 clinical trials. Top therapeutic interventions include alefacept, ustekinumab, and l-fucose.

At a glance

• Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
• Causal gene: ITGB2 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 831
• Clinical trials: 9

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000	0.1	Europe	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	leukocyte adhesion deficiency 1
Mondo ID	MONDO:0007293
MeSH	C535887
OMIM	116920
Orphanet	99842
DOID	DOID:0110910
NCIT	C4689
SNOMED CT	234582006
UMLS	C0398738
MedGen	98310
GARD	0006893
Is cancer (heuristic)	no

Also known as: ITGB2 leukocyte adhesion deficiency · lad · lad 1 · LAD-I · lad-I · lad-type I · LAD1 · leukocyte adhesion deficiency · leukocyte adhesion deficiency 1 · leukocyte adhesion deficiency caused by mutation in ITGB2 · leukocyte adhesion deficiency type 1 · leukocyte adhesion deficiency type I · leukocyte adhesion deficiency, type I · LFA 1 immunodeficiency · LFA-I deficiency · LFA1 immunodeficiency · lymphocyte function-associated antigen 1 immunodeficiency

Data availability: 831 ClinVar variants · 5 GenCC gene-disease records · 2 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › leukocyte adhesion deficiency › leukocyte adhesion deficiency 1

Related subtypes (2): leukocyte adhesion deficiency type II, leukocyte adhesion deficiency 3

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

291 likely benign, 188 uncertain significance, 39 pathogenic, 33 benign, 20 conflicting classifications of pathogenicity, 13 benign/likely benign, 9 likely pathogenic, 7 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1065606	NM_000211.5(ITGB2):c.[1756C>T;742-14C>A]		Pathogenic	no assertion criteria provided
427820	NM_000211.4(ITGB2):c.[576dupC];[706G>A]		Pathogenic	criteria provided, single submitter
100744	NM_000211.5(ITGB2):c.1030G>T (p.Glu344Ter)	ITGB2	Pathogenic	no assertion criteria provided
100747	NM_000211.5(ITGB2):c.1143del (p.Tyr382fs)	ITGB2	Pathogenic	no assertion criteria provided
100748	NM_000211.5(ITGB2):c.1877+2T>C	ITGB2	Pathogenic	no assertion criteria provided
100750	NM_000211.5(ITGB2):c.1907del (p.Lys636fs)	ITGB2	Pathogenic	no assertion criteria provided
100757	NM_000211.5(ITGB2):c.576dup (p.Asn193fs)	ITGB2	Pathogenic	no assertion criteria provided
100762	NM_000211.5(ITGB2):c.843del (p.Asn282fs)	ITGB2	Pathogenic	no assertion criteria provided
100763	NM_000211.5(ITGB2):c.897+1G>A	ITGB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
100764	NM_000211.5(ITGB2):c.897+1G>T	ITGB2	Pathogenic	no assertion criteria provided
1012309	NM_000211.5(ITGB2):c.1657+1G>T	ITGB2	Pathogenic	criteria provided, single submitter
1064458	NM_000211.5(ITGB2):c.305_306del (p.Lys102fs)	ITGB2	Pathogenic	no assertion criteria provided
1324597	NM_000211.5(ITGB2):c.1491C>A (p.Cys497Ter)	ITGB2	Pathogenic	criteria provided, single submitter
1324598	NM_000211.5(ITGB2):c.2200G>T (p.Glu734Ter)	ITGB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1365830	NM_000211.5(ITGB2):c.1057del (p.Val353fs)	ITGB2	Pathogenic	criteria provided, single submitter
1386540	NM_000211.5(ITGB2):c.1759del (p.Arg587fs)	ITGB2	Pathogenic	criteria provided, single submitter
1453796	NM_000211.5(ITGB2):c.1537_1538del (p.Val513fs)	ITGB2	Pathogenic	criteria provided, single submitter
1454255	NM_000211.5(ITGB2):c.1367dup (p.Ser457fs)	ITGB2	Pathogenic	criteria provided, single submitter
1455590	NM_000211.5(ITGB2):c.2036del (p.Gln679fs)	ITGB2	Pathogenic	criteria provided, single submitter
1705747	NM_000211.5(ITGB2):c.616C>T (p.His206Tyr)	ITGB2	Pathogenic	no assertion criteria provided
1936220	NM_000211.5(ITGB2):c.949C>T (p.Gln317Ter)	ITGB2	Pathogenic	criteria provided, single submitter
1966969	NM_000211.5(ITGB2):c.295del (p.Ser99fs)	ITGB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1982798	NM_000211.5(ITGB2):c.1168_1180del (p.Val390fs)	ITGB2	Pathogenic	criteria provided, single submitter
1987390	NM_000211.5(ITGB2):c.239del (p.Asp80fs)	ITGB2	Pathogenic	criteria provided, single submitter
2082269	NM_000211.5(ITGB2):c.186C>A (p.Cys62Ter)	ITGB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2138401	NM_000211.5(ITGB2):c.59-10C>A	ITGB2	Pathogenic	criteria provided, single submitter
2422587	NC_000021.8:g.(?46309171)(46310157_?)del	ITGB2	Pathogenic	criteria provided, single submitter
2585527	NM_000211.5(ITGB2):c.120del (p.Gly42fs)	ITGB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2630823	NM_000211.5(ITGB2):c.116del (p.Ser39fs)	ITGB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
265200	NM_000211.5(ITGB2):c.1602C>A (p.Cys534Ter)	ITGB2	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
ITGB2	Definitive	Autosomal recessive	leukocyte adhesion deficiency 1	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ITGB2	Orphanet:99842	Leukocyte adhesion deficiency type I

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ITGB2	HGNC:6155	ENSG00000160255	P05107	Integrin beta-2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ITGB2	Integrin beta-2	Integrin ITGAL:ITGB2 is a receptor for ICAM1, ICAM2 and ICAM3.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ITGB2	Other/Unknown	no		Integrin_bsu_VWA, Integrin_bsu_tail, Integrin_bsu_cyt_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	1
leukocyte	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ITGB2	249	broad	marker	granulocyte, monocyte, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ITGB2	3,884

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ITGB2	P05107	29

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Integrin cell surface interactions	1	134.3×	0.027	ITGB2
Toll Like Receptor 4 (TLR4) Cascade	1	131.3×	0.027	ITGB2
Toll-like Receptor Cascades	1	124.1×	0.027	ITGB2
Interleukin-4 and Interleukin-13 signaling	1	102.9×	0.027	ITGB2
Cell surface interactions at the vascular wall	1	95.2×	0.027	ITGB2
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	1	87.2×	0.027	ITGB2
Signaling by Interleukins	1	64.2×	0.028	ITGB2
Extracellular matrix organization	1	63.1×	0.028	ITGB2
Cytokine Signaling in Immune system	1	40.8×	0.038	ITGB2
Hemostasis	1	36.0×	0.039	ITGB2
Adaptive Immune System	1	29.8×	0.043	ITGB2
Innate Immune System	1	25.5×	0.046	ITGB2
Neutrophil degranulation	1	23.1×	0.047	ITGB2
Immune System	1	13.0×	0.077	ITGB2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of neutrophil degranulation	1	5617.3×	0.002	ITGB2
negative regulation of dopamine metabolic process	1	5617.3×	0.002	ITGB2
cellular extravasation	1	4213.0×	0.002	ITGB2
regulation of peptidyl-tyrosine phosphorylation	1	3370.4×	0.002	ITGB2
positive regulation of leukocyte adhesion to vascular endothelial cell	1	1404.3×	0.003	ITGB2
neutrophil migration	1	1404.3×	0.003	ITGB2
leukocyte migration involved in inflammatory response	1	1203.7×	0.003	ITGB2
obsolete cell-cell adhesion via plasma-membrane adhesion molecules	1	1123.5×	0.003	ITGB2
amyloid-beta clearance	1	936.2×	0.003	ITGB2
positive regulation of superoxide anion generation	1	887.0×	0.003	ITGB2
cellular response to low-density lipoprotein particle stimulus	1	887.0×	0.003	ITGB2
phagocytosis, engulfment	1	674.1×	0.003	ITGB2
cell adhesion mediated by integrin	1	674.1×	0.003	ITGB2
microglial cell activation	1	624.1×	0.003	ITGB2
receptor clustering	1	624.1×	0.003	ITGB2
heterotypic cell-cell adhesion	1	581.1×	0.003	ITGB2
positive regulation of protein targeting to membrane	1	561.7×	0.003	ITGB2
endodermal cell differentiation	1	495.6×	0.004	ITGB2
leukocyte cell-cell adhesion	1	468.1×	0.004	ITGB2
positive regulation of nitric oxide biosynthetic process	1	455.5×	0.004	ITGB2
endothelial cell migration	1	411.0×	0.004	ITGB2
receptor internalization	1	324.1×	0.005	ITGB2
neutrophil chemotaxis	1	285.6×	0.005	ITGB2
receptor-mediated endocytosis	1	221.7×	0.006	ITGB2
cell-matrix adhesion	1	163.6×	0.008	ITGB2
integrin-mediated signaling pathway	1	160.5×	0.008	ITGB2
regulation of cell shape	1	123.0×	0.010	ITGB2
positive regulation of angiogenesis	1	115.4×	0.010	ITGB2
cell-cell adhesion	1	101.5×	0.011	ITGB2
cell-cell signaling	1	69.6×	0.016	ITGB2

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
ITGB2	LIFITEGRAST

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ITGB2	2	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
LIFITEGRAST	4	ITGB2
LOVASTATIN	4	ITGB2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ITGB2	109	Binding:73, Functional:36

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
ITGB2	109

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

2 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
LIFITEGRAST	4	ITGB2
LOVASTATIN	4	ITGB2

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ITGB2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 9.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	4
PHASE3	2
PHASE2	1
PHASE1/PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05462587	PHASE3	RECRUITING	A Study to Evaluate Efficacy and Safety of AVTX-803 in Patients With Leukocyte Adhesion Deficiency Type II
NCT05754450	PHASE3	RECRUITING	An Extension Study Assessing the Safety and Efficacy of AVTX-803 in Subjects With Leukocyte Adhesion Deficiency Type II
NCT01998633	PHASE2	COMPLETED	Reduced Intensity Conditioning for Hemophagocytic Syndromes or Selected Primary Immune Deficiencies (BMT CTN 1204)
NCT03366142	PHASE1/PHASE2	COMPLETED	Ustekinumab (Anti-IL-12/23p40 Monoclonal Antibody) in Patients With Leukocyte Adhesion Deficiency Type 1 (LAD1) Who Have Inflammatory Pathology
NCT01917708	PHASE1	COMPLETED	Bone Marrow Transplant With Abatacept for Non-Malignant Diseases
NCT00128973	Not specified	RECRUITING	Evaluation of Patients With Immune Function Abnormalities
NCT01212055	Not specified	RECRUITING	Apheresis of Patients With Immunodeficiency
NCT06282432	Not specified	ACTIVE_NOT_RECRUITING	Long-Term Follow-Up (LTFU) for Gene Therapy of Leukocyte Adhesion Deficiency-I (LAD-I)
NCT01319851	Not specified	TERMINATED	Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ALEFACEPT	4	1
USTEKINUMAB	4	1
L-FUCOSE	3	2