ITGAL

Chr 16

integrin subunit alpha L

Also known as: CD11A, HNA-5, LFA-1, LFA1A

NCBI Gene: 3683ENSG00000005844UniProt: P20701

ITGAL encodes the integrin alpha L chain. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This I-domain containing alpha integrin combines with the beta 2 chain (ITGB2) to form the integrin lymphocyte function-associated antigen-1 (LFA-1), which is expressed on all leukocytes. LFA-1 plays a central role in leukocyte intercellular adhesion through interactions with its ligands, ICAMs 1-3 (intercellular adhesion molecules 1 through 3), and also functions in lymphocyte costimulatory signaling. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

128
ClinVar variants
13
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ITGAL
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 96 VUS of 128 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.41LOEUF
pLI 0.004
Z-score 5.29
OE 0.27 (0.19–0.41)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.18Z-score
OE missense 0.76 (0.71–0.82)
521 obs / 681.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.27 (0.19–0.41)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.76 (0.71–0.82)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.94
0≤1.21.6
LoF obs/exp: 17 / 62.0Missense obs/exp: 521 / 681.3Syn Z: 0.79

ClinVar Variant Classifications

128 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic2
VUS96
Likely Benign13
Benign6
11
Pathogenic
2
Likely Pathogenic
96
VUS
13
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
11
0
11
Likely Pathogenic
0
0
2
0
2
VUS
0
88
8
0
96
Likely Benign
0
11
0
2
13
Benign
0
1
2
3
6
Total0100235128

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

View in ClinVar →

Protein Context — Lollipop Plot

ITGAL · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
INTEGRIN, ALPHA-L; ITGAL
MIM #153370 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Integrated multi-omics identifies a CD54(+) iCAF-ITGAL(+) macrophage niche driving immunosuppression via CXCL8-PDL1 axis in cervical cancer.
Chen F et al.·Mol Cancer
2025
lncRNA PCBP1-AS1 mediated downregulation of ITGAL as a prognostic biomarker in lung adenocarcinoma.
Wang Q et al.·Aging (Albany NY)
2023
Clinical and serological findings associated with the expression of ITGAL, PRF1, and CD70 in systemic lupus erythematosus.
Balada E et al.·Clin Exp Rheumatol
2014
Mechanisms of immune escape and extramedullary tropism in leukemia cutis.
Penter L et al.·Blood
2026Functional
ITGAL expression in non-small-cell lung cancer tissue and its association with immune infiltrates.
Zhang R et al.·Front Immunol
2024
Integrated analysis highlights the significance role of ITGAL in lung adenocarcinoma.
Xiao Z et al.·J Cell Mol Med
2024
Novel common and rare genetic determinants of paraoxonase activity: FTO, SERPINA12, and ITGAL.
Kim DS et al.·J Lipid Res
2013
Human neutrophil antigens: Nature, clinical significance and detection.
Browne T et al.·Int J Immunogenet
2021Review
Transcriptome fingerprinting of aberrant fibroblast activation unlocks effective therapeutics to tackle cardiac fibrosis.
Cinato M et al.·Sci Adv
2025
Bioinformatics analysis and reveal potential crosstalk genetic and immune relationships between atherosclerosis and periodontitis.
Dong W et al.·Sci Rep
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools