ITGAX

Chr 16

integrin subunit alpha X

Also known as: CD11C, SLEB6

NCBI Gene: 3687ENSG00000140678UniProt: P20702OMIM: 151510

The integrin alpha X chain protein combines with the beta 2 chain to form a leukocyte-specific integrin (CR4) that mediates monocyte and neutrophil adhesion to endothelium and facilitates phagocytosis of complement-coated particles and erythrocytes. This gene is extremely intolerant to loss-of-function variants (pLI near 1.0), but no established Mendelian diseases have been reported from ITGAX mutations. Clinical phenotypes, if they exist, would likely involve immune dysfunction affecting leukocyte trafficking and inflammatory responses.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.72
Clinical Summary— ITGAX
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
9 unique Pathogenic / Likely Pathogenic· 163 VUS of 238 total submissions
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
0.72LOEUF
pLI 0.000
Z-score 3.39
OE 0.54 (0.41–0.72)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.55Z-score
OE missense 0.94 (0.88–1.00)
658 obs / 699.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.54 (0.41–0.72)
0≤0.351.4
Missense OE0.94 (0.88–1.00)
0≤0.61.4
Synonymous OE1.05
0≤1.21.6
LoF obs/exp: 35 / 64.4Missense obs/exp: 658 / 699.2Syn Z: -0.69
DN
0.74top 25%
GOF
0.7127th %ile
LOF
0.2387th %ile

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

DNprediction above median
GOFprediction 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

238 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic1
VUS163
Likely Benign23
Benign3
8
Pathogenic
1
Likely Pathogenic
163
VUS
23
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
1
0
1
VUS
0
156
7
0
163
Likely Benign
0
17
0
6
23
Benign
0
2
0
1
3
Total0175167198

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

View in ClinVar →

Protein Context — Lollipop Plot

ITGAX · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
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
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Integrated transcriptomics and single-cell analysis identify ITGAX⁺ macrophages as key immunosuppressive factors in the prostate cancer tumor microenvironment.
Shao Y et al.·Discov Oncol
2026Open Access
ITGAX downregulation activates NLRP3 inflammasome and ameliorates LPS-induced acute liver injury by regulating macrophage M1 polarization and the DNMT1/PPAR-γ axis.
Song W et al.·Biochem Biophys Res Commun
2025
Elevated ITGAX/CD11c in CSF-Derived Extracellular Vesicles Reflects Disability Progression in Multiple Sclerosis.
Iwahara N et al.·Neurol Neuroimmunol Neuroinflamm
2025Open Access
ITGAX promotes Th17-cell differentiation and drives pathogenesis in pediatric ulcerative colitis.
Xie W et al.·Histol Histopathol
2026
ITGAX promotes gastric cancer progression via epithelial-mesenchymal transition pathway.
Hu J et al.·Front Pharmacol
2024Open 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