ITGAX

Chr 16

integrin subunit alpha X

Also known as: CD11C, SLEB6

NCBI Gene: 3687 ENSG00000140678 UniProt: P20702 OMIM: 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.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes the integrin alpha X chain protein. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This protein combines with the beta 2 chain (ITGB2) to form a leukocyte-specific integrin referred to as inactivated-C3b (iC3b) receptor 4 (CR4). The alpha X beta 2 complex seems to overlap the properties of the alpha M beta 2 integrin in the adherence of neutrophils and monocytes to stimulated endothelium cells, and in the phagocytosis of complement coated particles. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.72

Clinical Summary— ITGAX

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

156 VUS of 222 total submissions

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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 OE?0.54 (0.41–0.72)

0≤0.351.4

Missense OE?0.94 (0.88–1.00)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 35 / 64.4Missense obs/exp: 658 / 699.2Syn Z: -0.69

This gene — mechanism propensity

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

222 submitted variants in ClinVar

ClinVar

Classification Summary

VUS156

Likely Benign23

Benign3

156

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	156	0	156
Likely Benign	17	6	23
Benign	2	1	3
Total	175	7	182

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap ITGAX — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →