ITGAM

Chr 16

integrin subunit alpha M

Also known as: CD11B, CR3A, HNA-4, MAC-1, MAC1A, MO1A, SLEB6

The integrin alpha M chain combines with integrin beta 2 to form a leukocyte receptor essential for neutrophil and monocyte adhesion to endothelium, phagocytosis of complement-coated particles, and neutrophil migration. Mutations cause leukocyte adhesion deficiency type 1, an autosomal recessive primary immunodeficiency characterized by recurrent severe bacterial infections, delayed wound healing, and absence of pus formation due to impaired neutrophil function. The gene shows high tolerance to loss-of-function variants, consistent with the recessive inheritance pattern where biallelic mutations are required for disease.

ResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.64
Clinical SummaryITGAM
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 unique Pathogenic / Likely Pathogenic· 341 VUS of 650 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.64LOEUF
pLI 0.000
Z-score 3.87
OE 0.46 (0.340.64)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.42Z-score
OE missense 0.85 (0.790.91)
582 obs / 686.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.46 (0.340.64)
00.351.4
Missense OE0.85 (0.790.91)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 28 / 60.5Missense obs/exp: 582 / 686.9Syn Z: 1.04
DN
0.7327th %ile
GOF
0.6931th %ile
LOF
0.2679th %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

650 submitted variants in ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic1
VUS341
Likely Benign262
Benign16
Conflicting1
9
Pathogenic
1
Likely Pathogenic
341
VUS
262
Likely Benign
16
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
9
0
9
Likely Pathogenic
0
0
1
0
1
VUS
19
273
42
7
341
Likely Benign
0
7
124
131
262
Benign
0
4
4
8
16
Conflicting
1
Total19284180146630

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

View in ClinVar →

Protein Context — Lollipop Plot

ITGAM · 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

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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