ITGAM

Chr 16

integrin subunit alpha M

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

NCBI Gene: 3684 ENSG00000169896 UniProt: P11215 OMIM: 120980

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes the integrin alpha M 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 a leukocyte-specific integrin referred to as macrophage receptor 1 ('Mac-1'), or inactivated-C3b (iC3b) receptor 3 ('CR3'). The alpha M beta 2 integrin is important in the adherence of neutrophils and monocytes to stimulated endothelium, and also in the phagocytosis of complement coated particles. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.64

Clinical Summary— ITGAM

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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

637 VUS of 1132 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?

0.64LOEUF

pLI 0.000

Z-score 3.87

OE 0.46 (0.34–0.64)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.42Z-score

OE missense 0.85 (0.79–0.91)

582 obs / 686.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.46 (0.34–0.64)

0≤0.351.4

Missense OE?0.85 (0.79–0.91)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 28 / 60.5Missense obs/exp: 582 / 686.9Syn Z: 1.04

This gene — mechanism propensity

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

1132 submitted variants in ClinVar

ClinVar

Classification Summary

VUS637

Likely Benign438

Benign30

Conflicting7

637

VUS

438

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	42	531	55	9	637
Likely Benign	0	7	206	225	438
Benign	0	10	11	9	30
Conflicting	—				7
Total	42	548	272	243	1,112

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap ITGAM — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →