ITGAD

Chr 16

integrin subunit alpha D

Also known as: ADB2, CD11D

NCBI Gene: 3681 ENSG00000156886 UniProt: Q13349 OMIM: 602453

The protein encoded by this gene forms the alpha subunit of integrin alpha-D/beta-2, a cell surface receptor that mediates leukocyte adhesion and activation by binding to ICAM3 and VCAM1. The gene is not highly constrained against loss-of-function variants and no established Mendelian diseases have been definitively linked to ITGAD mutations. This gene primarily functions in myeloid leukocyte biology and may have roles in immune processes including phagocytosis and vascular inflammation.

OMIM ResearchSummary from RefSeq, UniProt

This gene belongs to the beta-2 integrin family of membrane glycoproteins, which are are composed of non-covalently linked alpha and beta subunits to form a heterodimer. It encodes the alpha subunit of the cell surface heterodimers and is involved in the activation and adhesion functions of leukocytes. The gene is located about 11kb downstream of the integrin subunit alpha X gene, another member of the integrin family. It is expressed in the tissue and circulating myeloid leukocytes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.87

Clinical Summary— ITGAD

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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

175 VUS of 196 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?

0.87LOEUF

pLI 0.000

Z-score 2.44

OE 0.67 (0.53–0.87)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.85Z-score

OE missense 0.91 (0.85–0.97)

628 obs / 690.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.67 (0.53–0.87)

0≤0.351.4

Missense OE?0.91 (0.85–0.97)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 43 / 64.0Missense obs/exp: 628 / 690.9Syn Z: -1.02

This gene — mechanism propensity

0.6939th %ile

GOF

0.7029th %ile

LOF

0.2679th %ile

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

GOFprediction above median

DNprediction 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

196 submitted variants in ClinVar

ClinVar

Classification Summary

VUS175

Likely Benign12

175

VUS

Likely 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	175	0	175
Likely Benign	11	1	12
Benign	0	0	0
Total	186	1	187

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 ITGAD — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →