ICAM2

Chr 17

intercellular adhesion molecule 2

Also known as: CD102

The protein encoded by ICAM2 is a transmembrane glycoprotein that functions as a cell adhesion molecule, binding to LFA-1 on leukocytes and CD209 on dendritic cells to mediate immune cell adhesion, transendothelial migration, and lymphocyte recirculation. Mutations in ICAM2 cause disease through a predicted gain-of-function mechanism, though specific associated neurological phenotypes are not established in the provided data. The gene shows tolerance to loss-of-function variation (pLI 0.0007), suggesting haploinsufficiency is not the primary disease mechanism.

Summary from RefSeq, UniProt, Mechanism
0
Active trials
17
Pubs (1 yr)
10
P/LP submissions
0%
P/LP missense
1.25
LOEUF
GOF
Mechanism· predicted
Clinical SummaryICAM2
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· 41 VUS of 66 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.25LOEUF
pLI 0.001
Z-score 1.04
OE 0.64 (0.351.25)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.41Z-score
OE missense 0.91 (0.801.04)
157 obs / 172.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.64 (0.351.25)
00.351.4
Missense OE0.91 (0.801.04)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 6 / 9.4Missense obs/exp: 157 / 172.0Syn Z: 0.55
DN
0.73top 25%
GOF
0.76top 25%
LOF
0.2387th %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

66 submitted variants in ClinVar

Classification Summary

Pathogenic10
VUS41
Likely Benign7
10
Pathogenic
41
VUS
7
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
0
0
0
VUS
0
38
3
0
41
Likely Benign
0
7
0
0
7
Benign
0
0
0
0
0
Total04513058

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

View in ClinVar →

Protein Context — Lollipop Plot

ICAM2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →