CD226

Chr 18

CD226 molecule

Also known as: DNAM-1, DNAM1, PTA1, TLiSA1

This gene encodes a glycoprotein expressed on the surface of NK cells, platelets, monocytes and a subset of T cells. It is a member of the Ig-superfamily containing 2 Ig-like domains of the V-set. The protein mediates cellular adhesion of platelets and megakaryocytic cells to vascular endothelial cells. The protein also plays a role in megakaryocytic cell maturation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

0
Active trials
75
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.70
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryCD226
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.70LOEUF
pLI 0.039
Z-score 2.40
OE 0.33 (0.170.70)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.74Z-score
OE missense 0.85 (0.740.97)
159 obs / 187.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.33 (0.170.70)
00.351.4
Missense OE0.85 (0.740.97)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 5 / 15.1Missense obs/exp: 159 / 187.4Syn Z: -0.18
DN
0.77top 25%
GOF
0.73top 25%
LOF
0.2289th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CD226 · 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.

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Clinical Literature
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