TREM1

Chr 6

triggering receptor expressed on myeloid cells 1

Also known as: CD354, TREM-1

This gene encodes a receptor belonging to the Ig superfamily that is expressed on myeloid cells. This protein amplifies neutrophil and monocyte-mediated inflammatory responses triggered by bacterial and fungal infections by stimulating release of pro-inflammatory chemokines and cytokines, as well as increased surface expression of cell activation markers. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Jun 2011]

5
Active trials
0
Pathogenic / LP
0
ClinVar variants
108
Pubs (1 yr)
0.1
Missense Z
1.02
LOEUF
Clinical SummaryTREM1
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
5 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.02LOEUF
pLI 0.006
Z-score 1.52
OE 0.49 (0.251.02)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.08Z-score
OE missense 0.98 (0.851.13)
128 obs / 130.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.49 (0.251.02)
00.351.4
Missense OE0.98 (0.851.13)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 5 / 10.3Missense obs/exp: 128 / 130.7Syn Z: 0.36
DNGOF
DN
0.80top 25%
GOF
0.75top 25%
LOF
0.1894th %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

TREM1 · protein map & ClinVar variants

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

Clinical Literature
Landmark / reviewRecent case evidence