TREML1

Chr 6

triggering receptor expressed on myeloid cells like 1

Also known as: GLTL1825, PRO3438, TLT-1, TLT1, dJ238O23.3

NCBI Gene: 340205ENSG00000161911UniProt: Q86YW5

This gene encodes a member of the triggering receptor expressed on myeloid cells-like (TREM) family. The encoded protein is a type 1 single Ig domain orphan receptor localized to the alpha-granule membranes of platelets. The encoded protein is involved in platelet aggregation, inflammation, and cellular activation and has been linked to Gray platelet syndrome. Alternative splicing results in multiple transcript variants [provided by RefSeq, Nov 2012]

52
ClinVar variants
6
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TREML1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 43 VUS of 52 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.84LOEUF
pLI 0.000
Z-score -0.95
OE 1.29 (0.87–1.84)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.14Z-score
OE missense 0.97 (0.85–1.10)
170 obs / 175.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.29 (0.87–1.84)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.85–1.10)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.94
0≤1.21.6
LoF obs/exp: 16 / 12.4Missense obs/exp: 170 / 175.3Syn Z: 0.39

ClinVar Variant Classifications

52 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
VUS43
Likely Benign3
6
Pathogenic
43
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
0
0
0
VUS
0
43
0
0
43
Likely Benign
0
3
0
0
3
Benign
0
0
0
0
0
Total0466052

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

View in ClinVar →

Protein Context — Lollipop Plot

TREML1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A candidate regulatory variant at the TREM gene cluster associates with decreased Alzheimer's disease risk and increased TREML1 and TREM2 brain gene expression.
Carrasquillo MM et al.·Alzheimers Dement
2017Meta-analysis
Large-scale rare variant burden testing in Parkinson's disease.
Makarious MB et al.·Brain
2023
The Platelet-Specific Gene Signature in the Immunoglobulin G4-Related Disease Transcriptome.
Oguz AK et al.·Medicina (Kaunas)
2025
Combining proteomic markers to construct a logistic regression model for polycystic ovary syndrome.
Tong C et al.·Front Endocrinol (Lausanne)
2023Functional
The TREM Receptor Family in Cardiovascular Diseases: Functions, Mechanisms and Therapeutic Perspectives.
Liu W et al.·Int Immunopharmacol
2026Review
Key variants via the Alzheimer's Disease Sequencing Project whole genome sequence data.
Wang Y et al.·Alzheimers Dement
2024
Downregulation of TREM-like transcript-1 and collagen receptor α2 subunit, two novel RUNX1-targets, contributes to platelet dysfunction in familial platelet disorder with predisposition to acute myelogenous leukemia.
Glembotsky AC et al.·Haematologica
2019
TREM-like transcript-1 protects against inflammation-associated hemorrhage by facilitating platelet aggregation in mice and humans.
Washington AV et al.·J Clin Invest
2009
Development and internal validation of a novel model and markers to identify the candidates for lymph node metastasis in patients with prostate cancer.
Cao HM et al.·Medicine (Baltimore)
2019Cohort
Triggering receptor expressed on myeloid cells 1 (TREM-1) and cytokine gene variants in complicated and uncomplicated malaria.
Adukpo S et al.·Trop Med Int Health
2016
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools