TREML2

Chr 6

triggering receptor expressed on myeloid cells like 2

Also known as: C6orf76, TLT-2, TLT2, dJ238O23.1

NCBI Gene: 79865ENSG00000112195UniProt: Q5T2D2

TREML2 is located in a gene cluster on chromosome 6 with the single Ig variable (IgV) domain activating receptors TREM1 (MIM 605085) and TREM2 (MIM 605086), but it has distinct structural and functional properties (Allcock et al., 2003 [PubMed 12645956]).[supplied by OMIM, Mar 2008]

60
ClinVar variants
7
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TREML2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 43 VUS of 60 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.
1.72LOEUF
pLI 0.000
Z-score -0.35
OE 1.11 (0.72–1.72)
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.
0.29Z-score
OE missense 0.94 (0.82–1.07)
161 obs / 171.8 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.1.11 (0.72–1.72)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.94 (0.82–1.07)
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.1.03
0≤1.21.6
LoF obs/exp: 13 / 11.7Missense obs/exp: 161 / 171.8Syn Z: -0.21

ClinVar Variant Classifications

60 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
VUS43
Likely Benign9
Benign1
7
Pathogenic
43
VUS
9
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
0
0
0
VUS
0
42
1
0
43
Likely Benign
0
8
0
1
9
Benign
0
1
0
0
1
Total0518160

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

View in ClinVar →

Protein Context — Lollipop Plot

TREML2 · 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
Associations Between TREML2 Gene Variants and Alzheimer's Disease: Biomarkers, Neuroimage, and Cognition.
Li JQ et al.·J Alzheimers Dis
2023
TREML2 Gene Expression and Its Missense Variant rs3747742 Associate with White Matter Hyperintensity Volume and Alzheimer's Disease-Related Brain Atrophy in the General Population.
Kühn AL et al.·Int J Mol Sci
2022
A TREML2 missense variant influences specific hippocampal subfield volumes in cognitively normal elderly subjects.
Wang SY et al.·Brain Behav
2020
Missense variant in TREML2 protects against Alzheimer's disease.
Benitez BA et al.·Neurobiol Aging
2014
Potential drug targets for ovarian cancer identified through Mendelian randomization and colocalization analysis.
Liu S et al.·J Ovarian Res
2025
A risk assessment model of acute liver allograft rejection by genetic polymorphism of CD276.
Yu X et al.·Mol Genet Genomic Med
2019Functional
B7H3 expression and significance in idiopathic pulmonary fibrosis.
Fang C et al.·J Pathol
2022
A multi-omics approach combining causal inference and in vivo validation identifies key protein drivers of alcohol-associated liver disease.
Zhou Q et al.·Front Immunol
2025
Mendelian randomization of plasma proteomics identifies novel ALS-associated proteins and their GO enrichment and KEGG pathway analyses.
Lu C et al.·BMC Neurol
2025
Genetic and Immunological Characterization of Brain Metastases from Solid Cancers.
Deguchi S et al.·Anticancer Res
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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