TREML1

Summary

TREML1 (triggering receptor expressed on myeloid cells like 1, HGNC:20434) is a protein-coding gene on chromosome 6p21.1, encoding Trem-like transcript 1 protein (Q86YW5). Cell surface receptor that may play a role in the innate and adaptive immune response.

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

Source: NCBI Gene 340205 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 48 total
• MANE Select transcript: NM_178174

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20434
Approved symbol	TREML1
Name	triggering receptor expressed on myeloid cells like 1
Location	6p21.1
Locus type	gene with protein product
Status	Approved
Aliases	TLT1, dJ238O23.3
Ensembl gene	ENSG00000161911
Ensembl biotype	protein_coding
OMIM	609714
Entrez	340205

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000373127, ENST00000426005, ENST00000437044, ENST00000590581, ENST00000890491

RefSeq mRNA: 3 — MANE Select: NM_178174 NM_001271807, NM_001271808, NM_178174

CCDS: CCDS4851, CCDS64420, CCDS64421

Canonical transcript exons

ENST00000426005 — 6 exons

Exon	Start	End
ENSE00001061308	41153758	41154090
ENSE00001331931	41151282	41151384
ENSE00001860841	41149337	41149918
ENSE00003560413	41150261	41150313
ENSE00003675362	41150819	41150907
ENSE00003936563	41154246	41154347

Expression profiles

Bgee: expression breadth ubiquitous, 150 present calls, max score 97.59.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.0055 / max 251.8086, expressed in 53 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73524	0.8523	42
73525	0.1532	28

Top tissues by expression

240 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	97.59	gold quality
leukocyte	CL:0000738	96.93	gold quality
blood	UBERON:0000178	85.96	gold quality
granulocyte	CL:0000094	85.52	gold quality
tendon of biceps brachii	UBERON:0008188	73.76	silver quality
spleen	UBERON:0002106	72.07	gold quality
vermiform appendix	UBERON:0001154	71.95	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	71.80	gold quality
bone marrow cell	CL:0002092	71.75	gold quality
spinal cord	UBERON:0002240	69.66	gold quality
lymph node	UBERON:0000029	69.20	gold quality
bone marrow	UBERON:0002371	69.03	gold quality
right lung	UBERON:0002167	68.92	gold quality
upper lobe of left lung	UBERON:0008952	66.85	gold quality
left adrenal gland	UBERON:0001234	66.04	gold quality
left adrenal gland cortex	UBERON:0035825	65.60	gold quality
caecum	UBERON:0001153	65.12	gold quality
upper lobe of lung	UBERON:0008948	64.76	gold quality
substantia nigra	UBERON:0002038	64.67	gold quality
right adrenal gland cortex	UBERON:0035827	64.43	gold quality
gall bladder	UBERON:0002110	64.01	gold quality
right coronary artery	UBERON:0001625	63.93	gold quality
tibial nerve	UBERON:0001323	63.81	gold quality
adrenal cortex	UBERON:0001235	63.61	gold quality
right adrenal gland	UBERON:0001233	63.16	gold quality
midbrain	UBERON:0001891	62.89	gold quality
adrenal gland	UBERON:0002369	61.61	gold quality
rectum	UBERON:0001052	60.90	gold quality
right uterine tube	UBERON:0001302	60.62	gold quality
medial globus pallidus	UBERON:0002477	59.95	silver quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	43.11
E-MTAB-9221	yes	23.57
E-CURD-122	yes	22.53
E-HCAD-10	yes	17.44
E-HCAD-1	yes	8.60
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting TREML1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-548B-3P	99.38	67.26	1000
HSA-MIR-6507-3P	99.35	67.32	1059
HSA-MIR-1972	97.67	67.38	1172
HSA-MIR-3157-5P	97.41	67.61	998
HSA-MIR-7161-3P	96.79	68.79	798
HSA-MIR-4264	96.35	64.76	1480
HSA-MIR-635	96.00	65.54	687
HSA-MIR-6774-5P	95.94	65.18	722

Literature-anchored findings (GeneRIF, showing 21)

• initial characterization of TREM-like transcript (TLT)-1 results indicate it is likely that TLT-1 regulates the signaling of the TREM family receptors(TLT-1) (PMID:12393607)
• In contrast to previously characterized immunoreceptor tyrosine-based inhibition motif (ITIM) receptors, TLT1 enhances rather than inhibits calcium signaling in rat RBL-2H3 cells, a property dependent on the SHP-2 recruiting classical Tyr281 ITIM. (PMID:15128762)
• A soluble fragment of the TLT-1 extracellular domain is found in serum of humans and mice and that an isoform of similar mass is released from platelets following activation with thrombin. (PMID:16505478)
• Define a platelet specific function for TLT1 in regulation of aggregation. (PMID:17549298)
• Phenotypic heterogeneity in the Gray platelet syndrome extends to the expression of TREM family member, TLT-1. (PMID:18612537)
• antibody against the extracellular domain inhibits platelet aggregation in vitro (PMID:19230638)
• TLT-1 plays a protective role during inflammation by dampening the inflammatory response and facilitating platelet aggregation at sites of vascular injury (PMID:19436112)
• These results suggest that during inflammation, sTLT-1 may mediate hemostasis by enhancing actin polymerization, resulting in increased platelet aggregation and adherence to the endothelium. (PMID:20093931)
• Serum sTREM-1 level measurements may be helpful in diagnosing and predicting outcome for non-tuberculous mycobacterial lung disease. (PMID:22283904)
• Platelet-derived soluble TLT-1 is a potent endogenous regulator of sepsis-associated inflammation. (PMID:22551551)
• Levels of sTLT-1 in plasma from patients with potential acute coronary syndrome were compared with an age-matched control group with similar risk factors for cardiovascular disease. (PMID:25147325)
• Study characterized the expression of TREM genes in cerebellum and temporal cortex and determined TREML1 and TREM2 to be the only reliably expressed TREM genes in these brain regions; identified rs9357347 as a putative regulatory variant that is associated with protection from Alzheimer’s disease and with increased TREML1 and TREM2 brain levels. (PMID:27939925)
• TREM-like transcript 1: a more sensitive marker of platelet activation than P-selectin in humans and mice. (PMID:30120105)
• we show that gene expression profiling of RUNX1 knock-down or mutated MK provides a suitable approach to identify novel RUNX1 targets, among which downregulation of TREML1 and ITGA2 clearly contribute to the platelet phenotype of familial platelet disorder with predisposition to AML. (PMID:30545930)
• binding with macrophage membrane receptor, FcR1, initiates inflammatory signals in macrophages (PMID:31713591)
• Defining the TLT-1 interactome from resting and activated human platelets. (PMID:31923473)
• P-selectin (CD62P) and soluble TREM-like transcript-1 (sTLT-1) are associated with coronary artery disease: a case control study. (PMID:32831023)
• Low-soluble TREM-like transcript-1 levels early after severe burn reflect increased coagulation disorders and predict 30-day mortality. (PMID:33958244)
• TLT-1 Promotes Platelet-Monocyte Aggregate Formation to Induce IL-10-Producing B Cells in Tuberculosis. (PMID:35277419)
• Triggering receptor expressed on myeloid cells (TREM) like transcript-1 (TLT-1) reveals platelet activation in preeclampsia. (PMID:35348422)
• Decreased level of TREM like Transcript 1 (TLT-1) is associated with prematurity and promotes the in-utero inflammatory response to maternal lipopolysaccharide (LPS) exposure. (PMID:37766406)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Treml1	ENSMUSG00000023993
rattus_norvegicus	Treml1	ENSRNOG00000040109

Paralogs (13): TREM2 (ENSG00000095970), TMIGD3 (ENSG00000121933), CD300LG (ENSG00000161649), FCMR (ENSG00000162894), PIGR (ENSG00000162896), FCAMR (ENSG00000162897), CD300C (ENSG00000167850), CD300A (ENSG00000167851), CD300LB (ENSG00000178789), CD300LF (ENSG00000186074), CD300E (ENSG00000186407), CD300LD (ENSG00000204345), CD300H (ENSG00000284690)

Protein

Protein identifiers

Trem-like transcript 1 protein — Q86YW5 (reviewed: Q86YW5)

Alternative names: Triggering receptor expressed on myeloid cells-like protein 1

All UniProt accessions (1): Q86YW5

UniProt curated annotations — full annotation on UniProt →

Function. Cell surface receptor that may play a role in the innate and adaptive immune response.

Subunit / interactions. When phosphorylated, interacts with PTPN6. When phosphorylated, interacts with PTPN11.

Subcellular location. Cell membrane. Cytoplasm.

Tissue specificity. Detected in platelets, monocytic leukemia and in T-cell leukemia.

Post-translational modifications. Phosphorylated on tyrosine residues.

Isoforms (3)

UniProt ID	Names	Canonical?
Q86YW5-1	1	yes
Q86YW5-2	2, TLT1sv
Q86YW5-3	3

RefSeq proteins (3): NP_001258736, NP_001258737, NP_835468* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR052314	Immune_rcpt_domain	Family

UniProt features (32 total): strand 9, splice variant 3, helix 3, disulfide bond 2, sequence variant 2, topological domain 2, turn 2, region of interest 2, signal peptide 1, chain 1, lipid moiety-binding region 1, transmembrane region 1, domain 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2FRG	X-RAY DIFFRACTION	1.19
8CHE	X-RAY DIFFRACTION	1.49

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86YW5-F1	69.65	0.35

Antibody-complex structures (SAbDab): 1 — 8CHE

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 196

Disulfide bonds (2): 38–104, 52–59

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell

MSigDB gene sets: 80 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, GOBP_PLATELET_ACTIVATION, GOCC_CELL_SURFACE, AAAYRNCTG_UNKNOWN, GOBP_WOUND_HEALING, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, RYTTCCTG_ETS2_B, GOBP_HEMOSTASIS, GOBP_REGULATION_OF_BODY_FLUID_LEVELS, GOCC_PLATELET_ALPHA_GRANULE, GOCC_SECRETORY_VESICLE, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, VILIMAS_NOTCH1_TARGETS_DN, WIERENGA_STAT5A_TARGETS_DN

GO Biological Process (4): signal transduction (GO:0007165), calcium-mediated signaling (GO:0019722), platelet activation (GO:0030168), innate immune response (GO:0045087)

GO Molecular Function (2): transmembrane signaling receptor activity (GO:0004888), protein binding (GO:0005515)

GO Cellular Component (8): Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020), nuclear speck (GO:0016607), platelet alpha granule (GO:0031091), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
intracellular signaling cassette	1
cell activation	1
blood coagulation	1
immune response	1
defense response to symbiont	1
signaling receptor activity	1
binding	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
nuclear ribonucleoprotein granule	1
secretory granule	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

516 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TREML1	TREML2	Q5T2D2	971
TREML1	TREM1	Q9NP99	939
TREML1	TREM2	Q9NZC2	880
TREML1	GP6	Q9HCN6	797
TREML1	SELP	P16109	791
TREML1	TYROBP	O43914	732
TREML1	FCER1G	P30273	578
TREML1	MPIG6B	O95866	540
TREML1	PTPN11	Q06124	519
TREML1	TREML4	Q6UXN2	507
TREML1	FPR1	P21462	401
TREML1	FCGR1A	P12314	400
TREML1	FPR2	P25090	398
TREML1	CLEC1B	Q9P126	394
TREML1	GP1BA	P07359	348
TREML1	PEAR1	Q5VY43	348

IntAct

6 interactions, top by confidence:

A	B	Type	Score
TMBIM6	TREML1	psi-mi:“MI:0915”(physical association)	0.560
APP	TREML1	psi-mi:“MI:0915”(physical association)	0.400
TREML1	ATP1A3	psi-mi:“MI:0914”(association)	0.350
TMBIM6	TREML1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): PTPN11 (Affinity Capture-Western), TREML1 (Two-hybrid), PTPN6 (Affinity Capture-Western), TREML1 (Affinity Capture-RNA), PRSS8 (Affinity Capture-MS), ATP1A3 (Affinity Capture-MS), EZR (Affinity Capture-MS)

ESM2 similar proteins: A2A7V7, A2TGX5, A5D7B2, A8K4G0, D3ZQX2, D7PDD4, O15389, O43699, O95866, O95944, P0C1X9, P12318, P20138, P43626, Q02242, Q13291, Q1ERP8, Q2YFS3, Q3LRV9, Q3U497, Q566E6, Q60513, Q6DN72, Q6MG59, Q6SJQ0, Q6SJQ5, Q6SJQ7, Q6UXG3, Q7TSN2, Q80ZE3, Q86YW5, Q8BG84, Q8K558, Q8N109, Q8NHJ6, Q8NHK3, Q8R4Y0, Q8TDQ1, Q8VCH2, Q91Y57

Diamond homologs: A0A0K2S4Q6, A2TGX5, A8K4G0, G3X8R9, P01832, P01833, Q08708, Q1ERP8, Q2LA85, Q3U497, Q496F6, Q566E6, Q6SJQ0, Q6SJQ5, Q6SJQ7, Q6UXG3, Q6UXZ3, Q86YW5, Q8K249, Q8K558, Q8TDQ1, Q8VCH2, Q9UGN4, P0DUB1, P81265, Q9NP99

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

48 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

710 predictions. Top by Δscore:

Variant	Effect	Δscore
6:41149917:TT:T	acceptor_gain	1.0000
6:41149919:C:CC	acceptor_gain	1.0000
6:41150906:TG:T	acceptor_gain	1.0000
6:41150908:C:CC	acceptor_gain	1.0000
6:41151276:CAGTA:C	donor_loss	1.0000
6:41151277:AGTAC:A	donor_loss	1.0000
6:41151278:GTA:G	donor_loss	1.0000
6:41151279:TA:T	donor_loss	1.0000
6:41151280:A:C	donor_loss	1.0000
6:41151281:C:CG	donor_loss	1.0000
6:41151281:CCT:C	donor_gain	1.0000
6:41151290:AT:A	donor_gain	1.0000
6:41151291:T:TA	donor_gain	1.0000
6:41151394:C:T	acceptor_gain	1.0000
6:41151399:A:AC	acceptor_gain	1.0000
6:41151399:A:C	acceptor_gain	1.0000
6:41151406:C:CT	acceptor_gain	1.0000
6:41151407:A:T	acceptor_gain	1.0000
6:41149914:GGATT:G	acceptor_gain	0.9900
6:41149915:GATT:G	acceptor_gain	0.9900
6:41149918:TC:T	acceptor_loss	0.9900
6:41149920:T:A	acceptor_loss	0.9900
6:41150814:CCTA:C	donor_loss	0.9900
6:41150815:CTAC:C	donor_loss	0.9900
6:41150816:TA:T	donor_loss	0.9900
6:41150817:A:AC	donor_gain	0.9900
6:41150818:C:CC	donor_gain	0.9900
6:41150818:C:CG	donor_loss	0.9900
6:41150903:GGATG:G	acceptor_gain	0.9900
6:41150904:GATG:G	acceptor_gain	0.9900

AlphaMissense

1976 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:41153829:T:C	Y102C	0.994
6:41153981:C:A	W51C	0.993
6:41153981:C:G	W51C	0.993
6:41153823:C:G	C104S	0.992
6:41153824:A:T	C104S	0.992
6:41153987:C:A	K49N	0.992
6:41153987:C:G	K49N	0.992
6:41153983:A:G	W51R	0.990
6:41153983:A:T	W51R	0.990
6:41154021:C:G	C38S	0.990
6:41154022:A:T	C38S	0.990
6:41154022:A:G	C38R	0.987
6:41153824:A:G	C104R	0.985
6:41153829:T:G	Y102S	0.985
6:41153830:A:G	Y102H	0.985
6:41153830:A:C	Y102D	0.980
6:41153874:A:G	L87P	0.980
6:41153979:C:G	C52S	0.978
6:41153980:A:T	C52S	0.978
6:41153989:T:C	K49E	0.977
6:41153823:C:T	C104Y	0.976
6:41153989:T:G	K49Q	0.975
6:41154015:T:C	Y40C	0.975
6:41154020:G:C	C38W	0.975
6:41153892:T:C	D81G	0.974
6:41154021:C:T	C38Y	0.974
6:41153822:G:C	C104W	0.973
6:41153836:C:A	G100C	0.970
6:41153893:C:G	D81H	0.969
6:41153988:T:G	K49T	0.969

dbSNP variants (sampled 300 via entrez): RS1000509886 (6:41151619 A>G), RS1000560042 (6:41151908 T>C), RS1000993802 (6:41154853 T>A), RS1001549169 (6:41153941 A>G), RS1001998932 (6:41154963 C>T), RS1002166953 (6:41149973 T>A,C), RS1002281012 (6:41155221 C>T), RS1002405097 (6:41148934 T>C), RS1002414368 (6:41156798 G>T), RS1002771801 (6:41156429 A>T), RS1003422723 (6:41153463 A>G), RS1004690928 (6:41152055 C>A), RS1004992814 (6:41150546 C>T), RS1005054688 (6:41156932 C>T), RS1005231560 (6:41152371 C>A,T)

Disease associations

OMIM: gene MIM:609714 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006585_2448	Blood protein levels	3.000000e-08
GCST009391_613	Metabolite levels	1.000000e-06
GCST009391_674	Metabolite levels	6.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009793	isoleucine measurement
EFO:0009770	leucine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases abundance, increases expression	2
Tobacco Smoke Pollution	increases expression, increases methylation	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
CGP 52608	affects binding, increases reaction	1
Air Pollutants, Occupational	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression	1
Folic Acid	decreases expression	1
Nickel	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.