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TREM2 Gene(Protein Coding)

Triggering Receptor Expressed On Myeloid Cells 2

GCID:
GC06M041126
GIFtS:
53
Genes Participants
UDN Logo

Aliases for TREM2 Gene

Aliases for TREM2 Gene

  • Triggering Receptor Expressed On Myeloid Cells 2 2 3 5
  • Triggering Receptor Expressed On Myeloid Cells 2a 2 3
  • Triggering Receptor Expressed On Monocytes 2 3 4
  • TREM-2 3 4
  • Trem2a 3
  • Trem2b 3
  • Trem2c 3

External Ids for TREM2 Gene

Previous GeneCards Identifiers for TREM2 Gene

  • GC06M041128
  • GC06M041173
  • GC06M041234
  • GC06M040844

Summaries for TREM2 Gene

Entrez Gene Summary for TREM2 Gene

  • This gene encodes a membrane protein that forms a receptor signaling complex with the TYRO protein tyrosine kinase binding protein. The encoded protein functions in immune response and may be involved in chronic inflammation by triggering the production of constitutive inflammatory cytokines. Defects in this gene are a cause of polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2012]

GeneCards Summary for TREM2 Gene

TREM2 (Triggering Receptor Expressed On Myeloid Cells 2) is a Protein Coding gene. Diseases associated with TREM2 include Polycystic Lipomembranous Osteodysplasia With Sclerosing Leukoencephalopathy and Solitary Bone Cyst. Among its related pathways are Semaphorin interactions and Innate Immune System. Gene Ontology (GO) annotations related to this gene include receptor activity and lipopolysaccharide binding.

UniProtKB/Swiss-Prot for TREM2 Gene

  • Forms a receptor signaling complex with TYROBP and triggers activation of the immune responses in macrophages and dendritic cells. May have a role in chronic inflammations and may stimulate production of constitutive rather than inflammatory chemokines and cytokines.

Gene Wiki entry for TREM2 Gene

Additional gene information for TREM2 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for TREM2 Gene

Genomics for TREM2 Gene

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  1. Regulatory Element

GeneHancer (GH) Regulatory Elements for TREM2 Gene

Promoters and enhancers for TREM2 Gene
GeneHancer (GH) Identifier GH Type GH
Score		 GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites		 Gene Targets
GH06I041163 Promoter/Enhancer 0.9 EPDnew Ensembl 550.8 -0.1 -103 0.6 ZFHX2 EGR2 TREM2 LOC105375056 TREML2
GH06I041161 Enhancer 0.3 Ensembl 550.8 +1.1 1097 1.4 ZIC2 TREM2 TREML1 LOC105375056
GH06I041198 Promoter/Enhancer 1.8 EPDnew Ensembl ENCODE dbSUPER 11.6 -38.2 -38232 6.2 HDGF ATF1 SMAD1 ARNT TCF12 RUNX3 ZNF263 NCOA1 ZNF592 MBD2 TREML2 TREML4 TREML3P TREM2 USP49 ADCY10P1 NFYA TREML5P TREML1 ENSG00000218809
GH06I041208 Enhancer 0.7 ENCODE dbSUPER 11.6 -46.1 -46129 2.4 ZNF687 IKZF1 GABPB1 NR2C1 NR2C2 TREM2 TREML3P ENSG00000218809 TREML2
GH06I041181 Enhancer 1.3 FANTOM5 Ensembl ENCODE dbSUPER 0.4 -19.4 -19434 1.7 CTCF USF1 TEAD4 MAX RAD21 TCF12 ZNF143 ZNF654 L3MBTL2 TRIM22 TREM1 ADCY10P1 TREML1 TREML4 NFYA TREML2 TREM2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around TREM2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the TREM2 gene promoter:

Genomic Locations for TREM2 Gene

Genomic Locations for TREM2 Gene
chr6:41,158,506-41,163,198
(GRCh38/hg38)
Size:
4,693 bases
Orientation:
Minus strand
chr6:41,126,244-41,130,924
(GRCh37/hg19)

Genomic View for TREM2 Gene

Genes around TREM2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TREM2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TREM2 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for TREM2 Gene

Proteins for TREM2 Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for TREM2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9NZC2-TREM2_HUMAN
    Recommended name:
    Triggering receptor expressed on myeloid cells 2
    Protein Accession:
    Q9NZC2
    Secondary Accessions:
    • Q8N5H8
    • Q8WYN6

    Protein attributes for TREM2 Gene

    Size:
    230 amino acids
    Molecular mass:
    25447 Da
    Quaternary structure:
    • Monomer (PubMed:27995897). Interacts with TYROBP/DAP12 (By similarity).
    SequenceCaution:
    • Sequence=BAB78736.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for TREM2 Gene

    Alternative splice isoforms for TREM2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TREM2 Gene

Protein Expression for TREM2 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for TREM2 Gene

  • Glycosylation at isoforms=2, 320 and isoforms=2, 379
  • Modification sites at PhosphoSitePlus

Other Protein References for TREM2 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Abcam antibodies for TREM2
  • Santa Cruz Biotechnology (SCBT) Antibodies for TREM2

No data available for DME Specific Peptides for TREM2 Gene

Domains & Families for TREM2 Gene

Gene Families for TREM2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted membrane proteins
  • Predicted secreted proteins

Protein Domains for TREM2 Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for TREM2 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

genes like me logo Genes that share domains with TREM2: view

No data available for UniProtKB/Swiss-Prot for TREM2 Gene

Function for TREM2 Gene

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  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
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Molecular function for TREM2 Gene

UniProtKB/Swiss-Prot Function:
Forms a receptor signaling complex with TYROBP and triggers activation of the immune responses in macrophages and dendritic cells. May have a role in chronic inflammations and may stimulate production of constitutive rather than inflammatory chemokines and cytokines.

Phenotypes From GWAS Catalog for TREM2 Gene

Gene Ontology (GO) - Molecular Function for TREM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001530 lipopolysaccharide binding IEA --
GO:0004872 receptor activity TAS 10799849
GO:0005543 phospholipid binding IDA 27995897
GO:0042834 peptidoglycan binding IEA --
GO:0070891 lipoteichoic acid binding IEA --
genes like me logo Genes that share ontologies with TREM2: view
genes like me logo Genes that share phenotypes with TREM2: view

Human Phenotype Ontology for TREM2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for TREM2 Gene

MGI Knock Outs for TREM2:

Animal Model Products

miRNA for TREM2 Gene

miRTarBase miRNAs that target TREM2

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for TREM2 Gene

Localization for TREM2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TREM2 Gene

Isoform 1: Cell membrane; Single-pass type I membrane protein.
Isoform 2: Secreted.
Isoform 3: Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TREM2 gene
Compartment Confidence
plasma membrane 5
extracellular 5
lysosome 1

Gene Ontology (GO) - Cellular Components for TREM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005886 plasma membrane TAS --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IDA 11602640
GO:0043231 intracellular membrane-bounded organelle IDA --
genes like me logo Genes that share ontologies with TREM2: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for TREM2 Gene

Pathways & Interactions for TREM2 Gene

genes like me logo Genes that share pathways with TREM2: view

Pathways by source for TREM2 Gene

1 KEGG pathway for TREM2 Gene
1 Cell Signaling Technology pathway for TREM2 Gene

Interacting Proteins for TREM2 Gene

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)
http://version10.5.string-db.org/api/image/networkList?limit=0&targetmode=proteins&caller_identity=gene_cards&network_flavor=evidence&identifiers=9606.ENSP00000362205%0d%0a9606.ENSP00000384675%0d%0a9606.ENSP00000308176%0d%0a9606.ENSP00000240618%0d%0a9606.ENSP00000289153%0d%0a9606.ENSP00000338130%0d%0a
Selected Interacting proteins: ENSP00000362205 Q9NZC2-TREM2_HUMAN for TREM2 Gene via STRING IID

Symbol External ID(s) Details
HLA-B
HLA-A
HLA-DRB1
B2M
HLA-E

Gene Ontology (GO) - Biological Process for TREM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002588 positive regulation of antigen processing and presentation of peptide antigen via MHC class II IDA 11602640
GO:0006911 phagocytosis, engulfment IEA --
GO:0006959 humoral immune response TAS 10799849
GO:0032497 detection of lipopolysaccharide IEA --
GO:0032499 detection of peptidoglycan IEA --
genes like me logo Genes that share ontologies with TREM2: view

No data available for SIGNOR curated interactions for TREM2 Gene

Drugs & Compounds for TREM2 Gene

Products:

  1. Drug
No Compound Related Data Available

Transcripts for TREM2 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for TREM2 Gene

(3) REFSEQ mRNAs :
(5) Additional mRNA sequences :
(47) Selected AceView cDNA sequences:
(3) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for TREM2 Gene

Triggering receptor expressed on myeloid cells 2:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for TREM2 Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4a · 4b ^ 5
SP1: -
SP2:
SP3: - -

Relevant External Links for TREM2 Gene

GeneLoc Exon Structure for
TREM2
ECgene alternative splicing isoforms for
TREM2

Expression for TREM2 Gene

Products:

  1. Primer
  2. Gene Expression Assay

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for TREM2 Gene

mRNA expression in normal human tissues for TREM2 Gene
mRNA expression by GTEx for TREM2 GenemRNA expression by BioGPS for TREM2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for TREM2 Gene

This gene is overexpressed in Brain - Spinal cord (cervical c-1) (x9.9) and Brain - Substantia nigra (x6.2).

Protein differential expression in normal tissues from HIPED for TREM2 Gene

This gene is overexpressed in Pancreas (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for TREM2 Gene



Protein tissue co-expression partners for TREM2 Gene

NURSA nuclear receptor signaling pathways regulating expression of TREM2 Gene:

TREM2

SOURCE GeneReport for Unigene cluster for TREM2 Gene:

Hs.435295

mRNA Expression by UniProt/SwissProt for TREM2 Gene:

Q9NZC2-TREM2_HUMAN
Tissue specificity: Expressed on macrophages and dendritic cells but not on granulocytes or monocytes. In the CNS strongest expression seen in the basal ganglia, corpus callosum, medulla oblongata and spinal cord.

Evidence on tissue expression from TISSUES for TREM2 Gene

  • Nervous system(4.6)
  • Spleen(2.1)

Phenotype-based relationships between genes and organs from Gene ORGANizer for TREM2 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • integumentary
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • cerebellum
  • cranial nerve
  • ear
  • epiglottis
  • eye
  • face
  • head
  • jaw
  • larynx
  • mandible
  • maxilla
  • mouth
  • neck
  • nose
  • pharynx
  • skull
  • tongue
  • vocal cord
Thorax:
  • bronchus
  • chest wall
  • clavicle
  • esophagus
  • heart
  • lung
  • rib
  • rib cage
  • scapula
  • sternum
  • trachea
Abdomen:
  • biliary tract
  • liver
  • stomach
Pelvis:
  • pelvis
  • prostate
  • urinary bladder
Limb:
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
General:
  • blood vessel
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal column
  • spinal cord
  • vertebrae
genes like me logo Genes that share expression patterns with TREM2: view

Orthologs for TREM2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for TREM2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia TREM2 33 34
  • 99.42 (n)
cow
(Bos Taurus)
 Mammalia TREM2 33 34
  • 85.94 (n)
dog
(Canis familiaris)
 Mammalia TREM2 33 34
  • 84.28 (n)
mouse
(Mus musculus)
 Mammalia Trem2 33 16 34
  • 77.28 (n)
platypus
(Ornithorhynchus anatinus)
 Mammalia TREM2 34
  • 47 (a)
 OneToOne
oppossum
(Monodelphis domestica)
 Mammalia TREM2 34
  • 45 (a)
 OneToOne
chicken
(Gallus gallus)
 Aves TREM2 33
  • 59.09 (n)
TREM-A1 34
  • 30 (a)
 OneToOne
lizard
(Anolis carolinensis)
 Reptilia TREM2 34
  • 26 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia trem2 33
  • 49.9 (n)
Species where no ortholog for TREM2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rat (Rattus norvegicus)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)
  • zebrafish (Danio rerio)

Evolution for TREM2 Gene

ENSEMBL:
Gene Tree for TREM2 (if available)
TreeFam:
Gene Tree for TREM2 (if available)

Paralogs for TREM2 Gene

No data available for Paralogs for TREM2 Gene

Variants for TREM2 Gene

Products:

  1. SNP Genotyping and Copy Number Assay

Sequence variations from dbSNP and Humsavar for TREM2 Gene

SNP ID Clin Chr 06 pos Variation AA Info Type
rs104893998 pathogenic, Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 41,161,421(-) C/T coding_sequence_variant, intron_variant, stop_gained
rs104894001 pathogenic, Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 41,161,522(-) C/T coding_sequence_variant, intron_variant, stop_gained
rs104894002 pathogenic, Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 41,161,557(-) G/A coding_sequence_variant, intron_variant, stop_gained
rs121908402 pathogenic, Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 41,161,277(-) A/C coding_sequence_variant, intron_variant, missense_variant
rs139607688 uncertain-significance, Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 41,159,881(-) G/A/T coding_sequence_variant, missense_variant, synonymous_variant

Structural Variations from Database of Genomic Variants (DGV) for TREM2 Gene

Variant ID Type Subtype PubMed ID
nsv602970 CNV gain 21841781

Variation tolerance for TREM2 Gene

Residual Variation Intolerance Score: 90.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.40; 63.67% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TREM2 Gene

Human Gene Mutation Database (HGMD)
TREM2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TREM2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TREM2 Gene

Disorders for TREM2 Gene

MalaCards: The human disease database

(9) MalaCards diseases for TREM2 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search TREM2 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

TREM2_HUMAN
  • Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) [MIM:221770]: Recessively inherited disease characterized by a combination of psychotic symptoms rapidly progressing to presenile dementia and bone cysts restricted to wrists and ankles. PLOSL has a global distribution, although most of the patients have been diagnosed in Finland and Japan, with an estimated population prevalence of 2x10(-6) in the Finns. {ECO:0000269 PubMed:12080485}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for TREM2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with TREM2: view

No data available for Genatlas for TREM2 Gene

Publications for TREM2 Gene

  1. Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype. (PMID: 12080485) Paloneva J … Peltonen L (American journal of human genetics 2002) 2 3 4 58
  2. Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes. (PMID: 10799849) Bouchon A … Colonna M (Journal of immunology (Baltimore, Md. : 1950) 2000) 2 3 4 58
  3. A rare coding variant in TREM2 increases risk for Alzheimer's disease in Han Chinese. (PMID: 27067662) Jiang T … Yu JT (Neurobiology of aging 2016) 3 4 58
  4. Neurodegenerative disease mutations in TREM2 reveal a functional surface and distinct loss-of-function mechanisms. (PMID: 27995897) Kober DL … Brett TJ (eLife 2016) 3 4 58
  5. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 44 58

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