TREM2
protein-codingtriggering receptor expressed on myeloid cells 2, the group of V-set domain containing
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0014036
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0020750
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0009092
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0020750
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0020750
Submitter: Genomics England PanelApp
Inheritance Pattern: AR
Disease ID:MONDO:0020750
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Musculoskeletal; Neurologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TREM2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018965.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 36 | 37 | |||
| missense | 1 | 5 | 59 | 12 | 77 | |
| nonsense | 4 | 3 | 7 | |||
| start loss | 0 | |||||
| frameshift | 4 | 2 | 6 | |||
| splice donor/acceptor (+/-2bp) | 1 | 5 | 6 | |||
| Total | 10 | 15 | 60 | 48 | 0 | 133 |
Highest pathogenic variant AF is 0.00006505149
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_061838.1 | 5 | MANE Select | |
| Ensembl | ENSP00000362205.3 | 5 | MANE Select | |
| RefSeq | NP_001258750.1 | 4 | Standard | |
| Ensembl | ENSP00000342651.4 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Osteoclast differentiation - Homo sapiens (human)
- Microglia Pathogen Phagocytosis Pathway
- Developmental Biology
- DAP12 signaling
- DAP12 interactions
Biological Process
- positive regulation of antigen processing and presentation of peptide antigen via MHC class II
- phagocytosis, engulfment
- humoral immune response
- osteoclast differentiation
- detection of lipopolysaccharide
Molecular Function
- lipopolysaccharide binding
- phospholipid binding
- signaling receptor activity
- peptidoglycan binding
- lipoteichoic acid binding
Cellular Component
- extracellular region
- plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000373113
- Coding exons
- 5
- Length
- 4681
- Individuals with no LoFs
- 125720
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 28
- Defined
- 125748
- p
- 0.000111
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.245 | 125 | 133 | 0.940 | 0.00000760 | 1481 |
| Missense (PolyPhen) | 44 | 43.168 | 1.0193 | 495 | ||
| Synonymous | 1.27 | 46 | 58.4 | 0.788 | 0.00000353 | 480 |
| Loss of Function | -0.518 | 12 | 10.2 | 1.17 | 4.41e-7 | 105 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00014 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00013 | 0.00013 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- 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. {ECO:0000269|PubMed:10799849}.;
Recessive Scores
- pRec
- 0.155
Intolerance Scores
- LoFtool
- 0.838
- RVIS EVS
- 0.48
- RVIS percentile EVS
- 79.25
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0196
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |