TREM2

triggering receptor expressed on myeloid cells 2, the group of V-set domain containing

Basic information

Region (hg38): 6:41158505-41163186

Links

ENSG00000095970 ∙ NCBI:54209 ∙ OMIM:605086 ∙ HGNC:17761 ∙ Uniprot:Q9NZC2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 (Strong), mode of inheritance: AR
• polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 (Strong), mode of inheritance: AR
• polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 (Moderate), mode of inheritance: AR
• polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly (Supportive), mode of inheritance: AR
• polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 (Nasu-Hakola disease); Early-onset dementia without bone cysts	AR	General	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	Musculoskeletal; Neurologic	12080485; 15883308; 1854636; 21834902; 23318515

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TREM2 gene.

• not provided (121 variants)
• Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 (34 variants)
• Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1 (13 variants)
• not specified (9 variants)
• Inborn genetic diseases (7 variants)
• TREM2-related condition (3 variants)
• Frontotemporal dementia (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TREM2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	2	18		21
missense	2	2	64	12	1	81
nonsense	3	2		1		6
start loss						0
frameshift	3					3
inframe indel						0
splice donor/acceptor (+/-2bp)	1	1				2
splice region			2	2		4
non coding			3	10	2	15
Total	9	6	69	41	3

Highest pathogenic variant AF is 0.0000591

Variants in TREM2

This is a list of pathogenic ClinVar variants found in the TREM2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-41158595-C-T		TREM2-related disorder	Likely benign (Jul 31, 2019)
6-41158607-C-T		Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2	Uncertain significance (May 21, 2021)
6-41158608-C-A		Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2	Uncertain significance (Oct 05, 2022)
6-41158616-G-A		Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2	Uncertain significance (Jan 18, 2024)
6-41158641-G-A			Uncertain significance (May 27, 2022)
6-41158650-G-A			Likely benign (Aug 03, 2021)
6-41158653-T-C		Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1	Uncertain significance (Jun 14, 2016)
6-41158655-G-C			Uncertain significance (Dec 02, 2021)
6-41158656-TC-CT			Uncertain significance (Oct 03, 2023)
6-41158657-C-A			Conflicting classifications of pathogenicity (Dec 07, 2023)
6-41158659-C-G			Uncertain significance (Dec 24, 2021)
6-41158662-G-C			Uncertain significance (May 07, 2022)
6-41158663-C-G			Uncertain significance (Aug 17, 2023)
6-41158684-T-A			Likely benign (Dec 22, 2023)
6-41158691-C-T		Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 • not specified	Benign/Likely benign (Jan 24, 2024)
6-41158694-G-A			Likely benign (Jul 17, 2022)
6-41158703-A-G			Uncertain significance (Apr 25, 2022)
6-41158711-T-A			Uncertain significance (Mar 11, 2022)
6-41158716-T-A		Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2	Benign/Likely benign (Aug 24, 2023)
6-41158719-T-A			Uncertain significance (Aug 31, 2022)
6-41158719-T-C			Uncertain significance (May 12, 2022)
6-41158721-C-G			Uncertain significance (Aug 07, 2022)
6-41158734-C-T		Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 • TREM2-related disorder	Benign (Dec 22, 2023)
6-41158738-T-C			Uncertain significance (May 16, 2022)
6-41158762-C-T		TREM2-related disorder	Likely benign (Dec 26, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TREM2	protein_coding	protein_coding	ENST00000373113	5	4681

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.29e-9	0.0506	125720	0	28	125748	0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.245	125	133	0.940	0.00000760	1481
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000145	0.000145
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.000141	0.000139
European (Non-Finnish)	0.000133	0.000132
Middle Eastern	0.000109	0.000109
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: Osteoclast differentiation - Homo sapiens (human);Microglia Pathogen Phagocytosis Pathway;Developmental Biology;DAP12 signaling;DAP12 interactions;Innate Immune System;Immune System;Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell;Adaptive Immune System;Other semaphorin interactions;Semaphorin interactions;Axon guidance;RANKL (Consensus)

Recessive Scores

• pRec: 0.155

Intolerance Scores

• loftool: 0.838
• rvis_EVS: 0.48
• rvis_percentile_EVS: 79.25

Haploinsufficiency Scores

• pHI: 0.0439
• hipred: N
• hipred_score: 0.123

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0196

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Trem2
• Phenotype: immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• 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;detection of peptidoglycan;innate immune response;positive regulation of peptidyl-tyrosine phosphorylation;regulation of immune response;positive regulation of calcium-mediated signaling;positive regulation of ERK1 and ERK2 cascade;detection of lipoteichoic acid;cellular response to lipoteichoic acid;cellular response to peptidoglycan;dendritic cell differentiation;positive regulation of protein localization to plasma membrane;positive regulation of C-C chemokine receptor CCR7 signaling pathway;positive regulation of CD40 signaling pathway
• Cellular component: extracellular region;plasma membrane;integral component of membrane
• Molecular function: lipopolysaccharide binding;phospholipid binding;signaling receptor activity;peptidoglycan binding;lipoteichoic acid binding;scaffold protein binding