Search Results

TREM2 (64)

Mutation	Clinical Phenotype	Pathogenicity	Neuropathology	Biological Effect	Genomic Position	Genomic Region	Mutation Type Codon Change	Research Models	Primary Papers
E14X	Nasu-Hakola Disease	NHD : Pathogenic	Unknown.	Premature truncation codon; no transcripts detected.	rs386834143	Coding Exon 1	Point, Nonsense GAG to TAG	0	Paloneva et al., 2003
S16F		AD : Unclear Pathogenicity	Unknown.	Unknown.	rs777808487	Coding Exon 2	Point, Missense TCC to TTC	0	Sirkis et al., 2016
G17E		AD : Unclear Pathogenicity, FTD : Unclear Pathogenicity	Unknown.	Predicted benign by Polyphen-2, tolerated by SIFT, neutral by SNPs&Go.		Coding Exon 2	Point, Missense GGA to GAA	0	Cuyvers et al., 2014
V27M		AD : Unclear Pathogenicity	Unknown.	Normal protein maturation in HEK293 cells.	rs768745050	Coding Exon 2	Point, Missense GTG to ATG	0	Sirkis et al., 2016
A28V	Primary Progressive Aphasia, Progressive Nonfluent Aphasia	AD : Not Pathogenic, FTD : Unclear Pathogenicity	Unknown.	Normal protein maturation and increased cell-surface expression in HEK293 cells.	rs2234252	Coding Exon 2	Point, Missense GCG to GTG	0	Sims et al., 2017
S31F		AD : Unclear Pathogenicity	Unknown.	Normal protein maturation, decreased total and cell-surface expression in HEK293 cells.	rs746216516	Coding Exon 2	Point, Missense TCC to TTC	0	Sirkis et al., 2016
Q33X	Alzheimer's Disease, Frontotemporal Dementia, Nasu-Hakola Disease	NHD : Pathogenic, FTD : Pathogenic, AD : Possible Risk Modifier	Unknown for homozygous carriers; MRI showed cerebral atrophy. Heterozygous AD patient showed typical AD pathology.	Loss of TREM2 expression.	rs104894002	Coding Exon 2	Point, Nonsense CAG to TAG	0	Soragna et al., 2003; Guerreiro et al., 2013
Y38C	Frontotemporal Dementia	FTD : Pathogenic	Unknown; MRI shows cortical atrophy and white matter abnormalities.	Alters post-translational processing of TREM2, ligand binding, and TREM2-mediated phagocytosis.	rs797044603	Coding Exon 2	Point, Missense TAT to TGT	1	Guerreiro et al., 2013
D39E		AD : Not Pathogenic, FTD : Unclear Pathogenicity	Not applicable.	Predicted to be possibly damaging by Polyphen-2, but to be tolerated by SIFT and neutral by SNPs&Go.	rs200392967	Coding Exon 2	Point, Missense GAC to GAG	0	Sims et al., 2017
D39G		AD : Unclear Pathogenicity, FTD : Unclear Pathogenicity	Unknown.	Predicted to be benign by Polyphen-2, tolerated by SIFT, and neutral by SNPs&Go.		Coding Exon 2	Point, Missense GAC to GGC	0	Cuyvers et al., 2014
H43Y		AD : Unclear Pathogenicity	Unknown.	Predicted benign by PolyPhen2.		Coding Exon 2	Point, Missense CAC to TAC	0	Pottier et al., 2013
W44X	Nasu-Hakola Disease	NHD : Pathogenic	Brain atrophy reported.	Predicted to result in truncated protein lacking transmembrane and cytoplasmic domains.	rs104894001	Coding Exon 2	Point, Nonsense TGG to TGA	0	Paloneva et al., 2002
G45E		AD : Unclear Pathogenicity	Unknown.	Unknown.		Coding Exon 2	Point, Missense GGG to GAG	0	Jonsson et al., 2013
R47C	Behavioral variant FTD	AD : Unclear Pathogenicity, FTD : Pathogenic	Unknown, but MRI showed symmetric frontal and temporal lobe atrophy in homozygous carrier.	Normal protein maturation, decreased total and cell-surface expression in HEK293 cells.	rs753325601	Coding Exon 2	Point, Missense CGC to TGC	0	Sirkis et al., 2016; Ng et al., 2018
R47H	Alzheimer's Disease, Frontotemporal Dementia, Amyotrophic Lateral Sclerosis, Parkinson's Disease	AD : Risk Modifier, FTD : Possible Risk Modifier, PD : Possible Risk Modifier, ALS : Possible Risk Modifier	AD patients heterozygous for the R47H variant: generally typical AD pathology, but subtle differences compared to non-carriers, including decreased microglial coverage of amyloid plaques and accumulation of phagosomes in microglia.	Decreased ligand binding to TREM2 and impaired TREM2-mediated activation.	rs75932628	Coding Exon 2	Point, Missense CGC to CAC	13	Guerreiro et al., 2013; Jonsson et al., 2013
W50C	Nasu-Hakola Disease	NHD : Pathogenic	Unknown; imaging showed brain atrophy, diffuse white-matter hyperintensities, thinning of the corpus callosum, and basal ganglia calcification.	Unknown; predicted to be harmful in silico by Polyphen-2 and SIFT.		Coding Exon 2	Point, Missense GAG to TAG	0	Dardiotis et al., 2017
R52H		AD : Unclear Pathogenicity	Unknown.	Lower cell-surface expression than wild-type TREM2 when co-expressed with its adaptor protein DAP12 in a reporter cell line, but activation by phospholipids similar in cells expressing R52H and wild-type TREM2.	rs374851046	Coding Exon 2	Point, Missense CGC to CAC	0	Jin et al., 2014
G58A		AD : Unclear Pathogenicity, FTD : Unclear Pathogenicity	Unknown.	Predicted by Polyphen2 to be probably damaging, by SIFT to be tolerated, and by SNPs&Go to be neutral.		Coding Exon 2	Point, Missense GGC to GCC	0	Cuyvers et al., 2014
R62C		AD : Unclear Pathogenicity	Unknown.	Lower cell-surface expression than wild-type TREM2 when co-expressed with its adaptor protein DAP12 in a reporter cell line; activation by lipid ligands reduced in cells expressing R62C compared with cells expressing wild-type TREM2.	rs201258314	Coding Exon 2	Point, Missense CGT to TGT	0	Pottier et al., 2013; Song et al., 2017
R62H	Alzheimer's Disease	AD : Risk Modifier	AD patients heterozygous for the R62H variant: decreased microglial coverage of amyloid plaques and increased accumulation of phagosomes in microglia, compared to non-carriers.	Decreased ligand binding to TREM2 and impaired TREM2-mediated activation.	rs143332484	Coding Exon 2	Point, Missense CGT to CAT	0	Jin et al., 2014; Sims et al., 2017
T66M	Behavioral variant FTD	FTD : Pathogenic	Unknown; MRI showed frontal lobe atrophy, ventricular enlargement, and white-matter abnormalities in one homozygous carrier, and frontal and parietal lobe atrophy in two other homozygous carriers.	Greatly decreased cell-surface expression and shedding of sTREM2, reduced ligand binding, and impaired phagocytosis.	rs201258663	Coding Exon 2	Point, Missense ACG to ATG	1	Guerreiro et al., 2013
N68K		AD : Unclear Pathogenicity	Unknown.	Predicted benign by PolyPhen2; apparently normal protein folding.	rs753372932	Coding Exon 2	Point, Missense AAC to AAG	0	Guerreiro et al., 2013
L72V		AD : Unclear Pathogenicity	Unknown.	Predicted by SIFT to be tolerated but by Polyphen2 to be damaging.	rs765933093	Coding Exon 2	Point, Missense CTG to GTG	0	Ghani et al., 2016
W78X	Nasu-Hakola Disease	NHD : Pathogenic	Brain atrophy has been reported.	Predicted to result in truncated protein lacking transmembrane and cytoplasmic domains.	rs104893998	Coding Exon 2	Point, Nonsense TGG to TAG	0	Paloneva et al., 2002
D86V	Frontotemporal Dementia	FTD : Unclear Pathogenicity	Unknown; MRI of a patient carrying both the Y38C and D86V variants, showed cortical atrophy, thinning of the corpus callosum, periventricular white-matter abnormalities,ventricular enlargement and probable globus pallidus calcification.	Decreased cell-surface expression and defective N-linked glycosylation.		Coding Exon 2	Point, Missense GAC to GTC	0	Guerreiro et al., 2013
D87N	Alzheimer's Disease	AD : Possible Risk Modifier	Typical AD pathology in single described case (Braak Stage 6).	Decreased binding to lipoproteins in cell-free assay, but increased ligand-stimulated activation in reporter cell line.	rs142232675	Coding Exon 2	Point, Missense GAT to AAT	0	Guerreiro et al., 2013
G90VfsX99 (TREM2 269delG)	Nasu-Hakola Disease	NHD : Pathogenic	Unknown; MRI showed leukoencephalopathy and cerebral atrophy.	Unknown.	rs386834140	Coding Exon 2	Deletion GGT to GTG	0	Klünemann et al., 2005
T96K	Frontotemporal Dementia	FTD : Possible Risk Modifier	Unknown; carriers of the T96K/W191X/L211P variants have lower levels of sTREM2 in CSF, compared with noncarriers.	Increased binding to cell-derived ligands and increased activation by phospholipids seen in reporter cell line.	rs2234253	Coding Exon 2	Point, Missense ACG to AAG	0	Thelen et al., 2014
R98W		AD : Unclear Pathogenicity, FTD : Unclear Pathogenicity	Unknown.	Predicted to be probably damaging by PolyPhen2.	rs147564421	Coding Exon 2	Point, Missense CGG to TGG	0	Guerreiro et al., 2013
A105RfsX84 (TREM2 313delG)	Nasu-Hakola Disease	NHD : Pathogenic	Unknown; imaging showed cerebral atrophy, leukoencephalopathy, thinning of the corpus callosum, basal ganglia calcification.	Unknown.	rs386834141	Coding Exon 2	Deletion GCG to CGG	0	Klünemann et al., 2005
A105T	Primary Progressive Aphasia, Semantic Dementia	FTD : Unclear Pathogenicity	Unknown.	Predicted to be neutral by SIFT and by the PolyPhen 2 HumVar algorithm, but to be possibly damaging by PolyPhen2 HumDiv.		Coding Exon 2	Point, Missense GCG to ACG	0	Thelen et al., 2014
A105V		AD : Not Pathogenic	Unknown.	Unknown.	rs145080901	Coding Exon 2	Point, Missense GCG to GTG	0	Sims et al., 2017; Jin et al., 2015
S116C		AD : Unclear Pathogenicity, FTD : Unclear Pathogenicity	Unknown.	Cell-surface expression similar to that of wild-type TREM2 heterologously expressed in HEK293 cells.		Coding Exon 2	Point, Missense AGT to TGT	0	Borroni et al., 2014
V126G	Nasu-Hakola Disease	NHD : Pathogenic	Unknown; MRI showed leukoencephalopathy with sparing of arcuate fibers, cerebral atrophy, and thinning of the corpus callosum.	Poor cell-surface expression and defective for N-linked glycosylation in the Golgi.	rs121908402	Coding Exon 2	Point, Missense GTG to GGG	0	Klünemann et al., 2005
A130S		AD : Unclear Pathogenicity	Unknown.	Normal protein maturation when heterologously expressed in HEK293 cells.		Coding Exon 2	Point, Missense GCA to TCA	0	Sirkis et al., 2016
A130V		AD : Unclear Pathogenicity	Unknown.	Predicted by SIFT to be damaging.	rs201280312	Coding Exon 2	Point, Missense GCA to GTA	0	Jiao et al., 2014
D131D		AD : Not Pathogenic	Not applicable.	Unknown.	rs139607688	Coding Exon 3	Point, Silent GAC to GAT	0	Sims et al., 2017
L133L		AD : Unclear Pathogenicity, FTD : Unclear Pathogenicity	Unknown.	Unknown.	rs144250872	Coding Exon 3	Point, Silent CTG to CTT	0	Cuyvers et al., 2014
D134G	Frontotemporal Dementia, Nasu-Hakola Disease	NHD : Pathogenic, FTD : Unclear Pathogenicity	Brain atrophy.	Unknown.	rs28939079	Coding Exon 3	Point, Missense GAT to GGT	0	Paloneva et al., 2002
R136Q	Logopenic Progressive Aphasia	AD : Not Pathogenic, FTD : Unclear Pathogenicity	Unknown.	Normal protein maturation, slightly reduced cell-surface expression in HEK293 cells.	rs149622783	Coding Exon 3	Point, Missense CGG to CAG	0	Sims et al., 2017
R136W		AD : Unclear Pathogenicity	Unknown.	Normal protein maturation, decreased total and cell-surface expression in HEK 293 cells; when stimulated by phospholipids, reporter cells expressing the R136W variant responded similarly to cells expressing wild-type TREM2.	rs772641807	Coding Exon 3	Point, Missense CGG to TGG	0	Jin et al., 2014
E151K		AD : Not Pathogenic	Unknown.	Normal protein maturation but reduction in overall expression in HEK 293 cells; when stimulated by phospholipids, reporter cells expressing the E151K variant responded similarly to cells expressing wild-type TREM2.	rs79011726	Coding Exon 3	Point, Missense GAG to AAG	0	Jonsson et al., 2013; Sims et al., 2017
H157Y	Alzheimer's Disease	AD : Possible Risk Modifier	Unknown.	Increases shedding of sTREM2. Reduces activation in response to phospholipid ligands and decreases phagocytosis.	rs2234255	Coding Exon 3	Point, Missense CAC to TAC	0	Jiang et al., 2016; Jiang et al., 2016; Sims et al., 2017
S162R		AD : Unclear Pathogenicity, FTD : Unclear Pathogenicity	Unknown.	Normal protein maturation in HEK293 cells.	rs371702633	Coding Exon 4	Point, Missense AGC to AGG	0	Cuyvers et al., 2014; Sirkis et al., 2016
S183C		AD : Unclear Pathogenicity	Unknown.	Predicted to be possibly damaging by PolyPhen2.	rs200820365	Coding Exon 4 of transcript variant 2	Point, Missense AGC to TGC	0	Jiang et al., 2016
K186N	Nasu-Hakola Disease	NHD : Pathogenic	Brain atrophy.	Predicted to result in defects in signal transduction.	rs28937876	Coding Exon 4	Point, Missense AAG to AAT	0	Paloneva et al., 2002
W191X	Alzheimer's Disease	AD : Unclear Pathogenicity	Unknown.	Unknown.	rs2234258	Coding Exon 4 of transcript variant 2	Point, Nonsense TGG to TAG	0	Jin et al., 2015
A192T		AD : Not Pathogenic	Unknown.	Predicted to be possibly damaging by Polyphen2.	rs150277350	Coding Exon 4	Point, Missense GCC to ACC	0	Sims et al., 2017; Jiang et al., 2016
A196T		AD : Unclear Pathogenicity	Unknown.	Unknown.		Coding Exon 4	Point, Missense GCA to ACA	0	Sirkis et al., 2016
W198X	Behavioral variant FTD	FTD : Pathogenic	Unknown; frontal lobe atrophy seen on MRI.	Premature truncation.		Coding Exon 4	Point, Nonsense TGG to TGA	0	Giraldo et al., 2013
W200C		AD : Unclear Pathogenicity	Unknown.	Predicted to be probably damaging by Polyphen2.		Coding Exon 4 of transcript variant 2	Point, Missense TGG to TGC	0	Jiang et al., 2016
E202D		AD : Unclear Pathogenicity	Unknown.	Unknown.	rs530314472	Coding Exon 4 of transcript variant 2	Point, Missense GAG to GAT	0	Jin et al., 2014; Jin et al., 2015
L205P		AD : Unclear Pathogenicity	Unknown.	Predicted by SIFT to be damaging, but by Polyphen2 to be benign.		Coding Exon 4 of transcript variant 2	Point, Missense CTG to CCG	0	Ghani et al., 2016
L211P	Alzheimer's Disease, Frontotemporal Dementia	AD : Possible Risk Modifier, FTD : Possible Risk Modifier	Unknown; lower levels of sTREM2 in CSF of T96K/W191X/L211P carriers.	Predicted tolerated in silico by SIFT and benign by PolyPhen-2.	rs2234256	Coding Exon 4	Point, Missense CTG to CCG	0	Jin et al., 2015
H215Q		AD : Unclear Pathogenicity	Unknown.	Unknown.		Coding Exon 4	Point, Missense CAT to CAG	0	Jin et al., 2014
G219C		AD : Unclear Pathogenicity	Unknown.	Predicted by SIFT to be damaging but by Polyphen2 to be benign.	rs768583708	Coding Exon 4 of transcript variant 2	Point, Missense GGT to TGT	0	Ghani et al., 2016
T223I		AD : Not Pathogenic, FTD : Unclear Pathogenicity	Unknown.	Predicted by Polyphen2 to be benign, by SIFT to be tolerated and by SNPs&Go to be neutral; normal protein maturation in HEK293 cells.	rs138355759	Coding Exon 4	Point, Missense ACT to ATT	0	Sims et al., 2017
c.40+3 delAGG	Frontotemporal Dementia	FTD : Pathogenic	Unknown; MRI showed brain atrophy, including thinning of the corpus callosum.	Reduction in the level of TREM2 transcripts.		Non-Coding Intron 1	Deletion	0	Chouery et al., 2008
c.482+1 G>A	Progressive Nonfluent Aphasia	FTD : Pathogenic	Unknown; MRI showed periventricular white-matter hyperintensities, enlargement of the lateral ventricles, and thinning of the corpus callosum.	Unknown.		Non-Coding Intron 3	Point	0	Chee et al., 2017
c.482+2 T>C	Frontotemporal Dementia, Nasu-Hakola Disease	NHD : Pathogenic, FTD : Unclear Pathogenicity	Unknown; imaging showed brain atrophy, basal ganglia calcification, and hypoperfusion in the frontotemporal cortex of NHD patient.	Exon 3 skipping, with deletion of exons 2 and/or 4, and the presence of premature or original stop codons; two truncated TREM2 protein products detected, which are likely to be nonfunctional.	rs386834144	Non-Coding Intron 3	Point	0	Paloneva et al., 2002; Numasawa et al., 2011
rs2234258		AD : Unclear Pathogenicity, FTD : Unclear Pathogenicity	Unknown.	Unknown.	rs2234258	Non-Coding 3' UTR	Point	0	Cuyvers et al., 2014
rs7748513	Alzheimer's Disease	AD : Possible Risk Modifier	Unknown.	Unknown.	rs7748513	Non-Coding Intron 2	Point	0	Reitz et al., 2013
rs7748777	Alzheimer's Disease, ~ 1 year follow-up	AD : Possible Risk Modifier	Unknown.	Unknown.	rs7748777	Non-Coding Upstream	Point	0	Wang et al., 2015
rs9357347	Alzheimer's Disease	AD : Possible Risk Modifier	Unknown.	Predicted to influence transcription factor binding; 6 percent increase in expression of TREM2 and TREML1 in temporal cortex.	rs9357347	Non-Coding Intergenic - TREM locus	Point	0	Carrasquillo et al., 2017