Overview

Pathogenicity: Alzheimer's Disease : Unclear Pathogenicity
Reference Assembly: GRCh37/hg19
Position: Chr6:41129237 G>A
dbSNP ID: rs374851046
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Missense
Codon Change: CGC to CAC
Reference Isoform: TREM2 Isoform 1 (230 aa)
Genomic Region: Exon 2

Findings

In a Caucasian cohort, the R52H variant was found in one of 2077 Alzheimer’s patients and none of 1642 cognitively healthy controls (Jin et al., 2014).

Neuropathology

No data.

Biological Effect

The arginine-to-histidine substitution at amino acid 52 was predicted PolyPhen2 to be damaging (Jin et al., 2014). This variant exhibited somewhat lower cell-surface expression than wild-type TREM2 when co-expressed with its adaptor protein DAP12 in a reporter cell line; however activation by purified phospholipids was similar in cells expressing the R52H variant and wild-type TREM2 (Song et al., 2017).

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References

Paper Citations

1. Jin SC, Benitez BA, Karch CM, Cooper B, Skorupa T, Carrell D, Norton JB, Hsu S, Harari O, Cai Y, Bertelsen S, Goate AM, Cruchaga C. Coding variants in TREM2 increase risk for Alzheimer's disease. Hum Mol Genet. 2014 Nov 1;23(21):5838-46. Epub 2014 Jun 4 PubMed.
2. Song W, Hooli B, Mullin K, Jin SC, Cella M, Ulland TK, Wang Y, Tanzi RE, Colonna M. Alzheimer's disease-associated TREM2 variants exhibit either decreased or increased ligand-dependent activation. Alzheimers Dement. 2017 Apr;13(4):381-387. Epub 2016 Aug 9 PubMed.

Further Reading

No Available Further Reading