Mutations

TREM2 R62C

Overview

Pathogenicity: Alzheimer's Disease : Unclear Pathogenicity
Clinical Phenotype:
Reference Assembly: GRCh37/hg19
Position: Chr6:41129208 C>T
dbSNP ID: rs201258314
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: CGT to TGT
Reference Isoform: TREM2 Isoform 1 (230 aa)
Genomic Region: Exon 2

Findings

The R62C variant did not associate with Alzheimer’s disease in a cohort from the Alzheimer’s Disease Sequencing Project (5575 AD, 4808 controls; odds ratio 0.58, p = 0.65) (Song et al., 2017) or in a French study of early-onset AD (variant found in one of 726 AD patients and none of 738 controls, p = 0.48) (Pottier et al., 2013).

Neuropathology

No data.

Biological Effect

The arginine-to-cysteine substitution was predicted by PolyPhen2 to be probably damaging (Pottier et al., 2013). 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, and activation by lipid ligands was reduced in cells expressing the R62C variant compared with cells expressing wild-type TREM2 (Song et al., 2017).

 

Last Updated: 07 Feb 2018

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References

Paper Citations

  1. . 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.
  2. . TREM2 R47H variant as a risk factor for early-onset Alzheimer's disease. J Alzheimers Dis. 2013;35(1):45-9. PubMed.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . TREM2 R47H variant as a risk factor for early-onset Alzheimer's disease. J Alzheimers Dis. 2013;35(1):45-9. PubMed.
  2. . 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.

Other mutations at this position

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