Mutations

SORL1 R11P

Overview

Clinical Phenotype: Alzheimer's Disease
Position: (GRCh38/hg38):Chr11:121452363 G>C
Position: (GRCh37/hg19):Chr11:121323072 G>C
dbSNP ID: rs147575757
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected Protein Consequence: Missense
Codon Change: CGA to CCA
Reference Isoform: SORL1 Isoform 1 (2214 aa)
Genomic Region: Exon 1

Findings

This variant was found in two of 332 Alzheimer’s cases and none of 676 controls in a study of North American and British Caucasians, where its association with AD did not reach statistical significance (Sassi et al., 2016).

Subsequently, the R11P variant was reported in seven of 5198 AD cases and two of 4491 controls in a dataset from the Alzheimer’s Disease Sequencing Project, consisting of subjects of non-Hispanic Caucasian ancestry from whom whole-exome sequencing data were available (Campion et al., 2019).

No additional carriers were found among 1779 AD cases and 1273 controls from the Alzheimer Disease Exome Sequencing France project, 640 cases and 1268 controls from a multi-center Dutch sample, or 1256 cases and 1938 controls from the European Early Onset Dementia Consortium (Campion et al., 2019).

Functional Consequences

The variant was predicted to be deleterious by SIFT, neutral by Mutation Taster, and benign by PolyPhen-2 (Campion et al., 2019).

Last Updated: 18 Jul 2024

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References

Paper Citations

  1. Sassi C, Ridge PG, Nalls MA, Gibbs R, Ding J, Lupton MK, Troakes C, Lunnon K, Al-Sarraj S, Brown KS, Medway C, Lord J, Turton J, ARUK Consortium, Morgan K, Powell JF, Kauwe JS, Cruchaga C, Bras J, Goate AM, Singleton AB, Guerreiro R, Hardy J. Influence of Coding Variability in APP-Aβ Metabolism Genes in Sporadic Alzheimer's Disease. PLoS One. 2016;11(6):e0150079. Epub 2016 Jun 1 PubMed.
  2. Campion D, Charbonnier C, Nicolas G. SORL1 genetic variants and Alzheimer disease risk: a literature review and meta-analysis of sequencing data. Acta Neuropathol. 2019 Aug;138(2):173-186. Epub 2019 Mar 25 PubMed.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. Sassi C, Ridge PG, Nalls MA, Gibbs R, Ding J, Lupton MK, Troakes C, Lunnon K, Al-Sarraj S, Brown KS, Medway C, Lord J, Turton J, ARUK Consortium, Morgan K, Powell JF, Kauwe JS, Cruchaga C, Bras J, Goate AM, Singleton AB, Guerreiro R, Hardy J. Influence of Coding Variability in APP-Aβ Metabolism Genes in Sporadic Alzheimer's Disease. PLoS One. 2016;11(6):e0150079. Epub 2016 Jun 1 PubMed.

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