SORL1 (Sortilin-related receptor) variants and mutations

SORL1 (also known as Sortilin-related receptor) is a human protein-coding gene encoding a sortilin-related receptor protein. It sorts APP and other cargo between endosomes, Golgi, and the cell surface, helping keep APP away from amyloidogenic processing compartments. Rare loss-of-function variants and common variation can substantially increase Alzheimer disease risk. This analysis covers 2,870 SORL1 variants and mutations. Of these, 76% have computational variant effect predictions. Disease context includes Alzheimer disease, dementia, and early-onset autosomal dominant Alzheimer disease. Example SORL1 variants include A2E, A2G, and A2T.

Variant analysis overview

Gene: SORL1
Protein: Sortilin-related receptor
UniProt accession: Q92673
Organism: Homo sapiens
Variants analyzed: 2870
Variant scope: all variants
Completed: 2026-08-21

Variant and mutation evidence

Variant composition: 2,460 unspecified-consequence records; 257 missense variants; 104 synonymous variants; 27 frameshift variants; 16 stop-gained variants; 2 in-frame deletions; 1 in-frame insertions; 1 splice-region variants; 2 substitution
Prediction scores: 2,177 variants have prediction scores (76% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: Alzheimer disease, dementia, early-onset autosomal dominant Alzheimer disease, neurodegenerative disease, smoking initiation, liver disorder, complex hereditary spastic paraplegia, cannabis dependence, late-onset Alzheimers disease, wet macular degeneration, Microscopic hematuria, breast disorder.

Protein structure and variant hotspots

Protein features: 1 transmembrane segments; 19 domains; 29 post-translational modification sites.
Structural context: 1,942 variants have structural context.
PTM context: 31 variants overlap post-translational modification sites.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.

Notable SORL1 variants

Examples include A2E, A2G, A2T, A2S, A2V, A2A, T3A, T3K. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

SORL1 analysis run — SORL1 (2,870 variants) — completed 2026-08-21