GRN (Progranulin) variants and mutations

GRN (also known as Progranulin) is a human protein-coding gene encoding a progranulin protein. It is secreted and proteolytically processed into granulins and has roles in lysosomal function, inflammation, neuronal survival, and tissue repair. Heterozygous loss-of-function variants cause frontotemporal dementia through progranulin haploinsufficiency, while biallelic loss causes neuronal ceroid lipofuscinosis. This analysis covers 1,037 GRN variants and mutations. Of these, 78% have computational variant effect predictions. Disease context includes neuronal ceroid lipofuscinosis 11, GRN-related frontotemporal lobar degeneration with Tdp43 inclusions, and CLN11 disease. Example GRN variants include M1I, M1T, and M1V.

Variant analysis overview

Gene: GRN
Protein: Progranulin
UniProt accession: P28799
Organism: Homo sapiens
Variants analyzed: 1037
Variant scope: all variants
Completed: 2026-08-21

Variant and mutation evidence

Variant composition: 794 unspecified-consequence records; 98 missense variants; 105 synonymous variants; 16 frameshift variants; 1 protein altering variant; 7 splice-region variants; 4 stop-gained variants; 1 in-frame deletions; 1 in-frame insertions; 10 substitution
Prediction scores: 810 variants have prediction scores (78% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: neuronal ceroid lipofuscinosis 11, GRN-related frontotemporal lobar degeneration with Tdp43 inclusions, CLN11 disease, frontotemporal dementia, adult neuronal ceroid lipofuscinosis, Alzheimer disease, dementia, hereditary disease, amyotrophic lateral sclerosis, neuronal ceroid lipofuscinosis, infantile neuronal ceroid lipofuscinosis, primary progressive aphasia.

Protein structure and variant hotspots

Protein features: 5 post-translational modification sites.
PTM context: 10 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, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable GRN variants

Examples include M1I, M1T, M1V, W2*, T3A, T3I, T3S, T3N. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

GRN analysis run — GRN (1,037 variants) — completed 2026-08-21