GRN
Chr 17granulin precursor
Also known as: CLN11, FTD2, GEP, GP88, PCDGF, PEPI, PGRN
Progranulin is a secreted glycoprotein that regulates cell growth and is important in development, wound healing, and inflammatory responses. Mutations cause frontotemporal dementia and primary progressive aphasia through autosomal dominant inheritance, typically via haploinsufficiency from loss-of-function variants, while biallelic mutations cause autosomal recessive neuronal ceroid lipofuscinosis type 11. The dominant conditions result from reduced progranulin levels leading to neurodegeneration, while the recessive form involves more severe loss of protein function.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Some data sources returned errors (1)
omim: Error: OMIM fetch failed: 429
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
500 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 43 | 1 | 7 | 0 | 51 |
Likely Pathogenic | 15 | 1 | 2 | 0 | 18 |
VUS | 3 | 205 | 16 | 6 | 230 |
Likely Benign | 0 | 3 | 60 | 91 | 154 |
Benign | 0 | 0 | 8 | 0 | 8 |
Conflicting | — | 20 | |||
| Total | 61 | 210 | 93 | 97 | 481 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
GRN · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Phase 1/2 Clinical Trial of LY3884963 in Patients With Frontotemporal Dementia With Progranulin Mutations (FTD-GRN)
ACTIVE NOT RECRUITINGDevelopment of Targeted RNA-Seq for Amyotrophic Lateral Sclerosis Diagnosis
RECRUITINGARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD)
RECRUITINGNatural History and Longitudinal Clinical Assessments in NCL / Batten Disease, the International DEM-CHILD Database
RECRUITINGA Study to Evaluate the Safety and Effect of AVB-101, a Gene Therapy Product, in Subjects With a Genetic Sub-type of Frontotemporal Dementia (FTD-GRN)
RECRUITINGPET Imaging Tau Accumulation in FTLD and Atypical Alzheimer's Using [18F]-PI-2620
RECRUITINGA Study of PBFT02 in Participants With FTD and Mutations in the Granulin Precursor (GRN) or C9ORF72 Genes
RECRUITINGCytokines, Neuroplasticity Modulators, and Biomarkers in Spinal Canal Stenosis and Endoscopic Decompression
NOT YET RECRUITINGTracking and Predicting How Brain Damage Spreads in Neurodegenerative Diseases
ENROLLING BY INVITATIONExternal Resources
Links to major genomics databases and tools