GRN
Chr 17ADARgranulin precursor
Also known as: CLN11, FTD2, GEP, GP88, PCDGF, PEPI, PGRN
Granulins are a family of secreted, glycosylated peptides that are cleaved from a single precursor protein with 7.5 repeats of a highly conserved 12-cysteine granulin/epithelin motif. The 88 kDa precursor protein, progranulin, is also called proepithelin and PC cell-derived growth factor. Cleavage of the signal peptide produces mature granulin which can be further cleaved into a variety of active, 6 kDa peptides. These smaller cleavage products are named granulin A, granulin B, granulin C, etc. Epithelins 1 and 2 are synonymous with granulins A and B, respectively. Both the peptides and intact granulin protein regulate cell growth. However, different members of the granulin protein family may act as inhibitors, stimulators, or have dual actions on cell growth. Granulin family members are important in normal development, wound healing, and tumorigenesis. [provided by RefSeq, Jul 2008]
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene — mechanism propensity
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.
References
ClinVar Variant Classifications
829 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 | 97 | 6 | 6 | 1 | 110 |
Likely Pathogenic | 25 | 1 | 2 | 0 | 28 |
VUS | 5 | 307 | 24 | 9 | 345 |
Likely Benign | 0 | 9 | 87 | 153 | 249 |
Benign | 0 | 1 | 15 | 1 | 17 |
Conflicting | — | 36 | |||
| Total | 127 | 324 | 134 | 164 | 785 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →10 pathogenic / likely-pathogenic (of 11) ClinVar copy-number / structural variants overlap GRN — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →
Protein Context — Lollipop Plot
GRN · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD)
RECRUITINGPhase 1/2 Clinical Trial of LY3884963 in Patients With Frontotemporal Dementia With Progranulin Mutations (FTD-GRN)
ACTIVE NOT RECRUITINGCytokines, Neuroplasticity Modulators, and Biomarkers in Spinal Canal Stenosis and Endoscopic Decompression
NOT YET RECRUITINGPET Imaging Tau Accumulation in FTLD and Atypical Alzheimer's Using [18F]-PI-2620
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)
RECRUITINGNatural History and Longitudinal Clinical Assessments in NCL / Batten Disease, the International DEM-CHILD Database
RECRUITINGA Study of PBFT02 in Participants With FTD and Mutations in the Granulin Precursor (GRN) or C9ORF72 Genes
ACTIVE NOT RECRUITINGTracking and Predicting How Brain Damage Spreads in Neurodegenerative Diseases
ENROLLING BY INVITATIONDevelopment of Targeted RNA-Seq for Amyotrophic Lateral Sclerosis Diagnosis
RECRUITINGExternal Resources
Links to major genomics databases and tools