GRN Gene (Granulin Precursor): Genetics, Function, and Clinical Significance
Comprehensive resource on the GRN gene, its associated diseases, expression patterns, mutations, and protein function.
Gene Information Card
| Symbol | GRN |
|---|---|
| Full Name | Granulin Precursor |
| Gene Type | Protein coding |
| Chromosomal Location | 17q21.31 |
| NCBI Gene ID | 2896 ncbi.nlm.nih.gov/gene/2896 |
| Ensembl ID | ENSG00000030582 |
| UniProt ID | P28799 |
| OMIM ID | 138945 |
| HGNC ID | 4601 |
| Aliases | CLN11, GEP, GP88, PCDGF, PEPI, PGRN |
Description
The GRN gene encodes progranulin, a secreted glycoprotein that undergoes proteolytic cleavage to generate multiple granulin peptides. Progranulin is involved in various cellular processes including inflammation, wound healing, and neuronal survival. Mutations in GRN are associated with frontotemporal dementia (FTD) and neuronal ceroid lipofuscinosis (NCL).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Frontotemporal Dementia (FTD) | Haploinsufficiency due to loss-of-function mutations leads to reduced progranulin levels, causing neurodegeneration. | OMIM, ClinVar |
| Neuronal Ceroid Lipofuscinosis 11 (CLN11) | Biallelic mutations cause complete loss of progranulin, leading to lysosomal storage disorder. | OMIM, ClinVar |
| Alzheimer's Disease (risk modifier) | GRN variants may influence neuroinflammation and amyloid pathology, though not a direct cause. | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | High | High expression in neurons and microglia |
| Lung | Moderate | Expressed in alveolar macrophages |
| Liver | Moderate | Hepatocyte expression |
| Kidney | Low | Tubular cells |
| Spleen | Moderate | Immune cells |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | High | Neuronal model |
| U87 (glioblastoma) | High | Glial cells |
| HepG2 (hepatocellular carcinoma) | Moderate | Liver cancer cell line |
| A549 (lung carcinoma) | Low | Epithelial cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1477C>T (p.Arg493*) | Nonsense | Rare | Loss-of-function, haploinsufficiency |
| c.675_676delCA (p.Thr225SerfsTer28) | Frameshift | Rare | Loss-of-function, haploinsufficiency |
| c.26C>A (p.Ala9Asp) | Missense | Rare | Loss-of-function, reduced secretion |
| c.911G>A (p.Arg304His) | Missense | Rare | Loss-of-function, reduced secretion |
Mutation functional classification
Loss of Function (LOF)
Most GRN mutations are loss-of-function, leading to haploinsufficiency (FTD) or complete deficiency (CLN11).
Gain of Function (GOF)
No evidence of gain-of-function mutations in GRN.
Dominant Negative (DN)
No evidence of dominant-negative effects; disease is primarily due to reduced protein levels.
View complete mutation data：
Gene Ontology (GO)
| • growth factor activity | • protein binding |
| • extracellular region | • lysosome |
| • regulation of cell proliferation | • inflammatory response |
Pathways
• Lysosomal degradation pathway
• Neuroinflammation signaling
• Wound healing response
Protein Summary
Progranulin (PGRN) is a secreted glycoprotein that is cleaved into granulin peptides. It plays roles in cell growth, inflammation, and neuronal survival. In the brain, PGRN is expressed in neurons and microglia, and its deficiency leads to neurodegeneration. PGRN also functions as a lysosomal chaperone, and its loss causes lysosomal dysfunction.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GRN Knockout HEK293 Cell Line | EDJ-KQ3553 | Human | 2896 | Details Get a Quote |
| GRN Knockout A-549 Cell Line | EDJ-KQ25411 | Human | 2896 | Details Get a Quote |
| GRN Knockout HCT 116 Cell Line | EDJ-KQ25412 | Human | 2896 | Details Get a Quote |
| GRN Knockout HeLa Cell Line | EDJ-KQ25413 | Human | 2896 | Details Get a Quote |
