GFAP (Glial Fibrillary Acidic Protein): Structure, Function, and Clinical Significance
A comprehensive biomedical overview of the GFAP gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | GFAP |
|---|---|
| Full Name | Glial fibrillary acidic protein |
| Gene Type | Protein coding |
| Chromosomal Location | 17q21.31 |
| NCBI Gene ID | 2670 ncbi.nlm.nih.gov/gene/2670 |
| Ensembl ID | ENSG00000131095 |
| UniProt ID | P14136 |
| OMIM ID | 137780 |
| HGNC ID | 4235 |
| Aliases | FLJ45472, GFAP, intermediate filament protein |
Description
The GFAP gene encodes glial fibrillary acidic protein, a class-III intermediate filament protein expressed primarily in astrocytes and other glial cells. GFAP is essential for the structural integrity of astrocytes, contributing to cell shape, motility, and signaling. Mutations in GFAP are associated with Alexander disease, a rare neurodegenerative disorder. GFAP also serves as a biomarker for various neurological injuries and diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alexander Disease | Heterozygous missense mutations in GFAP lead to gain-of-function or dominant-negative effects, causing protein aggregation and Rosenthal fiber formation, which disrupt astrocyte function and lead to neurodegeneration. | OMIM #137780; ClinVar; multiple publications |
| Glial Tumors | GFAP expression is used as a diagnostic marker for astrocytic tumors; altered expression and mutations may contribute to tumor progression, though the exact mechanism is not fully defined. | COSMIC; literature |
| Multiple Sclerosis | GFAP levels are elevated in cerebrospinal fluid and serum, reflecting astrocyte damage and reactive gliosis in demyelinating lesions. | ClinVar; literature |
| Traumatic Brain Injury | GFAP is released into blood after brain injury; elevated levels serve as a biomarker for diagnosis and prognosis. | Literature; FDA-approved tests |
| Neurodegenerative Diseases | GFAP upregulation is observed in Alzheimer's disease and other tauopathies, indicating astrocytic activation and neuroinflammation. | Literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | High (e.g., >100 nTPM) | High |
| Spinal Cord | High | High |
| Peripheral Nervous System | Low to Moderate | Low |
| Heart | Not detected | Low |
| Liver | Not detected | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Astrocytes (primary) | High | Major cell type expressing GFAP |
| U87MG (glioblastoma) | High | Astrocytoma cell line |
| U251 (glioma) | High | Astrocytoma cell line |
| SH-SY5Y (neuroblastoma) | Low | Neuronal-like, low GFAP |
| HeLa (cervical carcinoma) | Not detected | Non-glial origin |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R79H | Missense | Rare (found in Alexander disease) | Gain-of-function; protein aggregation |
| R239C | Missense | Common in Alexander disease | Dominant-negative; disrupts filament assembly |
| R416W | Missense | Rare | Gain-of-function; increased aggregation |
| E373K | Missense | Rare | Dominant-negative; altered filament dynamics |
| Deletion of exon 1 | Structural variant | Very rare | Loss-of-function; reduced protein expression |
Mutation functional classification
Loss of Function (LOF)
Complete loss of GFAP function is not commonly observed in disease; homozygous knockout mice show subtle phenotypes, suggesting redundancy with other intermediate filaments. Some rare truncating mutations may lead to haploinsufficiency, but the primary disease mechanism is not loss-of-function.
Gain of Function (GOF)
Most Alexander disease mutations are gain-of-function, leading to abnormal protein accumulation, aggregation, and disruption of astrocyte function. These mutations often increase GFAP stability or promote aberrant filament assembly.
Dominant Negative (DN)
Several mutations act in a dominant-negative manner, interfering with the assembly of normal GFAP filaments and causing toxicity. This is particularly evident in heterozygous mutations that disrupt the rod domain.
View complete mutation data：
Gene Ontology (GO)
| • structural constituent of cytoskeleton | • intermediate filament binding |
| • protein binding | • cell differentiation |
| • astrocyte development | • response to wound healing |
| • neuroinflammatory response |
Pathways
• Intermediate filament organization
• Astrocyte activation and gliosis
• Neuroinflammation signaling
• Cytoskeletal signaling
Protein Summary
GFAP is a 432-amino-acid protein (UniProt P14136) with a molecular weight of ~49.8 kDa. It forms intermediate filaments in astrocytes, providing mechanical support and maintaining cell shape. GFAP is involved in cell communication, blood-brain barrier maintenance, and response to injury. Its expression is upregulated in reactive gliosis. Post-translational modifications, such as phosphorylation, regulate filament dynamics. Mutations in GFAP cause Alexander disease, a leukodystrophy characterized by Rosenthal fibers. GFAP is also a clinical biomarker for brain injury and neurodegeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GFAP Knockout HEK293 Cell Line | EDJ-KQ464 | Human | 2670 | Details Get a Quote |
| GFAP Knockout A-549 Cell Line | EDJ-KQ18773 | Human | 2670 | Details Get a Quote |
| GFAP Knockout HeLa Cell Line | EDJ-KQ53329 | Human | 2670 | Details Get a Quote |
| GFAP Knockout HCT 116 Cell Line | EDJ-KQ70297 | Human | 2670 | Details Get a Quote |
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