GFAP
Chr 17ADglial fibrillary acidic protein
Also known as: ALXDRD
The protein forms intermediate filaments in mature astrocytes and serves as a specific marker for these glial cells during development. Mutations cause Alexander disease, a rare astrocyte disorder of the central nervous system, inherited in an autosomal dominant pattern. The pathogenic mechanism involves a dominant-negative effect where mutant protein disrupts normal astrocyte function.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports gain-of-function. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
GFAP · 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
A Phase 2b/3 Clinical Study Evaluating T3D-959 in Mild-to-Moderate Alzheimer's Disease Subjects
NOT YET RECRUITINGA Study of ANAVEX3-71 in Adults With Schizophrenia
ACTIVE NOT RECRUITINGBiomarker-based Trial of NPC-1 for Alzheimer's Pathology
RECRUITINGA Patient-tailored Genetic/Biomarker/iPSC Combined Approach in ALS - PERMEALS
RECRUITINGIndole-3-PROpionic Acid Clinical Trials - Multiple Sclerosis
RECRUITINGSafety, Tolerability and Exploratory Efficacy of EC5026 in Parkinson's Disease (STEP Study)
RECRUITINGEvaluation of the Efficacy of Calcium a -Ketoglutarate(AKG-Ca) in Improving Human Aging
ACTIVE NOT RECRUITINGDevelopment of a Database to Investigate Digital and Blood-Based Biomarkers and Their Relationship to Tau and Amyloid PET Imaging in Older Participants Who Are Cognitively Normal (CN), Have Mild Cognitive Impairment (MCI), or Have Mild-to-Moderate AD Dementia
RECRUITINGA Nutritional Intervention for Body, Brain, and Longevity Effects (NIBBLE)
NOT YET RECRUITINGThe Signature of Alzheimer's Disease in Subjective Cognitive Decline
RECRUITINGSafety and Efficacy of AMT-130 in European Adults With Early Manifest Huntington's Disease
ACTIVE NOT RECRUITINGStudy to Evaluate the Efficacy and Safety of KDS2010 in Patients With Alzheimer's Disease With Mild Cognitive Impairment and Mild Dementia Due to Alzheimer's Disease
RECRUITINGExternal Resources
Links to major genomics databases and tools