GFAP

Chr 17

glial fibrillary acidic protein

Also known as: ALXDRD

This gene encodes one of the major intermediate filament proteins of mature astrocytes. It is used as a marker to distinguish astrocytes from other glial cells during development. Mutations in this gene cause Alexander disease, a rare disorder of astrocytes in the central nervous system. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Oct 2008]

Primary Disease Associations & Inheritance

UniProtAlexander disease
294
ClinVar variants
20
Pathogenic / LP
0.00
pLI score
12
Active trials
Clinical SummaryGFAP
🧬
Gene-Disease Validity (ClinGen)
Alexander disease · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
20 Pathogenic / Likely Pathogenic· 161 VUS of 294 total submissions
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (2)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.03LOEUF
pLI 0.000
Z-score 1.48
OE 0.63 (0.411.03)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.93Z-score
OE missense 0.84 (0.760.94)
233 obs / 276.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.63 (0.411.03)
00.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.84 (0.760.94)
00.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.73
01.21.6
LoF obs/exp: 12 / 19.0Missense obs/exp: 233 / 276.5Syn Z: 2.28

ClinVar Variant Classifications

294 submitted variants in ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic11
VUS161
Likely Benign72
Benign28
Conflicting13
9
Pathogenic
11
Likely Pathogenic
161
VUS
72
Likely Benign
28
Benign
13
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
6
2
0
9
Likely Pathogenic
1
9
1
0
11
VUS
13
128
20
0
161
Likely Benign
0
10
19
43
72
Benign
0
4
20
4
28
Conflicting
13
Total151576247294

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

Gene2Phenotype Curations

GFAP-related Alexander disease

definitive
ADDominant NegativeAltered Gene Product Structure
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

No OMIM entries found.

📖
GeneReview available — GFAP
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Amyotrophic Lateral Sclerosis (ALS)

A Patient-tailored Genetic/Biomarker/iPSC Combined Approach in ALS - PERMEALS

RECRUITING
NCT06917924A.O.U. Città della Salute e della ScienzaStarted 2023-05-20
lumbar puncture
Cerebral Blood FlowAPOE 4

A Nutritional Intervention for Body, Brain, and Longevity Effects (NIBBLE)

NOT YET RECRUITING
NCT06682767Phase NACedars-Sinai Medical CenterStarted 2026-03
FMD1 (LNT22-017-1)Dietary Guidance
Dentatorubral-Pallidoluysian Atrophy

Dentatorubral-pallidoluysian Atrophy Natural History and Biomarkers Study

RECRUITING
NCT06273150University College, LondonStarted 2022-05-01
Positive genetic test for pathological expansion in ATN1
ALS (Amyotrophic Lateral Sclerosis)

This Study Evaluates the Safety, Target Engagement, and Preliminary Efficacy of Galunisertib (TGF-βR1/ALK5 Inhibitor)Combined With Nerandomilast (PDE4 Inhibitor) in GREM2-positive ALS, a Biomarker-defined Subgroup Hypothesized to Reflect Heightened TGF-β/SMAD-driven Astrocytic and Fibrotic Signaling

NOT YET RECRUITING
NCT07321860Phase PHASE2, PHASE3Gipfel Life Sciences GmbHStarted 2026-06-30
Galunisertib + Nerandomilast Combination
Neurodegenerative DisordersParkinson DiseaseAlzheimer Disease

An Innovative Method in SAliva Samples for the Early Differential Diagnosis of High-impact NeuroDegenerative Diseases Through Raman Spectroscopy

ENROLLING BY INVITATION
NCT06875739Fondazione Don Carlo Gnocchi OnlusStarted 2025-02-14
Alzheimer Disease, Late OnsetMild Cognitive ImpairmentSubjective Cognitive Decline

Establish Diagnostic and Prognostic Models for Preclinical AD Patients Based on Multimodal MRI, Behavioral, Genetic, and Plasma Biomarkers

RECRUITING
NCT06561906The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolStarted 2020-09-01
Multimodal magnetic resonance imaging scanning, behavioral, genetic and plasma biomarker testing
Glioma

Clinical Study for the Safety and Therapeutic Efficacy of the AI-QMMM Designed TamavaqTM Personalised Vaccine in Patients With Newly Diagnosed Glioma.

RECRUITING
NCT07077616Phase EARLY_PHASE1Biogenea Pharmaceuticals Ltd.Started 2025-07-01
Biological: personalized vaccine Based on genetic and transcriptional sequencing information, personalized peptide vaccines would be designed and produced;
Alzheimer's Disease

A Phase 2b/3 Clinical Study Evaluating T3D-959 in Mild-to-Moderate Alzheimer's Disease Subjects

NOT YET RECRUITING
NCT06964230Phase PHASE2, PHASE3T3D Therapeutics, Inc.Started 2026-10-26
T3D-959Placebo Comparator
Huntington Disease

Safety and Efficacy of AMT-130 in European Adults With Early Manifest Huntington's Disease

ACTIVE NOT RECRUITING
NCT05243017Phase PHASE1, PHASE2UniQure Biopharma B.V.Started 2021-10-07
intra-striatal rAAV5-miHTT
Parkinson&#39;s Disease (PD)

Safety, Tolerability and Exploratory Efficacy of EC5026 in Parkinson's Disease (STEP Study)

RECRUITING
NCT07142044Phase PHASE1, PHASE2EicOsis Human Health Inc.Started 2025-10
EC5026 oral tabletPlacebo
Amyotrophic Lateral Sclerosis (ALS)

Identification of Early Markers for ALS

RECRUITING
NCT07213440Phase NAInstitut National de la Santé Et de la Recherche Médicale, FranceStarted 2024-09-30
lumbar puncture
Mild Cognitive ImpairmentAlzheimer's DiseaseAlzheimer's Disease, Early Onset

Development 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

RECRUITING
NCT06584357GAP Innovations, PBCStarted 2024-09-26
Biomarker Data CollectionMK6240