GFAP

Chr 17

glial fibrillary acidic protein

Also known as: ALXDRD

NCBI Gene: 2670 ENSG00000131095 UniProt: P14136

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.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtAlexander disease

Clinical highlights

Gene-disease validity (ClinGen)

Alexander disease · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

A dominant-negative effect is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

3156

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.03

LOEUF

DN*

Mechanism· G2P

📖

GeneReview available — GFAP

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.03LOEUF

pLI 0.000

Z-score 1.48

OE 0.63 (0.41–1.03)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.93Z-score

OE missense 0.84 (0.76–0.94)

233 obs / 276.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.63 (0.41–1.03)

0≤0.351.4

Missense OE?0.84 (0.76–0.94)

0≤0.61.4

Synonymous OE?0.73

0≤1.21.6

LoF obs/exp: 12 / 19.0Missense obs/exp: 233 / 276.5Syn Z: 2.28

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

VCEP specificationsLeukodystrophyPilot

Panel ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

📖

GeneReview available — GFAP

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Lupus

Exploring Biological Mechanisms Underlying the TEACH Intervention for Adolescents With Lupus

NOT YET RECRUITING

NCT07771088Phase NAThe Hospital for Sick ChildrenStarted 2026-09-01

TEACH

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

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

Frontotemporal DementiaFTDFTD-GRN

A 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)

RECRUITING

NCT06064890Phase PHASE1, PHASE2AviadoBio LtdStarted 2023-08-30

Intrathalamic AAV.PGRN administrationIntrathalamic AVB-101

Down Syndrome Regression Disorder (DSRD)Down Syndrome (Trisomy 21)Neuroinflammatory / Neuropsychiatric Disorder

An Open-Label Phase II Feasibility Study for the Use of Ublituximab in Adults With Down Syndrome Regression Disorder

NOT YET RECRUITING

NCT07812181Phase PHASE2Jonathan SantoroStarted 2026-10-01

Ublituximab

Parkinson's Disease (PD)

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

RECRUITING

NCT07142044Phase PHASE1, PHASE2EicOsis Human Health Inc.Started 2025-11-01