GeneBe

GFAP

glial fibrillary acidic protein, the group of Intermediate filaments Type III

Basic information

Region (hg38): 17:44903159-44916937

Links

ENSG00000131095 ∙ NCBI:2670 ∙ OMIM:137780 ∙ HGNC:4235 ∙ Uniprot:P14136 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • Alexander disease (Definitive), mode of inheritance: AD
  • Alexander disease (Strong), mode of inheritance: AD
  • Alexander disease type II (Supportive), mode of inheritance: AD
  • Alexander disease (Strong), mode of inheritance: AD
  • Alexander disease (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Alexander diseaseADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingNeurologic15409268; 13665382; 11138011; 11567214; 12034785; 12447932; 12034796; 14557587; 12975300; 15732097; 15732098; 16505300; 17894839; 17438228; 20301351; 21822933; 21917775; 21987397; 22118268; 22198646; 22488673; 22619055; 23254569; 23364391; 23634874

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GFAP gene.

  • not_provided (421 variants)
  • Alexander_disease (166 variants)
  • Inborn_genetic_diseases (47 variants)
  • not_specified (29 variants)
  • GFAP-related_disorder (24 variants)
  • Progressive_ventriculomegaly (1 variants)
  • Metachromatic_leukodystrophy (1 variants)
  • Spastic_paraplegia,_intellectual_disability,_nystagmus,_and_obesity (1 variants)
  • Scoliosis (1 variants)
  • Hereditary_spastic_paraplegia (1 variants)
  • See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GFAP gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002055.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
5
clinvar
47
clinvar
6
clinvar
 58
missense
41
clinvar
31
clinvar
237
clinvar
23
clinvar
1
clinvar
 333
nonsense
11
clinvar
 11
start loss
0
frameshift
1
clinvar
1
clinvar
9
clinvar
 11
splice donor/acceptor (+/-2bp)
1
clinvar
6
clinvar
 7
Total 43 32 268 70 7

Highest pathogenic variant AF is 0.000006816058

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
GFAPprotein_codingprotein_codingENST00000586793 711930
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.000001460.8541257190291257480.000115
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.9292332760.8430.00001732793
Missense in Polyphen72105.150.684751117
Synonymous2.28831140.7280.00000662915
Loss of Function1.481219.00.6330.00000105196

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0004880.000486
Ashkenazi Jewish0.0001020.0000992
East Asian0.0001630.000163
Finnish0.00004620.0000462
European (Non-Finnish)0.00008870.0000879
Middle Eastern0.0001630.000163
South Asian0.0001310.000131
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: GFAP, a class-III intermediate filament, is a cell- specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells.;
Disease
DISEASE: Alexander disease (ALXDRD) [MIM:203450]: A rare disorder of the central nervous system. The most common form affects infants and young children, and is characterized by progressive failure of central myelination, usually leading to death within the first decade. Infants with Alexander disease develop a leukodystrophy with macrocephaly, seizures, and psychomotor retardation. Patients with juvenile or adult forms typically experience ataxia, bulbar signs and spasticity, and a more slowly progressive course. Histologically, Alexander disease is characterized by Rosenthal fibers, homogeneous eosinophilic inclusions in astrocytes. {ECO:0000269|PubMed:11138011, ECO:0000269|PubMed:11567214, ECO:0000269|PubMed:11595337, ECO:0000269|PubMed:12034785, ECO:0000269|PubMed:12034796, ECO:0000269|PubMed:12581808, ECO:0000269|PubMed:12944715, ECO:0000269|PubMed:12975300, ECO:0000269|PubMed:15030911, ECO:0000269|PubMed:15732097, ECO:0000269|PubMed:17043438, ECO:0000269|PubMed:17805552, ECO:0000269|PubMed:17894839, ECO:0000269|PubMed:17934883, ECO:0000269|PubMed:17960815, ECO:0000269|PubMed:18004641, ECO:0000269|PubMed:18079314, ECO:0000269|PubMed:19412928, ECO:0000269|PubMed:20359319, ECO:0000269|PubMed:21917775, ECO:0000269|PubMed:23364391, ECO:0000269|PubMed:23743246, ECO:0000269|PubMed:24742911}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Jak-STAT signaling pathway - Homo sapiens (human);Neural Crest Differentiation;Spinal Cord Injury;Signaling by ERBB4;Signal Transduction;prion pathway;Nuclear signaling by ERBB4;Signaling by ERBB4;Signaling by Receptor Tyrosine Kinases (Consensus)

Recessive Scores

pRec
0.955

Intolerance Scores

loftool
0.0205
rvis_EVS
0.62
rvis_percentile_EVS
83.47

Haploinsufficiency Scores

pHI
0.618
hipred
N
hipred_score
0.442
ghis
0.427

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.527

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Gfap
Phenotype
growth/size/body region phenotype; muscle phenotype; homeostasis/metabolism phenotype; immune system phenotype; cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);

Gene ontology

Biological process
response to wounding;positive regulation of Schwann cell proliferation;negative regulation of neuron projection development;astrocyte development;extracellular matrix organization;neuron projection regeneration;regulation of protein complex assembly;intermediate filament organization;regulation of neurotransmitter uptake;Bergmann glial cell differentiation;long-term synaptic potentiation;regulation of chaperone-mediated autophagy
Cellular component
cytoplasm;lysosome;cytosol;intermediate filament;myelin sheath;cell body;astrocyte end-foot;cytoplasmic side of lysosomal membrane
Molecular function
integrin binding;structural constituent of cytoskeleton;protein binding;kinase binding;identical protein binding