GFAP

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

Basic information

Region (hg38): 17:44903158-44916937

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Alexander disease	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	15409268; 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 (356 variants)
• Alexander disease (131 variants)
• Inborn genetic diseases (23 variants)
• not specified (19 variants)
• Primary ciliary dyskinesia 17 (10 variants)
• Primary ciliary dyskinesia (8 variants)
• GFAP-related condition (6 variants)
• Progressive ventriculomegaly (1 variants)
• GFAP-related disorders (1 variants)
• Seizure;Intellectual disability (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	32	9	43
missense	30	15	124	10	2	181
nonsense			11			11
start loss						0
frameshift		1	6			7
inframe indel		1	3			4
splice donor/acceptor (+/-2bp)			3			3
splice region			6	5	2	13
non coding		1	17	36	32	86
Total	30	18	166	78	43

Highest pathogenic variant AF is 0.00000658

Variants in GFAP

This is a list of pathogenic ClinVar variants found in the GFAP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-44903401-G-A		Primary ciliary dyskinesia 17	Uncertain significance (Jan 13, 2018)
17-44903502-C-T		Primary ciliary dyskinesia 17	Uncertain significance (Jan 13, 2018)
17-44903550-C-T		Primary ciliary dyskinesia 17	Uncertain significance (Jan 13, 2018)
17-44903556-T-C		Primary ciliary dyskinesia 17	Uncertain significance (Jan 12, 2018)
17-44903601-C-A		Primary ciliary dyskinesia 17	Uncertain significance (Jan 12, 2018)
17-44903604-C-T		Primary ciliary dyskinesia 17	Uncertain significance (Jan 12, 2018)
17-44903606-C-A		Primary ciliary dyskinesia 17	Uncertain significance (Jan 13, 2018)
17-44903606-C-T		Primary ciliary dyskinesia • Primary ciliary dyskinesia 17	Uncertain significance (Jan 13, 2018)
17-44903612-G-A		Primary ciliary dyskinesia 17	Uncertain significance (Jan 13, 2018)
17-44903638-G-A		Primary ciliary dyskinesia 17	Uncertain significance (Jan 12, 2018)
17-44905727-G-A		Primary ciliary dyskinesia	Likely benign (Jun 14, 2016)
17-44905825-A-G		Primary ciliary dyskinesia	Likely benign (Jun 14, 2016)
17-44906273-G-A		Primary ciliary dyskinesia	Likely benign (Jun 14, 2016)
17-44906346-C-T		Primary ciliary dyskinesia	Likely benign (Jun 14, 2016)
17-44906533-A-T		Primary ciliary dyskinesia	Likely benign (Jun 14, 2016)
17-44907009-G-A		Primary ciliary dyskinesia	Likely benign (Jun 14, 2016)
17-44907315-G-C			not provided (-)
17-44907319-G-C		Primary ciliary dyskinesia	Benign/Likely benign (Jun 14, 2016)
17-44907331-C-T		Alexander disease	Benign/Likely benign (Jun 14, 2016)
17-44907369-T-A		Alexander disease	not provided (-)
17-44907382-TA-T			Uncertain significance (Jan 30, 2024)
17-44907384-A-G			Uncertain significance (Jan 01, 2017)
17-44907397-G-T			Likely benign (May 17, 2023)
17-44907398-A-T			Uncertain significance (Dec 02, 2021)
17-44907407-G-A			Likely benign (Nov 03, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GFAP	protein_coding	protein_coding	ENST00000586793	7	11930

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000146	0.854	125719	0	29	125748	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.929	233	276	0.843	0.0000173	2793
Missense in Polyphen		72	105.15	0.68475		1117
Synonymous	2.28	83	114	0.728	0.00000662	915
Loss of Function	1.48	12	19.0	0.633	0.00000105	196

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000488	0.000486
Ashkenazi Jewish	0.000102	0.0000992
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000887	0.0000879
Middle Eastern	0.000163	0.000163
South Asian	0.000131	0.000131
Other	0.00	0.00

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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