GFRA1: GDNF Family Receptor Alpha 1
A key receptor for GDNF signaling in neuronal survival and development
Gene Information Card
| Symbol | GFRA1 |
|---|---|
| Full Name | GDNF family receptor alpha 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 10q25.3 |
| NCBI Gene ID | 2674 ncbi.nlm.nih.gov/gene/2674 |
| Ensembl ID | ENSG00000151892 |
| UniProt ID | P56159 |
| OMIM ID | 601496 |
| HGNC ID | 4243 |
| Aliases | GDNFR, GFR-ALPHA-1, RETL1, TRNR1 |
Description
GFRA1 (GDNF Family Receptor Alpha 1) encodes a glycosylphosphatidylinositol (GPI)-anchored cell surface receptor that binds glial cell line-derived neurotrophic factor (GDNF) and mediates its signaling through the RET receptor tyrosine kinase. This receptor is essential for the survival, proliferation, and differentiation of dopaminergic neurons, motor neurons, and enteric neurons. GFRA1 is also involved in kidney development and spermatogenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hirschsprung disease | Loss-of-function variants impair GDNF-RET signaling, disrupting enteric neuron migration | ClinVar, OMIM |
| Congenital central hypoventilation syndrome | GFRA1 mutations may contribute to autonomic nervous system dysfunction | OMIM |
| Neuroblastoma | GFRA1 overexpression or amplification may promote tumor growth via RET activation | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Kidney | 8.3 | Medium |
| Testis | 6.7 | Low |
| Lung | 4.2 | Low |
| Liver | 1.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 15.2 | Neuroblastoma cell line; high expression |
| HEK293 | 2.1 | Low expression |
| HeLa | 0.8 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.226C>T (p.Arg76Cys) | Missense | Rare | Impaired GDNF binding; associated with Hirschsprung disease |
| c.389G>A (p.Arg130His) | Missense | Rare | Reduced cell surface expression; Hirschsprung disease |
| c.739C>T (p.Arg247Trp) | Missense | Rare | Disrupted RET interaction; Hirschsprung disease |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Arg76Cys, p.Arg130His) reduce GDNF binding or cell surface expression, impairing RET signaling.
Gain of Function (GOF)
Not well documented; GFRA1 amplification in neuroblastoma may enhance RET signaling.
Dominant Negative (DN)
No dominant-negative mutations reported for GFRA1.
View complete mutation data：
Gene Ontology (GO)
| • GO:0019899 (GO:0019899) | • GO:0038023 (GO:0038023) |
| • GO:0043235 (GO:0043235) | • GO:0048406 (GO:0048406) |
| • GO:0005886 (GO:0005886) | • GO:0007169 (GO:0007169) |
Pathways
• GDNF-RET signaling pathway
• MAPK signaling pathway
• PI3K-Akt signaling pathway
• Neurotrophin signaling pathway
Protein Summary
GFRA1 is a 465-amino acid GPI-anchored protein that functions as a co-receptor for GDNF. It forms a ternary complex with GDNF and RET, leading to RET dimerization and activation of downstream signaling cascades including MAPK and PI3K-Akt. The protein is expressed in neuronal tissues, kidney, and testis. Mutations in GFRA1 are associated with Hirschsprung disease and may contribute to neuroblastoma.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GFRA1 Knockout HEK293 Cell Line | EDJ-KQ1117 | Human | 2674 | Details Get a Quote |
| GFRA1 Knockout A-549 Cell Line | EDJ-KQ20304 | Human | 2674 | Details Get a Quote |
| GFRA1 Knockout HeLa Cell Line | EDJ-KQ53331 | Human | 2674 | Details Get a Quote |
| GFRA1 Knockout HCT 116 Cell Line | EDJ-KQ70298 | Human | 2674 | Details Get a Quote |
