GFRA3: GDNF Family Receptor Alpha 3
A key receptor in neurotrophic signaling and cancer biology
Gene Information Card
| Symbol | GFRA3 |
|---|---|
| Full Name | GDNF Family Receptor Alpha 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 5q31.2 |
| NCBI Gene ID | 2676 ncbi.nlm.nih.gov/gene/2676 |
| Ensembl ID | ENSG00000113520 |
| UniProt ID | O60609 |
| OMIM ID | 601960 |
| HGNC ID | 4245 |
| Aliases | GDNFRALPHA3, GFRALPHA3 |
Description
GFRA3 encodes a glycosylphosphatidylinositol (GPI)-anchored receptor that binds artemin, a member of the GDNF family of neurotrophic factors. It forms a complex with the RET receptor tyrosine kinase to mediate cell survival, migration, and differentiation. GFRA3 is primarily expressed in the nervous system and is implicated in neuroblastoma, medullary thyroid carcinoma, and other cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neuroblastoma | GFRA3 overexpression enhances RET signaling, promoting tumor cell survival and proliferation. | PMID: 14559845 |
| Medullary Thyroid Carcinoma | Co-expression with RET mutations amplifies oncogenic signaling. | PMID: 10666372 |
| Hirschsprung Disease | Reduced GFRA3 expression impairs RET-mediated enteric neuron development. | PMID: 11532986 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 5.2 | Medium |
| Spinal Cord | 3.8 | Low |
| Adrenal Gland | 2.1 | Low |
| Thyroid | 1.5 | Not detected |
| Testis | 0.9 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 6.4 | High expression; used in RET signaling studies |
| HEK293 (embryonic kidney) | 0.3 | Low endogenous expression |
| MCF7 (breast cancer) | 0.1 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.01% | Loss of start codon; likely loss of function |
| c.200C>T (p.Thr67Ile) | Missense | <0.01% | Unknown significance; reported in ClinVar |
| c.500G>A (p.Arg167Gln) | Missense | <0.01% | Potential gain of function in neuroblastoma |
Mutation functional classification
Loss of Function (LOF)
Mutations that disrupt GPI anchor attachment or ligand binding reduce RET activation and neuronal survival.
Gain of Function (GOF)
Missense variants that enhance GFRA3-RET complex stability may promote oncogenic signaling.
Dominant Negative (DN)
Not well characterized; truncated forms could interfere with wild-type receptor function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• RET signaling (Reactome: R-HSA-8853659)
• GDNF family ligand-receptor interaction (KEGG: hsa04370)
• Signaling by GDNF (WikiPathways: WP358)
Protein Summary
GFRA3 is a 400-amino-acid GPI-anchored receptor that binds artemin with high affinity. It lacks intrinsic catalytic activity but recruits and activates the RET tyrosine kinase upon ligand binding. The protein is essential for the development of the sympathetic nervous system and is implicated in neuroblastoma and thyroid cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GFRA3 Knockout HEK293 Cell Line | EDJ-KQ4702 | Human | 2676 | Details Get a Quote |
| GFRA3 Knockout HeLa Cell Line | EDJ-KQ53333 | Human | 2676 | Details Get a Quote |
| GFRA3 Knockout A-549 Cell Line | EDJ-KQ61813 | Human | 2676 | Details Get a Quote |
| GFRA3 Knockout HCT 116 Cell Line | EDJ-KQ70300 | Human | 2676 | Details Get a Quote |
