GFRA3 as a Radioligand Therapy Target
GFRA3, GDNF family receptor alpha 3, is a cell-surface protein (membrane receptor). In Human Protein Atlas immunohistochemistry, GFRA3 staining is highest in testicular cancer (100% of samples positive), colorectal cancer (100% of samples positive) and melanoma (100% of samples positive). Evidence on whether GFRA3 internalizes is mixed. Clinical status: Discovery-stage (no clinical drug program).
Is GFRA3 a good radioligand therapy target?
Scored against the six criteria that decide whether a protein can become a radioligand therapy:
- ✅ Cell-surface accessibility: Localized to the cell surface, so a radioligand can reach it from circulation.
- ✅ Tumor expression: High IHC staining in testicular cancer, 100% of samples positive.
- ⚠️ Internalization: Mixed evidence.
- ⚠️ Clinical precedent: Discovery-stage (no clinical drug program)
- ❔ Shedding: Not yet assessed.
- ❔ Normal-tissue dosimetry: Check kidney, liver, bone marrow and salivary expression in the Human Protein Atlas tissue atlas.
GFRA3 expression in cancer
Protein expression of GFRA3 across 20 cancer types from Human Protein Atlas immunohistochemistry. The score is a weighted staining intensity from 0 to 1; "% positive" is the share of patient samples with detectable staining.
| Cancer type | IHC score | Level | % positive |
|---|---|---|---|
| Testicular Cancer | 0.89 | High | 100% |
| Colorectal Cancer | 0.73 | High | 100% |
| Melanoma | 0.73 | High | 100% |
| Bladder Cancer | 0.70 | High | 100% |
| Ovarian Cancer | 0.69 | High | 100% |
| Head and Neck Cancer | 0.67 | High | 100% |
| Breast Cancer | 0.67 | High | 100% |
| Thyroid Cancer | 0.67 | High | 100% |
| Cervical Cancer | 0.67 | High | 100% |
| Pancreatic Cancer | 0.67 | High | 100% |
| Gastric Cancer | 0.67 | High | 100% |
| Prostate Cancer | 0.60 | High | 100% |
| Neuroendocrine Tumors | 0.58 | High | 100% |
| Endometrial Cancer | 0.56 | High | 83% |
| Kidney Cancer | 0.50 | Medium | 90% |
| Lung Cancer | 0.48 | Medium | 86% |
| Liver Cancer | 0.44 | Medium | 92% |
| Skin Cancer | 0.39 | Medium | 75% |
| Glioma | 0.33 | Medium | 83% |
| Lymphoma | 0.25 | Medium | 42% |
Is GFRA3 internalized?
Uncertain. Insufficient literature found.
GFRA3 clinical trials
Discovery-stage (no clinical drug program). Nuclens hasn't indexed trials for GFRA3 yet. Search ClinicalTrials.gov for GFRA3 trials.
GFRA3 normal tissue expression
Normal-tissue expression in dose-limiting organs (kidney, liver, bone marrow, salivary glands) drives radioligand dosimetry risk. Nuclens is re-validating its normal-tissue values, so they are not shown here yet. See GFRA3 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
GFRA3 gene essentiality (DepMap)
CRISPR knockout effect across 1249 cancer cell lines: -0.03 (not essential). Radioligands kill by radiation, not by blocking the target, so essentiality matters less than for inhibitors. A non-essential target can still be an excellent radioligand target.
Related testicular cancer radioligand targets
HER3 (ERBB3) · c-MET (MET) · STEAP2 · KIT · SSTR2 · TMEFF2 · Mesothelin (MSLN) · HER2 (ERBB2)
See all radioligand therapy targets in testicular cancer.
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Subcellular localization: UniProt via Open Targets (CC BY 4.0 / CC0). Tumor immunohistochemistry: Human Protein Atlas (CC BY-SA 4.0). Clinical trials: ClinicalTrials.gov (public domain). Gene essentiality: DepMap (CC BY 4.0). Internalization and shedding: AI-extracted from PubMed abstracts, so verify against the cited papers before relying on them. Nuclens is a first-pass triage layer, not a substitute for wet-lab validation or clinical dosimetry. Derived expression data on this page is shared under CC BY-SA 4.0.