GPR139 as a Radioligand Therapy Target
GPR139, G protein-coupled receptor 139, is a cell-surface protein (GPCR). In Human Protein Atlas immunohistochemistry, GPR139 staining is highest in head and neck cancer (100% of samples positive), thyroid cancer (100% of samples positive) and lung cancer (100% of samples positive). Published literature reports that GPR139 internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Discovery-stage (no clinical drug program).
Is GPR139 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 head and neck cancer, 100% of samples positive.
- ✅ Internalization: Reported to internalize, which favors radionuclide retention.
- ⚠️ 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.
GPR139 expression in cancer
Protein expression of GPR139 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 |
|---|---|---|---|
| Head and Neck Cancer | 1.00 | High | 100% |
| Thyroid Cancer | 1.00 | High | 100% |
| Lung Cancer | 1.00 | High | 100% |
| Testicular Cancer | 1.00 | High | 100% |
| Liver Cancer | 1.00 | High | 100% |
| Ovarian Cancer | 0.97 | High | 100% |
| Melanoma | 0.97 | High | 100% |
| Lymphoma | 0.97 | High | 100% |
| Pancreatic Cancer | 0.94 | High | 100% |
| Endometrial Cancer | 0.94 | High | 100% |
| Gastric Cancer | 0.94 | High | 100% |
| Skin Cancer | 0.93 | High | 100% |
| Cervical Cancer | 0.92 | High | 100% |
| Kidney Cancer | 0.91 | High | 100% |
| Breast Cancer | 0.89 | High | 100% |
| Prostate Cancer | 0.89 | High | 100% |
| Glioma | 0.89 | High | 100% |
| Neuroendocrine Tumors | 0.83 | High | 100% |
| Bladder Cancer | 0.82 | High | 100% |
| Colorectal Cancer | 0.81 | High | 100% |
Is GPR139 internalized?
Yes. We performed a novel real-time GPR139 internalization assay.
Sources: PMID 36736525. AI-extracted from abstracts, so verify before citing.
GPR139 clinical trials
Discovery-stage (no clinical drug program). Nuclens hasn't indexed trials for GPR139 yet. Search ClinicalTrials.gov for GPR139 trials.
GPR139 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 GPR139 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
GPR139 gene essentiality (DepMap)
CRISPR knockout effect across 1212 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 head and neck cancer radioligand targets
EGFR · c-MET (MET) · HER3 (ERBB3) · ITGAV · SSTR2 · B7-H3 (CD276) · STEAP2 · Mesothelin (MSLN)
See all radioligand therapy targets in head and neck cancer.
See how GPR139 ranks against 15,000 targets for your indication.
Run a free analysisData sources
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.