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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SSTR3
somatostatin receptor 3
Chromosome 22 · 22q13.1
NCBI Gene: 6753Ensembl: ENSG00000278195.3HGNC: HGNC:11332UniProt: P32745
69PubMed Papers
20Diseases
7Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Receptor
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
ciliumprotein bindingG protein-coupled receptor activityneuron projectionacromegalyneoplasmneuroendocrine neoplasmpituitary-dependent Cushing's disease
✦AI Summary

SSTR3 is a G protein-coupled receptor that functions as a receptor for somatostatin-14 and -28, mediating inhibition of adenylyl cyclase through pertussis toxin-sensitive Gi proteins 1. The receptor plays critical roles in negatively regulating hormone release and cell proliferation, making it a therapeutic target for neuroendocrine tumors 1. SSTR3 localizes to primary cilia through ciliary localization sequences in its C-terminal tail and third intracellular loop, where it functions as a specialized signaling compartment alongside other GPCRs 2. Within cilia, SSTR3 undergoes regulated ubiquitin-mediated retrieval via the BBSome-TOM1L2 complex to enable appropriate signal transduction 3. Clinically, SSTR3 expression is elevated in non-functioning pituitary neuroendocrine tumors (NF-PitNETs) and pancreatic neuroendocrine tumors (Pan-NETs), which respond poorly to conventional somatostatin analogs targeting SSTR2 and SSTR5 45. Novel SSTR3-selective agonists like ITF2984 demonstrate superior antiproliferative and proapoptotic effects in these tumor types, reducing cell proliferation by 40.8% and increasing apoptosis by 41.4% in NF-PitNETs 4. These findings support SSTR3-targeted therapies as promising alternatives for NETs with high SSTR3 expression 5.

Sources cited
1
SSTR3 is a Gi-coupled receptor that negatively regulates hormone release and cell proliferation; therapeutic target for neuroendocrine tumors
PMID: 39361640
2
SSTR3 localizes to primary cilia through ciliary localization sequences in C-terminal tail and third intracellular loop
PMID: 33599752
3
SSTR3 undergoes ubiquitin-mediated retrieval from cilia via BBSome-TOM1L2 complex interaction
PMID: 37019113
4
SSTR3-selective agonist ITF2984 reduces cell proliferation by 40.8% and increases apoptosis by 41.4% in NF-PitNET cells; tumors express high SSTR3 levels
PMID: 38612419
5
Pan-NETs express high SSTR3 levels and respond to SSTR3-selective agonist ITF2984 with antiproliferative and proapoptotic effects comparable to pasireotide
PMID: 39733775
Disease Associationsⓘ20
acromegalyOpen Targets
0.60Moderate
neoplasmOpen Targets
0.57Moderate
neuroendocrine neoplasmOpen Targets
0.55Moderate
pituitary-dependent Cushing's diseaseOpen Targets
0.52Moderate
carcinoid tumorOpen Targets
0.52Moderate
neuroendocrine carcinomaOpen Targets
0.41Moderate
cancerOpen Targets
0.39Weak
hepatocellular carcinomaOpen Targets
0.37Weak
metastasisOpen Targets
0.37Weak
hypothyroidismOpen Targets
0.36Weak
diabetic retinopathyOpen Targets
0.36Weak
digestive system neuroendocrine neoplasmOpen Targets
0.34Weak
pancreatic carcinomaOpen Targets
0.33Weak
Autosomal dominant polycystic kidney diseaseOpen Targets
0.33Weak
DiarrheaOpen Targets
0.32Weak
breast cancerOpen Targets
0.29Weak
pancreatic neuroendocrine tumorOpen Targets
0.28Weak
portal hypertensionOpen Targets
0.27Weak
colorectal cancerOpen Targets
0.26Weak
proliferative diabetic retinopathyOpen Targets
0.26Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets7
LUTETIUM OXODOTREOTIDE LU-177Approved
Somatostatin receptor binding agent
neuroendocrine neoplasm
OCTREOTIDEApproved
Somatostatin receptor agonist
acromegaly
OCTREOTIDE ACETATEApproved
Somatostatin receptor agonist
PASIREOTIDEApproved
Somatostatin receptor 2 agonist
PASIREOTIDE DIASPARTATEPhase II
Somatostatin receptor 3 agonist
Hypoglycemia
PASIREOTIDE PAMOATEApproved
Somatostatin receptor 2 agonist
SOMATOSTATINPhase III
Somatostatin receptor agonist
Autosomal dominant polycystic kidney disease
Related Genes
BBS5Protein interaction100%TTC8Protein interaction100%BBIP1Protein interaction100%BBS7Protein interaction100%CORTProtein interaction100%GNAI1Protein interaction97%
Tissue Expression6 tissues
Ovary
100%
Brain
50%
Bone Marrow
27%
Lung
1%
Liver
0%
Heart
0%
Gene Interaction Network
Click a node to explore
SSTR3BBS5TTC8BBIP1BBS7CORTGNAI1
PROTEIN STRUCTURE
Preparing viewer…
PDB8XIR · 2.52 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.88LoF Tolerant
pLIⓘ
0.17Tolerant
Observed/Expected LoF0.89 [0.25–1.88]
RankingsWhere SSTR3 stands among ~20K protein-coding genes
  • #6,853of 20,598
    Most Researched69
  • #314of 1,025
    FDA-Approved Drug Targets5
  • #17,099of 17,882
    Most Constrained (LOEUF)1.88
Genes detectedSSTR3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
PMID: 22896865
1.00
2
Selective ligand recognition and activation of somatostatin receptors SSTR1 and SSTR3.
PMID: 39361640
Proc Natl Acad Sci U S A · 2024
0.90
3
PMID: 23136682
0.80
4
HTR6 and SSTR3 targeting to primary cilia.
PMID: 33599752
Biochem Soc Trans · 2021
0.70
5
PMID: 20641226
0.60