SCG3: Secretogranin III – A Key Regulator of Secretory Granule Biogenesis and Neuroendocrine Function
Comprehensive genomic, proteomic, and clinical overview of SCG3, a granin family member implicated in neuroendocrine tumors and neurological disorders.
Gene Information Card
| Symbol | SCG3 |
|---|---|
| Full Name | Secretogranin III |
| Gene Type | Protein coding |
| Chromosomal Location | 15q21.1 |
| NCBI Gene ID | 29106 ncbi.nlm.nih.gov/gene/29106 |
| Ensembl ID | ENSG00000137807 |
| UniProt ID | Q8WXD2 |
| OMIM ID | 611796 |
| HGNC ID | 10698 |
| Aliases | SgIII, 1B1075, HXB1 |
Description
SCG3 (secretogranin III) is a member of the granin family of neuroendocrine secretory proteins. It is involved in the biogenesis and sorting of secretory granules, particularly in neuroendocrine cells. SCG3 binds to cholesterol-rich membranes and facilitates the aggregation of peptide hormones and neuropeptides. It is widely expressed in endocrine tissues and the brain, and its dysregulation is linked to neuroendocrine tumors, Alzheimer's disease, and other neurological conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neuroendocrine tumors (NETs) | SCG3 overexpression promotes secretory granule formation and hormone storage, contributing to tumor phenotype. | Elevated SCG3 serum levels reported in NET patients (PMID: 22960625). |
| Alzheimer's disease | SCG3 is upregulated in cerebrospinal fluid and brain tissue; may reflect altered secretory pathway in neurodegeneration. | CSF proteomics studies (PMID: 25772935). |
| Pheochromocytoma | SCG3 expression correlates with catecholamine secretion and tumor aggressiveness. | Immunohistochemistry and RNA-seq data (COSMIC). |
| Pituitary adenoma | SCG3 is a marker of secretory activity and tumor subtype. | Expression profiling (PMID: 19088123). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | Medium |
| Pituitary gland | 45.2 | High |
| Adrenal gland | 38.1 | High |
| Pancreas | 22.3 | Medium |
| Thyroid | 15.8 | Medium |
| Testis | 8.4 | Low |
| Liver | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 18.6 | Neuronal model |
| PC-12 (pheochromocytoma) | 42.3 | High expression; used for secretory studies |
| HeLa (cervical carcinoma) | 2.1 | Low expression |
| HEK293 (embryonic kidney) | 1.5 | Low expression |
| INS-1 (insulinoma) | 35.7 | Pancreatic beta-cell model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.437C>T (p.Pro146Leu) | Missense | <0.01% | Unknown; rare population variant |
| c.832G>A (p.Gly278Arg) | Missense | <0.01% | Predicted benign (ClinVar) |
| c.1120_1121insA (p.Thr374Asnfs*5) | Frameshift | <0.01% | Loss of function; likely pathogenic (ClinVar) |
Mutation functional classification
Loss of Function (LOF)
Frameshift insertion c.1120_1121insA leads to premature truncation and loss of granin function.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
No evidence for dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Secretory granule biogenesis and exocytosis
• Neuroendocrine hormone processing
• Chromogranin/secretogranin pathway
Protein Summary
Secretogranin III (SgIII) is a 468-amino-acid acidic glycoprotein belonging to the granin family. It is localized to secretory granules in neuroendocrine cells and neurons. SgIII binds to cholesterol-rich membranes via its N-terminal domain and promotes the aggregation of peptide hormones. It is processed by prohormone convertases to generate bioactive fragments. The protein is involved in granule biogenesis, hormone sorting, and regulated secretion. Elevated levels are observed in neuroendocrine tumors and Alzheimer's disease, making it a potential biomarker.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SCG3 Knockout HEK293 Cell Line | EDJ-KQ8987 | Human | 29106 | Details Get a Quote |
| SCG3 Knockout HeLa Cell Line | EDJ-KQ56097 | Human | 29106 | Details Get a Quote |
| SCG3 Knockout A-549 Cell Line | EDJ-KQ64583 | Human | 29106 | Details Get a Quote |
| SCG3 Knockout HCT 116 Cell Line | EDJ-KQ73037 | Human | 29106 | Details Get a Quote |
