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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SCGN
secretagogin, EF-hand calcium binding protein
Chromosome 6 · 6p22.2
NCBI Gene: 10590Ensembl: ENSG00000079689.16HGNC: HGNC:16941UniProt: O76038
35PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytosolprotein bindingdendriteterminal boutonagingneurodegenerative diseasecoronary artery diseasetype 2 diabetes mellitus
✦AI Summary

SCGN (secretagogin) is a hexa-EF-hand calcium-binding protein that functions as a multifaceted regulator of neuroendocrine and immune processes 1. Structurally, SCGN contains three calcium-binding domains and localizes to synaptic terminals, dendrites, and the nucleus 2. Its primary mechanism involves calcium-dependent interaction with SNAP-25, a SNARE complex component essential for regulated exocytosis and hormone secretion 2. Additionally, SCGN functions as a calcium-dependent molecular chaperone that prevents protein aggregation and responds to cellular stress 1. Disease relevance is substantial across multiple systems. SCGN deficiency causes autism spectrum disorder through disrupted oxytocin signaling and abnormal immune activation 3. Loss-of-function mutations impair intestinal neuroendocrine function, precipitating early-onset ulcerative colitis 4. In pancreatic biology, SCGN regulates insulin secretion and is implicated in diabetes pathogenesis 5. Conversely, in clear cell renal cell carcinoma, SCGN suppression occurs during progression, while restoration enhances macrophage recruitment via NF-κB-mediated chemokine secretion, improving immunotherapy responsiveness 6. High SCGN expression correlates with better ccRCC prognosis 7. Finally, SCGN methylation patterns serve as epigenetic biomarkers for chr6 age estimation in forensic applications 8. These diverse roles position SCGN as a critical regulator of synaptic function, neuroendocrine secretion, immune homeostasis, and proteostasis.

Sources cited
1
SCGN deficiency causes autism spectrum disorder through disruption of oxytocin signaling and abnormal immune activation
PMID: 36588101
2
SCGN regulates chemokine secretion and macrophage recruitment via NF-κB signaling in renal cell carcinoma
PMID: 39664565
3
SCGN CpG methylation sites correlate with chronological age and can be used as epigenetic age biomarkers
PMID: 28854399
4
High SCGN expression is associated with better prognosis in clear cell renal cell carcinoma patients
PMID: 37977033
5
SCGN mutations impair neuroendocrine hormone release and cause early-onset ulcerative colitis through defective SNARE complex localization
PMID: 31663849
6
SCGN regulates insulin secretion in pancreatic β-cells and is implicated in diabetes pathogenesis
PMID: 30772140
7
SCGN is a calcium-dependent molecular chaperone that prevents protein aggregation and responds to oxidative stress
PMID: 35870554
8
SCGN interacts with SNAP-25 in a calcium-dependent manner to regulate SNARE-mediated exocytosis and controls neuronal development
PMID: 32156735
Disease Associationsⓘ20
agingOpen Targets
0.40Moderate
neurodegenerative diseaseOpen Targets
0.35Weak
coronary artery diseaseOpen Targets
0.34Weak
type 2 diabetes mellitusOpen Targets
0.31Weak
Varicose veinsOpen Targets
0.31Weak
iron metabolism diseaseOpen Targets
0.30Weak
non-alcoholic fatty liver diseaseOpen Targets
0.29Weak
cervical carcinomaOpen Targets
0.27Weak
rheumatoid arthritisOpen Targets
0.24Weak
hypertensionOpen Targets
0.24Weak
anemia (phenotype)Open Targets
0.23Weak
ulcerative colitisOpen Targets
0.21Weak
insomniaOpen Targets
0.21Weak
polycythemia veraOpen Targets
0.21Weak
cardiovascular diseaseOpen Targets
0.20Weak
hematologic diseaseOpen Targets
0.20Weak
Increased blood pressureOpen Targets
0.17Weak
myocardial infarctionOpen Targets
0.16Weak
denturesOpen Targets
0.14Weak
Iron deficiency anemiaOpen Targets
0.14Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
DOC2AProtein interaction90%SNAP25Protein interaction87%SNAP23Protein interaction87%MLF2Protein interaction73%CROCCProtein interaction73%DDAH2Protein interaction72%
Tissue Expression6 tissues
Brain
100%
Heart
2%
Liver
1%
Ovary
0%
Bone Marrow
0%
Lung
0%
Gene Interaction Network
Click a node to explore
SCGNDOC2ASNAP25SNAP23MLF2CROCCDDAH2
PROTEIN STRUCTURE
Preparing viewer…
PDB8BAV · 2.30 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.38LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.92 [0.63–1.38]
RankingsWhere SCGN stands among ~20K protein-coding genes
  • #11,060of 20,598
    Most Researched35
  • #14,338of 17,882
    Most Constrained (LOEUF)1.38
Genes detectedSCGN
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
SCGN deficiency is a risk factor for autism spectrum disorder.
PMID: 36588101
Signal Transduct Target Ther · 2023
1.00
2
SCGN recruits macrophages by regulating chemokine secretion in clear cell renal cell carcinoma.
PMID: 39664565
Int J Biol Sci · 2024
0.90
3
Detection and evaluation of DNA methylation markers found at SCGN and KLF14 loci to estimate human age.
PMID: 28854399
Forensic Sci Int Genet · 2017
0.80
4
SCGN and STAT3 expressions are associated with the prognosis of ccRCC.
PMID: 37977033
Pathol Res Pract · 2023
0.70
5
PMID: 31663849
Elife · 2019
0.60