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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SEPTIN5
septin 5
Chromosome 22 · 22q11.21
NCBI Gene: 5413Ensembl: ENSG00000184702.21HGNC: HGNC:9164UniProt: Q99719
67PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
plasma membraneprotein bindingregulation of exocytosissynaptic vesiclehair colorMacrothrombocytopeniaalcohol drinkingMeniere disease
✦AI Summary

SEPTIN5 is a filament-forming cytoskeletal GTPase that plays critical roles in exocytosis and cellular architecture. In pancreatic β-cells, SEPTIN5 assembles at microtubule-plasma membrane contact sites to anchor insulin secretory granules, and its deletion enhances glucose-stimulated insulin secretion by increasing granule dynamics and access to the plasma membrane, suggesting therapeutic potential for type 2 diabetes 1. In neurons, SEPTIN5 regulates synaptic vesicle exocytosis and undergoes phosphorylation at serine 327 that increases during early Alzheimer's disease pathology, correlating with decreased SEPTIN5 protein levels and affecting amyloid precursor protein processing and autophagy markers 2. SEPTIN5 has been identified as an autoimmune target in rare neurological disorders: antibodies against SEPTIN5 are associated with autoimmune cerebellar ataxia and vestibulocerebellar syndromes, emerging as important diagnostic biomarkers in patients presenting with cerebellar symptoms and ataxia 3, 4. These findings establish SEPTIN5 as a multifunctional protein linking metabolic regulation, neurodegeneration, and autoimmune neurological disease, with potential clinical applications in diabetes management and autoimmune encephalitis diagnosis.

Sources cited
1
SEPTIN5 deletion enhances insulin secretion in β-cells by releasing microtubule-tethered granules and improves glucose-stimulated insulin secretion in type 2 diabetes models
PMID: 40108136
2
SEPTIN5 S327 phosphorylation increases in early Alzheimer's disease neurofibrillary pathology and affects amyloid precursor protein processing and synaptic plasticity
PMID: 34954322
3
Antibodies against SEPTIN5 have been identified in patients with autoimmune cerebellar ataxia and other autoimmune movement disorders
PMID: 39088289
4
SEPTIN5 is a target of autoimmune antibodies in vestibulocerebellar syndromes and serves as a biomarker for autoimmune disorders affecting vestibular and cerebellar function
PMID: 31958862
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
hair colorOpen Targets
0.40Moderate
MacrothrombocytopeniaOpen Targets
0.34Weak
alcohol drinkingOpen Targets
0.31Weak
Meniere diseaseOpen Targets
0.25Weak
acute myeloid leukemiaOpen Targets
0.19Weak
clear cell renal carcinomaOpen Targets
0.19Weak
squamous cell lung carcinomaOpen Targets
0.19Weak
gastric adenocarcinomaOpen Targets
0.19Weak
prostate adenocarcinomaOpen Targets
0.19Weak
esophageal squamous cell carcinomaOpen Targets
0.19Weak
cutaneous melanomaOpen Targets
0.19Weak
breast carcinomaOpen Targets
0.18Weak
Duodenal AdenocarcinomaOpen Targets
0.18Weak
Eccrine PorocarcinomaOpen Targets
0.18Weak
esophageal adenocarcinomaOpen Targets
0.18Weak
gastroesophageal junction adenocarcinomaOpen Targets
0.18Weak
metaplastic breast carcinomaOpen Targets
0.18Weak
multiple myelomaOpen Targets
0.18Weak
skin basal cell carcinomaOpen Targets
0.18Weak
skin squamous cell carcinomaOpen Targets
0.18Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
STX4Protein interaction100%SEPTIN7Protein interaction99%SEPTIN2Protein interaction99%SYPProtein interaction98%GP1BBProtein interaction90%GNB1LProtein interaction90%
Tissue Expression6 tissues
Brain
100%
Ovary
28%
Lung
11%
Liver
4%
Bone Marrow
3%
Heart
2%
Gene Interaction Network
Click a node to explore
SEPTIN5STX4SEPTIN7SEPTIN2SYPGP1BBGNB1L
PROTEIN STRUCTURE
Preparing viewer…
PDB6WCU · 1.80 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.49Moderately Constrained
pLIⓘ
0.99Intolerant
Observed/Expected LoF0.32 [0.22–0.49]
RankingsWhere SEPTIN5 stands among ~20K protein-coding genes
  • #7,016of 20,598
    Most Researched67
  • #2,881of 17,882
    Most Constrained (LOEUF)0.49 · top quartile
Genes detectedSEPTIN5
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease: International MOGAD Panel proposed criteria.
PMID: 36706773
Lancet Neurol · 2023
1.00
2
Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management.
PMID: 33649022
J Neurol Neurosurg Psychiatry · 2021
0.90
3
Autoimmune Movement Disorders.
PMID: 39088289
Continuum (Minneap Minn) · 2024
0.80
4
Stiff person spectrum disorder diagnosis, misdiagnosis, and suggested diagnostic criteria.
PMID: 37212351
Ann Clin Transl Neurol · 2023
0.70
5
Autoimmune Vestibulocerebellar Syndromes.
PMID: 31958862
Semin Neurol · 2020
0.60