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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SEPTIN2
septin 2
Chromosome 2 · 2q37.3
NCBI Gene: 4735Ensembl: ENSG00000168385.18HGNC: HGNC:7729UniProt: A0A384N6H6
208PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytoskeleton organizationnon-motile ciliumseptin complexmicrotubule cytoskeletonosteoarthritis, hipschizophreniatotal hip arthroplastyhypothyroidism
✦AI Summary

SEPTIN2 is a filament-forming cytoskeletal GTPase that plays critical roles in multiple cellular processes. The protein forms complexes with other septins, including SEPTIN6, SEPTIN7, and SEPTIN12, which are essential for cytoskeletal organization and cell division 1. In spermatogenesis, SEPTIN2 forms filamentous structures at the sperm annulus required for sperm tail integrity and motility, and mediates head-tail junction through interactions with SUN5 and SEPTIN12 2. The protein regulates actin cytoskeleton organization and controls cell morphology by interacting with ARHGAP25 to suppress lamellipodia formation 3. SEPTIN2 is subject to post-translational modifications that affect its function: S-nitrosylation at cysteine 111 drives aortic aneurysm development by activating the TIAM1-RAC1 inflammatory pathway 4, while folate-dependent methylation is crucial for GTP binding activity and cilium formation during neural tube closure 1. In disease contexts, SEPTIN2 acts as a tumor suppressor in glioblastoma, where its knockdown inhibits cell proliferation through p53/p21 and MEK/ERK pathways 5, and suppresses inflammatory macrophage activation by regulating ER stress responses 6. Hypoxia-induced downregulation of SEPTIN2 impairs male fertility by disrupting spermatogonial proliferation through PP2A-mediated AKT dephosphorylation 7.

Sources cited
1
SEPTIN2 forms complexes with SEPTIN6 and SEPTIN7, and its methylation affects GTP binding activity and cilium formation during neural tube closure
PMID: 28432198
2
SEPTIN2 forms filamentous structures at sperm annulus and mediates sperm head-tail junction through interactions with SUN5 and SEPTIN12
PMID: 38870534
3
SEPTIN2 regulates cell morphology by interacting with ARHGAP25 to suppress lamellipodia formation and cell spreading
PMID: 40205813
4
S-nitrosylation of SEPTIN2 at cysteine 111 drives aortic aneurysm development by activating TIAM1-RAC1 inflammatory pathway
PMID: 38357802
5
SEPTIN2 acts as tumor suppressor in glioblastoma, with knockdown inhibiting proliferation through p53/p21 and MEK/ERK pathways
PMID: 29724999
6
SEPTIN2 suppresses inflammatory macrophage activation by regulating ER stress responses
PMID: 37978190
7
Hypoxia-induced SEPTIN2 downregulation impairs male fertility by disrupting spermatogonial proliferation through PP2A-mediated AKT dephosphorylation
PMID: 40487848
Disease Associationsⓘ20
osteoarthritis, hipOpen Targets
0.27Weak
schizophreniaOpen Targets
0.27Weak
total hip arthroplastyOpen Targets
0.26Weak
hypothyroidismOpen Targets
0.22Weak
skin cancerOpen Targets
0.21Weak
smoking behaviorOpen Targets
0.21Weak
prostate carcinomaOpen Targets
0.20Weak
androgenetic alopeciaOpen Targets
0.20Weak
squamous cell carcinomaOpen Targets
0.17Weak
thyroid diseaseOpen Targets
0.16Weak
coronary artery diseaseOpen Targets
0.16Weak
Ischemic strokeOpen Targets
0.16Weak
venous thromboembolismOpen Targets
0.15Weak
skin neoplasmOpen Targets
0.14Weak
chronic lymphocytic leukemiaOpen Targets
0.13Weak
Abnormality of the skeletal systemOpen Targets
0.12Weak
colorectal carcinomaOpen Targets
0.10Suggestive
hepatocellular carcinomaOpen Targets
0.09Suggestive
breast cancerOpen Targets
0.08Suggestive
glioblastoma multiformeOpen Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SEPTIN4Protein interaction100%SEPTIN1Protein interaction99%SEPTIN12Protein interaction99%SEPTIN5Protein interaction99%SQSTM1Protein interaction90%CDC42EP4Protein interaction85%
Tissue Expression6 tissues
Brain
100%
Heart
96%
Bone Marrow
62%
Ovary
59%
Lung
54%
Liver
32%
Gene Interaction Network
Click a node to explore
SEPTIN2SEPTIN4SEPTIN1SEPTIN12SEPTIN5SQSTM1CDC42EP4
PROTEIN STRUCTURE
Preparing viewer…
PDB6UPQ · 1.86 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.98LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.72 [0.53–0.98]
RankingsWhere SEPTIN2 stands among ~20K protein-coding genes
  • #2,015of 20,598
    Most Researched208 · top 10%
  • #9,427of 17,882
    Most Constrained (LOEUF)0.98
Genes detectedSEPTIN2
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
S-Nitrosylation of Septin2 Exacerbates Aortic Aneurysm and Dissection by Coupling the TIAM1-RAC1 Axis in Macrophages.
PMID: 38357802
Circulation · 2024
1.00
2
SEPTIN2 suppresses an IFN-γ-independent, proinflammatory macrophage activation pathway.
PMID: 37978190
Nat Commun · 2023
0.90
3
Repression of Septin9 and Septin2 suppresses tumor growth of human glioblastoma cells.
PMID: 29724999
Cell Death Dis · 2018
0.80
4
Functional interdependence between septin and actin cytoskeleton.
PMID: 15541171
BMC Cell Biol · 2004
0.76
5
Septin2 regulates ARHGAP25-mediated suppression of lamellipodia formation and cell spreading.
PMID: 40205813
FEBS Lett · 2025
0.70