SEPTIN2

Summary

SEPTIN2 (septin 2, HGNC:7729) is a protein-coding gene on chromosome 2q37.3, encoding Septin-2 (Q15019). Filament-forming cytoskeletal GTPase.

Enables identical protein binding activity. Predicted to be involved in several processes, including cilium assembly; cytoskeleton-dependent cytokinesis; and smoothened signaling pathway. Predicted to act upstream of or within regulation of L-glutamate import across plasma membrane and regulation of protein localization. Located in several cellular components, including cytoskeleton; photoreceptor connecting cilium; and sperm annulus. Part of septin complex.

Source: NCBI Gene 4735 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 68 total
• Druggable target: yes
• MANE Select transcript: NM_004404

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7729
Approved symbol	SEPTIN2
Name	septin 2
Location	2q37.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0158, hNedd5, Pnutl3, Septin-2
Ensembl gene	ENSG00000168385
Ensembl biotype	protein_coding
OMIM	601506
Entrez	4735

Gene structure

Transcript identifiers

Ensembl transcripts: 103 — 81 protein_coding, 11 protein_coding_CDS_not_defined, 9 retained_intron, 2 nonsense_mediated_decay

ENST00000360051, ENST00000366210, ENST00000391971, ENST00000391973, ENST00000401990, ENST00000402092, ENST00000407017, ENST00000407971, ENST00000411484, ENST00000420786, ENST00000421717, ENST00000425899, ENST00000428282, ENST00000428524, ENST00000429791, ENST00000434955, ENST00000436795, ENST00000437066, ENST00000441533, ENST00000443492, ENST00000445030, ENST00000449239, ENST00000451310, ENST00000457335, ENST00000457874, ENST00000461048, ENST00000462147, ENST00000464128, ENST00000466211, ENST00000467971, ENST00000469175, ENST00000469434, ENST00000473479, ENST00000475474, ENST00000475823, ENST00000476841, ENST00000481500, ENST00000482304, ENST00000484167, ENST00000484648, ENST00000484740, ENST00000492978, ENST00000494824, ENST00000495463, ENST00000616972, ENST00000876194, ENST00000876195, ENST00000876196, ENST00000876197, ENST00000876198, ENST00000876199, ENST00000876200, ENST00000876201, ENST00000876202, ENST00000876203, ENST00000876204, ENST00000876205, ENST00000876206, ENST00000876207, ENST00000876208, ENST00000876209, ENST00000876210, ENST00000876211, ENST00000876212, ENST00000876213, ENST00000876214, ENST00000876215, ENST00000876216, ENST00000876217, ENST00000876218, ENST00000876219, ENST00000876220, ENST00000876221, ENST00000876222, ENST00000876223, ENST00000876224, ENST00000919258, ENST00000919259, ENST00000919260, ENST00000919261, ENST00000919262, ENST00000919263, ENST00000919264, ENST00000919265, ENST00000919266, ENST00000919267, ENST00000919268, ENST00000919269, ENST00000919270, ENST00000945231, ENST00000945232, ENST00000945233, ENST00000945234, ENST00000945235, ENST00000945236, ENST00000945237, ENST00000945238, ENST00000945239, ENST00000945240, ENST00000945241, ENST00000945242, ENST00000945243, ENST00000945244

RefSeq mRNA: 31 — MANE Select: NM_004404 NM_001008491, NM_001008492, NM_001282972, NM_001282973, NM_001321029, NM_001321030, NM_001321031, NM_001321032, NM_001321033, NM_001321034, NM_001321035, NM_001349287, NM_001349288, NM_001349289, NM_001349290, NM_001349291, NM_001349302, NM_001349304, NM_001349305, NM_001349306, NM_001349307, NM_001349308, NM_001349309, NM_001349310, NM_001349311, NM_001349312, NM_001349313, NM_001349314, NM_001349315, NM_004404, NM_006155

CCDS: CCDS2548, CCDS63195, CCDS74682, CCDS86930

Canonical transcript exons

ENST00000391971 — 13 exons

Exon	Start	End
ENSE00001140455	241348134	241348191
ENSE00001140465	241346166	241346249
ENSE00001147389	241350073	241350203
ENSE00001345072	241351967	241354027
ENSE00003485934	241337673	241337790
ENSE00003592688	241343752	241343897
ENSE00003593371	241335975	241336098
ENSE00003620664	241337382	241337516
ENSE00003645936	241342992	241343093
ENSE00003646772	241325993	241326113
ENSE00003679843	241324216	241324241
ENSE00003785657	241335126	241335212
ENSE00003843954	241315925	241315982

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 138.2418 / max 1617.6651, expressed in 1828 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
26517	107.1438	1822
26512	13.7693	1795
26509	4.7679	1635
26510	3.6519	1559
26516	2.0703	1085
26518	2.0340	1137
26514	1.3042	895
26525	0.9592	578
26523	0.7482	460
26520	0.6956	232

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.48	gold quality
cranial nerve II	UBERON:0000941	99.45	gold quality
germinal epithelium of ovary	UBERON:0001304	99.44	gold quality
secondary oocyte	CL:0000655	99.43	gold quality
parietal pleura	UBERON:0002400	99.40	gold quality
pleura	UBERON:0000977	99.38	gold quality
corpus callosum	UBERON:0002336	99.38	gold quality
endometrium	UBERON:0001295	99.37	gold quality
visceral pleura	UBERON:0002401	99.37	gold quality
lateral globus pallidus	UBERON:0002476	99.37	gold quality
calcaneal tendon	UBERON:0003701	99.33	gold quality
epithelial cell of pancreas	CL:0000083	99.31	gold quality
superficial temporal artery	UBERON:0001614	99.31	gold quality
body of pancreas	UBERON:0001150	99.30	gold quality
skin of hip	UBERON:0001554	99.29	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.29	gold quality
ganglionic eminence	UBERON:0004023	99.29	gold quality
smooth muscle tissue	UBERON:0001135	99.28	gold quality
choroid plexus epithelium	UBERON:0003911	99.26	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.26	gold quality
globus pallidus	UBERON:0001875	99.24	gold quality
medial globus pallidus	UBERON:0002477	99.24	gold quality
gall bladder	UBERON:0002110	99.22	gold quality
pancreas	UBERON:0001264	99.21	gold quality
middle frontal gyrus	UBERON:0002702	99.21	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.20	gold quality
islet of Langerhans	UBERON:0000006	99.17	gold quality
renal glomerulus	UBERON:0000074	99.17	gold quality
urethra	UBERON:0000057	99.16	gold quality
embryo	UBERON:0000922	99.16	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-5	yes	38.96
E-CURD-122	yes	9.45
E-MTAB-7249	no	16121.45
E-MTAB-7303	no	469.42
E-GEOD-93593	no	15.42
E-MTAB-10137	no	4.20
E-CURD-112	no	3.07
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

139 targeting SEPTIN2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358

Literature-anchored findings (GeneRIF, showing 40)

• Nedd5 is involved in the process of cytokinesis in human brain tumours. (PMID:12125979)
• septins may form a mitotic scaffold for CENP-E and other effectors to coordinate cytokinesis with chromosome congression and segregation (PMID:15774761)
• Nedd5 C-terminal is a novel autoantigen in systemic lupus erythematosus (SLE) patients and may be a valuable tool for diagnosing neuropsychiatric SLE. (PMID:15987492)
• protein encoded by SEPT2 is highly homologous to septins 1, 4 and 5 and is involved in the coordination of several key steps of mitosis (PMID:16682951)
• septin 2, 6, and 7 complexes make up polymerized filaments (PMID:16914550)
• crystal structures of the human SEPT2 G domain and the heterotrimeric human SEPT2-SEPT6-SEPT7 complex (PMID:17637674)
• Demonstrate connection between septins/SOCS7/NCK signaling and the DNA damage response. (PMID:17803907)
• Study shows that in epithelial cells septin 2 fibers colocalize with a subset of microtubule tracks composed of polyglutamylated tubulin. (PMID:18209106)
• A novel MLL-SEPT2 fusion variant in therapy-related myelodysplastic syndrome is reported. (PMID:18656699)
• confirmed that the phosphorylation of SEPT2 on Ser218 by CK2 was crucial to the proliferation of HCC. These results suggest that SEPT2 might be a promising target for liver cancer therapy (PMID:19165576)
• SEPT2 is essential for the InlB-mediated entry of Listeria, but SEPT11 is not, which distinguishes the roles of different mammalian septins (PMID:19234302)
• This protein has been found differentially expressed in thalami from patients with schizophrenia. (PMID:20471030)
• septin-2 plays a fundamental role in regulating barrier function by altering cortical actin expression. (PMID:20870893)
• Data show that Septins of the SEPT6 group preferentially interacted with septins of the SEPT2 group, SEPT3 group and SEPT7 group. (PMID:21082023)
• the role of SEPT2 and SEPT11 in the InlB-Met interactions (PMID:21504731)
• Data illustrated roles of SEPT9 that might contribute to hetero-trimeric septin complex formation. SEPT9 can substitute for septins of the SEPT2 group and partially for SEPT7. (PMID:21767235)
• The SEPT2 provides the directional guidance cues necessary for polarizing the epithelial microtubule network. (PMID:21788367)
• The results shown in study support the hypothesis that single Septin 2, when present in excess or with unbalanced stoichiometries, may be unstable and assemble into amyloid-like structures. (PMID:21967827)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• SEPT2 forms a 1:1:1 complex with SEPT7 and SEPT9. (PMID:23572511)
• Data indicate that forchlorfenuron (FCF) exhibits differential binding preference for septins SEPT2 and SEPT3. (PMID:24787956)
• Authors report here that the septins SEPT2, -9, -11, and probably -7 form fibrillar structures around the chlamydial inclusion. (PMID:25293760)
• Suggest PPAR-gamma activation down-regulates hepatocellular carcinoma cell SEPT2 levels to prevent tumor growth. (PMID:25592041)
• These results suggest that SEPTIN2-mediated cytoskeletal rearrangement and STATHMIN-mediated differentiation may contribute to changes in cell morphology and differentiation of H/RS cells with CD99 upregulation in Hodgkin lymphoma. (PMID:26000982)
• From the nucleotide-free structure some interesting conclusions about the nucleotide binding properties of Cdc11 can be drawn; especially when aligning the structure with the structure of GDP bound Sept2 (PMID:26780475)
• septins protect ErbB2 from ubiquitylation, endocytosis and lysosomal degradation. Septin oligomerization regulates persistent expression of ErbB2/HER2 in gastric cancer cells. (PMID:27048593)
• The results showed that SEPT2 has an oncogenic function through accelerated cell proliferation and invasion in biliary tract cancers, and is negatively regulated by miR-140-5p. (PMID:27155525)
• Depletion of septin 2 reduces Drp1 recruitment to mitochondria and results in hyperfused mitochondria and delayed FCCP-induced fission. (PMID:27215606)
• Study discloses both SEPT2 and SEPT7 are essential for breast cancer cell migration and invasion by controlling MEK/ERK MAPKs activation. (PMID:27557506)
• Repression of SEPTIN2 and SEPTIN9 suppresses tumor growth of human glioblastoma cells and tumor progression in a mouse model. (PMID:29724999)
• Results demonstrate that in stored platelets, septine-2 and septin-6 mRNAs have miR- 223 target sites, septin-2 and septin-6 are in complex with Ago-2. The results demonstrate that like in nucleated cells, enucleated platelets also have microRNA-based mechanisms for the regulation of their septins. (PMID:29943706)
• HCC with high expression of CDK2 and SEPT2 might be more aggressive and respond poorly to current therapy. (PMID:30444001)
• Analysis of the enrichment of gene ontology cellular components highlighted some important interactions between molecules involved in the spliceosome with septin 2 and septin 7 in particular. (PMID:31420262)
• Septin2 mediates podosome maturation and endothelial cell invasion associated with angiogenesis. (PMID:31865373)
• The long non-coding RNA LINC00473 contributes to cell proliferation via JAK-STAT3 signaling pathway by regulating miR-195-5p/SEPT2 axis in prostate cancer. (PMID:32440687)
• Molecular Recognition at Septin Interfaces: The Switches Hold the Key. (PMID:32910969)
• Junctional Localization of Septin 2 Is Required for Organization of Junctional Proteins in Static Endothelial Monolayers. (PMID:33147991)
• MicroRNA7445p is downregulated in colorectal cancer and targets SEPT2 to suppress the malignant phenotype. (PMID:33200802)
• Orientational Ambiguity in Septin Coiled Coils and its Structural Basis. (PMID:33639214)
• The LncRNA FGD5-AS1/miR-497-5p axis regulates septin 2 (SEPT2) to accelerate cancer progression and increase cisplatin-resistance in laryngeal squamous cell carcinoma. (PMID:34003510)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	septin2	ENSDARG00000027590
mus_musculus	Septin2	ENSMUSG00000026276
rattus_norvegicus	Septin2	ENSRNOG00000017952

Paralogs (12): SEPTIN3 (ENSG00000100167), SEPTIN7 (ENSG00000122545), SEPTIN6 (ENSG00000125354), SEPTIN11 (ENSG00000138758), SEPTIN12 (ENSG00000140623), SEPTIN14 (ENSG00000154997), SEPTIN8 (ENSG00000164402), SEPTIN1 (ENSG00000180096), SEPTIN9 (ENSG00000184640), SEPTIN5 (ENSG00000184702), SEPTIN10 (ENSG00000186522), TMEM250 (ENSG00000238227)

Protein

Protein identifiers

Septin-2 — Q15019 (reviewed: Q15019)

Alternative names: Neural precursor cell expressed developmentally down-regulated protein 5

All UniProt accessions (21): A0A1B0GXJ2, A0A384N6H6, B5MCX3, B5MD47, C9IY94, C9IZU3, C9J2Q4, C9J938, C9JB25, C9JFT1, C9JG93, C9JQJ4, C9JSE7, C9JT15, C9JZI2, Q15019, F8WB65, F8WCX3, H7C1T1, H7C2Y0, H7C310

UniProt curated annotations — full annotation on UniProt →

Function. Filament-forming cytoskeletal GTPase. Forms a filamentous structure with SEPTIN12, SEPTIN6, SEPTIN2 and probably SEPTIN4 at the sperm annulus which is required for the structural integrity and motility of the sperm tail during postmeiotic differentiation. Required for normal organization of the actin cytoskeleton. Plays a role in the biogenesis of polarized columnar-shaped epithelium by maintaining polyglutamylated microtubules, thus facilitating efficient vesicle transport, and by impeding MAP4 binding to tubulin. Required for the progression through mitosis. Forms a scaffold at the midplane of the mitotic splindle required to maintain CENPE localization at kinetochores and consequently chromosome congression. During anaphase, may be required for chromosome segregation and spindle elongation. Plays a role in ciliogenesis and collective cell movements. In cilia, required for the integrity of the diffusion barrier at the base of the primary cilium that prevents diffusion of transmembrane proteins between the cilia and plasma membranes: probably acts by regulating the assembly of the tectonic-like complex (also named B9 complex) by localizing TMEM231 protein. May play a role in the internalization of 2 intracellular microbial pathogens, Listeria monocytogenes and Shigella flexneri.

Subunit / interactions. Septins polymerize into heterooligomeric protein complexes that form filaments, and associate with cellular membranes, actin filaments and microtubules (PubMed:17637674, PubMed:25588830, Ref.36). GTPase activity is required for filament formation. Filaments are assembled from asymmetrical heterotrimers, composed of SEPTIN2, SEPTIN6 and SEPTIN7 that associate head-to-head to form a hexameric unit. Interaction between SEPTIN2 and SEPTIN7 seems indirect. Interacts with SEPTIN5. Interaction with SEPTIN4 not detected. Interacts with SEPTIN9. Component of a septin core octameric complex consisting of SEPTIN12, SEPTIN7, SEPTIN6 and SEPTIN2 or SEPTIN4 in the order 12-7-6-2-2-6-7-12 or 12-7-6-4-4-6-7-12 and located in the sperm annulus. Interacts with MAP4. Interacts with DZIP1L.

Subcellular location. Cytoplasm. Cytoskeleton. Spindle. Chromosome. Centromere. Kinetochore. Cleavage furrow. Midbody. Cell cortex. Cell projection. Cilium membrane. Cilium. Flagellum.

Tissue specificity. Widely expressed. Up-regulated in liver cancer.

Miscellaneous. Coordinated expression with SEPTIN6 and SEPTIN7.

Similarity. Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. Septin GTPase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q15019-1	1	yes
Q15019-2	2
Q15019-3	3

RefSeq proteins (31): NP_001008491, NP_001008492, NP_001269901, NP_001269902, NP_001307958, NP_001307959, NP_001307960, NP_001307961, NP_001307962, NP_001307963, NP_001307964, NP_001336216, NP_001336217, NP_001336218, NP_001336219, NP_001336220, NP_001336231, NP_001336233, NP_001336234, NP_001336235, NP_001336236, NP_001336237, NP_001336238, NP_001336239, NP_001336240, NP_001336241, NP_001336242, NP_001336243, NP_001336244, NP_004395, NP_006146 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008113	Septin2	Family
IPR016491	Septin	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR030379	G_SEPTIN_dom	Domain

Pfam: PF00735

UniProt features (51 total): helix 11, strand 11, binding site 6, modified residue 4, mutagenesis site 4, region of interest 4, turn 4, splice variant 2, sequence conflict 2, chain 1, domain 1, site 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
6UPQ	X-RAY DIFFRACTION	1.86
6UPR	X-RAY DIFFRACTION	2.3
6UPA	X-RAY DIFFRACTION	2.51
2QNR	X-RAY DIFFRACTION	2.6
2QA5	X-RAY DIFFRACTION	3.4
7M6J	ELECTRON MICROSCOPY	3.6
2QAG	X-RAY DIFFRACTION	4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15019-F1	82.30	0.42

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 156 (important for dimerization)

Ligand- & substrate-binding residues (6): 241; 256; 44–51; 78; 104; 183–191

Post-translational modifications (4): 17, 190, 211, 218

Mutagenesis-validated functional residues (4):

Position	Phenotype
156	loss of dimerization.
218	loss of phosphorylation.
260	loss of dimerization.
270	loss of dimerization.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5620912	Anchoring of the basal body to the plasma membrane
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-5617833	Cilium Assembly

MSigDB gene sets: 304 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GOBP_REGULATION_OF_ORGANIC_ACID_TRANSPORT, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOCC_CELL_SURFACE, HSIAO_HOUSEKEEPING_GENES, GOBP_MALE_GAMETE_GENERATION, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, GOBP_ORGANIC_ACID_TRANSPORT, MORF_SKP1A, ONKEN_UVEAL_MELANOMA_UP, GOBP_CYTOKINESIS, BLALOCK_ALZHEIMERS_DISEASE_UP, MORF_CTBP1, GOBP_CILIUM_ORGANIZATION, GOBP_AMINO_ACID_TRANSPORT

GO Biological Process (9): regulation of L-glutamate import across plasma membrane (GO:0002036), smoothened signaling pathway (GO:0007224), spermatogenesis (GO:0007283), intracellular protein localization (GO:0008104), cell differentiation (GO:0030154), regulation of protein localization (GO:0032880), cilium assembly (GO:0060271), cytoskeleton-dependent cytokinesis (GO:0061640), cell division (GO:0051301)

GO Molecular Function (8): GTPase activity (GO:0003924), GTP binding (GO:0005525), enzyme regulator activity (GO:0030234), identical protein binding (GO:0042802), cadherin binding (GO:0045296), molecular adaptor activity (GO:0060090), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (32): kinetochore (GO:0000776), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), spindle (GO:0005819), plasma membrane (GO:0005886), cilium (GO:0005929), axoneme (GO:0005930), septin ring (GO:0005940), cell surface (GO:0009986), actin cytoskeleton (GO:0015629), microtubule cytoskeleton (GO:0015630), midbody (GO:0030496), septin complex (GO:0031105), cell division site (GO:0032153), cleavage furrow (GO:0032154), photoreceptor connecting cilium (GO:0032391), intercellular bridge (GO:0045171), synapse (GO:0045202), ciliary membrane (GO:0060170), extracellular exosome (GO:0070062), sperm annulus (GO:0097227), sperm principal piece (GO:0097228), non-motile cilium (GO:0097730), chromosome, centromeric region (GO:0000775), chromosome (GO:0005694), cytoskeleton (GO:0005856), cell cortex (GO:0005938), membrane (GO:0016020), motile cilium (GO:0031514), ciliary transition zone (GO:0035869), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Assembly of the 9+0 primary cilium	1
Organelle biogenesis and maintenance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
cytoskeleton	4
binding	2
intracellular membraneless organelle	2
cell cortex	2
septin cytoskeleton	2
regulation of amino acid import across plasma membrane	1
regulation of organic acid transport	1
L-glutamate import across plasma membrane	1
cell surface receptor signaling pathway	1
developmental process involved in reproduction	1
male gamete generation	1
macromolecule localization	1
cellular developmental process	1
intracellular protein localization	1
regulation of localization	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
cytokinesis	1
cellular process	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
catalytic activity	1
molecular function regulator activity	1
protein binding	1
cell adhesion molecule binding	1
molecular_function	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
condensed chromosome, centromeric region	1
supramolecular complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1

Protein interactions and networks

STRING

1455 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SEPTIN2	SEPTIN7	Q16181	828
SEPTIN2	SEPTIN6	Q14141	822
SEPTIN2	SEPTIN4	O43236	681
SEPTIN2	ANLN	Q9NQW6	659
SEPTIN2	NPHP1	O15259	651
SEPTIN2	DZIP1L	Q8IYY4	636
SEPTIN2	GP1BB	P13224	634
SEPTIN2	MAP4	P27816	625
SEPTIN2	SNAP25	P13795	604
SEPTIN2	WDPCP	O95876	576
SEPTIN2	SEPTIN9	Q9UHD8	516
SEPTIN2	HSPA8	P11142	509
SEPTIN2	SYP	P08247	495
SEPTIN2	B9D1	Q9UPM9	464
SEPTIN2	CDC42EP2	O14613	460

IntAct

141 interactions, top by confidence:

A	B	Type	Score
SEPTIN6	SEPTIN2	psi-mi:“MI:0915”(physical association)	0.950
SEPTIN2	SEPTIN6	psi-mi:“MI:0915”(physical association)	0.950
SEPTIN2	SEPTIN6	psi-mi:“MI:0403”(colocalization)	0.950
SEPTIN2	SEPTIN6	psi-mi:“MI:0914”(association)	0.950
SEPTIN6	SEPTIN2	psi-mi:“MI:0914”(association)	0.950
SEPTIN7	SEPTIN6	psi-mi:“MI:0914”(association)	0.850
SEPTIN9	SEPTIN2	psi-mi:“MI:0914”(association)	0.840
SEPTIN9	SEPTIN2	psi-mi:“MI:0915”(physical association)	0.840
SEPTIN12	SEPTIN6	psi-mi:“MI:0914”(association)	0.830
SEPTIN12	SEPTIN6	psi-mi:“MI:0403”(colocalization)	0.830
SEPTIN5	SEPTIN2	psi-mi:“MI:0915”(physical association)	0.800
SEPTIN2	SEPTIN5	psi-mi:“MI:0915”(physical association)	0.800
SEPTIN9	SEPTIN6	psi-mi:“MI:0914”(association)	0.800
SEPTIN3	SEPTIN6	psi-mi:“MI:0914”(association)	0.800

BioGRID (300): SEPT2 (Two-hybrid), SEPT5 (Two-hybrid), SEPT6 (Two-hybrid), PLEKHF2 (Two-hybrid), SEPT2 (Reconstituted Complex), SEPT2 (Affinity Capture-MS), SEPT2 (Affinity Capture-MS), SEPT2 (Affinity Capture-MS), SEPT2 (Affinity Capture-MS), SEPT2 (Affinity Capture-MS), DAZAP2 (Two-hybrid), SEPT6 (Two-hybrid), SEPT2 (Reconstituted Complex), RNF40 (Co-fractionation), SEPT10 (Co-fractionation)

ESM2 similar proteins: A0A3Q0KDV9, A1L0Y5, A2BGU8, A2VE99, A4FUM1, A5PJU9, B0KWP7, B1H120, B1MTN8, B2KIE9, B3GNI6, B5FW69, O55131, P32468, P39826, P42207, P42208, P42209, P48009, Q09116, Q0VC68, Q0VCP4, Q14141, Q15019, Q16181, Q2NKY7, Q3SZN0, Q5BKN4, Q5EB96, Q5R1W1, Q5R481, Q5R8U3, Q5RA66, Q5ZMH1, Q63ZQ1, Q6AXA6, Q6GLZ5, Q6IRQ5, Q6Q137, Q8C1B7

Diamond homologs: A0A096MJN4, A0A3Q0KDV9, A1L0Y5, A2BGU8, A2VE99, A4FUM1, A5D7Q3, A5PJU9, A6QQL3, B0BNF1, B0KWP7, B1H120, B1MTN8, B2KIE9, B3GNI6, B5FW69, G1UB61, O36023, O43236, O55131, O60165, P25342, P28661, P32457, P32458, P32468, P39826, P39827, P40797, P41901, P42207, P42208, P42209, P48008, P48009, P48010, P54359, Q04921, Q08DM7, Q09116

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CSNK2A1	down-regulates	SEPTIN2	phosphorylation
SEPTIN2	“form complex”	SEPT6/SEPT2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 109 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
cytoskeleton-dependent cytokinesis	12	100.3×	1e-19
positive regulation of protein import into nucleus	5	21.9×	9e-04
intracellular protein localization	14	15.3×	2e-10

Disease & clinical

Clinical variants and AI predictions

ClinVar

68 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2311 predictions. Top by Δscore:

Variant	Effect	Δscore
2:241325991:A:AG	acceptor_gain	1.0000
2:241325992:G:GG	acceptor_gain	1.0000
2:241325992:GCAAC:G	acceptor_gain	1.0000
2:241335212:GG:G	donor_loss	1.0000
2:241335213:G:GC	donor_loss	1.0000
2:241335973:A:AG	acceptor_gain	1.0000
2:241335974:G:GG	acceptor_gain	1.0000
2:241335974:GAAA:G	acceptor_gain	1.0000
2:241335974:GAAAA:G	acceptor_gain	1.0000
2:241336094:GATTG:G	donor_gain	1.0000
2:241336095:A:G	donor_gain	1.0000
2:241336099:G:GG	donor_gain	1.0000
2:241337380:A:AG	acceptor_gain	1.0000
2:241337381:G:GC	acceptor_gain	1.0000
2:241337381:GT:G	acceptor_gain	1.0000
2:241337381:GTT:G	acceptor_gain	1.0000
2:241337788:AGGG:A	donor_loss	1.0000
2:241337789:GG:G	donor_gain	1.0000
2:241337790:GG:G	donor_gain	1.0000
2:241337790:GGT:G	donor_loss	1.0000
2:241337791:G:GG	donor_gain	1.0000
2:241337791:GTG:G	donor_loss	1.0000
2:241337792:T:G	donor_loss	1.0000
2:241342982:A:AG	acceptor_gain	1.0000
2:241342983:T:G	acceptor_gain	1.0000
2:241342988:TCAG:T	acceptor_loss	1.0000
2:241342989:CAG:C	acceptor_loss	1.0000
2:241342990:A:AG	acceptor_gain	1.0000
2:241342990:A:G	acceptor_loss	1.0000
2:241342991:G:GG	acceptor_gain	1.0000

AlphaMissense

2403 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:241326038:G:A	G19R	1.000
2:241326038:G:C	G19R	1.000
2:241326039:G:A	G19E	1.000
2:241326041:T:C	F20L	1.000
2:241326042:T:C	F20S	1.000
2:241326042:T:G	F20C	1.000
2:241326043:T:A	F20L	1.000
2:241326043:T:G	F20L	1.000
2:241326051:T:A	L23H	1.000
2:241326051:T:C	L23P	1.000
2:241326065:C:G	H28D	1.000
2:241326069:G:C	R29P	1.000
2:241326073:A:C	K30N	1.000
2:241326073:A:T	K30N	1.000
2:241326074:T:C	S31P	1.000
2:241326086:G:C	G35R	1.000
2:241326086:G:T	G35C	1.000
2:241326087:G:A	G35D	1.000
2:241326089:T:C	F36L	1.000
2:241326090:T:C	F36S	1.000
2:241326091:T:A	F36L	1.000
2:241326091:T:G	F36L	1.000
2:241326096:T:C	F38S	1.000
2:241326113:G:C	G44R	1.000
2:241335126:G:A	G44D	1.000
2:241335126:G:T	G44V	1.000
2:241335140:G:A	G49R	1.000
2:241335140:G:C	G49R	1.000
2:241335141:G:A	G49E	1.000
2:241335141:G:T	G49V	1.000

dbSNP variants (sampled 300 via entrez): RS1000077919 (2:241329065 T>C,G), RS1000097346 (2:241329486 A>G), RS1000134804 (2:241329279 C>T), RS1000161216 (2:241339567 G>A), RS1000197078 (2:241343979 A>C,G), RS1000329569 (2:241348612 T>A,C), RS1000358132 (2:241324127 A>G), RS1000385073 (2:241349025 C>G,T), RS1000390957 (2:241318944 T>G), RS1000506075 (2:241315267 G>A), RS1000549606 (2:241329665 C>T), RS1000558367 (2:241315371 C>T), RS1000569450 (2:241351448 G>C), RS1000616658 (2:241339839 C>A,G,T), RS1000631335 (2:241329238 A>C,G)

Disease associations

OMIM: gene MIM:601506 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90013406_30	Liver enzyme levels (alkaline phosphatase)	9.000000e-16

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066337 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

49 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	3
bisphenol A	decreases expression, increases expression	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
indirubin	decreases expression	1
4-aminophenylarsenoxide	decreases reaction, affects binding	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
microcystin RR	increases expression	1
JP8 aviation fuel	decreases expression	1
U 0126	affects expression, affects reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	increases secretion, affects cotreatment	1
bisphenol B	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	increases oxidation, affects cotreatment, increases abundance	1
Dactinomycin	affects cotreatment, increases secretion	1
Ellagic Acid	increases expression	1
Furaldehyde	affects localization, decreases expression, affects cotreatment	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652414	Binding	Binding affinity to human Sep2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.