SEPTIN1

Summary

SEPTIN1 (septin 1, HGNC:2879) is a protein-coding gene on chromosome 16p11.2, encoding Septin-1 (Q8WYJ6). Filament-forming cytoskeletal GTPase.

This gene is a member of the septin family of GTPases. Members of this family are required for cytokinesis and the maintenance of cellular morphology. This gene encodes a protein that can form homo- and heterooligomeric filaments, and may contribute to the formation of neurofibrillary tangles in Alzheimer’s disease. Alternatively spliced transcript variants have been found but the full-length nature of these variants has not been determined.

Source: NCBI Gene 1731 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 9 total
• MANE Select transcript: NM_001365977

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2879
Approved symbol	SEPTIN1
Name	septin 1
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	PNUTL3, Septin-1
Ensembl gene	ENSG00000180096
Ensembl biotype	protein_coding
OMIM	612897
Entrez	1731

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 5 retained_intron, 3 protein_coding_CDS_not_defined, 2 protein_coding, 1 nonsense_mediated_decay

ENST00000321367, ENST00000562152, ENST00000563743, ENST00000563957, ENST00000566517, ENST00000567783, ENST00000568577, ENST00000570039, ENST00000572252, ENST00000573615, ENST00000652617

RefSeq mRNA: 2 — MANE Select: NM_001365977 NM_001365977, NM_052838

CCDS: CCDS10678

Canonical transcript exons

ENST00000321367 — 11 exons

Exon	Start	End
ENSE00001223015	30378135	30378520
ENSE00003471602	30381127	30381244
ENSE00003514981	30381760	30381883
ENSE00003522451	30381339	30381473
ENSE00003559621	30382525	30382561
ENSE00003568550	30382093	30382179
ENSE00003571844	30382275	30382365
ENSE00003580404	30378610	30378700
ENSE00003639741	30379018	30379183
ENSE00003657602	30379932	30380033
ENSE00003664063	30379435	30379534

Expression profiles

Bgee: expression breadth ubiquitous, 186 present calls, max score 98.50.

FANTOM5 (CAGE): breadth broad, TPM avg 7.8609 / max 362.6877, expressed in 245 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157047	6.9922	224
157048	0.5738	91
207836	0.1562	88
157049	0.1193	51
157050	0.0195	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.50	gold quality
vermiform appendix	UBERON:0001154	95.90	gold quality
spleen	UBERON:0002106	94.95	gold quality
lymph node	UBERON:0000029	94.87	gold quality
thymus	UBERON:0002370	91.40	gold quality
blood	UBERON:0000178	90.28	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.30	gold quality
bone marrow cell	CL:0002092	88.07	gold quality
mucosa of transverse colon	UBERON:0004991	85.76	gold quality
caecum	UBERON:0001153	85.29	gold quality
small intestine	UBERON:0002108	85.06	gold quality
rectum	UBERON:0001052	84.70	gold quality
sural nerve	UBERON:0015488	84.32	gold quality
right hemisphere of cerebellum	UBERON:0014890	81.11	gold quality
gall bladder	UBERON:0002110	80.85	gold quality
cerebellar hemisphere	UBERON:0002245	80.84	gold quality
cerebellar cortex	UBERON:0002129	80.69	gold quality
body of uterus	UBERON:0009853	80.12	gold quality
transverse colon	UBERON:0001157	80.05	gold quality
leukocyte	CL:0000738	79.97	gold quality
tonsil	UBERON:0002372	79.88	gold quality
putamen	UBERON:0001874	79.76	gold quality
colonic epithelium	UBERON:0000397	79.68	gold quality
skin of abdomen	UBERON:0001416	79.52	gold quality
right coronary artery	UBERON:0001625	79.43	gold quality
right uterine tube	UBERON:0001302	79.38	gold quality
nucleus accumbens	UBERON:0001882	79.12	gold quality
left uterine tube	UBERON:0001303	79.03	gold quality
apex of heart	UBERON:0002098	79.00	gold quality
skin of leg	UBERON:0001511	78.99	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	346.36
E-MTAB-10042	yes	16.01
E-ANND-3	yes	13.08
E-MTAB-8410	yes	13.02
E-MTAB-4850	no	1347.59
E-GEOD-70580	no	722.75
E-CURD-120	no	6.91
E-HCAD-5	no	2.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting SEPTIN1, 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-4328	99.57	71.06	4094
HSA-MIR-6878-5P	98.49	67.91	2142
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-4314	97.50	67.30	1369
HSA-MIR-3192-5P	96.98	65.76	1926
HSA-MIR-6089	89.72	61.35	324
HSA-MIR-25-5P	87.02	64.95	84

Literature-anchored findings (GeneRIF, showing 4)

• Aurora-B binds and phosphorylates Septin1. (PMID:16179162)
• An increase in Sept1 expression in all oral squamous-cell carcinoma-derived cell lines compared to human normal oral keratinocytes and oral premalignant lesions suggest that Sept1 expression could contribute to cancer progression, proliferation, or both. (PMID:17912427)
• The SEPT1 may participate in cell-cell and/or cell-substrate interaction in DJM-1 and exert its function in a coordinated manner with other septins. (PMID:23087102)
• SEPT1 function depends on the Golgi matrix protein GOLGA2 and on centrosomal proteins, including CEP170 and components of gamma-tubulin ring complex, to facilitate the perinuclear concentration of Golgi membranes. (PMID:30709970)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Septin1	ENSMUSG00000000486
rattus_norvegicus	Septin1	ENSRNOG00000017804
drosophila_melanogaster	Septin1	FBGN0011710
drosophila_melanogaster	Septin2	FBGN0014029
caenorhabditis_elegans		WBGENE00006795

Paralogs (12): SEPTIN3 (ENSG00000100167), SEPTIN7 (ENSG00000122545), SEPTIN6 (ENSG00000125354), SEPTIN11 (ENSG00000138758), SEPTIN12 (ENSG00000140623), SEPTIN14 (ENSG00000154997), SEPTIN8 (ENSG00000164402), SEPTIN2 (ENSG00000168385), SEPTIN9 (ENSG00000184640), SEPTIN5 (ENSG00000184702), SEPTIN10 (ENSG00000186522), TMEM250 (ENSG00000238227)

Protein

Protein identifiers

Septin-1 — Q8WYJ6 (reviewed: Q8WYJ6)

Alternative names: LARP, Peanut-like protein 3, Serologically defined breast cancer antigen NY-BR-24

All UniProt accessions (3): Q8WYJ6, I3L2M1, J3KNL2

UniProt curated annotations — full annotation on UniProt →

Function. Filament-forming cytoskeletal GTPase. May play a role in cytokinesis (Potential).

Subunit / interactions. Septins polymerize into heterooligomeric protein complexes that form filaments, and can associate with cellular membranes, actin filaments and microtubules. GTPase activity is required for filament formation. Interacts with AURKB.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Midbody.

Tissue specificity. Expressed at high levels in lymphoid and hematopoietic tissues.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WYJ6-1	1	yes
Q8WYJ6-2	2

RefSeq proteins (2): NP_001352906, NP_443070 (=MANE)

Domains & families (InterPro)

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

Pfam: PF00735

UniProt features (32 total): binding site 6, mutagenesis site 6, modified residue 5, region of interest 4, sequence conflict 4, splice variant 2, chain 1, domain 1, sequence variant 1, helix 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6WBE	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WYJ6-F1	76.68	0.16

Functional residue map

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

Ligand- & substrate-binding residues (6): 176–184; 234; 250; 37–44; 71; 97

Post-translational modifications (5): 211, 253, 256, 312, 320

Mutagenesis-validated functional residues (6):

Position	Phenotype
24	no effect on phosphorylation.
211	no effect on phosphorylation.
253	great reduction in phosphorylation.
312	great reduction in phosphorylation.
317	no effect on phosphorylation.
320	great reduction in phosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 150 (showing top): GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_LOCALIZATION, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_EXOCYTOSIS, GOBP_ORGANELLE_FISSION, GOBP_CYTOKINESIS, chr16p11, GOCC_CENTROSOME, GOBP_SECRETION, GOBP_ORGANELLE_ASSEMBLY, PID_AURORA_B_PATHWAY, PU1_Q6

GO Biological Process (6): spindle assembly involved in female meiosis (GO:0007056), intracellular protein localization (GO:0008104), regulation of exocytosis (GO:0017157), meiotic metaphase chromosome alignment (GO:0051311), cytoskeleton-dependent cytokinesis (GO:0061640), cell division (GO:0051301)

GO Molecular Function (6): GTPase activity (GO:0003924), GTP binding (GO:0005525), identical protein binding (GO:0042802), molecular adaptor activity (GO:0060090), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (10): centrosome (GO:0005813), septin ring (GO:0005940), synaptic vesicle (GO:0008021), microtubule cytoskeleton (GO:0015630), midbody (GO:0030496), septin complex (GO:0031105), cell division site (GO:0032153), meiotic spindle (GO:0072687), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
binding	2
cytoskeleton	2
cell cortex	2
septin cytoskeleton	2
female meiotic nuclear division	1
meiotic spindle assembly	1
macromolecule localization	1
exocytosis	1
regulation of vesicle-mediated transport	1
regulation of secretion by cell	1
meiotic chromosome segregation	1
metaphase chromosome alignment	1
meiotic cell cycle	1
meiotic cell cycle process	1
cytokinesis	1
cellular process	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1
molecular_function	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
centriole	1
microtubule organizing center	1
exocytic vesicle	1
presynapse	1
protein-containing complex	1
spindle	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

862 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SEPTIN1	SEPTIN4	O43236	826
SEPTIN1	AURKB	Q96GD4	725
SEPTIN1	SEPTIN11	Q9NVA2	568
SEPTIN1	SEPTIN10	Q9P0V9	533
SEPTIN1	SPAG4	Q9NPE6	475
SEPTIN1	MAPT	P10636	459
SEPTIN1	CDC42EP5	Q6NZY7	447
SEPTIN1	ANLN	Q9NQW6	438
SEPTIN1	SEPTIN5	Q99719	428
SEPTIN1	CDC42EP2	O14613	396
SEPTIN1	S1PR1	P21453	390
SEPTIN1	CCDC102A	Q96A19	339
SEPTIN1	PTPN21	Q16825	337
SEPTIN1	MAP4	P27816	325
SEPTIN1	RABEP2	Q9H5N1	325

IntAct

117 interactions, top by confidence:

A	B	Type	Score
SEPTIN1	SEPTIN5	psi-mi:“MI:0915”(physical association)	0.870
SEPTIN5	SEPTIN1	psi-mi:“MI:0915”(physical association)	0.870
SEPTIN1	SEPTIN6	psi-mi:“MI:0915”(physical association)	0.830
SEPTIN6	SEPTIN1	psi-mi:“MI:0915”(physical association)	0.830
SEPTIN12	SEPTIN1	psi-mi:“MI:0915”(physical association)	0.800
SEPTIN1	SEPTIN12	psi-mi:“MI:0915”(physical association)	0.800
SEPTIN1	SEPTIN1	psi-mi:“MI:0915”(physical association)	0.740
SEPTIN1	AURKB	psi-mi:“MI:0915”(physical association)	0.700
AURKB	SEPTIN1	psi-mi:“MI:0915”(physical association)	0.700
SEPTIN1	AURKB	psi-mi:“MI:0403”(colocalization)	0.700
SEPTIN1	AURKB	psi-mi:“MI:0217”(phosphorylation reaction)	0.700
SEPTIN1	SEPTIN3	psi-mi:“MI:0915”(physical association)	0.670
SEPTIN1	SEPTIN11	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (96): SEPT1 (Two-hybrid), SEPT5 (Two-hybrid), SEPT6 (Two-hybrid), TEX11 (Two-hybrid), SEPT12 (Two-hybrid), AMOT (Two-hybrid), SEPT4 (Affinity Capture-MS), SEPT5 (Affinity Capture-MS), SEPT2 (Affinity Capture-MS), SEPT7 (Affinity Capture-MS), SEPT6 (Affinity Capture-MS), SEPT8 (Affinity Capture-MS), SEPT11 (Affinity Capture-MS), SEPT10 (Affinity Capture-MS), SEPT9 (Affinity Capture-MS)

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

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 35 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	7	175.5×	1e-12
intracellular protein localization	8	26.2×	5e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

2383 predictions. Top by Δscore:

Variant	Effect	Δscore
16:30378697:CTTA:C	acceptor_gain	1.0000
16:30378698:TTA:T	acceptor_gain	1.0000
16:30378699:TA:T	acceptor_gain	1.0000
16:30378701:C:CC	acceptor_gain	1.0000
16:30378705:G:T	acceptor_gain	1.0000
16:30378709:CAG:C	acceptor_gain	1.0000
16:30378710:A:T	acceptor_gain	1.0000
16:30378711:G:C	acceptor_gain	1.0000
16:30378711:G:GC	acceptor_gain	1.0000
16:30379013:CTCA:C	donor_loss	1.0000
16:30379014:TCA:T	donor_loss	1.0000
16:30379016:ACC:A	donor_loss	1.0000
16:30379017:C:CA	donor_loss	1.0000
16:30379179:CTCCA:C	acceptor_gain	1.0000
16:30379180:TCCA:T	acceptor_gain	1.0000
16:30379181:CCA:C	acceptor_gain	1.0000
16:30379181:CCAC:C	acceptor_gain	1.0000
16:30379182:CA:C	acceptor_gain	1.0000
16:30379182:CAC:C	acceptor_gain	1.0000
16:30379184:C:CC	acceptor_gain	1.0000
16:30379912:T:A	donor_gain	1.0000
16:30379930:ACC:A	donor_loss	1.0000
16:30379931:C:CG	donor_loss	1.0000
16:30379945:T:TA	donor_gain	1.0000
16:30380036:C:CT	acceptor_gain	1.0000
16:30380037:A:T	acceptor_gain	1.0000
16:30381123:A:AC	donor_gain	1.0000
16:30381124:C:CC	donor_gain	1.0000
16:30381124:CA:C	donor_gain	1.0000
16:30381387:T:TA	donor_gain	1.0000

AlphaMissense

2722 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:30378620:T:A	K336I	0.999
16:30379114:A:G	L277P	0.999
16:30379515:A:T	V227D	0.999
16:30381182:A:T	V168D	0.999
16:30381378:A:T	V134D	0.999
16:30381388:C:G	D131H	0.999
16:30382161:T:A	K38I	0.999
16:30378519:A:G	L340P	0.998
16:30378619:T:A	K336N	0.998
16:30378619:T:G	K336N	0.998
16:30379524:G:T	P224H	0.998
16:30381133:C:A	K184N	0.998
16:30381133:C:G	K184N	0.998
16:30381371:G:C	C136W	0.998
16:30381387:T:G	D131A	0.998
16:30381811:A:G	L85P	0.998
16:30382297:A:C	F24L	0.998
16:30382297:A:T	F24L	0.998
16:30382299:A:G	F24L	0.998
16:30379075:C:G	R290P	0.997
16:30379450:A:G	W249R	0.997
16:30379450:A:T	W249R	0.997
16:30381173:T:A	K171I	0.997
16:30381373:A:G	C136R	0.997
16:30381381:C:G	R133P	0.997
16:30381382:G:C	R133G	0.997
16:30381387:T:A	D131V	0.997
16:30381402:C:A	R126L	0.997
16:30381402:C:G	R126P	0.997
16:30381426:A:G	L118P	0.997

dbSNP variants (sampled 300 via entrez): RS1000626290 (16:30383346 G>A,T), RS1000670604 (16:30382523 A>C), RS1001465514 (16:30383435 C>T), RS1001526053 (16:30378102 C>T), RS1002467867 (16:30381870 C>T), RS1002828678 (16:30379610 A>C,G), RS1003143961 (16:30384751 G>A), RS1003183055 (16:30378580 C>T), RS1003542365 (16:30381158 A>G), RS1003931757 (16:30380100 A>C,T), RS1004168258 (16:30381410 G>C), RS1004905365 (16:30382124 G>A,C,T), RS1005340333 (16:30381552 T>C), RS1006090038 (16:30380499 A>G), RS1006161978 (16:30380175 C>T)

Disease associations

OMIM: gene MIM:612897 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010703_269	Brain morphology (MOSTest)	4.000000e-13
GCST010796_3833	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-09
GCST010796_3834	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases abundance, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
abrine	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Diuron	decreases expression	1
Nickel	increases expression	1
Thiram	decreases expression	1
Valproic Acid	increases methylation	1
Metribolone	increases expression	1
Asbestos, Serpentine	increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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