SEPTIN3

Summary

SEPTIN3 (septin 3, HGNC:10750) is a protein-coding gene on chromosome 22q13.2, encoding Neuronal-specific septin-3 (Q9UH03). Filament-forming cytoskeletal GTPase.

This gene belongs to the septin family of GTPases. Members of this family are required for cytokinesis. Expression is upregulated by retinoic acid in a human teratocarcinoma cell line. The specific function of this gene has not been determined. Alternative splicing of this gene results in several transcript variants encoding different isoforms.

Source: NCBI Gene 55964 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 42 total
• MANE Select transcript: NM_001363845

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10750
Approved symbol	SEPTIN3
Name	septin 3
Location	22q13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000100167
Ensembl biotype	protein_coding
OMIM	608314
Entrez	55964

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000396417, ENST00000396425, ENST00000396426, ENST00000406029, ENST00000449288, ENST00000460267, ENST00000644076

RefSeq mRNA: 15 — MANE Select: NM_001363845 NM_001363845, NM_001389668, NM_001389669, NM_001389670, NM_001389671, NM_001389672, NM_001389673, NM_001389674, NM_001389675, NM_001389676, NM_001389677, NM_001389678, NM_001389679, NM_019106, NM_145733

CCDS: CCDS14026, CCDS14027, CCDS87030

Canonical transcript exons

ENST00000644076 — 12 exons

Exon	Start	End
ENSE00000656333	41985984	41986112
ENSE00003464447	41992664	41992763
ENSE00003488876	41981645	41981836
ENSE00003538406	41989567	41989684
ENSE00003541225	41994621	41994714
ENSE00003555316	41994290	41994341
ENSE00003588971	41991573	41991668
ENSE00003595981	41996902	41998221
ENSE00003605481	41987206	41987287
ENSE00003650387	41987622	41987759
ENSE00003820011	41971474	41972996
ENSE00003823202	41969443	41969677

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 99.60.

FANTOM5 (CAGE): breadth broad, TPM avg 7.9086 / max 341.3816, expressed in 578 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192526	7.2189	565
192525	0.4945	114
192527	0.1141	59
192524	0.0505	26
192528	0.0305	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.60	gold quality
ganglionic eminence	UBERON:0004023	99.40	gold quality
right frontal lobe	UBERON:0002810	98.69	gold quality
ventricular zone	UBERON:0003053	98.57	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.51	gold quality
anterior cingulate cortex	UBERON:0009835	98.49	gold quality
prefrontal cortex	UBERON:0000451	98.48	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.33	gold quality
frontal cortex	UBERON:0001870	98.31	gold quality
cerebellar hemisphere	UBERON:0002245	98.26	gold quality
cerebellar cortex	UBERON:0002129	98.24	gold quality
neocortex	UBERON:0001950	98.20	gold quality
amygdala	UBERON:0001876	98.16	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.14	gold quality
postcentral gyrus	UBERON:0002581	98.12	gold quality
cerebral cortex	UBERON:0000956	98.11	gold quality
superior frontal gyrus	UBERON:0002661	98.05	gold quality
entorhinal cortex	UBERON:0002728	97.96	gold quality
cerebellum	UBERON:0002037	97.89	gold quality
Ammon’s horn	UBERON:0001954	97.88	gold quality
temporal lobe	UBERON:0001871	97.66	gold quality
caudate nucleus	UBERON:0001873	97.49	gold quality
nucleus accumbens	UBERON:0001882	97.41	gold quality
parietal lobe	UBERON:0001872	97.23	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.67	gold quality
hypothalamus	UBERON:0001898	96.57	gold quality
putamen	UBERON:0001874	96.09	gold quality
brain	UBERON:0000955	95.59	gold quality
forebrain	UBERON:0001890	95.44	gold quality
middle temporal gyrus	UBERON:0002771	94.00	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.70

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 6)

• Data show that Septins of the SEPT6 group preferentially interacted with septins of the SEPT2 group, SEPT3 group and SEPT7 group. (PMID:21082023)
• septins from the SEPT3 subgroup may be important determinants of polymerization by occupying the terminal position in octameric units which themselves form the building blocks of at least some heterofilaments (PMID:23163726)
• Data indicate that forchlorfenuron (FCF) exhibits differential binding preference for septins SEPT2 and SEPT3. (PMID:24787956)
• SUMOylation of human septins is critical for septin filament bundling and cytokinesis. (PMID:29051266)
• argeted RNA sequencing was used to screen 60 melanoma patient-derived xenograft (PDX) models for BRAF fusions. We identified three unique BRAF fusions, including a novel SEPT3-BRAF fusion, occurring in four tumors (4/60, 6.7%), all of which were “pan-negative” (lacking other common mutations) (4/18, 22.2%). (PMID:30254212)
• Molecular Recognition at Septin Interfaces: The Switches Hold the Key. (PMID:32910969)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	septin3	ENSDARG00000030656
mus_musculus	Septin3	ENSMUSG00000022456
rattus_norvegicus	Septin3	ENSRNOG00000007686
drosophila_melanogaster	Septin2	FBGN0014029
caenorhabditis_elegans		WBGENE00006795

Paralogs (12): SEPTIN7 (ENSG00000122545), SEPTIN6 (ENSG00000125354), SEPTIN11 (ENSG00000138758), SEPTIN12 (ENSG00000140623), SEPTIN14 (ENSG00000154997), SEPTIN8 (ENSG00000164402), SEPTIN2 (ENSG00000168385), SEPTIN1 (ENSG00000180096), SEPTIN9 (ENSG00000184640), SEPTIN5 (ENSG00000184702), SEPTIN10 (ENSG00000186522), TMEM250 (ENSG00000238227)

Protein

Protein identifiers

Neuronal-specific septin-3 — Q9UH03 (reviewed: Q9UH03)

All UniProt accessions (4): Q9UH03, A0A2R8Y4H2, B1AHR1, B1AHR2

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.

Subcellular location. Cytoplasm. Cytoskeleton. Synapse.

Tissue specificity. Brain-specific.

Post-translational modifications. Phosphorylated by PKG on serine residues. Phosphorylated by PKG on Ser-91.

Induction. Up-regulated during neuronal differentiation.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UH03-1	1, A, SEP3A	yes
Q9UH03-2	2, B, SEP3B
Q9UH03-3	3, C, SEP3C

RefSeq proteins (15): NP_001350774, NP_001376597, NP_001376598, NP_001376599, NP_001376600, NP_001376601, NP_001376602, NP_001376603, NP_001376604, NP_001376605, NP_001376606, NP_001376607, NP_001376608, NP_061979, NP_663786 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008114	Septin3	Family
IPR016491	Septin	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR030379	G_SEPTIN_dom	Domain

Pfam: PF00735

UniProt features (45 total): helix 12, strand 12, binding site 5, turn 5, region of interest 4, splice variant 3, chain 1, domain 1, modified residue 1, compositionally biased region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
4Z54	X-RAY DIFFRACTION	1.83
4Z51	X-RAY DIFFRACTION	1.86
6UQQ	X-RAY DIFFRACTION	2.75
3SOP	X-RAY DIFFRACTION	2.88

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UH03-F1	82.49	0.57

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 (5): 265; 280; 68–75; 102; 208–216

Post-translational modifications (1): 91

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 133 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GGGTGGRR_PAX4_03, AATGGAG_MIR136, CAGCTG_AP4_Q5, CATTTCA_MIR203, GOBP_CYTOKINESIS, USF_01, HEN1_01, TAATGTG_MIR323, GTGACTT_MIR224, RODRIGUES_DCC_TARGETS_DN, GTGTGAG_MIR342, AP4_01, GOBP_CYTOSKELETON_DEPENDENT_CYTOKINESIS, GOBP_CELL_DIVISION

GO Biological Process (3): intracellular protein localization (GO:0008104), 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 (8): septin ring (GO:0005940), microtubule cytoskeleton (GO:0015630), septin complex (GO:0031105), cell division site (GO:0032153), presynapse (GO:0098793), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), synapse (GO:0045202)

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
macromolecule localization	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
protein-containing complex	1
synapse	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
cell junction	1

Protein interactions and networks

STRING

1396 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SEPTIN3	SEPTIN4	O43236	860
SEPTIN3	PRKG1	P14619	841
SEPTIN3	PDE5A	O76074	601
SEPTIN3	SEPTIN5	Q99719	597
SEPTIN3	SEPTIN7	Q16181	513
SEPTIN3	SEPTIN6	Q14141	490
SEPTIN3	IFT27	Q9BW83	468
SEPTIN3	PHETA2	Q6ICB4	447
SEPTIN3	SEPTIN11	Q9NVA2	445
SEPTIN3	DNAJC22	Q8N4W6	445
SEPTIN3	CDC42EP5	Q6NZY7	429
SEPTIN3	ANKRD52	Q8NB46	421
SEPTIN3	A0A087WZY1	A0A087WZY1	413
SEPTIN3	PRH1	P02810	409
SEPTIN3	PLK2	Q9NYY3	400

IntAct

106 interactions, top by confidence:

A	B	Type	Score
SEPTIN2	SEPTIN6	psi-mi:“MI:0914”(association)	0.950
SEPTIN6	SEPTIN2	psi-mi:“MI:0914”(association)	0.950
SEPTIN12	SEPTIN6	psi-mi:“MI:0914”(association)	0.830
SEPTIN6	SEPTIN3	psi-mi:“MI:0915”(physical association)	0.800
SEPTIN3	SEPTIN6	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
RNF8	SEPTIN3	psi-mi:“MI:0915”(physical association)	0.780
SEPTIN3	RNF8	psi-mi:“MI:0915”(physical association)	0.780
SEPTIN12	SEPTIN4	psi-mi:“MI:0914”(association)	0.730
SDCBP	SEPTIN3	psi-mi:“MI:0915”(physical association)	0.720
SEPTIN3	CKS1B	psi-mi:“MI:0915”(physical association)	0.720
SEPTIN3	MOB1A	psi-mi:“MI:0915”(physical association)	0.720
SEPTIN3	SDCBP	psi-mi:“MI:0915”(physical association)	0.720
CKS1B	SEPTIN3	psi-mi:“MI:0915”(physical association)	0.720
MOB1A	SEPTIN3	psi-mi:“MI:0915”(physical association)	0.720
SEPTIN3	SEPTIN3	psi-mi:“MI:0915”(physical association)	0.670
SEPTIN1	SEPTIN3	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (106): SEPT3 (Two-hybrid), SEPT3 (Two-hybrid), SEPT3 (Two-hybrid), SEPT3 (Two-hybrid), SEPT3 (Two-hybrid), SEPT3 (Two-hybrid), SEPT3 (Two-hybrid), SEPT3 (Two-hybrid), SEPT3 (Affinity Capture-MS), SEPT3 (Affinity Capture-MS), SEPT4 (Affinity Capture-MS), SEPT2 (Affinity Capture-MS), SEPT7 (Affinity Capture-MS), SEPT14 (Affinity Capture-MS), SEPT5 (Affinity Capture-MS)

ESM2 similar proteins: A0A096MJN4, A2BGU8, A4FUM1, A5D7Q3, A5PJU9, A6QQL3, B0BNF1, B0KWP7, B1H120, B1MTN8, B2KIE9, B3GNI6, B5FW69, O36023, O43236, P28661, P32468, P40797, P42209, P48010, Q08DM7, Q0VC68, Q0VCP4, Q14141, Q2KJB1, Q3SZN0, Q4R4X5, Q4R555, Q4V8G5, Q5EB96, Q5PQK1, Q5R6R7, Q5REG8, Q6AXA6, Q6IRQ5, Q8C1B7, Q8C650, Q8CHH9, Q8IYM1, Q92599

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

1 interactions.

A	Effect	B	Mechanism
PRKG1	“up-regulates activity”	SEPTIN3	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 63 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	10	129.4×	4e-17
intracellular protein localization	10	16.9×	1e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1444 predictions. Top by Δscore:

Variant	Effect	Δscore
22:41981831:T:TA	donor_gain	1.0000
22:41987199:C:G	acceptor_gain	1.0000
22:41987204:A:AG	acceptor_gain	1.0000
22:41987205:G:GA	acceptor_gain	1.0000
22:41987332:G:GT	donor_gain	1.0000
22:41987332:G:T	donor_gain	1.0000
22:41987617:A:AG	acceptor_gain	1.0000
22:41987618:TCA:T	acceptor_loss	1.0000
22:41987620:A:AG	acceptor_gain	1.0000
22:41987620:AGCT:A	acceptor_gain	1.0000
22:41987620:AGCTG:A	acceptor_gain	1.0000
22:41987621:G:A	acceptor_loss	1.0000
22:41987621:G:GA	acceptor_gain	1.0000
22:41987621:GC:G	acceptor_gain	1.0000
22:41987621:GCT:G	acceptor_gain	1.0000
22:41987621:GCTG:G	acceptor_gain	1.0000
22:41987621:GCTGG:G	acceptor_gain	1.0000
22:41987694:G:GT	donor_gain	1.0000
22:41987760:G:GG	donor_gain	1.0000
22:41989557:T:A	acceptor_gain	1.0000
22:41989559:T:TA	acceptor_gain	1.0000
22:41989563:CCAGC:C	acceptor_loss	1.0000
22:41989564:CAGCT:C	acceptor_loss	1.0000
22:41989565:A:AG	acceptor_gain	1.0000
22:41989565:AGCTT:A	acceptor_gain	1.0000
22:41989566:G:A	acceptor_loss	1.0000
22:41989566:G:GA	acceptor_gain	1.0000
22:41989566:GC:G	acceptor_gain	1.0000
22:41989566:GCT:G	acceptor_gain	1.0000
22:41989566:GCTT:G	acceptor_gain	1.0000

AlphaMissense

5578 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:41981836:G:C	G68R	1.000
22:41985999:G:A	G73D	1.000
22:41987236:T:C	L121P	1.000
22:41987669:T:C	L154P	1.000
22:41987693:G:C	R162T	1.000
22:41987693:G:T	R162M	1.000
22:41987694:G:C	R162S	1.000
22:41987694:G:T	R162S	1.000
22:41987716:C:A	R170S	1.000
22:41989635:C:A	A207D	1.000
22:41994638:T:C	L312P	1.000
22:41994677:G:C	R325T	1.000
22:41994677:G:T	R325M	1.000
22:41994678:G:C	R325S	1.000
22:41994678:G:T	R325S	1.000
22:41981761:G:C	G43R	0.999
22:41981762:G:A	G43D	0.999
22:41985984:G:A	G68D	0.999
22:41985984:G:T	G68V	0.999
22:41985993:G:A	G71E	0.999
22:41985998:G:C	G73R	0.999
22:41985999:G:T	G73V	0.999
22:41986001:A:C	K74Q	0.999
22:41986002:A:T	K74I	0.999
22:41986004:T:C	S75P	0.999
22:41986011:T:C	L77P	0.999
22:41986023:T:C	L81P	0.999
22:41987236:T:A	L121Q	0.999
22:41987242:T:A	V123D	0.999
22:41987256:G:C	G128R	0.999

dbSNP variants (sampled 300 via entrez): RS1000082910 (22:41974234 G>T), RS1000083081 (22:41984307 T>G), RS1000183224 (22:41980484 C>T), RS1000462505 (22:41987363 C>A,T), RS1000654027 (22:41972060 T>C), RS1000723010 (22:41972385 C>T), RS1000766377 (22:41986890 C>A), RS1000899262 (22:41978900 G>GGAGGAT), RS1000922030 (22:41991909 A>C,T), RS1001136337 (22:41972357 TC>T), RS1001223439 (22:41993956 T>A), RS1001378336 (22:41995163 C>G), RS1001762370 (22:41995519 C>G), RS1002050344 (22:41973191 C>G,T), RS1002090412 (22:41971377 G>A)

Disease associations

OMIM: gene MIM:608314 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002539_95	Schizophrenia	2.000000e-09
GCST004364_23	Intelligence	3.000000e-10
GCST004364_5	Intelligence	3.000000e-10
GCST004521_160	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST004521_244	Autism spectrum disorder or schizophrenia	4.000000e-09
GCST006269_787	General cognitive ability	3.000000e-09
GCST006803_13	Schizophrenia	2.000000e-14
GCST008403_16	Arterial stiffness index	3.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004517	arterial stiffness measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

4 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs739296	Toxicity	3	codeine	adverse events
rs739296	Toxicity	3	oxycodone	adverse events
rs739296	Toxicity	3	hydrocodone	adverse events
rs739296	Toxicity	3	tramadol	adverse events

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs739296	SEPTIN3, WBP2NL	3	0.00	4	hydrocodone;codeine;oxycodone;tramadol
rs56234624	SEPTIN3		0.00	0
rs1062753	SEPTIN3, WBP2NL		0.00	0
rs11914200	SEPTIN3		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cisplatin	affects expression, affects cotreatment, increases expression	2
2,4,6-tribromophenol	decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases expression	1
sulforaphane	decreases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
tetrabromobisphenol A	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
pentanal	increases expression	1
scriptaid	affects expression	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	affects cotreatment, increases expression	1
ICG 001	affects expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Vorinostat	decreases expression	1
Aldehydes	increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Lipopolysaccharides	decreases expression, affects cotreatment	1
Naled	affects expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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