SEPTIN7

Summary

SEPTIN7 (septin 7, HGNC:1717) is a protein-coding gene on chromosome 7p14.2, encoding Septin-7 (Q16181). Filament-forming cytoskeletal GTPase. It is a selective cancer dependency (DepMap: 59.5% of cell lines).

This gene encodes a protein that is highly similar to the CDC10 protein of Saccharomyces cerevisiae. The protein also shares similarity with Diff 6 of Drosophila and with H5 of mouse. Each of these similar proteins, including the yeast CDC10, contains a GTP-binding motif. The yeast CDC10 protein is a structural component of the 10 nm filament which lies inside the cytoplasmic membrane and is essential for cytokinesis. This human protein functions in gliomagenesis and in the suppression of glioma cell growth, and it is required for the association of centromere-associated protein E with the kinetochore. Alternative splicing results in multiple transcript variants. Several related pseudogenes have been identified on chromosomes 5, 7, 9, 10, 11, 14, 17 and 19.

Source: NCBI Gene 989 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 49 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 59.5% of screened cell lines
• MANE Select transcript: NM_001788

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1717
Approved symbol	SEPTIN7
Name	septin 7
Location	7p14.2
Locus type	gene with protein product
Status	Approved
Aliases	CDC3, SEPT7A, Septin-7
Ensembl gene	ENSG00000122545
Ensembl biotype	protein_coding
OMIM	603151
Entrez	989

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 9 protein_coding, 6 protein_coding_CDS_not_defined, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000350320, ENST00000399034, ENST00000399035, ENST00000425198, ENST00000435235, ENST00000473201, ENST00000475109, ENST00000485569, ENST00000492940, ENST00000493626, ENST00000634591, ENST00000634600, ENST00000634700, ENST00000635047, ENST00000635175, ENST00000635420, ENST00000635669, ENST00000672279, ENST00000705486

RefSeq mRNA: 5 — MANE Select: NM_001788 NM_001011553, NM_001242956, NM_001363715, NM_001375299, NM_001788

CCDS: CCDS75582, CCDS87494, CCDS94085, CCDS94086

Canonical transcript exons

ENST00000350320 — 14 exons

Exon	Start	End
ENSE00000832354	35890668	35890793
ENSE00000832356	35903076	35903215
ENSE00001263591	35882484	35882576
ENSE00001606979	35883891	35883987
ENSE00001662836	35898248	35898383
ENSE00001677112	35885828	35885879
ENSE00003476218	35879823	35879940
ENSE00003489138	35832798	35832900
ENSE00003534423	35873641	35873775
ENSE00003555918	35872666	35872766
ENSE00003613005	35904254	35907110
ENSE00003615147	35863552	35863658
ENSE00003749079	35801057	35801270
ENSE00003784003	35831492	35831496

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 131.0230 / max 6573.9553, expressed in 1816 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
78113	122.0240	1812
78111	3.7969	1274
78110	3.1505	1251
78112	1.3167	756
78115	0.7349	327

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	99.84	gold quality
subthalamic nucleus	UBERON:0001906	99.67	gold quality
occipital lobe	UBERON:0002021	99.64	gold quality
lateral globus pallidus	UBERON:0002476	99.64	gold quality
ventricular zone	UBERON:0003053	99.64	gold quality
inferior vagus X ganglion	UBERON:0005363	99.64	gold quality
prefrontal cortex	UBERON:0000451	99.62	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.62	gold quality
primary visual cortex	UBERON:0002436	99.62	gold quality
calcaneal tendon	UBERON:0003701	99.61	gold quality
endothelial cell	CL:0000115	99.58	gold quality
amygdala	UBERON:0001876	99.57	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.57	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.56	gold quality
medulla oblongata	UBERON:0001896	99.54	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.54	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.54	gold quality
superior vestibular nucleus	UBERON:0007227	99.54	gold quality
pons	UBERON:0000988	99.52	gold quality
putamen	UBERON:0001874	99.52	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.52	gold quality
ganglionic eminence	UBERON:0004023	99.51	gold quality
cranial nerve II	UBERON:0000941	99.49	gold quality
midbrain	UBERON:0001891	99.48	gold quality
substantia nigra	UBERON:0002038	99.48	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.48	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.47	gold quality
ventral tegmental area	UBERON:0002691	99.46	gold quality
temporal lobe	UBERON:0001871	99.45	gold quality
substantia nigra pars compacta	UBERON:0001965	99.45	gold quality

Single-cell (SCXA)

Detected in 25 experiment(s), a significant marker in 17.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	90.75
E-MTAB-10287	yes	64.99
E-HCAD-25	yes	49.38
E-HCAD-10	yes	41.39
E-MTAB-8142	yes	38.99
E-GEOD-84465	yes	25.98
E-HCAD-11	yes	25.75
E-MTAB-8410	yes	18.47
E-CURD-88	yes	16.31
E-MTAB-7316	yes	15.07
E-MTAB-10042	yes	12.50
E-CURD-46	yes	12.33
E-GEOD-134144	yes	11.52
E-GEOD-137537	yes	6.99
E-HCAD-9	yes	5.29

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, GATA3, GLI1

miRNA regulators (miRDB)

204 targeting SEPTIN7, 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-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 59.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Sept7/9b/11 form a complex that has effects on filament elongation, bundling, or disruption (PMID:15485874)
• 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)
• SEPT7 forms a link between kinetochore distribution of CENP-E and the mitotic spindle checkpoint. (PMID:18460473)
• SEPT7 gene can inhibit the invasion and migration ability of U251 glioma cells by reversing imbalanced state of MMPs/TIMPs, downregulating expression of integrin alpha(v)beta(3) and altering structure of tubulin-alpha. (PMID:18543212)
• regulated but the expression of CDK9, CDC20 and CLK3 was down- regulated in azoospermic testes. (PMID:19426592)
• SEPT7 plays an important role in the glioma cell invasion. (PMID:19916744)
• This study demonstrates that SEPT7 is involved in gliomagenesis and suppresses glioma cell growth. (PMID:20035367)
• SEPT7 is involved in the regulation of sperm maturation. (PMID:20352323)
• The expression of SEPT7 mRNA was significantly decreased by 6.9% in subjects with schizophrenia. (PMID:20385374)
• Data show that Septins of the SEPT6 group preferentially interacted with septins of the SEPT2 group, SEPT3 group and SEPT7 group. (PMID:21082023)
• SEPT7 gene expression is decreased in follicular variant of papillary thyroid carcinoma. (PMID:21509594)
• Mutagenic analyses revealed that mutation of a potential phosphorylation site in SEPT7 (Y318) regulates the interaction with other septins. (PMID:21767235)
• The SEPT7 provides the directional guidance cues necessary for polarizing the epithelial microtubule network. (PMID:21788367)
• Sept7 occupies the ends of hexameric building blocks which assemble into non-polarised filaments. (PMID:21824007)
• the purification, crystallization and structure for the GTP-binding domain of human septin 7 (PMID:22064074)
• Myeloid K562 cells express three SEPT9 isoforms, all of which have an equal propensity to hetero-oligomerize with SEPT7-containing hexamers to generate octameric heteromers. (PMID:22956766)
• SEPT2 forms a 1:1:1 complex with SEPT7 and SEPT9. (PMID:23572511)
• Overexpression of the yeast septin7 ortholog CDC10 also conferred resistance to the negative effects of copper as well as protecting cells from the overexpression of Bax. (PMID:24055994)
• In response to Candida albicans infection, SEPT7 forms a complex with endothelial cell N-cadherin, is required for normal accumulation of N-cadherin around hyphae, and is necessary for maximal fungal endocytosis. (PMID:24345743)
• Significantly lower SEPT7 expression in all expressional categories in encapsulated papillary thyroid carcinoma, follicular variant group may be a sign of different molecular signature in this type of tissue. (PMID:24685401)
• Significantly lower SEPT7 expression in encapsulated follicular variant of papillary thyroid carcinoma may be a sign of different molecular signature in this type of tissue. (PMID:24685401)
• Septin6 and Septin7 GTP binding proteins regulate AP-3- and ESCRT-dependent multivesicular body biogenesis (PMID:25380047)
• Results show that SEPT7 is involved in glioma cell migration with the assistance of cofilin phosphomediated cytoskeleton locomotion. (PMID:26846171)
• Low SEPT7 expression is associated with glioma cell invasion. (PMID:27006177)
• Study discloses both SEPT2 and SEPT7 are essential for breast cancer cell migration and invasion by controlling MEK/ERK MAPKs activation. (PMID:27557506)
• The results of this study found that bipolar Neural crest cells progenitors lose their polarity, retracting their processes to round for division, but generate neurons with bipolar morphology by emitting processes from the same locations as the progenitor. (PMID:28817802)
• SUMOylation of human septins is critical for septin filament bundling and cytokinesis. (PMID:29051266)
• SEPT7 overexpression and knockdown sept7 protein suppress the expression of 78 kDa glucoseregulated protein (GRP78), C/EBPhomologous protein (CHOP), pro-caspase3 and cleaved caspase3 and eIf 2alpha protein. (PMID:29344665)
• The present study identified that SEPT7 was a potential target of miR5903p and demonstrated that SEPT7 is associated with mediating the proapoptotic effect of miR5903p in human osteoblast cell line hFOB 1.19. (PMID:29568931)
• The role of septin 7 in cell proliferation, cytokinesis, nervous and reproductive systems, as well as the underlying molecular events linking septin 7 to various diseases, such as Alzheimer’s disease, schizophrenia, neuropsychiatric systemic lupus erythematosus, tumour. (PMID:29602250)
• we have identified septin 7, an essential cellular component implicated in the final steps of cell division, as a strong Bt-dependent gene regulatory protein binding to the promoter of CALB2. (PMID:29699512)
• This study revealed septin7 may potentially play a proapoptotic role in podocyte under diabetic conditions. (PMID:30361092)
• present two high-resolution structures of the SEPT7 GTPase domain complexed with GDP. The higher resolution structures provide unambiguous insight into the interactions at the G-interface where a structural motif based on an antiparallel beta-bridge allows for the rationalization of why some septins show nucleotide-dependent beta-strand slippage and others do not. (PMID:31009756)
• 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)
• SEPT7 regulates Ca(2+) entry through Orai channels in human neural progenitor cells and neurons. (PMID:32682163)
• Septin 7 is a centrosomal protein that ensures S phase entry and microtubule nucleation by maintaining the abundance of p150(glued). (PMID:32869310)
• Molecular Recognition at Septin Interfaces: The Switches Hold the Key. (PMID:32910969)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	septin7a	ENSDARG00000087647
mus_musculus	Septin7	ENSMUSG00000001833
rattus_norvegicus	AABR07033045.1	ENSRNOG00000000713
rattus_norvegicus	Septin7	ENSRNOG00000006545
rattus_norvegicus		ENSRNOG00000082485
rattus_norvegicus		ENSRNOG00000090102
rattus_norvegicus		ENSRNOG00000090776
drosophila_melanogaster	pnut	FBGN0013726
caenorhabditis_elegans	unc-59	WBGENE00006793

Paralogs (12): SEPTIN3 (ENSG00000100167), 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

Septin-7 — Q16181 (reviewed: Q16181)

Alternative names: CDC10 protein homolog

All UniProt accessions (10): A0A024RA87, A0A0U1RQW0, A0A0U1RRE1, A0A0U1RRH9, A0A0U1RRM2, A0A5F9ZGZ7, E7EPK1, E7ES33, G3V1Q4, Q16181

UniProt curated annotations — full annotation on UniProt →

Function. Filament-forming cytoskeletal GTPase. Required for normal organization of the actin cytoskeleton. Required for normal progress through mitosis. Involved in cytokinesis. Required for normal association of CENPE with the kinetochore. Plays a role in ciliogenesis and collective cell movements. 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.

Subunit / interactions. Septins polymerize into heterooligomeric protein complexes that form filaments, and associate with cellular membranes, actin filaments and microtubules. 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. Within the trimer, directly interacts with SEPTIN6, while interaction with SEPTIN2 seems indirect. In the absence of SEPTIN6, forms homodimers. Interacts directly with CENPE and links CENPE to septin filaments composed of SEPTIN2, SEPTIN6 and SEPTIN7. Interacts with SEPTIN5 and SEPTIN8. Interacts with SEPTIN9 and SEPTIN11. 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; the SEPTIN12:SEPTIN7 association is mediated by the respective GTP-binding domains.

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

Tissue specificity. Widely expressed.

Miscellaneous. Coordinated expression with SEPTIN2 and SEPTIN6.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q16181-1	1	yes
Q16181-2	2

RefSeq proteins (5): NP_001011553, NP_001229885, NP_001350644, NP_001362228, NP_001779* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008115	Septin7	Family
IPR016491	Septin	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR030379	G_SEPTIN_dom	Domain

Pfam: PF00735

UniProt features (56 total): strand 13, helix 11, modified residue 8, binding site 6, region of interest 5, turn 5, sequence conflict 2, initiator methionine 1, chain 1, domain 1, splice variant 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
6N0B	X-RAY DIFFRACTION	1.74
8SJJ	X-RAY DIFFRACTION	1.78
6N12	X-RAY DIFFRACTION	2.23
6UQQ	X-RAY DIFFRACTION	2.75
3T5D	X-RAY DIFFRACTION	3.3
3TW4	X-RAY DIFFRACTION	3.35
7M6J	ELECTRON MICROSCOPY	3.6
2QAG	X-RAY DIFFRACTION	4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16181-F1	80.75	0.35

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): 57–64; 90; 116; 195–203; 250; 265

Post-translational modifications (8): 2, 30, 77, 228, 334, 373, 424, 426

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5687128	MAPK6/MAPK4 signaling
R-HSA-162582	Signal Transduction
R-HSA-5683057	MAPK family signaling cascades

MSigDB gene sets: 329 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, WENDT_COHESIN_TARGETS_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, MORF_CDK2, TACAATC_MIR508, GOBP_MALE_GAMETE_GENERATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GGGTGGRR_PAX4_03, AAAYRNCTG_UNKNOWN, CAGCTG_AP4_Q5, YY1_Q6, MORF_TERF1

GO Biological Process (8): spermatogenesis (GO:0007283), intracellular protein localization (GO:0008104), regulation of embryonic cell shape (GO:0016476), cell differentiation (GO:0030154), cilium assembly (GO:0060271), cytoskeleton-dependent cytokinesis (GO:0061640), positive regulation of non-motile cilium assembly (GO:1902857), cell division (GO:0051301)

GO Molecular Function (8): GTPase activity (GO:0003924), structural molecule activity (GO:0005198), GTP binding (GO:0005525), 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 (23): kinetochore (GO:0000776), stress fiber (GO:0001725), nucleus (GO:0005634), spindle (GO:0005819), cytosol (GO:0005829), axoneme (GO:0005930), septin ring (GO:0005940), microtubule cytoskeleton (GO:0015630), midbody (GO:0030496), septin complex (GO:0031105), cell division site (GO:0032153), cleavage furrow (GO:0032154), extracellular exosome (GO:0070062), sperm annulus (GO:0097227), non-motile cilium (GO:0097730), chromosome, centromeric region (GO:0000775), chromosome (GO:0005694), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), apical plasma membrane (GO:0016324), motile cilium (GO:0031514), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
MAPK family signaling cascades	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
intracellular membraneless organelle	4
cytoskeleton	3
molecular_function	2
binding	2
cell cortex	2
septin cytoskeleton	2
developmental process involved in reproduction	1
male gamete generation	1
macromolecule localization	1
regulation of cell shape	1
regulation of embryonic development	1
cellular developmental process	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
positive regulation of cilium assembly	1
regulation of non-motile cilium assembly	1
non-motile cilium assembly	1
cellular process	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1
cell adhesion molecule binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
condensed chromosome, centromeric region	1
supramolecular complex	1
actomyosin	1
contractile actin filament bundle	1
intracellular membrane-bounded organelle	1
microtubule cytoskeleton	1
cytoplasm	1

Protein interactions and networks

STRING

2004 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SEPTIN7	SEPTIN6	Q14141	985
SEPTIN7	SEPTIN9	Q9UHD8	970
SEPTIN7	SEPTIN4	O43236	920
SEPTIN7	HDAC6	Q9UBN7	864
SEPTIN7	SEPTIN2	Q15019	828
SEPTIN7	SEPTIN11	Q9NVA2	800
SEPTIN7	SEPTIN5	Q99719	798
SEPTIN7	SOCS7	O14512	775
SEPTIN7	SOCS4	Q8WXH5	775
SEPTIN7	CDC42EP5	Q6NZY7	749
SEPTIN7	CENPE	Q02224	748
SEPTIN7	SEPTIN8	Q92599	721
SEPTIN7	ANK1	P16157	703
SEPTIN7	ANK3	Q12955	702
SEPTIN7	NCK1	P16333	694

IntAct

160 interactions, top by confidence:

A	B	Type	Score
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
SEPTIN2	SEPTIN6	psi-mi:“MI:0915”(physical association)	0.950
SEPTIN7	SEPTIN6	psi-mi:“MI:0914”(association)	0.850
SEPTIN7	SEPTIN6	psi-mi:“MI:0915”(physical association)	0.850
SEPTIN9	SEPTIN2	psi-mi:“MI:0914”(association)	0.840
SEPTIN12	SEPTIN6	psi-mi:“MI:0914”(association)	0.830
SEPTIN12	SEPTIN6	psi-mi:“MI:0403”(colocalization)	0.830
SEPTIN7	SEPTIN11	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
SEPTIN9	SEPTIN7	psi-mi:“MI:0915”(physical association)	0.770
SEPTIN5	SEPTIN7	psi-mi:“MI:0915”(physical association)	0.740
SEPTIN8	SEPTIN7	psi-mi:“MI:0915”(physical association)	0.740
SEPTIN12	SEPTIN7	psi-mi:“MI:0403”(colocalization)	0.730

BioGRID (340): SEPT7 (Two-hybrid), REL (Two-hybrid), SEPT10 (Two-hybrid), AP3B1 (Co-localization), AP3B1 (Affinity Capture-Western), SEPT7 (Dosage Rescue), SEPT7 (Dosage Rescue), SEPT7 (Dosage Rescue), SEPT7 (Affinity Capture-MS), SEPT7 (Affinity Capture-MS), SEPT7 (Affinity Capture-MS), SEPT7 (Affinity Capture-MS), SEPT7 (Affinity Capture-MS), SEPT10 (Co-fractionation), SEPT11 (Co-fractionation)

ESM2 similar proteins: A0A3Q0KDV9, A2BGU8, A2VE99, A4FUM1, A6QQL3, B0BNF1, B0KWP7, B1H120, B1MTN8, B2KIE9, B3GNI6, B5FW69, O36023, O55131, P32468, P39826, P48009, P54359, Q09883, Q0VC68, Q0VCP4, Q14141, Q16181, Q2KJB1, Q2NKY7, Q3SZN0, Q4R555, Q5R1W1, Q5R481, Q5R8U3, Q642H3, Q6AXA6, Q6GLZ5, Q6IRQ5, Q6Q137, Q6ZU15, Q8C1B7, Q8C650, Q8CHH9, Q99719

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

3 interactions.

A	Effect	B	Mechanism
SEPTIN7	“form complex”	SEPT6/SEPT7	binding
SEPTIN7	“up-regulates activity”	CENPE	binding
AR	“down-regulates quantity by repression”	SEPTIN7	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 112 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	97.3×	2e-19
intracellular protein localization	14	14.8×	2e-10

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2459 predictions. Top by Δscore:

Variant	Effect	Δscore
7:35831343:T:TA	acceptor_gain	1.0000
7:35831348:T:TA	acceptor_gain	1.0000
7:35831351:T:A	acceptor_gain	1.0000
7:35831353:T:TA	acceptor_gain	1.0000
7:35831359:A:AG	acceptor_gain	1.0000
7:35831359:AAT:A	acceptor_gain	1.0000
7:35831359:AATG:A	acceptor_gain	1.0000
7:35831360:A:G	acceptor_gain	1.0000
7:35831360:AT:A	acceptor_gain	1.0000
7:35831361:T:A	acceptor_gain	1.0000
7:35831361:T:G	acceptor_gain	1.0000
7:35831362:G:A	acceptor_gain	1.0000
7:35832792:T:A	acceptor_gain	1.0000
7:35832793:GTCA:G	acceptor_loss	1.0000
7:35832795:CA:C	acceptor_loss	1.0000
7:35832796:A:AC	acceptor_loss	1.0000
7:35832796:A:AG	acceptor_gain	1.0000
7:35832797:G:GT	acceptor_gain	1.0000
7:35832797:G:T	acceptor_loss	1.0000
7:35832797:GC:G	acceptor_gain	1.0000
7:35832797:GCA:G	acceptor_gain	1.0000
7:35832799:A:AG	acceptor_gain	1.0000
7:35832899:GG:G	donor_gain	1.0000
7:35832900:GG:G	donor_gain	1.0000
7:35865508:ATC:A	donor_gain	1.0000
7:35872663:CA:C	acceptor_loss	1.0000
7:35872664:A:AC	acceptor_loss	1.0000
7:35872664:A:AG	acceptor_gain	1.0000
7:35872664:AGGT:A	acceptor_gain	1.0000
7:35872665:G:GG	acceptor_gain	1.0000

AlphaMissense

2930 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:35832825:G:A	G32R	1.000
7:35832825:G:C	G32R	1.000
7:35832826:G:A	G32E	1.000
7:35832828:T:C	F33L	1.000
7:35832829:T:C	F33S	1.000
7:35832830:T:A	F33L	1.000
7:35832830:T:G	F33L	1.000
7:35832838:T:A	L36H	1.000
7:35832838:T:C	L36P	1.000
7:35832876:T:C	F49L	1.000
7:35832878:T:A	F49L	1.000
7:35832878:T:G	F49L	1.000
7:35832900:G:C	G57R	1.000
7:35832900:G:T	G57C	1.000
7:35863552:G:A	G57D	1.000
7:35863552:G:T	G57V	1.000
7:35863566:G:A	G62R	1.000
7:35863566:G:C	G62R	1.000
7:35863567:G:A	G62E	1.000
7:35863567:G:T	G62V	1.000
7:35863570:A:T	K63M	1.000
7:35863571:G:C	K63N	1.000
7:35863571:G:T	K63N	1.000
7:35863587:T:C	S69P	1.000
7:35872715:T:C	L109P	1.000
7:35872736:G:A	G116E	1.000
7:35872738:T:C	F117L	1.000
7:35872740:T:A	F117L	1.000
7:35872740:T:G	F117L	1.000
7:35872742:G:A	G118E	1.000

dbSNP variants (sampled 300 via entrez): RS1000005122 (7:35843136 C>G), RS1000024317 (7:35878154 C>T), RS1000085905 (7:35889790 CG>C), RS1000098443 (7:35801895 C>T), RS1000151082 (7:35884284 C>T), RS1000208269 (7:35826142 C>A), RS1000237486 (7:35860635 A>G), RS1000239934 (7:35901507 C>T), RS1000286311 (7:35906865 AG>A,AGG), RS1000328993 (7:35895478 C>G), RS1000354758 (7:35807827 T>C), RS1000386817 (7:35813285 A>G), RS1000434200 (7:35860896 G>T), RS1000465258 (7:35812922 A>C,G), RS1000557978 (7:35831427 C>T)

Disease associations

OMIM: gene MIM:603151 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004121_32	Fibrinogen levels	4.000000e-08
GCST004122_6	Fibrinogen levels	9.000000e-09
GCST90011770_9	Glaucoma (primary open-angle)	1.000000e-06
GCST90014045_2	Lung cancer prognosis in former smokers	1.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007936	disease prognosis measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067068 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.49	Kd	3212	nM	CHEMBL5653589
5.49	ED50	3212	nM	CHEMBL5653589
5.48	Kd	3336	nM	CHEMBL3752910
5.48	ED50	3336	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149374: Binding affinity to human Sep7 incubated for 45 mins by Kinobead based pull down assay	kd	3.2123	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149374: Binding affinity to human Sep7 incubated for 45 mins by Kinobead based pull down assay	kd	3.3363	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, affects cotreatment, increases abundance	3
bisphenol A	increases expression, decreases expression	2
1-Methyl-4-phenylpyridinium	increases expression, affects expression, affects reaction	2
Cadmium Chloride	increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
kojic acid	decreases expression	1
potassium nitrate	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
CD 437	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
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
bromovanin	decreases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Arsenic Trioxide	increases expression	1
Arsenates	affects cotreatment, increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Atrazine	affects cotreatment, increases expression	1
Curcumin	increases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Ivermectin	decreases expression	1
Lead	affects expression	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
CHEMBL5652416	Binding	Binding affinity to human Sep7 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.