SEPTIN6

Summary

SEPTIN6 (septin 6, HGNC:15848) is a protein-coding gene on chromosome Xq24, encoding Septin-6 (Q14141). Filament-forming cytoskeletal GTPase.

This gene is a member of the septin family of GTPases. Members of this family are required for cytokinesis. One version of pediatric acute myeloid leukemia is the result of a reciprocal translocation between chromosomes 11 and X, with the breakpoint associated with the genes encoding the mixed-lineage leukemia and septin 2 proteins. This gene encodes four transcript variants encoding three distinct isoforms. An additional transcript variant has been identified, but its biological validity has not been determined.

Source: NCBI Gene 23157 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 151 total
• Druggable target: yes
• MANE Select transcript: NM_145799

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15848
Approved symbol	SEPTIN6
Name	septin 6
Location	Xq24
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0128, SEP2, SEPT2, MGC16619, MGC20339, Septin-6
Ensembl gene	ENSG00000125354
Ensembl biotype	protein_coding
OMIM	300683
Entrez	23157

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 14 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000343984, ENST00000354228, ENST00000354416, ENST00000360156, ENST00000394610, ENST00000460411, ENST00000467310, ENST00000481072, ENST00000489216, ENST00000867103, ENST00000867104, ENST00000913204, ENST00000913205, ENST00000913206, ENST00000948508, ENST00000948509, ENST00000948510

RefSeq mRNA: 5 — MANE Select: NM_145799 NM_001410710, NM_015129, NM_145799, NM_145800, NM_145802

CCDS: CCDS14583, CCDS14584, CCDS14585, CCDS94661

Canonical transcript exons

ENST00000394610 — 11 exons

Exon	Start	End
ENSE00000854480	119637027	119637195
ENSE00000854482	119640692	119640788
ENSE00000854485	119649937	119650098
ENSE00001455353	119616945	119620051
ENSE00001649048	119633360	119633492
ENSE00001710959	119652854	119653040
ENSE00003594905	119625335	119625379
ENSE00003603169	119663482	119663677
ENSE00003657116	119675554	119675668
ENSE00003693275	119629318	119629508
ENSE00003844636	119693076	119693168

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 98.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 45.2835 / max 806.6993, expressed in 1737 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200301	35.8568	1681
200302	8.5948	1598
200303	0.3527	176
200294	0.2060	93
200300	0.1009	45
200292	0.0888	42
200293	0.0836	37

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	98.15	gold quality
lymph node	UBERON:0000029	97.81	gold quality
granulocyte	CL:0000094	97.07	gold quality
right adrenal gland cortex	UBERON:0035827	96.84	gold quality
vermiform appendix	UBERON:0001154	96.80	gold quality
right adrenal gland	UBERON:0001233	96.71	gold quality
adrenal cortex	UBERON:0001235	96.68	gold quality
left adrenal gland	UBERON:0001234	96.67	gold quality
adrenal gland	UBERON:0002369	96.64	gold quality
left adrenal gland cortex	UBERON:0035825	96.56	gold quality
blood	UBERON:0000178	96.05	gold quality
bone marrow cell	CL:0002092	95.85	gold quality
spleen	UBERON:0002106	95.70	gold quality
adrenal tissue	UBERON:0018303	95.57	gold quality
endothelial cell	CL:0000115	95.19	gold quality
leukocyte	CL:0000738	94.38	gold quality
sural nerve	UBERON:0015488	94.28	gold quality
mononuclear cell	CL:0000842	94.09	gold quality
monocyte	CL:0000576	94.08	gold quality
caecum	UBERON:0001153	93.93	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.69	gold quality
seminal vesicle	UBERON:0000998	93.26	gold quality
cortical plate	UBERON:0005343	93.03	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.77	gold quality
bone marrow	UBERON:0002371	92.73	gold quality
tonsil	UBERON:0002372	92.64	gold quality
cerebellar vermis	UBERON:0004720	92.46	gold quality
pons	UBERON:0000988	92.08	gold quality
calcaneal tendon	UBERON:0003701	91.85	gold quality
right testis	UBERON:0004534	91.74	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	44.11
E-CURD-112	yes	39.51
E-CURD-122	yes	35.24
E-GEOD-134144	yes	33.31
E-MTAB-10287	yes	32.45
E-HCAD-1	yes	30.37
E-HCAD-13	yes	21.04
E-MTAB-8410	yes	14.39
E-ANND-3	yes	13.45
E-ENAD-27	yes	6.28
E-MTAB-10042	yes	6.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

56 targeting SEPTIN6, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-652-5P	99.91	67.49	505
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-3681-5P	99.82	66.88	387
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-6849-5P	99.64	66.00	352
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-4728-3P	99.47	68.94	981
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-3152-3P	99.10	66.35	678
HSA-MIR-4717-3P	99.06	66.34	1072

Literature-anchored findings (GeneRIF, showing 21)

• MLL-SEPTIN6 fusion recurs in novel translocation of chromosomes 3, X, and 11 in infant acute myelomonocytic leukaemia and in t(X;11) in infant acute myeloid leukaemia (PMID:12096348)
• Molecular analysis using rtPCR followed by sequencing confirmed the expression of an MLL-SEPT6 fusion transcript with a novel sequence. (PMID:16843108)
• septin 2, 6, and 7 complexes make up polymerized filaments (PMID:16914550)
• These results indicate that the host proteins hnRNP A1 and septin 6 play important roles in the replication of HCV through RNA-protein and protein-protein interactions. (PMID:17229681)
• 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)
• co-expression of SEPT12 altered the filamentous structure of SEPT6 in Hela cells (PMID:18047794)
• Data show that Septins of the SEPT6 group preferentially interacted with septins of the SEPT2 group, SEPT3 group and SEPT7 group. (PMID:21082023)
• The SEPT6 provides the directional guidance cues necessary for polarizing the epithelial microtubule network. (PMID:21788367)
• Septin6 and Septin7 GTP binding proteins regulate AP-3- and ESCRT-dependent multivesicular body biogenesis (PMID:25380047)
• MiR-223-3p might target gene SEPT6 and promoted the biological behavior of prostate cancer. (PMID:25519054)
• SUMOylation of human septins is critical for septin filament bundling and cytokinesis. (PMID:29051266)
• 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)
• regulates various biological behaviors in hepatic stellate cells through TGF-beta1/Smad, mitogen-activated protein kinases and phosphatidylinositol-3-kinase/protein kinase B signaling pathways, thus promoting liver fibrosis (PMID:30315255)
• Septin2 mediates podosome maturation and endothelial cell invasion associated with angiogenesis. (PMID:31865373)
• Molecular Recognition at Septin Interfaces: The Switches Hold the Key. (PMID:32910969)
• LncRNA AFAP1-AS1 Knockdown Represses Cell Proliferation, Migration, and Induced Apoptosis in Breast Cancer by Downregulating SEPT2 Via Sponging miR-497-5p. (PMID:32955920)
• Orientational Ambiguity in Septin Coiled Coils and its Structural Basis. (PMID:33639214)
• LSD1-mediated stabilization of SEPT6 protein activates the TGF-beta1 pathway and regulates non-small-cell lung cancer metastasis. (PMID:33664458)
• SEPT6 drives hepatocellular carcinoma cell proliferation, migration and invasion via the Hippo/YAP signaling pathway. (PMID:33846777)
• An atomic model for the human septin hexamer by cryo-EM. (PMID:34116125)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	septin6	ENSDARG00000010721
mus_musculus	Septin6	ENSMUSG00000050379
rattus_norvegicus	Septin6	ENSRNOG00000043182
drosophila_melanogaster	Septin2	FBGN0014029
caenorhabditis_elegans		WBGENE00006795

Paralogs (12): SEPTIN3 (ENSG00000100167), SEPTIN7 (ENSG00000122545), SEPTIN11 (ENSG00000138758), SEPTIN12 (ENSG00000140623), SEPTIN14 (ENSG00000154997), SEPTIN8 (ENSG00000164402), SEPTIN2 (ENSG00000168385), SEPTIN1 (ENSG00000180096), SEPTIN9 (ENSG00000184640), SEPTIN5 (ENSG00000184702), SEPTIN10 (ENSG00000186522), TMEM250 (ENSG00000238227)

Protein

Protein identifiers

Septin-6 — Q14141 (reviewed: Q14141)

All UniProt accessions (4): Q14141, B1AMS2, Q541S4, Q548C9

UniProt curated annotations — full annotation on UniProt →

Function. Filament-forming cytoskeletal GTPase. Required for normal organization of the actin cytoskeleton. Involved in cytokinesis. May play a role in HCV RNA replication. 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 SEPTIN2 and SEPTIN7. Also interacts with SEPTIN9 and SEPTIN12. Interaction with SEPTIN12 alters filament structure. 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 SOCS7. Interacts with HNRNPA1. (Microbial infection) Interacts with HCV NS5B.

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

Tissue specificity. Widely expressed.

Miscellaneous. Coordinated expression with SEPTIN2 and SEPTIN7.

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

Isoforms (4)

UniProt ID	Names	Canonical?
Q14141-1	II	yes
Q14141-2	I, III
Q14141-3	IV
Q14141-4	V

RefSeq proteins (5): NP_001397639, NP_055944, NP_665798, NP_665799, NP_665801 (=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 (49 total): helix 12, strand 11, binding site 5, modified residue 5, splice variant 4, region of interest 4, turn 2, initiator methionine 1, chain 1, domain 1, sequence conflict 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6WBP	X-RAY DIFFRACTION	1.8
6UPA	X-RAY DIFFRACTION	2.51
7M6J	ELECTRON MICROSCOPY	3.6
2QAG	X-RAY DIFFRACTION	4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14141-F1	81.27	0.31

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): 104; 185–193; 239; 254; 49–56

Post-translational modifications (5): 2, 27, 367, 416, 418

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 284 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GOBP_MITOTIC_CYTOKINESIS, WALLACE_PROSTATE_CANCER_RACE_UP, JI_RESPONSE_TO_FSH_UP, YAGI_AML_WITH_INV_16_TRANSLOCATION, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GOBP_MALE_GAMETE_GENERATION, SHEPARD_BMYB_MORPHOLINO_DN, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_CYTOKINESIS, ROZANOV_MMP14_TARGETS_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_DN, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN

GO Biological Process (6): mitotic cytokinesis (GO:0000281), spermatogenesis (GO:0007283), intracellular protein localization (GO:0008104), cell differentiation (GO:0030154), cytoskeleton-dependent cytokinesis (GO:0061640), cell division (GO:0051301)

GO Molecular Function (5): GTPase activity (GO:0003924), GTP binding (GO:0005525), molecular adaptor activity (GO:0060090), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (20): kinetochore (GO:0000776), spindle (GO:0005819), septin ring (GO:0005940), synaptic vesicle (GO:0008021), microtubule cytoskeleton (GO:0015630), midbody (GO:0030496), septin complex (GO:0031105), cell division site (GO:0032153), cleavage furrow (GO:0032154), septin collar (GO:0032173), axon terminus (GO:0043679), sperm annulus (GO:0097227), chromosome, centromeric region (GO:0000775), chromosome (GO:0005694), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), motile cilium (GO:0031514), cell projection (GO:0042995), presynapse (GO:0098793)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
intracellular membraneless organelle	4
cytoskeleton	3
septin cytoskeleton	3
binding	2
cell cortex	2
presynapse	2
mitotic cell cycle	1
cytoskeleton-dependent cytokinesis	1
mitotic cell cycle process	1
developmental process involved in reproduction	1
male gamete generation	1
macromolecule localization	1
cellular developmental process	1
cytokinesis	1
cellular process	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
molecular_function	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
condensed chromosome, centromeric region	1
supramolecular complex	1
microtubule cytoskeleton	1
exocytic vesicle	1
protein-containing complex	1
cell division site	1
plasma membrane region	1
neuron projection terminus	1
distal axon	1
sperm flagellum	1
chromosomal region	1
intracellular anatomical structure	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1
synapse	1

Protein interactions and networks

STRING

962 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SEPTIN6	SEPTIN7	Q16181	985
SEPTIN6	SEPTIN4	O43236	922
SEPTIN6	SEPTIN9	Q9UHD8	919
SEPTIN6	CDC42EP5	Q6NZY7	893
SEPTIN6	HNRNPA1	P09651	830
SEPTIN6	SEPTIN2	Q15019	822
SEPTIN6	SEPTIN5	Q99719	804
SEPTIN6	SOCS7	O14512	785
SEPTIN6	SOCS4	Q8WXH5	781
SEPTIN6	MLLT6	P55198	742
SEPTIN6	SEPTIN11	Q9NVA2	724
SEPTIN6	MLLT10	P55197	709
SEPTIN6	NCK1	P16333	698
SEPTIN6	MLLT1	Q03111	666
SEPTIN6	ANLN	Q9NQW6	661

IntAct

210 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
PIK3CA	PIK3R2	psi-mi:“MI:0914”(association)	0.900
SEPTIN5	SEPTIN6	psi-mi:“MI:0915”(physical association)	0.870
SEPTIN6	SEPTIN5	psi-mi:“MI:0915”(physical association)	0.870
SEPTIN7	SEPTIN6	psi-mi:“MI:0914”(association)	0.850
SEPTIN7	SEPTIN6	psi-mi:“MI:0915”(physical association)	0.850

BioGRID (164): SEPT6 (Two-hybrid), SEPT6 (Two-hybrid), SEPT6 (Two-hybrid), SEPT6 (Two-hybrid), SEPT6 (Two-hybrid), SEPT3 (Two-hybrid), PLEKHF2 (Two-hybrid), MORN4 (Two-hybrid), SEPT6 (Affinity Capture-MS), SEPT6 (Affinity Capture-MS), SEPT6 (Affinity Capture-MS), SEPT6 (Affinity Capture-MS), SEPT4 (Affinity Capture-MS), SEPT2 (Affinity Capture-MS), SEPT7 (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

3 interactions.

A	Effect	B	Mechanism
SEPTIN6	“form complex”	SEPT6/SEPT2	binding
SEPTIN6	“form complex”	SEPT6/SEPT7	binding
SEPTIN12	down-regulates	SEPTIN6	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 83 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Downstream signal transduction	5	36.6×	6e-05
Constitutive Signaling by Aberrant PI3K in Cancer	7	17.1×	6e-05
VEGFA-VEGFR2 Pathway	5	13.4×	2e-03
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	7	13.0×	2e-04
PIP3 activates AKT signaling	7	9.0×	1e-03
RAF/MAP kinase cascade	7	8.2×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
cytoskeleton-dependent cytokinesis	12	130.1×	6e-21
peptidyl-tyrosine phosphorylation	5	28.5×	3e-04
intracellular protein localization	13	18.4×	1e-10
phosphatidylinositol 3-kinase/protein kinase B signal transduction	5	14.2×	5e-03
cellular response to insulin stimulus	5	11.5×	8e-03
neuron migration	6	10.8×	5e-03
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	7	7.4×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1819 predictions. Top by Δscore:

Variant	Effect	Δscore
X:119629313:CTT:C	donor_loss	1.0000
X:119629314:TTAC:T	donor_loss	1.0000
X:119629315:TAC:T	donor_loss	1.0000
X:119629316:A:AC	donor_gain	1.0000
X:119629316:A:C	donor_loss	1.0000
X:119629317:C:CA	donor_gain	1.0000
X:119629317:CT:C	donor_gain	1.0000
X:119629317:CTT:C	donor_gain	1.0000
X:119629317:CTTT:C	donor_gain	1.0000
X:119629317:CTTTT:C	donor_gain	1.0000
X:119629504:TGCAG:T	acceptor_gain	1.0000
X:119629505:GCAG:G	acceptor_gain	1.0000
X:119629506:CAG:C	acceptor_gain	1.0000
X:119629506:CAGC:C	acceptor_gain	1.0000
X:119629507:AG:A	acceptor_gain	1.0000
X:119629508:GC:G	acceptor_loss	1.0000
X:119629509:C:CC	acceptor_gain	1.0000
X:119629509:CTGG:C	acceptor_loss	1.0000
X:119629510:T:A	acceptor_loss	1.0000
X:119629513:C:CT	acceptor_gain	1.0000
X:119629514:A:T	acceptor_gain	1.0000
X:119629521:C:CT	acceptor_gain	1.0000
X:119629523:C:CT	acceptor_gain	1.0000
X:119629524:A:T	acceptor_gain	1.0000
X:119633493:C:CC	acceptor_gain	1.0000
X:119637193:CAA:C	acceptor_gain	1.0000
X:119637196:C:CC	acceptor_gain	1.0000
X:119640690:AC:A	donor_gain	1.0000
X:119640691:CC:C	donor_gain	1.0000
X:119649928:C:CA	donor_gain	1.0000

AlphaMissense

2846 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:119629507:A:G	L364P	1.000
X:119633379:A:G	L357P	1.000
X:119633411:G:C	F346L	1.000
X:119633411:G:T	F346L	1.000
X:119633413:A:G	F346L	1.000
X:119629486:A:G	L371P	0.999
X:119629494:A:C	F368L	0.999
X:119629494:A:T	F368L	0.999
X:119629496:A:G	F368L	0.999
X:119633371:C:G	A360P	0.999
X:119633400:A:T	V350D	0.999
X:119633403:C:G	R349P	0.999
X:119633412:A:C	F346C	0.999
X:119633412:A:G	F346S	0.999
X:119637075:A:G	L303P	0.999
X:119637087:C:G	R299P	0.999
X:119637088:G:T	R299S	0.999
X:119637126:A:G	L286P	0.999
X:119640707:A:G	W258R	0.999
X:119640707:A:T	W258R	0.999
X:119640769:A:T	V237D	0.999
X:119650013:A:G	L205P	0.999
X:119652981:A:G	L134P	0.999
X:119652993:A:G	L130P	0.999
X:119633379:A:T	L357H	0.998
X:119633400:A:G	V350A	0.998
X:119637075:A:T	L303Q	0.998
X:119637088:G:C	R299G	0.998
X:119637159:C:G	R275P	0.998
X:119637162:A:G	L274P	0.998

dbSNP variants (sampled 300 via entrez): RS1000014500 (X:119689950 C>T), RS1000053348 (X:119687670 T>C), RS1000073965 (X:119694387 G>A), RS1000130207 (X:119637744 T>C), RS1000188155 (X:119654328 G>A), RS1000208208 (X:119665722 C>A), RS1000208916 (X:119617492 G>A), RS1000209448 (X:119677726 T>C), RS1000234685 (X:119627776 C>G), RS1000267227 (X:119628725 C>A), RS1000302923 (X:119653897 C>G,T), RS1000345570 (X:119641732 C>G,T), RS1000370563 (X:119669047 A>G), RS1000473350 (X:119678166 G>A), RS1000601436 (X:119631327 C>T)

Disease associations

OMIM: gene MIM:300683 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000817_14	Height	1.000000e-08
GCST001942_6	Prostate cancer	5.000000e-09
GCST010145_12	Cerebrospinal fluid immune biomarker levels	6.000000e-09
GCST011999_14	Hepatitis C (spontaneous viral clearance)	2.000000e-06
GCST90002395_648	Mean platelet volume	2.000000e-09
GCST90014023_18	Type 1 diabetes	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008191	obsolete_interleukin 8 measurement
EFO:0009785	remission

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067384 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	8
trichostatin A	affects cotreatment, increases expression, affects expression	4
Cyclosporine	decreases expression	3
sulforaphane	decreases expression	2
entinostat	affects cotreatment, increases expression	2
belinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation	2
Doxorubicin	decreases expression, affects response to substance	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
aflatoxin B2	increases methylation	1
hydroquinone	decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
jinfukang	increases expression	1
NSC 689534	decreases expression, affects binding	1
Arsenic Trioxide	increases expression	1
Vorinostat	increases expression	1
Acetaminophen	decreases 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
CHEMBL5652415	Binding	Binding affinity to human Sep6 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

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_F1SW	HyCyte Ramos KO-hSEPTIN6	Cancer cell line	Male
CVCL_TK62	HAP1 SEPT6 (-) 1	Cancer cell line	Male
CVCL_TK63	HAP1 SEPT6 (-) 2	Cancer cell line	Male
CVCL_TK64	HAP1 SEPT6 (-) 3	Cancer cell line	Male
CVCL_XS57	HAP1 SEPT6 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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