SYT7

Summary

SYT7 (synaptotagmin 7, HGNC:11514) is a protein-coding gene on chromosome 11q12.2, encoding Synaptotagmin-7 (O43581). Ca(2+) sensor involved in Ca(2+)-dependent exocytosis of secretory and synaptic vesicles through Ca(2+) and phospholipid binding to the C2 domain.

This gene is a member of the synaptotagmin gene family and encodes a protein similar to other family members that mediate calcium-dependent regulation of membrane trafficking in synaptic transmission. A similar protein in rodents mediates hormone secretion and lysosome exocytosis. In humans, expression of this gene has been associated with prostate cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 9066 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 49 total
• MANE Select transcript: NM_001365809

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11514
Approved symbol	SYT7
Name	synaptotagmin 7
Location	11q12.2
Locus type	gene with protein product
Status	Approved
Aliases	IPCA-7, SYT-VII, MGC150517
Ensembl gene	ENSG00000011347
Ensembl biotype	protein_coding
OMIM	604146
Entrez	9066

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000263846, ENST00000535826, ENST00000539008, ENST00000539246, ENST00000539468, ENST00000540677, ENST00000540831, ENST00000542670, ENST00000542836, ENST00000545053, ENST00000933166, ENST00000933167, ENST00000968863

RefSeq mRNA: 6 — MANE Select: NM_001365809 NM_001252065, NM_001300773, NM_001365809, NM_001370211, NM_001411007, NM_004200

CCDS: CCDS31577, CCDS58139, CCDS73298, CCDS91486, CCDS91487

Canonical transcript exons

ENST00000539008 — 13 exons

Exon	Start	End
ENSE00000487980	61551384	61551463
ENSE00001304461	61556104	61556207
ENSE00002212859	61547177	61547308
ENSE00003461771	61524363	61524532
ENSE00003568171	61542211	61542579
ENSE00003581590	61532989	61533124
ENSE00003590146	61523827	61523941
ENSE00003590618	61527915	61528185
ENSE00003604507	61538144	61538266
ENSE00003663857	61546031	61546255
ENSE00003683119	61523075	61523274
ENSE00003896855	61513714	61518731
ENSE00003897299	61580790	61581076

Expression profiles

Bgee: expression breadth ubiquitous, 170 present calls, max score 96.91.

FANTOM5 (CAGE): breadth broad, TPM avg 6.1289 / max 180.5606, expressed in 807 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120008	3.7844	690
120009	1.4156	438
120012	0.2687	125
120000	0.2094	113
120013	0.2032	114
120011	0.1160	54
120014	0.0485	28
120010	0.0444	14
120007	0.0386	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	96.91	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.74	gold quality
right frontal lobe	UBERON:0002810	94.72	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.08	gold quality
prefrontal cortex	UBERON:0000451	93.63	gold quality
cerebellar cortex	UBERON:0002129	93.47	gold quality
cerebellar hemisphere	UBERON:0002245	93.45	gold quality
cerebellar vermis	UBERON:0004720	92.81	gold quality
frontal cortex	UBERON:0001870	92.70	gold quality
cerebellum	UBERON:0002037	92.52	gold quality
anterior cingulate cortex	UBERON:0009835	92.46	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.39	gold quality
neocortex	UBERON:0001950	91.89	gold quality
right lobe of liver	UBERON:0001114	90.68	gold quality
pituitary gland	UBERON:0000007	90.43	gold quality
parotid gland	UBERON:0001831	90.14	gold quality
cerebral cortex	UBERON:0000956	89.95	gold quality
adenohypophysis	UBERON:0002196	89.39	gold quality
cortical plate	UBERON:0005343	89.05	gold quality
superior frontal gyrus	UBERON:0002661	88.72	gold quality
nucleus accumbens	UBERON:0001882	88.70	gold quality
buccal mucosa cell	CL:0002336	88.64	gold quality
forebrain	UBERON:0001890	88.27	gold quality
brain	UBERON:0000955	88.07	gold quality
postcentral gyrus	UBERON:0002581	87.69	gold quality
parietal lobe	UBERON:0001872	87.58	gold quality
amygdala	UBERON:0001876	87.37	gold quality
saliva-secreting gland	UBERON:0001044	87.07	gold quality
lateral nuclear group of thalamus	UBERON:0002736	87.07	gold quality
liver	UBERON:0002107	86.79	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	19.92
E-CURD-114	yes	11.52
E-ENAD-27	yes	11.27
E-GEOD-83139	yes	10.47
E-ANND-3	yes	5.11

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

166 targeting SYT7, 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-4283	100.00	66.42	2097
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-6845-3P	99.94	66.88	1439

Literature-anchored findings (GeneRIF, showing 19)

• identified the conserved alternative splicing events in the spacer domain of Syt VII; also shown that Syt VIIa-GFP is mainly localized in the perinuclear region and tips of neurites (dense-core vesicles), and not in the plasma membrane (PMID:12071850)
• The membrane dissociation of SYT7 C2A domain but not SYT1 C2A domain is slowed by Na(2)SO(4) and trehalose, solutes that enhance the hydrophobic effect. (PMID:22966849)
• the results suggest that the two C2 domains of Syt7 bind independently to planar membranes, in contrast to reported interdomain cooperativity in Syt1 (PMID:25437758)
• RNA knockdown of Syt-7 in human islets reduced first- and second-phase glucose-stimulated insulin secretion attributed to the reduction of exocytosis of predocked and newcomer insulin secretory granules (PMID:27207520)
• Plexin C1 deficiency permits synaptotagmin 7-mediated macrophage migration and enhances mammalian lung fibrosis (PMID:27609773)
• Data indicate that small protein sequence changes in the Ca(2+)-binding loops of the C2 domains may give rise to the difference in binding kinetics between Syt-1 and Syt-7 isoforms. (PMID:27997124)
• the downregulation of SYT7 inhibited glioblastoma growth by promoting cellular apoptosis. (PMID:28990113)
• results identify a function for Syt7 at synapses that exhibit overall depression, and demonstrate that facilitation has an unexpected and important function in producing frequency-invariant transmission (PMID:29088700)
• Transcriptome data identified the overexpression of synaptotagmin VII (SYT7) in gastric cancer tissues with hepatic metastasis (PMID:29858600)
• The oncogenic role of SYT7 in lung cancer.the oncogenic roles of SYT7 in lung cancer.SYT7 interacts with P53 and to potentiate the interaction between P53 and MDM2. (PMID:30647108)
• Membrane-Binding Cooperativity and Coinsertion by C2AB Tandem Domains of Synaptotagmins 1 and 7 (PMID:30795874)
• Silencing of synaptotagmin 7 regulates osteosarcoma cell proliferation, apoptosis, and migration. (PMID:31631310)
• The Syt7 mRNA level was significantly attenuated in the bipolar disorder patient plasma compared to the healthy controls. (PMID:32041882)
• High SYT7 expression is associated with poor prognosis in human non-small cell lung carcinoma. (PMID:32825966)
• Syt-7 overexpression predicts poor prognosis and promotes cell proliferation in hepatocellular carcinoma. (PMID:33052751)
• Synaptotagmin-7 deficiency induces mania-like behavioral abnormalities through attenuating GluN2B activity. (PMID:33229564)
• SYT7 plays a role in promoting thyroid cancer by mediating HMGB3 ubiquitination. (PMID:35073278)
• SYT7 is a key player in increasing exosome secretion and promoting angiogenesis in non-small-cell lung cancer. (PMID:37774826)
• The 8-oxoguanine DNA glycosylase-synaptotagmin 7 pathway increases extracellular vesicle release and promotes tumour metastasis during oxidative stress. (PMID:39235072)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	syt7a	ENSDARG00000063568
danio_rerio	syt7b	ENSDARG00000078060
mus_musculus	Syt7	ENSMUSG00000024743
rattus_norvegicus	Syt7	ENSRNOG00000026432
drosophila_melanogaster	Syt7	FBGN0039900
caenorhabditis_elegans		WBGENE00004926

Paralogs (31): SYT13 (ENSG00000019505), SYT1 (ENSG00000067715), RPH3A (ENSG00000089169), SYTL4 (ENSG00000102362), SYT17 (ENSG00000103528), SYT10 (ENSG00000110975), SYT5 (ENSG00000129990), SYT11 (ENSG00000132718), SYT4 (ENSG00000132872), SYT6 (ENSG00000134207), SYTL2 (ENSG00000137501), SYT16 (ENSG00000139973), SYTL1 (ENSG00000142765), SYT14 (ENSG00000143469), SYT2 (ENSG00000143858), SYTL5 (ENSG00000147041), SYT8 (ENSG00000149043), DOC2A (ENSG00000149927), SYTL3 (ENSG00000164674), TC2N (ENSG00000165929), SYT9 (ENSG00000170743), SYT12 (ENSG00000173227), RPH3AL (ENSG00000181031), C2CD4C (ENSG00000183186), C2CD4A (ENSG00000198535), SYT15 (ENSG00000204176), C2CD4B (ENSG00000205502), SYT3 (ENSG00000213023), C2CD4D (ENSG00000225556), DOC2B (ENSG00000272636), SYT15B (ENSG00000277758)

Protein

Protein identifiers

Synaptotagmin-7 — O43581 (reviewed: O43581)

Alternative names: IPCA-7, Prostate cancer-associated protein 7, Synaptotagmin VII

All UniProt accessions (3): O43581, F5GX00, F5H8G7

UniProt curated annotations — full annotation on UniProt →

Function. Ca(2+) sensor involved in Ca(2+)-dependent exocytosis of secretory and synaptic vesicles through Ca(2+) and phospholipid binding to the C2 domain. Ca(2+) induces binding of the C2-domains to phospholipid membranes and to assembled SNARE-complexes; both actions contribute to triggering exocytosis. SYT7 binds Ca(2+) with high affinity and slow kinetics compared to other synaptotagmins. Involved in Ca(2+)-triggered lysosomal exocytosis, a major component of the plasma membrane repair. Ca(2+)-regulated delivery of lysosomal membranes to the cell surface is also involved in the phagocytic uptake of particles by macrophages. Ca(2+)-triggered lysosomal exocytosis also plays a role in bone remodeling by regulating secretory pathways in osteoclasts and osteoblasts. In case of infection, involved in participates cell invasion by Trypanosoma cruzi via Ca(2+)-triggered lysosomal exocytosis. Involved in cholesterol transport from lysosome to peroxisome by promoting membrane contacts between lysosomes and peroxisomes: probably acts by promoting vesicle fusion by binding phosphatidylinositol-4,5-bisphosphate on peroxisomal membranes. Acts as a key mediator of synaptic facilitation, a process also named short-term synaptic potentiation: synaptic facilitation takes place at synapses with a low initial release probability and is caused by influx of Ca(2+) into the axon terminal after spike generation, increasing the release probability of neurotransmitters. Probably mediates synaptic facilitation by directly increasing the probability of release. May also contribute to synaptic facilitation by regulating synaptic vesicle replenishment, a process required to ensure that synaptic vesicles are ready for the arrival of the next action potential: SYT7 is required for synaptic vesicle replenishment by acting as a sensor for Ca(2+) and by forming a complex with calmodulin. Also acts as a regulator of Ca(2+)-dependent insulin and glucagon secretion in beta-cells. Triggers exocytosis by promoting fusion pore opening and fusion pore expansion in chromaffin cells. Also regulates the secretion of some non-synaptic secretory granules of specialized cells.

Subunit / interactions. Homodimer. Can also form heterodimers with SYT6, SYT9 and SYT10. Interacts with calmodulin (CALM1, CALM2 or CALM3). Interacts with CD63; required for localization to lysosomes. Interacts with APP.

Subcellular location. Cell membrane. Presynaptic cell membrane. Cytoplasmic vesicle. Secretory vesicle. Synaptic vesicle membrane. Lysosome membrane. Phagosome membrane. Peroxisome membrane. Secretory vesicle membrane.

Tissue specificity. Expressed in a variety of adult and fetal tissues.

Post-translational modifications. Palmitoylated at its vesicular N-terminus; palmitoylation is required for localization to lysosome and phagocytosis in macrophages.

Cofactor. Binds 3 Ca(2+) ions per C2 domain.

Domain organisation. The C2 domains bind Ca(2+) and membranes. Binding to membranes involves Ca(2+)-dependent phospholipid binding. Compared to other members of the family, the C2 domains of SYT7 dock and insert into cellular membranes in response to intracellular Ca(2+) concentrations that are lower than those required for other synaptotagmins. The two C2 domains bind independently to planar membranes, without interdomain cooperativity. Moreover, SYT7 C2 domains insert more deeply into membranes compared to other synaptotagmins.

Miscellaneous. Major isoform.

Similarity. Belongs to the synaptotagmin family.

Isoforms (6)

UniProt ID	Names	Canonical?
O43581-1	1	yes
O43581-2	2
O43581-3	3
O43581-4	4
O43581-5	5
O43581-6	6, Synaptotagmin VIIbeta, Syt7beta

RefSeq proteins (6): NP_001238994, NP_001287702, NP_001352738, NP_001357140, NP_001397936, NP_004191 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR001565	Synaptotagmin	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR037732	C2A_Synaptotagmin-7	Domain
IPR037741	C2B_Synaptotagmin-7	Domain

Pfam: PF00168

UniProt features (56 total): binding site 22, strand 11, modified residue 5, splice variant 5, topological domain 2, domain 2, sequence conflict 2, chain 1, transmembrane region 1, sequence variant 1, helix 1, turn 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2D8K	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43581-F1	80.23	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 (22): 172; 225; 225; 227; 227; 227; 230; 233; 233; 297; 297; 303 …

Post-translational modifications (5): 52, 58, 61, 119, 122

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6794361	Neurexins and neuroligins
R-HSA-112316	Neuronal System
R-HSA-6794362	Protein-protein interactions at synapses

MSigDB gene sets: 290 (showing top): RNGTGGGC_UNKNOWN, GOBP_REGULATION_OF_VESICLE_FUSION, TAATAAT_MIR126, BENPORATH_ES_WITH_H3K27ME3, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_DEPENDENT_EXOCYTOSIS, GOBP_VACUOLE_ORGANIZATION, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GOBP_VESICLE_ORGANIZATION, GOBP_INSULIN_SECRETION, MAZ_Q6, GOBP_MEMBRANE_FUSION, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_REGULATION_OF_HORMONE_LEVELS

GO Biological Process (22): plasma membrane repair (GO:0001778), vesicle fusion (GO:0006906), phagocytosis (GO:0006909), vesicle-mediated transport (GO:0016192), regulation of calcium ion-dependent exocytosis (GO:0017158), synaptic vesicle recycling (GO:0036465), positive regulation of calcium ion-dependent exocytosis (GO:0045956), regulation of bone remodeling (GO:0046850), calcium ion-regulated exocytosis of neurotransmitter (GO:0048791), regulation of phagocytosis (GO:0050764), regulation of insulin secretion (GO:0050796), regulation of glucagon secretion (GO:0070092), vesicle-mediated cholesterol transport (GO:0090119), phagosome-lysosome fusion (GO:0090385), calcium-dependent activation of synaptic vesicle fusion (GO:0099502), regulation of synaptic vesicle endocytosis (GO:1900242), short-term synaptic potentiation (GO:1990926), calcium ion regulated lysosome exocytosis (GO:1990927), exocytosis (GO:0006887), calcium-ion regulated exocytosis (GO:0017156), regulation of endocytosis (GO:0030100), positive regulation of transport (GO:0051050)

GO Molecular Function (10): SNARE binding (GO:0000149), calcium ion binding (GO:0005509), calmodulin binding (GO:0005516), calcium-dependent phospholipid binding (GO:0005544), phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), syntaxin binding (GO:0019905), clathrin binding (GO:0030276), calcium ion sensor activity (GO:0061891), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (22): lysosome (GO:0005764), lysosomal membrane (GO:0005765), peroxisome (GO:0005777), peroxisomal membrane (GO:0005778), cytosol (GO:0005829), plasma membrane (GO:0005886), synaptic vesicle (GO:0008021), axon (GO:0030424), phagocytic vesicle membrane (GO:0030670), synaptic vesicle membrane (GO:0030672), dense core granule (GO:0031045), early phagosome (GO:0032009), presynaptic membrane (GO:0042734), synapse (GO:0045202), extracellular exosome (GO:0070062), hippocampal mossy fiber to CA3 synapse (GO:0098686), endomembrane system (GO:0012505), membrane (GO:0016020), transport vesicle membrane (GO:0030658), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995), secretory vesicle (GO:0099503)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Protein-protein interactions at synapses	1
Neuronal System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
calcium-ion regulated exocytosis	4
vesicle-mediated transport	3
protein binding	3
cellular anatomical structure	3
transport	2
synaptic vesicle exocytosis	2
regulation of endocytosis	2
regulation of peptide hormone secretion	2
cytoplasm	2
presynapse	2
phagocytic vesicle	2
plasma membrane organization	1
wound healing	1
vesicle organization	1
organelle membrane fusion	1
endocytosis	1
cellular process	1
regulation of regulated secretory pathway	1
establishment of localization in cell	1
synaptic vesicle cycle	1
regulation of calcium ion-dependent exocytosis	1
positive regulation of regulated secretory pathway	1
regulation of tissue remodeling	1
bone remodeling	1
phagocytosis	1
insulin secretion	1
regulation of protein secretion	1
glucagon secretion	1
cytosolic transport	1
intracellular cholesterol transport	1
phagolysosome assembly	1
vesicle fusion	1
positive regulation of synaptic vesicle fusion to presynaptic active zone membrane	1
synaptic vesicle endocytosis	1
regulation of synaptic vesicle recycling	1
regulation of synaptic plasticity	1
secretion by cell	1
vesicle fusion to plasma membrane	1
regulated exocytosis	1
metal ion binding	1

Protein interactions and networks

STRING

1126 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYT7	VAMP7	P51809	974
SYT7	STX4	Q12846	953
SYT7	SNAP23	O00161	880
SYT7	CPLX1	O14810	838
SYT7	SNAP25	P13795	826
SYT7	PALM	O75781	736
SYT7	ZDHHC13	Q8IUH4	689
SYT7	LAMP1	P11279	684
SYT7	STX7	O15400	671
SYT7	VAMP2	P19065	659
SYT7	DYSF	O75923	639
SYT7	TGM4	P49221	634
SYT7	STX1A	Q16623	592
SYT7	CTSK	P43235	592
SYT7	ZDHHC17	Q8IUH5	588

IntAct

14 interactions, top by confidence:

A	B	Type	Score
SIAH1	SYT7	psi-mi:“MI:0915”(physical association)	0.560
SYT7	SIAH1	psi-mi:“MI:0915”(physical association)	0.560
SYT7	NPM1	psi-mi:“MI:0915”(physical association)	0.400
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
CACNA1C	IGLL5	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
CDH1	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
CDH5	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
FERMT2	SYT7	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): SYT7 (Two-hybrid), SYT7 (Affinity Capture-RNA), SYT7 (Proximity Label-MS), SYT7 (Affinity Capture-MS), SYT7 (Affinity Capture-MS), SYT7 (Proximity Label-MS), SYT7 (Proximity Label-MS), NPM1 (Proximity Label-MS), SYT7 (Affinity Capture-MS), SYT7 (Affinity Capture-MS), SYNCRIP (Reconstituted Complex), SYT7 (Affinity Capture-Western), SYT7 (Affinity Capture-MS), SYT7 (Affinity Capture-MS), SYT7 (Affinity Capture-MS)

ESM2 similar proteins: A2A690, A2RSQ0, A5PJM7, A6QL63, B2RYF1, D4ABL6, E9PV86, F1LTE0, O43581, O75864, O94759, P60762, Q13507, Q3ULA2, Q4V860, Q4V8I4, Q4VBD2, Q5R6F2, Q5RB16, Q5T7P8, Q5ZLG8, Q62746, Q6DN14, Q6GQW0, Q6NXT6, Q6NZH6, Q6P5H6, Q6ZN54, Q6ZUT9, Q7TT45, Q7Z6G3, Q7Z6J6, Q8BKR5, Q8K4Q0, Q8N122, Q8TBP0, Q8TF64, Q91X46, Q91YD4, Q99J78

Diamond homologs: A0A075F932, A0FGR8, A4IJ05, K8FE10, O00445, O00750, O08625, O08835, O35681, O43581, P04409, P05128, P05129, P05130, P05696, P10102, P10829, P13677, P17252, P20444, P21521, P21579, P21707, P24505, P24506, P24507, P29101, P34693, P40748, P40749, P41823, P41885, P46096, P46097, P47191, P47708, P47709, P47861, P48018, P50232

SIGNOR signaling

0 interactions.

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	40
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3285 predictions. Top by Δscore:

Variant	Effect	Δscore
11:61523069:CCCTA:C	donor_loss	1.0000
11:61523070:CCTA:C	donor_loss	1.0000
11:61523071:CTA:C	donor_loss	1.0000
11:61523072:TA:T	donor_loss	1.0000
11:61523073:A:C	donor_loss	1.0000
11:61523074:C:CG	donor_loss	1.0000
11:61523078:G:A	donor_gain	1.0000
11:61523270:GGGGT:G	acceptor_gain	1.0000
11:61523271:GGGT:G	acceptor_gain	1.0000
11:61523272:GGT:G	acceptor_gain	1.0000
11:61523273:GT:G	acceptor_gain	1.0000
11:61523275:C:CC	acceptor_gain	1.0000
11:61523821:CCGTA:C	donor_loss	1.0000
11:61523822:CGTA:C	donor_loss	1.0000
11:61523823:GTACC:G	donor_loss	1.0000
11:61523824:TACCT:T	donor_loss	1.0000
11:61523825:A:C	donor_loss	1.0000
11:61524361:A:AC	donor_gain	1.0000
11:61524361:ACACT:A	donor_gain	1.0000
11:61524362:C:CA	donor_gain	1.0000
11:61524362:CA:C	donor_gain	1.0000
11:61524362:CACT:C	donor_gain	1.0000
11:61524362:CACTC:C	donor_gain	1.0000
11:61524366:C:CA	donor_gain	1.0000
11:61524367:C:A	donor_gain	1.0000
11:61524388:T:TA	donor_gain	1.0000
11:61524392:T:TA	donor_gain	1.0000
11:61527910:CTCA:C	donor_loss	1.0000
11:61527911:TCACC:T	donor_loss	1.0000
11:61527912:CACC:C	donor_loss	1.0000

AlphaMissense

4487 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:61518637:A:G	L401P	1.000
11:61518637:A:T	L401Q	1.000
11:61518644:G:C	H399D	1.000
11:61518645:C:A	W398C	1.000
11:61518645:C:G	W398C	1.000
11:61518647:A:G	W398R	1.000
11:61518647:A:T	W398R	1.000
11:61518687:C:A	W384C	1.000
11:61518687:C:G	W384C	1.000
11:61518688:C:G	W384S	1.000
11:61518689:A:G	W384R	1.000
11:61518689:A:T	W384R	1.000
11:61518724:A:G	L372P	1.000
11:61523079:C:A	G368V	1.000
11:61523079:C:T	G368D	1.000
11:61523080:C:A	G368C	1.000
11:61523080:C:G	G368R	1.000
11:61523080:C:T	G368S	1.000
11:61523082:A:T	I367N	1.000
11:61523106:T:G	D359A	1.000
11:61523107:C:G	D359H	1.000
11:61523111:G:C	D357E	1.000
11:61523111:G:T	D357E	1.000
11:61523112:T:A	D357V	1.000
11:61523112:T:G	D357A	1.000
11:61523113:C:G	D357H	1.000
11:61523118:A:T	V355D	1.000
11:61523166:A:G	F339S	1.000
11:61523183:G:C	F333L	1.000
11:61523183:G:T	F333L	1.000

dbSNP variants (sampled 300 via entrez): RS1000044125 (11:61517715 G>A), RS1000055057 (11:61537179 T>C), RS1000072786 (11:61577046 G>A,C), RS1000112747 (11:61518671 G>A), RS1000162642 (11:61532594 G>A), RS1000188255 (11:61577353 G>A), RS1000226507 (11:61554675 G>A,T), RS1000298074 (11:61532853 C>T), RS1000326200 (11:61568153 C>T), RS1000355119 (11:61564635 G>A), RS1000379533 (11:61521071 A>G), RS1000384692 (11:61564908 G>A), RS1000385647 (11:61584462 C>T), RS1000406486 (11:61526871 T>A), RS1000484880 (11:61568538 G>A,C,T)

Disease associations

OMIM: gene MIM:604146 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): myoepithelial tumor (MONDO:0002380)

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002446_1	Plasma omega-6 polyunsaturated fatty acid levels (linoleic acid)	4.000000e-274
GCST002446_7	Plasma omega-6 polyunsaturated fatty acid levels (linoleic acid)	3.000000e-21
GCST002449_6	Plasma omega-6 polyunsaturated fatty acid levels (arachidonic acid)	0.000000e+00
GCST002449_8	Plasma omega-6 polyunsaturated fatty acid levels (arachidonic acid)	7.000000e-147
GCST003275_5	Mean arterial pressure	8.000000e-12
GCST005316_357	Intelligence (MTAG)	5.000000e-08
GCST009391_1583	Metabolite levels	6.000000e-06
GCST009391_2014	Metabolite levels	1.000000e-06
GCST009391_446	Metabolite levels	3.000000e-06

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0005680	omega-6 polyunsaturated fatty acid measurement
EFO:0006340	mean arterial pressure
EFO:0004337	intelligence
EFO:0010349	cholesteryl ester 20:5 measurement
EFO:0010348	cholesteryl ester 20:4 measurement
EFO:0010386	phosphatidylcholine 38:4 measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009208	Myoepithelioma	C04.557.435.585

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	6
sodium arsenite	decreases expression, increases expression	3
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Aflatoxin B1	increases methylation	2
Particulate Matter	increases abundance, increases expression	2
dicrotophos	increases expression	1
methyleugenol	decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sulforaphane	decreases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	decreases expression	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
pentanal	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	increases expression	1
NSC 689534	affects binding, increases expression	1
Rosiglitazone	decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9TQ	Ubigene HEK293 SYT7 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03600649	PHASE1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT05266196	PHASE1/PHASE2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	PHASE1/PHASE2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06625190	PHASE1/PHASE2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT06244420	Not specified	COMPLETED	Malignant Myoepithelioma of Bone and Soft Tissues: Diagnostic Imaging and Histology in Relation to Prognosis