ESYT1

Summary

ESYT1 (extended synaptotagmin 1, HGNC:29534) is a protein-coding gene on chromosome 12q13.2, encoding Extended synaptotagmin-1 (Q9BSJ8). Binds calcium (via the C2 domains) and translocates to sites of contact between the endoplasmic reticulum and the cell membrane in response to increased cytosolic calcium levels.

Enables identical protein binding activity and phospholipid transfer activity. Involved in intermembrane lipid transfer. Located in endoplasmic reticulum membrane.

Source: NCBI Gene 23344 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 218 total
• Druggable target: yes
• MANE Select transcript: NM_015292

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29534
Approved symbol	ESYT1
Name	extended synaptotagmin 1
Location	12q13.2
Locus type	gene with protein product
Status	Approved
Aliases	MBC2, KIAA0747
Ensembl gene	ENSG00000139641
Ensembl biotype	protein_coding
OMIM	616670
Entrez	23344

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 23 protein_coding, 5 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000267113, ENST00000394048, ENST00000547667, ENST00000548142, ENST00000550179, ENST00000550515, ENST00000550878, ENST00000550986, ENST00000551112, ENST00000551790, ENST00000911047, ENST00000911048, ENST00000911049, ENST00000911050, ENST00000911051, ENST00000911052, ENST00000911053, ENST00000911054, ENST00000911055, ENST00000911056, ENST00000911057, ENST00000911058, ENST00000938575, ENST00000938576, ENST00000969684, ENST00000969685, ENST00000969686, ENST00000969687, ENST00000969688, ENST00000969689

RefSeq mRNA: 2 — MANE Select: NM_015292 NM_001184796, NM_015292

CCDS: CCDS53801, CCDS8904

Canonical transcript exons

ENST00000394048 — 31 exons

Exon	Start	End
ENSE00000939440	56130582	56130623
ENSE00000939445	56131244	56131316
ENSE00000939448	56132209	56132332
ENSE00000939449	56132421	56132597
ENSE00000939450	56132719	56132801
ENSE00000939451	56133417	56133465
ENSE00000939452	56133588	56133674
ENSE00000939453	56133781	56133873
ENSE00000939455	56134342	56134428
ENSE00000939457	56136744	56136893
ENSE00000939458	56137218	56137373
ENSE00000939468	56142835	56142933
ENSE00000939469	56143017	56143148
ENSE00000939470	56143228	56143333
ENSE00000939471	56143580	56143629
ENSE00001144170	56134110	56134181
ENSE00002289459	56128267	56128709
ENSE00002401286	56143823	56144674
ENSE00003489530	56138026	56138074
ENSE00003501030	56130791	56130925
ENSE00003506527	56138927	56139013
ENSE00003525967	56138768	56138839
ENSE00003529664	56142578	56142732
ENSE00003534242	56137499	56137675
ENSE00003556471	56131477	56131566
ENSE00003570851	56131040	56131113
ENSE00003572223	56142285	56142425
ENSE00003610384	56137832	56137914
ENSE00003654339	56131749	56131804
ENSE00003674436	56138404	56138499
ENSE00003678707	56138183	56138272

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 97.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.6032 / max 298.9179, expressed in 1820 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
126069	45.4073	1820
126065	8.8941	1775
126068	0.9337	693
126071	0.1908	77
126070	0.0713	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adipose tissue of abdominal region	UBERON:0007808	97.64	gold quality
omental fat pad	UBERON:0010414	97.61	gold quality
peritoneum	UBERON:0002358	97.60	gold quality
adipose tissue	UBERON:0001013	97.44	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.43	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.42	gold quality
lower esophagus	UBERON:0013473	97.40	gold quality
granulocyte	CL:0000094	97.35	gold quality
right uterine tube	UBERON:0001302	97.29	gold quality
mucosa of stomach	UBERON:0001199	97.25	gold quality
body of uterus	UBERON:0009853	97.17	gold quality
subcutaneous adipose tissue	UBERON:0002190	97.12	gold quality
right coronary artery	UBERON:0001625	97.07	gold quality
connective tissue	UBERON:0002384	96.98	gold quality
descending thoracic aorta	UBERON:0002345	96.94	gold quality
popliteal artery	UBERON:0002250	96.75	gold quality
tibial artery	UBERON:0007610	96.74	gold quality
coronary artery	UBERON:0001621	96.71	gold quality
left coronary artery	UBERON:0001626	96.70	gold quality
aorta	UBERON:0000947	96.65	gold quality
right ovary	UBERON:0002118	96.60	gold quality
ascending aorta	UBERON:0001496	96.58	gold quality
thoracic aorta	UBERON:0001515	96.58	gold quality
smooth muscle tissue	UBERON:0001135	96.57	gold quality
left uterine tube	UBERON:0001303	96.51	gold quality
islet of Langerhans	UBERON:0000006	96.44	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.35	gold quality
left ovary	UBERON:0002119	96.18	gold quality
nerve	UBERON:0001021	96.02	gold quality
tibial nerve	UBERON:0001323	96.02	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.39
E-CURD-112	no	2.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

56 targeting ESYT1, 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-9-5P	100.00	72.28	2361
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-324-3P	99.26	66.31	1034

Literature-anchored findings (GeneRIF, showing 8)

• E-Syt1 is a mediator of cancer cell invasion. (PMID:22659450)
• The extended synaptotagmins (E-Syt1, E-Syt2, and E-Syt3) are endoplasmic reticulum-anchored proteins. They form homo- and heteromeric complexes that mediate contacts with the plasma membrane. Such contacts are critically dependent on the presence of PI(4,5)P2 in this membrane and are additionally regulated by cytosolic Ca2+ via the Ca2+-sensing property of E-Syt1. (PMID:23791178)
• This study identified and confirmed ESYT1 protein changes within the postsynaptic density in schizophrenia. (PMID:25048004)
• ESyt2 and ESyt3, but not ESyt1, interact with activated FGFR1. (PMID:25922075)
• knockdown of ESYT1 (and family members ESYT2 and ESYT3) significantly decreased ANO1 current density. (PMID:29154949)
• a main effect of Ca(2+) on E-Syt1 is to reverse an autoinhibited state and to couple membrane tethering with lipid transport. (PMID:29222176)
• E-syt1 Re-arranges STIM1 Clusters to Stabilize Ring-shaped ER-PM Contact Sites and Accelerate Ca(2+) Store Replenishment. (PMID:30850711)
• PERK recruits E-Syt1 at ER-mitochondria contacts for mitochondrial lipid transport and respiration. (PMID:36821088)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	esyt1b	ENSDARG00000014239
danio_rerio	esyt1a	ENSDARG00000034714
mus_musculus	Esyt1	ENSMUSG00000025366
rattus_norvegicus	Esyt1	ENSRNOG00000060753
drosophila_melanogaster	Esyt2	FBGN0266758

Paralogs (2): ESYT2 (ENSG00000117868), ESYT3 (ENSG00000158220)

Protein

Protein identifiers

Extended synaptotagmin-1 — Q9BSJ8 (reviewed: Q9BSJ8)

Alternative names: Membrane-bound C2 domain-containing protein

All UniProt accessions (2): Q9BSJ8, F8VZB1

UniProt curated annotations — full annotation on UniProt →

Function. Binds calcium (via the C2 domains) and translocates to sites of contact between the endoplasmic reticulum and the cell membrane in response to increased cytosolic calcium levels. Helps tether the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane. Acts as an inhibitor of ADGRD1 G-protein-coupled receptor activity in absence of cytosolic calcium. Binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport.

Subunit / interactions. Interacts with ESYT2 and ESYT3. Interacts with ADGRD1; inhibiting the G-protein-coupled receptor activity of ADGRD1. Interaction with ADGRD1 is abolished when cytosolic calcium increases, relieving ADGRD1 G-protein-coupled receptor activity. Interacts (phosphorylated form) with SLC2A4.

Subcellular location. Endoplasmic reticulum membrane. Cell membrane.

Tissue specificity. Widely expressed.

Post-translational modifications. Phosphorylated on Ser residues in insulin-treated adipocytes (in vitro); this promotes interaction with SLC2A4.

Domain organisation. Anchored to the endoplasmic reticulum membrane by a transmembrane hairpin structure; both N-terminus and C-terminus are cytoplasmic. The C2 domains mediate lipid and calcium binding. The N-terminal C2 domain binds calcium ions and is important for calcium-dependent lipid binding and interaction with membranes. Two calcium ions are bound at a high-affinity site and a third calcium ion is bound with lower affinity. May bind up to four calcium ions. In contrast, the second C2 domain apparently does not bind calcium. The third C2 domain mediates interaction with membranes enriched in phosphatidylinositol 4,5-bisphosphate and is required for translocation to the cell membrane in response to increased cytosolic calcium levels. The SMP-LTD domain is a barrel-like domain that can bind various types of glycerophospholipids in its interior.

Similarity. Belongs to the extended synaptotagmin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BSJ8-1	1	yes
Q9BSJ8-2	2

RefSeq proteins (2): NP_001171725, NP_056107* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR031468	SMP_LBD	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR037733	Ext_Synaptotagmin_C2A	Domain
IPR037749	Ext_Synaptotagmin_C2B	Domain
IPR037752	C2C_KIAA1228	Domain
IPR039010	Synaptotagmin_SMP	Domain
IPR051634	Extended_Synaptotagmin	Family

Pfam: PF00168, PF17047

UniProt features (53 total): binding site 12, modified residue 10, domain 6, mutagenesis site 5, sequence conflict 5, region of interest 4, topological domain 3, compositionally biased region 2, transmembrane region 2, chain 1, coiled-coil region 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BSJ8-F1	78.29	0.29

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 (12): 344; 345; 345; 357; 404; 404; 406; 406; 406; 408; 410; 411

Post-translational modifications (10): 1, 324, 817, 820, 941, 948, 949, 963, 1009, 1034

Mutagenesis-validated functional residues (5):

Position	Phenotype
406	no effect on translocation to sites of contact between the endoplasmic reticulum and the cell membrane.
663	abolishes location at the cell membrane; when associated with a-675 and 722-a–a-729.
675	abolishes location at the cell membrane; when associated with a-675 and 722-a–a-729.
722–729	abolishes location at the cell membrane; when associated with a-663 and a-675.
724	loss of translocation to sites of contact between the endoplasmic reticulum and the cell membrane.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013404	RAC2 GTPase cycle
R-HSA-9013405	RHOD GTPase cycle
R-HSA-9013408	RHOG GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle
R-HSA-9035034	RHOF GTPase cycle
R-HSA-9845576	Glycosphingolipid transport

MSigDB gene sets: 305 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, MATTIOLI_MGUS_VS_PCL, MORF_CDK2, GOBP_MEMBRANE_DOCKING, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_DN, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_PHOSPHOLIPID_TRANSPORT, MULLIGHAN_NPM1_SIGNATURE_3_DN, LIU_CMYB_TARGETS_UP, GOBP_MEMBRANE_ORGANIZATION, MORF_AATF, GOBP_ENDOPLASMIC_RETICULUM_ORGANIZATION, RUAN_RESPONSE_TO_TNF_DN

GO Biological Process (4): obsolete endoplasmic reticulum-plasma membrane tethering (GO:0061817), intermembrane lipid transfer (GO:0120009), lipid transport (GO:0006869), phospholipid transport (GO:0015914)

GO Molecular Function (10): calcium ion binding (GO:0005509), calcium-dependent phospholipid binding (GO:0005544), phosphatidylethanolamine binding (GO:0008429), phosphatidylcholine binding (GO:0031210), phosphatidylinositol binding (GO:0035091), identical protein binding (GO:0042802), phospholipid transfer activity (GO:0120014), protein binding (GO:0005515), lipid binding (GO:0008289), metal ion binding (GO:0046872)

GO Cellular Component (4): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
RHO GTPase cycle	6
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phospholipid binding	4
lipid transport	2
cation binding	2
binding	2
membrane organization	1
transport	1
lipid localization	1
organophosphate ester transport	1
metal ion binding	1
quaternary ammonium group binding	1
anion binding	1
protein binding	1
phospholipid transport	1
lipid transfer activity	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1168 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ESYT1	CCDC112	Q8NEF3	765
ESYT1	STIM1	Q13586	759
ESYT1	ORAI1	Q96D31	692
ESYT1	PITPNM1	O00562	677
ESYT1	OSBP	P22059	636
ESYT1	C2CD2L	O14523	621
ESYT1	SARAF	Q96BY9	599
ESYT1	STIM2	Q9P246	599
ESYT1	STIMATE	Q86TL2	594
ESYT1	GRAMD2A	Q8IUY3	575
ESYT1	OSBPL5	Q9H0X9	559
ESYT1	VAPA	Q9P0L0	542
ESYT1	PITPNM2	Q9BZ72	524
ESYT1	OSBPL8	Q9BZF1	499
ESYT1	GRAMD1A	Q96CP6	499

IntAct

234 interactions, top by confidence:

A	B	Type	Score
ESYT1	ESYT2	psi-mi:“MI:0915”(physical association)	0.770
ESYT1	ESYT2	psi-mi:“MI:0914”(association)	0.770
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
ESYT1	ESYT3	psi-mi:“MI:0915”(physical association)	0.620
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
RAB8A	WDR91	psi-mi:“MI:0914”(association)	0.600
ESYT1	ESYT1	psi-mi:“MI:0915”(physical association)	0.590
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
SCGN	SNAP23	psi-mi:“MI:0914”(association)	0.550
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
ANKRD22	ESYT2	psi-mi:“MI:0914”(association)	0.530
TSPAN11	IGLL5	psi-mi:“MI:0914”(association)	0.530
CNGA3	C2CD2L	psi-mi:“MI:0914”(association)	0.530
FAM241A	NRP1	psi-mi:“MI:0914”(association)	0.530
SLC30A2	RER1	psi-mi:“MI:0914”(association)	0.530
SYNJ2BP	FLOT1	psi-mi:“MI:0914”(association)	0.530
UGT1A1	ESYT1	psi-mi:“MI:0915”(physical association)	0.500
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
	ESYT1	psi-mi:“MI:0915”(physical association)	0.400
	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (610): ESYT1 (Affinity Capture-MS), ESYT1 (Affinity Capture-MS), SYNJ2BP (Affinity Capture-MS), ESYT2 (Affinity Capture-MS), ARL6IP5 (Affinity Capture-MS), YIF1B (Affinity Capture-MS), ESYT1 (Affinity Capture-MS), ESYT1 (Affinity Capture-MS), ESYT1 (Affinity Capture-MS), ESYT1 (Affinity Capture-MS), ESYT1 (Affinity Capture-MS), ESYT1 (Affinity Capture-MS), ESYT1 (Proximity Label-MS), ESYT1 (Proximity Label-MS), ESYT1 (Proximity Label-MS)

ESM2 similar proteins: A0A8I3NFE2, A0FGR8, A0FGR9, A2AP18, A4IJ05, O08625, O08874, O15357, O75038, P51432, P70218, P70268, Q01970, Q12851, Q3TZZ7, Q3U7R1, Q4VX76, Q5DTI8, Q5FWL4, Q5M7N9, Q5R8Q5, Q5RAG2, Q5RCK6, Q5RJH2, Q61161, Q62807, Q63433, Q6DN12, Q6XYQ8, Q7ZWU7, Q812E4, Q86SS6, Q8K394, Q8TDW5, Q920M7, Q925C0, Q92918, Q99JE6, Q99N48, Q9BSJ8

Diamond homologs: A0A075F932, A0FGR8, A0FGR9, A4IJ05, A6QP06, O00443, O00445, O00750, O08625, O08835, O35681, P04409, P05128, P05129, P10829, P21521, P21579, P21707, P24505, P24506, P24507, P29101, P34693, P40748, P40749, P41823, P46096, P46097, P47191, P47708, P47709, P47861, P48018, P50232, P59926, P63318, P63319, P70169, P70610, P70611

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 221 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
Activation of BAD and translocation to mitochondria	5	26.4×	2e-04
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	5	23.3×	2e-04
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	23.3×	2e-04
Activation of BH3-only proteins	5	17.2×	5e-04
RAF activation	6	14.0×	3e-04
Signaling by high-kinase activity BRAF mutants	6	13.2×	3e-04
MAP2K and MAPK activation	6	11.9×	6e-04
Signaling by RAF1 mutants	6	11.6×	6e-04

GO biological processes:

GO term	Partners	Fold	FDR
endoplasmic reticulum organization	6	13.6×	2e-03
Ras protein signal transduction	7	7.7×	7e-03
endoplasmic reticulum to Golgi vesicle-mediated transport	10	7.3×	6e-04
MAPK cascade	8	6.6×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	179
Likely benign	4
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

4036 predictions. Top by Δscore:

Variant	Effect	Δscore
12:56120509:A:AG	acceptor_gain	1.0000
12:56120509:AGT:A	acceptor_gain	1.0000
12:56120510:G:GG	acceptor_gain	1.0000
12:56120510:GT:G	acceptor_gain	1.0000
12:56120510:GTG:G	acceptor_gain	1.0000
12:56128707:TGGG:T	donor_loss	1.0000
12:56128709:GGTG:G	donor_loss	1.0000
12:56128710:G:C	donor_loss	1.0000
12:56130788:CAG:C	acceptor_loss	1.0000
12:56130789:A:AG	acceptor_gain	1.0000
12:56130789:AGATT:A	acceptor_gain	1.0000
12:56130790:G:GA	acceptor_gain	1.0000
12:56130790:GA:G	acceptor_gain	1.0000
12:56130790:GAT:G	acceptor_gain	1.0000
12:56130790:GATT:G	acceptor_gain	1.0000
12:56130790:GATTG:G	acceptor_gain	1.0000
12:56130921:AAAAG:A	donor_gain	1.0000
12:56130924:AGG:A	donor_loss	1.0000
12:56130927:T:G	donor_loss	1.0000
12:56131037:TAGC:T	acceptor_loss	1.0000
12:56131038:A:AG	acceptor_gain	1.0000
12:56131038:A:AT	acceptor_loss	1.0000
12:56131039:G:GG	acceptor_gain	1.0000
12:56131039:GC:G	acceptor_gain	1.0000
12:56131039:GCC:G	acceptor_gain	1.0000
12:56131039:GCCA:G	acceptor_gain	1.0000
12:56131039:GCCAT:G	acceptor_gain	1.0000
12:56131112:AGGTA:A	donor_loss	1.0000
12:56131113:GGTAA:G	donor_loss	1.0000
12:56131114:GT:G	donor_loss	1.0000

AlphaMissense

7106 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:56131764:T:A	W274R	0.998
12:56131764:T:C	W274R	0.998
12:56132580:T:A	W382R	0.998
12:56132580:T:C	W382R	0.998
12:56132582:G:C	W382C	0.998
12:56132582:G:T	W382C	0.998
12:56137658:T:A	W700R	0.998
12:56137658:T:C	W700R	0.998
12:56143284:T:A	V1059D	0.998
12:56130864:T:A	V169D	0.997
12:56132547:A:C	S371R	0.997
12:56132549:T:A	S371R	0.997
12:56132549:T:G	S371R	0.997
12:56134176:A:C	S514R	0.997
12:56134178:C:A	S514R	0.997
12:56134178:C:G	S514R	0.997
12:56128707:T:A	W130R	0.996
12:56128707:T:C	W130R	0.996
12:56130885:T:C	L176P	0.996
12:56132431:G:C	R332P	0.996
12:56137548:A:C	D663A	0.996
12:56137660:G:C	W700C	0.996
12:56137660:G:T	W700C	0.996
12:56128570:G:A	G84D	0.995
12:56130900:T:C	F181S	0.995
12:56134369:T:A	W525R	0.995
12:56134369:T:C	W525R	0.995
12:56137659:G:C	W700S	0.995
12:56128709:G:C	W130C	0.994
12:56128709:G:T	W130C	0.994

dbSNP variants (sampled 300 via entrez): RS1000041287 (12:56138645 A>C,G), RS1000068915 (12:56144518 G>A), RS1000699052 (12:56127192 G>A,T), RS1000736291 (12:56143296 C>T), RS1000793408 (12:56127518 T>A), RS1000969050 (12:56139742 C>G,T), RS1001042528 (12:56140032 A>G), RS1001425119 (12:56143260 A>G), RS1001861365 (12:56139401 C>A,T), RS1001905609 (12:56143710 A>G), RS1001936374 (12:56126715 C>G), RS1002003476 (12:56133164 C>T), RS1002333489 (12:56139719 C>T), RS1002514226 (12:56136469 T>G), RS1002549396 (12:56143935 G>A)

Disease associations

OMIM: gene MIM:616670 | 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
GCST001156_8	Systemic sclerosis	6.000000e-08
GCST004367_1	Anorexia nervosa	4.000000e-09
GCST008916_124	Asthma	1.000000e-16
GCST010002_217	Refractive error	6.000000e-174

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3621033 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.03	Kd	9.367	nM	CHEMBL3752910
8.03	ED50	9.367	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 6 total; 1 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148342: Binding affinity to human ESYT1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0094	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, affects cotreatment	2
Acetaminophen	increases expression	2
Air Pollutants	decreases expression, affects expression, increases abundance	2
Air Pollutants, Occupational	affects expression, decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Valproic Acid	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	increases expression, affects cotreatment, affects localization, decreases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
cobaltous chloride	decreases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
benzo(e)pyrene	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
bisphenol B	increases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
Arsenic Trioxide	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Caffeine	increases phosphorylation	1
Carbamazepine	affects expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Diazinon	increases methylation	1
Dieldrin	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3624154	Binding	Binding affinity to E-Syt1 in human PC3 cells at 600 nM by affinity chromatography analysis	Identification and characterization of β-sitosterol target proteins. — Bioorg Med Chem Lett

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SM46	HAP1 ESYT1 (-) 1	Cancer cell line	Male
CVCL_SM47	HAP1 ESYT1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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