ESYT2

Summary

ESYT2 (extended synaptotagmin 2, HGNC:22211) is a protein-coding gene on chromosome 7q36.3, encoding Extended synaptotagmin-2 (A0FGR8). Tethers the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane.

Enables calcium ion binding activity; identical protein binding activity; and phospholipid binding activity. Predicted to be involved in endocytosis; endoplasmic reticulum-plasma membrane tethering; and lipid transport. Located in several cellular components, including cytoplasmic side of plasma membrane; endoplasmic reticulum membrane; and endoplasmic reticulum-plasma membrane contact site.

Source: NCBI Gene 57488 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 206 total
• Druggable target: yes
• MANE Select transcript: NM_001367773

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22211
Approved symbol	ESYT2
Name	extended synaptotagmin 2
Location	7q36.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1228, CHR2SYT
Ensembl gene	ENSG00000117868
Ensembl biotype	protein_coding
OMIM	616691
Entrez	57488

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 23 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000251527, ENST00000275418, ENST00000435514, ENST00000483958, ENST00000497111, ENST00000652148, ENST00000880533, ENST00000934763, ENST00000934764, ENST00000934765, ENST00000934766, ENST00000934767, ENST00000944350, ENST00000944351, ENST00000944352, ENST00000944353, ENST00000944354, ENST00000944355, ENST00000944356, ENST00000944357, ENST00000944358, ENST00000944359, ENST00000944360, ENST00000944361, ENST00000944362, ENST00000944363

RefSeq mRNA: 2 — MANE Select: NM_001367773 NM_001367773, NM_020728

CCDS: CCDS34791, CCDS94243

Canonical transcript exons

ENST00000275418 — 23 exons

Exon	Start	End
ENSE00000730906	158748194	158748280
ENSE00000730915	158760058	158760147
ENSE00000897636	158763083	158763165
ENSE00000897643	158764677	158764853
ENSE00000897649	158767654	158767774
ENSE00000897656	158773341	158773396
ENSE00001086752	158759486	158759581
ENSE00001086766	158743529	158743678
ENSE00001251229	158749649	158749723
ENSE00001251320	158761496	158761544
ENSE00001549714	158730997	158734252
ENSE00001599679	158829089	158829509
ENSE00001704685	158752781	158752843
ENSE00003481933	158799031	158799072
ENSE00003519772	158788345	158788417
ENSE00003522548	158793650	158793726
ENSE00003532857	158788004	158788093
ENSE00003662301	158797942	158798076
ENSE00003712056	158734422	158734471
ENSE00003716644	158737048	158737179
ENSE00003723213	158741523	158741896
ENSE00003749667	158739023	158739121
ENSE00003751011	158735503	158735608

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 98.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.9137 / max 384.9708, expressed in 1803 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
87124	11.8749	1774
87123	4.5995	1576
87119	0.3840	191
87118	0.3442	155
205025	0.2442	101
87117	0.2419	122
87121	0.1064	36
87122	0.0779	23
87116	0.0407	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
layer of synovial tissue	UBERON:0007616	98.36	gold quality
calcaneal tendon	UBERON:0003701	98.35	gold quality
saphenous vein	UBERON:0007318	98.12	gold quality
synovial joint	UBERON:0002217	97.96	gold quality
endothelial cell	CL:0000115	97.87	gold quality
urethra	UBERON:0000057	97.71	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.48	gold quality
tendon	UBERON:0000043	97.19	gold quality
left ventricle myocardium	UBERON:0006566	96.89	gold quality
upper arm skin	UBERON:0004263	96.83	gold quality
skin of hip	UBERON:0001554	96.44	gold quality
popliteal artery	UBERON:0002250	96.25	gold quality
tibial artery	UBERON:0007610	96.25	gold quality
pancreatic ductal cell	CL:0002079	96.23	gold quality
epithelial cell of pancreas	CL:0000083	96.21	gold quality
tibialis anterior	UBERON:0001385	96.21	gold quality
mucosa of stomach	UBERON:0001199	96.15	gold quality
aorta	UBERON:0000947	96.12	gold quality
palpebral conjunctiva	UBERON:0001812	96.03	gold quality
kidney epithelium	UBERON:0004819	95.96	gold quality
ascending aorta	UBERON:0001496	95.94	gold quality
thoracic aorta	UBERON:0001515	95.94	gold quality
superficial temporal artery	UBERON:0001614	95.79	gold quality
seminal vesicle	UBERON:0000998	95.77	gold quality
penis	UBERON:0000989	95.74	gold quality
right coronary artery	UBERON:0001625	95.73	gold quality
descending thoracic aorta	UBERON:0002345	95.72	gold quality
adrenal tissue	UBERON:0018303	95.48	gold quality
nipple	UBERON:0002030	95.46	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.29	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	21.34
E-CURD-119	yes	8.98
E-ANND-3	yes	8.19
E-MTAB-6058	no	245.98
E-MTAB-6142	no	91.92

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

171 targeting ESYT2, 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-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-374A-5P	99.90	71.34	2923

Literature-anchored findings (GeneRIF, showing 5)

• 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)
• 2.44 A resolution the crystal structure of a fragment of extended synaptotagmin 2, including an SMP domain and two adjacent C2 domains; evidence for a role of SMP-domain-containing proteins in the control of lipid transfer at membrane contact sites (PMID:24847877)
• ESyt2 and ESyt3, but not ESyt1, interact with activated FGFR1. (PMID:25922075)
• The short isoform of extended synaptotagmin-2 controls Ca(2+) dynamics in T cells via interaction with STIM1. (PMID:32879390)
• Circular RNA circESYT2 serves as a microRNA-665 sponge to promote the progression of hepatocellular carcinoma through ENO2. (PMID:38710213)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	esyt2a	ENSDARG00000030824
danio_rerio	esyt2b	ENSDARG00000078964
mus_musculus	Esyt2	ENSMUSG00000021171
rattus_norvegicus	Esyt2	ENSRNOG00000032391
drosophila_melanogaster	Esyt2	FBGN0266758
caenorhabditis_elegans		WBGENE00020443

Paralogs (2): ESYT1 (ENSG00000139641), ESYT3 (ENSG00000158220)

Protein

Protein identifiers

Extended synaptotagmin-2 — A0FGR8 (reviewed: A0FGR8)

Alternative names: Chr2Syt

All UniProt accessions (3): A0FGR8, A0A499FIX8, H7BXI1

UniProt curated annotations — full annotation on UniProt →

Function. Tethers the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane. Binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport. Plays a role in FGF signaling via its role in the rapid internalization of FGFR1 that has been activated by FGF1 binding; this occurs most likely via the AP-2 complex. Promotes the localization of SACM1L at endoplasmic reticulum-plasma membrane contact sites (EPCS).

Subunit / interactions. Homodimer. Interacts with ESYT1 and ESYT3. Interacts with FGFR1 that has been activated by FGF1 binding. Interacts with the AP-2 complex; identified in a complex with the AP-2 complex and FGFR1.

Subcellular location. Cell membrane. Endoplasmic reticulum membrane.

Tissue specificity. Widely expressed with high level in cerebellum.

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 location at the cell membrane. The SMP-LTD domain is a barrel-like domain that binds glycerophospholipids in its interior; can bind two lipid molecules simultaneously. Binds a variety of lipids, including phosphatidylethanolamine, phosphatidylcholine and phosphatidylinositol.

Similarity. Belongs to the extended synaptotagmin family.

Isoforms (5)

UniProt ID	Names	Canonical?
A0FGR8-1	1	yes
A0FGR8-2	2
A0FGR8-4	4
A0FGR8-5	5
A0FGR8-6	6

RefSeq proteins (2): NP_001354702, NP_065779 (=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 (108 total): strand 34, binding site 13, helix 11, modified residue 11, turn 7, splice variant 7, mutagenesis site 5, sequence conflict 4, domain 4, topological domain 3, region of interest 3, transmembrane region 2, sequence variant 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
4NPJ	X-RAY DIFFRACTION	2.1
4P42	X-RAY DIFFRACTION	2.44
4NPK	X-RAY DIFFRACTION	2.55
2DMG	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A0FGR8-F1	74.44	0.38

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 (13): 400; 401; 401; 413; 460; 460; 461; 462; 462; 462; 464; 466 …

Post-translational modifications (11): 691, 693, 705, 736, 738, 739, 743, 748, 755, 758, 761

Mutagenesis-validated functional residues (5):

Position	Phenotype
401	abolishes calcium binding; when associated with a-413.
413	abolishes calcium binding; when associated with a-401.
413	strongly reduces calcium binding.
466	impairs binding of the third calcium ion, but has no effect on the binding of the other two calcium ions.
833–840	abolishes location at the cell membrane.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9845576	Glycosphingolipid transport

MSigDB gene sets: 197 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_MEMBRANE_DOCKING, GTGCCTT_MIR506, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, ATGCTGG_MIR338, BROWN_MYELOID_CELL_DEVELOPMENT_UP, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_DN, SENESE_HDAC1_TARGETS_UP, GOBP_ENDOPLASMIC_RETICULUM_ORGANIZATION, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, GOBP_IMPORT_INTO_CELL, GOBP_LIPID_LOCALIZATION

GO Biological Process (3): lipid transport (GO:0006869), endocytosis (GO:0006897), obsolete endoplasmic reticulum-plasma membrane tethering (GO:0061817)

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), cadherin binding (GO:0045296), protein binding (GO:0005515), lipid binding (GO:0008289), metal ion binding (GO:0046872)

GO Cellular Component (8): endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasmic side of plasma membrane (GO:0009898), membrane (GO:0016020), organelle membrane contact site (GO:0044232), endoplasmic reticulum-plasma membrane contact site (GO:0140268), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phospholipid binding	3
cellular anatomical structure	3
cation binding	2
binding	2
cytoplasm	2
transport	1
lipid localization	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
metal ion binding	1
quaternary ammonium group binding	1
anion binding	1
protein binding	1
cell adhesion molecule binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
plasma membrane	1
cytoplasmic side of membrane	1
organelle	1
organelle membrane contact site	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1004 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ESYT2	DYNC2I1	Q8WVS4	703
ESYT2	C2CD2L	O14523	584
ESYT2	OSBPL8	Q9BZF1	570
ESYT2	ORAI1	Q96D31	526
ESYT2	PITPNM1	O00562	525
ESYT2	NCAPG2	Q86XI2	522
ESYT2	OSBPL5	Q9H0X9	520
ESYT2	MBLAC2	Q68D91	490
ESYT2	OSBP	P22059	487
ESYT2	GRAMD2A	Q8IUY3	487
ESYT2	KIAA2013	Q8IYS2	479
ESYT2	VAPA	Q9P0L0	477
ESYT2	ARMCX3	Q9UH62	468
ESYT2	STIM2	Q9P246	466
ESYT2	VMP1	Q96GC9	456

IntAct

196 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
ESYT1	ESYT2	psi-mi:“MI:0403”(colocalization)	0.770
ESYT2	ESYT1	psi-mi:“MI:0915”(physical association)	0.770
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
ESYT2	ESYT2	psi-mi:“MI:0915”(physical association)	0.680
ESYT2	ESYT2	psi-mi:“MI:0407”(direct interaction)	0.680
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
ESYT3	ESYT2	psi-mi:“MI:0915”(physical association)	0.620
ESYT3	ESYT2	psi-mi:“MI:0403”(colocalization)	0.620

BioGRID (484): ESYT2 (Affinity Capture-MS), ESYT2 (Affinity Capture-MS), ESYT2 (Affinity Capture-MS), ESYT2 (Proximity Label-MS), ESYT2 (Affinity Capture-MS), ESYT2 (Affinity Capture-MS), ESYT2 (Affinity Capture-MS), ESYT2 (Affinity Capture-MS), ESYT2 (Affinity Capture-MS), ESYT2 (Affinity Capture-MS), ESYT2 (Affinity Capture-MS), ESYT2 (Affinity Capture-MS), ESYT2 (Affinity Capture-MS), ESYT2 (Affinity Capture-MS), ESYT2 (Affinity Capture-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, 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.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 139 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
Signaling by high-kinase activity BRAF mutants	6	21.6×	9e-05
MAP2K and MAPK activation	6	19.5×	9e-05
RAF activation	5	19.1×	4e-04
Signaling by RAF1 mutants	6	19.0×	9e-05
Signaling by moderate kinase activity BRAF mutants	6	17.3×	1e-04
Paradoxical activation of RAF signaling by kinase inactive BRAF	6	17.3×	1e-04
Signaling downstream of RAS mutants	6	17.3×	1e-04
Negative regulation of MAPK pathway	5	15.1×	8e-04

GO biological processes:

GO term	Partners	Fold	FDR
zinc ion transmembrane transport	6	37.0×	1e-05
intracellular zinc ion homeostasis	5	21.1×	7e-04
endoplasmic reticulum organization	5	18.5×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	154
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

5262 predictions. Top by Δscore:

Variant	Effect	Δscore
7:158735496:CACTT:C	donor_loss	1.0000
7:158735497:ACTT:A	donor_loss	1.0000
7:158735499:TTACT:T	donor_loss	1.0000
7:158735500:TACTT:T	donor_loss	1.0000
7:158735501:A:AC	donor_gain	1.0000
7:158735501:A:C	donor_loss	1.0000
7:158735502:C:CT	donor_gain	1.0000
7:158735502:CT:C	donor_gain	1.0000
7:158735502:CTTT:C	donor_gain	1.0000
7:158735502:CTTTG:C	donor_gain	1.0000
7:158735604:CAAAG:C	acceptor_gain	1.0000
7:158737181:T:C	acceptor_gain	1.0000
7:158739037:G:GT	donor_gain	1.0000
7:158741517:A:AC	donor_gain	1.0000
7:158741521:A:AC	donor_gain	1.0000
7:158741522:C:CC	donor_gain	1.0000
7:158748190:ATACC:A	donor_loss	1.0000
7:158748192:ACCT:A	donor_loss	1.0000
7:158748193:C:A	donor_loss	1.0000
7:158748198:A:C	donor_gain	1.0000
7:158748276:CGAAT:C	acceptor_gain	1.0000
7:158748278:AATC:A	acceptor_loss	1.0000
7:158748281:C:CC	acceptor_gain	1.0000
7:158748281:C:CG	acceptor_loss	1.0000
7:158748282:T:A	acceptor_loss	1.0000
7:158749729:C:T	acceptor_gain	1.0000
7:158752853:C:CT	acceptor_gain	1.0000
7:158759482:CTA:C	donor_loss	1.0000
7:158759483:TA:T	donor_loss	1.0000
7:158759484:A:AC	donor_gain	1.0000

AlphaMissense

5654 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:158735548:C:A	K875N	1.000
7:158735548:C:G	K875N	1.000
7:158735558:A:T	V872D	1.000
7:158737138:A:T	V825D	1.000
7:158739080:A:G	L792P	1.000
7:158739092:C:T	G788E	1.000
7:158739093:C:A	G788W	1.000
7:158748253:A:G	W584R	1.000
7:158748253:A:T	W584R	1.000
7:158764692:C:A	W438C	1.000
7:158764692:C:G	W438C	1.000
7:158764694:A:G	W438R	1.000
7:158764694:A:T	W438R	1.000
7:158773381:A:G	W331R	1.000
7:158773381:A:T	W331R	1.000
7:158793659:A:G	L268P	1.000
7:158799042:A:G	W197R	1.000
7:158799042:A:T	W197R	1.000
7:158829091:A:G	W186R	1.000
7:158829091:A:T	W186R	1.000
7:158734244:A:G	L910P	0.999
7:158734244:A:T	L910H	0.999
7:158734423:A:G	W907R	0.999
7:158734423:A:T	W907R	0.999
7:158735507:C:A	G889V	0.999
7:158735507:C:T	G889D	0.999
7:158735508:C:G	G889R	0.999
7:158735550:T:C	K875E	0.999
7:158735552:A:T	V874E	0.999
7:158735556:C:G	A873P	0.999

dbSNP variants (sampled 300 via entrez): RS1000045701 (7:158824738 T>C,G), RS1000065802 (7:158742524 T>C), RS1000097392 (7:158809582 A>C), RS1000118006 (7:158781433 TGTGA>T), RS1000140436 (7:158753144 G>A), RS1000199009 (7:158821806 T>G), RS1000225160 (7:158779018 A>G), RS1000228027 (7:158825488 A>G,T), RS1000231625 (7:158744646 G>A,T), RS1000237936 (7:158783415 G>A,C), RS1000254293 (7:158781311 CTG>C), RS1000260077 (7:158815207 C>A,G,T), RS1000276351 (7:158768137 T>C), RS1000282659 (7:158809910 T>C,G), RS1000301757 (7:158827436 C>A)

Disease associations

OMIM: gene MIM:616691 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST003124_33	Mild influenza (H1N1) infection	2.000000e-08
GCST004599_62	Mean platelet volume	2.000000e-25
GCST009066_14	Mosaic loss of chromosome Y (Y chromosome dosage)	2.000000e-09
GCST009067_16	Mosaic loss of chromosome Y (Y chromosome dosage)	1.000000e-06
GCST010002_267	Refractive error	2.000000e-37
GCST011920_2	Hearing loss in noise exposure	2.000000e-06
GCST90002395_708	Mean platelet volume	2.000000e-27
GCST90002395_709	Mean platelet volume	4.000000e-15
GCST90002402_41	Platelet count	1.000000e-17

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:1001488	influenza A (H1N1)
EFO:0007783	mosaic loss of chromosome Y measurement
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066250 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1061735	Efficacy	3	methylphenidate	Attention Deficit Disorder with Hyperactivity

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1061735	ESYT2	3	0.00	1	methylphenidate

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
7.54	Kd	28.59	nM	CHEMBL5653589
7.54	ED50	28.59	nM	CHEMBL5653589
7.39	Kd	40.99	nM	CHEMBL3752910
7.39	ED50	40.99	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	2148343: Binding affinity to human ESYT2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0286	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148343: Binding affinity to human ESYT2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0410	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	5
trichostatin A	affects cotreatment, increases expression	3
bisphenol A	decreases expression, increases expression	2
bisphenol S	affects cotreatment, increases methylation, increases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
pyrogallol 1,3-dimethyl ether	decreases expression, increases expression, affects cotreatment, affects localization	1
decabromobiphenyl ether	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
tetrabromobisphenol A	decreases expression	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	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
bisphenol B	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
PCI 5002	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Bortezomib	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
CHEMBL5651385	Binding	Binding affinity to human ESYT2 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

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SM48	HAP1 ESYT2 (-) 1	Cancer cell line	Male
CVCL_SM49	HAP1 ESYT2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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