SYNJ2

Summary

SYNJ2 (synaptojanin 2, HGNC:11504) is a protein-coding gene on chromosome 6q25.3, encoding Synaptojanin-2 (O15056). Inositol 5-phosphatase which may be involved in distinct membrane trafficking and signal transduction pathways.

The gene is a member of the inositol-polyphosphate 5-phosphatase family. The encoded protein interacts with the ras-related C3 botulinum toxin substrate 1, which causes translocation of the encoded protein to the plasma membrane where it inhibits clathrin-mediated endocytosis. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 8871 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 279 total
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_003898

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11504
Approved symbol	SYNJ2
Name	synaptojanin 2
Location	6q25.3
Locus type	gene with protein product
Status	Approved
Aliases	INPP5H
Ensembl gene	ENSG00000078269
Ensembl biotype	protein_coding
OMIM	609410
Entrez	8871

Gene structure

Transcript identifiers

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

ENST00000355585, ENST00000367112, ENST00000367113, ENST00000367122, ENST00000449320, ENST00000485863, ENST00000638626, ENST00000640338, ENST00000640569

RefSeq mRNA: 3 — MANE Select: NM_003898 NM_001178088, NM_001410947, NM_003898

CCDS: CCDS5254, CCDS87462, CCDS94025

Canonical transcript exons

ENST00000355585 — 27 exons

Exon	Start	End
ENSE00000412332	158089839	158089947
ENSE00000765557	158088660	158088772
ENSE00000765558	158086855	158086989
ENSE00000765559	158084001	158084174
ENSE00000765560	158083429	158083597
ENSE00000765564	158076626	158076782
ENSE00000765569	158066444	158066635
ENSE00000765574	158061992	158062164
ENSE00000765575	158059257	158059353
ENSE00000830220	158081432	158081510
ENSE00000830227	158069533	158069673
ENSE00000830228	158068647	158068728
ENSE00000830230	158064826	158064991
ENSE00000830232	158064601	158064750
ENSE00000894234	158092926	158093104
ENSE00000894235	158074580	158074738
ENSE00000894238	158033455	158033680
ENSE00001204724	158017204	158017290
ENSE00001204730	157981863	157982088
ENSE00001217886	158078164	158078281
ENSE00001760278	158028756	158029026
ENSE00001890001	158095618	158099176
ENSE00002152303	158043316	158043399
ENSE00002180718	158054967	158055028
ENSE00003476528	158081109	158081327
ENSE00003511952	158063791	158063872
ENSE00003750250	158071602	158071794

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 98.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.7140 / max 434.1932, expressed in 1711 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
70797	9.3168	1697
70811	2.1240	280
70802	1.5001	201
70809	0.1149	57
70810	0.1067	53
70804	0.1054	52
70796	0.1002	44
70798	0.0965	16
70812	0.0887	62
70824	0.0538	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
inferior vagus X ganglion	UBERON:0005363	98.84	gold quality
medial globus pallidus	UBERON:0002477	97.74	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.37	gold quality
spinal cord	UBERON:0002240	97.21	gold quality
subthalamic nucleus	UBERON:0001906	97.20	gold quality
medulla oblongata	UBERON:0001896	97.00	gold quality
pons	UBERON:0000988	96.91	gold quality
globus pallidus	UBERON:0001875	96.86	gold quality
superior vestibular nucleus	UBERON:0007227	96.62	gold quality
corpus callosum	UBERON:0002336	95.68	gold quality
inferior olivary complex	UBERON:0002127	95.36	gold quality
ventral tegmental area	UBERON:0002691	95.11	gold quality
dorsal plus ventral thalamus	UBERON:0001897	94.97	gold quality
cartilage tissue	UBERON:0002418	93.75	gold quality
cranial nerve II	UBERON:0000941	93.48	gold quality
type B pancreatic cell	CL:0000169	93.27	gold quality
substantia nigra pars reticulata	UBERON:0001966	93.14	gold quality
olfactory bulb	UBERON:0002264	93.00	silver quality
tongue squamous epithelium	UBERON:0006919	92.93	silver quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	92.88	gold quality
vena cava	UBERON:0004087	92.59	silver quality
midbrain	UBERON:0001891	92.47	gold quality
parietal lobe	UBERON:0001872	92.30	gold quality
postcentral gyrus	UBERON:0002581	92.17	gold quality
substantia nigra	UBERON:0002038	92.05	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	91.62	silver quality
corpus epididymis	UBERON:0004359	91.15	gold quality
lateral globus pallidus	UBERON:0002476	90.94	gold quality
CA1 field of hippocampus	UBERON:0003881	90.50	gold quality
Ammon’s horn	UBERON:0001954	90.47	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	63.83
E-ANND-3	yes	6.41

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

91 targeting SYNJ2, 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-8485	100.00	77.57	4731
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-6861-3P	99.60	68.46	444

Literature-anchored findings (GeneRIF, showing 12)

• Since Syn 2 is a phosphatidylinositol 4,5-biphosphatase involved in cell growth and rearrangement of actin filaments, the increased Syn 2 expression may correlate with the hairy cell leukemia etiology or the characteristic morphologic alterations. (PMID:14562116)
• contributes to the role of Rac1 in cell invasion and migration by regulating the formation of invadopodia and lamellipodia (PMID:15548694)
• Identification of inactivating mutations in the JAK1, SYNJ2, and CLPTM1 genes in prostate cancer cells (PMID:16102578)
• SYNJ2 is a target gene of the BACH1 transcription factor according to ChIP-seq analysis in HEK 293 cells. (PMID:21555518)
• SYNJ2 is a novel gene in which variation is potentially associated with cognitive abilities. (PMID:22045296)
• Single nucleotide polymorphisms in SYNJ2 are associated with personality disorders. (PMID:22213687)
• Src-mediated phosphorylation of SYNJ2 contributes to invadopodia formation. (PMID:23076136)
• The genetic interactions associated with ILVatrophy rate in this study may be mapping variants inSYNJ2andPI4KAthat interact to decrease synthesisof PIP. (PMID:24077433)
• Synaptojanin 2 is a druggable mediator of metastasis and the gene is overexpressed and amplified in breast cancer. (PMID:25605973)
• Results, combined with previous studies, suggest that rs9365723, located on SYNJ2, is associated with the risk of CRC in a Chinese population. (PMID:26616230)
• Identifying the Prognostic Risk Factors of Synaptojanin 2 and Its Underlying Perturbations Pathways in Hepatocellular Carcinoma. (PMID:33641617)
• SYNJ2 is a novel and potential biomarker for the prediction and treatment of cancers: from lung squamous cell carcinoma to pan-cancer. (PMID:35581615)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
mus_musculus	Synj2	ENSMUSG00000023805
rattus_norvegicus	Synj2	ENSRNOG00000017114
drosophila_melanogaster	CG9784	FBGN0030761
drosophila_melanogaster	CG6805	FBGN0034179
drosophila_melanogaster	Synj	FBGN0034691
drosophila_melanogaster	sp3	FBGN0038890
caenorhabditis_elegans		WBGENE00006763
caenorhabditis_elegans	sac-2	WBGENE00012353

Paralogs (13): FIG4 (ENSG00000112367), OCRL (ENSG00000122126), INPP5K (ENSG00000132376), INPP5E (ENSG00000148384), SYNJ1 (ENSG00000159082), INPPL1 (ENSG00000165458), INPP5D (ENSG00000168918), SH2D1A (ENSG00000183918), INPP5J (ENSG00000185133), SH2D1B (ENSG00000198574), INPP5F (ENSG00000198825), INPP5B (ENSG00000204084), SACM1L (ENSG00000211456)

Protein

Protein identifiers

Synaptojanin-2 — O15056 (reviewed: O15056)

Alternative names: Synaptic inositol 1,4,5-trisphosphate 5-phosphatase 2

All UniProt accessions (6): O15056, A0A1W2PR85, E7ER60, H0YEV8, H7BY56, Q5TA15

UniProt curated annotations — full annotation on UniProt →

Function. Inositol 5-phosphatase which may be involved in distinct membrane trafficking and signal transduction pathways. May mediate the inhibitory effect of Rac1 on endocytosis.

Subunit / interactions. Binds to GRB2. Isoform 2A binds to SYNJ2BP/OMP25. Isoform 2B2 C-terminal proline-rich region binds to a variety of SH3 domain-containing proteins including SH3GL1, SH3GL2, SH3GL3 and GRB2.

Subcellular location. Cytoplasm. Cell membrane. Membrane raft. Presynapse. Cytoskeleton.

Similarity. Belongs to the synaptojanin family. In the central section; belongs to the inositol 1,4,5-trisphosphate 5-phosphatase family.

Isoforms (3)

UniProt ID	Names	Canonical?
O15056-1	2B2	yes
O15056-2	2B1
O15056-3	2A

RefSeq proteins (3): NP_001171559, NP_001397876, NP_003889* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000300	IPPc	Domain
IPR000504	RRM_dom	Domain
IPR002013	SAC_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR015047	SYNJ1/2_RRM	Domain
IPR034973	SYNJ2_RRM	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR036691	Endo/exonu/phosph_ase_sf	Homologous_superfamily
IPR046985	IP5	Family

Pfam: PF02383, PF08952, PF22669

Catalyzed reactions (Rhea), 1 shown:

• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-phosphate) + phosphate (RHEA:22764)

UniProt features (30 total): compositionally biased region 7, strand 5, region of interest 5, helix 4, splice variant 3, domain 2, modified residue 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1UFW	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15056-F1	68.47	0.32

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 1124, 1191

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-1660499	Synthesis of PIPs at the plasma membrane
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-1430728	Metabolism
R-HSA-1483255	PI Metabolism
R-HSA-1483257	Phospholipid metabolism
R-HSA-199991	Membrane Trafficking
R-HSA-556833	Metabolism of lipids
R-HSA-5653656	Vesicle-mediated transport

MSigDB gene sets: 223 (showing top): GOBP_LIPID_MODIFICATION, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, MORF_MSH3, PEREZ_TP63_TARGETS, GOBP_PHOSPHOLIPID_DEPHOSPHORYLATION, MORF_BRCA1, MORF_ATRX, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_3_PHOSPHATE_BIOSYNTHETIC_PROCESS, MORF_RAD51L3

GO Biological Process (8): phosphatidylinositol biosynthetic process (GO:0006661), phosphatidylinositol dephosphorylation (GO:0046856), synaptic vesicle endocytosis (GO:0048488), membrane organization (GO:0061024), lipid metabolic process (GO:0006629), phospholipid metabolic process (GO:0006644), phosphatidylinositol-3-phosphate biosynthetic process (GO:0036092), glycerolipid metabolic process (GO:0046486)

GO Molecular Function (12): RNA binding (GO:0003723), phosphatidylinositol-3-phosphate phosphatase activity (GO:0004438), phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity (GO:0004439), phosphatidylinositol phosphate 4-phosphatase activity (GO:0034596), phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity (GO:0043813), phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity (GO:0052629), inositol-1,4,5-trisphosphate 5-phosphatase activity (GO:0052658), nucleic acid binding (GO:0003676), protein binding (GO:0005515), hydrolase activity (GO:0016787), phosphatase activity (GO:0016791), phosphatidylinositol phosphate phosphatase activity (GO:0052866)

GO Cellular Component (10): cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), membrane (GO:0016020), membrane raft (GO:0045121), perinuclear region of cytoplasm (GO:0048471), presynapse (GO:0098793), cell projection (GO:0042995), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
PI Metabolism	1
Membrane Trafficking	1
Phospholipid metabolism	1
Metabolism of lipids	1
Vesicle-mediated transport	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
phosphatidylinositol metabolic process	2
lipid metabolic process	2
phosphatidylinositol phosphate 5-phosphatase activity	2
phosphatidylinositol-3,5-bisphosphate phosphatase activity	2
binding	2
cytoplasm	2
biosynthetic process	1
phospholipid dephosphorylation	1
synaptic vesicle recycling	1
presynaptic endocytosis	1
cellular component organization	1
primary metabolic process	1
organophosphate metabolic process	1
phosphatidylinositol phosphate biosynthetic process	1
nucleic acid binding	1
phosphatidylinositol monophosphate phosphatase activity	1
phosphatidylinositol-4,5-bisphosphate phosphatase activity	1
phosphatidylinositol phosphate phosphatase activity	1
phosphatidylinositol-3-phosphate biosynthetic process	1
inositol-polyphosphate 5-phosphatase activity	1
catalytic activity	1
phosphoric ester hydrolase activity	1
phosphatase activity	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
membrane microdomain	1
synapse	1
cell junction	1

Protein interactions and networks

STRING

1608 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYNJ2	SH3GL2	Q99962	971
SYNJ2	AMPH	P49418	951
SYNJ2	BIN1	O00499	932
SYNJ2	SYNJ2BP	P57105	892
SYNJ2	SH3GL1	Q99961	886
SYNJ2	SH3GL3	Q99963	831
SYNJ2	SNX9	Q9Y5X1	817
SYNJ2	WASL	O00401	814
SYNJ2	ITSN1	Q15811	800
SYNJ2	EPS15	P42566	792
SYNJ2	EPN2	O95208	787
SYNJ2	EPN3	Q9H201	778
SYNJ2	GRB2	P29354	759
SYNJ2	SNAP91	O60641	708
SYNJ2	STON2	Q8WXE9	705

IntAct

48 interactions, top by confidence:

A	B	Type	Score
SH3KBP1	SYNJ2	psi-mi:“MI:0915”(physical association)	0.740
GRB2	SYNJ2	psi-mi:“MI:0915”(physical association)	0.680
SH3KBP1	USP27X	psi-mi:“MI:0914”(association)	0.640
SNX9	WASL	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
SYNJ2	SFN	psi-mi:“MI:0915”(physical association)	0.540
GRB2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
PARP2	SYNJ2	psi-mi:“MI:0557”(adp ribosylation reaction)	0.440
SYNJ2	ABL1	psi-mi:“MI:0915”(physical association)	0.400
SYNJ2	FYN	psi-mi:“MI:0915”(physical association)	0.400
NCK1	SYNJ2	psi-mi:“MI:0915”(physical association)	0.400
PIK3R1	SYNJ2	psi-mi:“MI:0915”(physical association)	0.400
SYNJ2	H3C13	psi-mi:“MI:0915”(physical association)	0.400
SYNJ2	PRKDC	psi-mi:“MI:0915”(physical association)	0.400
SYNJ2	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
SYNJ2	ITSN2	psi-mi:“MI:0915”(physical association)	0.370
YWHAG	C1orf226	psi-mi:“MI:0914”(association)	0.350
YWHAH	SHTN1	psi-mi:“MI:0914”(association)	0.350
YWHAQ	SHTN1	psi-mi:“MI:0914”(association)	0.350
YWHAE	DEPDC5	psi-mi:“MI:0914”(association)	0.350
YWHAG	BRAF	psi-mi:“MI:0914”(association)	0.350

BioGRID (73): SYNJ2 (Proximity Label-MS), SYNJ2 (Affinity Capture-MS), SYNJ2 (Affinity Capture-RNA), SYNJ2 (Affinity Capture-MS), SYNJ2 (Affinity Capture-RNA), SYNJ2 (Proximity Label-MS), SYNJ2 (Affinity Capture-MS), SYNJ2 (Proximity Label-MS), SYNJ2 (Affinity Capture-MS), HIST1H2BH (Proximity Label-MS), PRKDC (Proximity Label-MS), SYNJ2BP (Two-hybrid), SYNJ2 (Reconstituted Complex), SYNJ2 (Proximity Label-MS), SYNJ2 (Proximity Label-MS)

ESM2 similar proteins: A1L244, A4VCH0, A6QL88, F4JIN3, G5ECL2, I1R9A6, I1S489, O13943, O14127, O15056, O18964, O43001, O43426, O55207, O60162, P0C9C0, P0C9C1, P0C9C2, P32368, P34203, P34260, P40559, P46580, P50942, P91133, Q00942, Q09600, Q12271, Q18891, Q55AW9, Q5R921, Q60V75, Q62910, Q6GM29, Q7X911, Q7XVN7, Q8CHC4, Q8RW97, Q8TGA2, Q94A27

Diamond homologs: A1L244, A4VCH0, A6QL88, A8E7C5, O14127, O15056, O18964, O43001, O43426, O55207, O60162, P32368, P42837, P50942, Q12271, Q55AW9, Q5R921, Q62910, Q6GM29, Q7X911, Q7Z9H9, Q8CDA1, Q8CHC4, Q96328, Q9C5G5, Q9D2G5, Q9EP69, Q9ES21, Q9NTJ5, Q9W0I6, Q9Y2H2, A0FI79, A8MR21, D3ZGS3, G5ECL2, O14306, O76745, O80560, P32019, P34370

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 38 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	6	134.3×	5e-10
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	118.5×	6e-10
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	118.5×	6e-10
Activation of BH3-only proteins	6	87.6×	3e-09
Nephrin family interactions	5	70.0×	2e-07
RHO GTPases activate PKNs	7	65.3×	8e-10
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	5	52.5×	7e-07
Intrinsic Pathway for Apoptosis	6	51.7×	6e-08

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of actin filament polymerization	5	44.6×	5e-05
intracellular protein localization	6	17.0×	2e-04
cell migration	5	8.3×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	229
Likely benign	18
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

5335 predictions. Top by Δscore:

Variant	Effect	Δscore
6:157982084:GCTGG:G	donor_gain	1.0000
6:157982085:CTGGG:C	donor_loss	1.0000
6:157982087:GG:G	donor_gain	1.0000
6:157982087:GGGT:G	donor_loss	1.0000
6:157982088:GG:G	donor_gain	1.0000
6:157982088:GGT:G	donor_loss	1.0000
6:157982089:G:GG	donor_gain	1.0000
6:157982089:GTGA:G	donor_loss	1.0000
6:157982090:T:A	donor_loss	1.0000
6:158017201:CA:C	acceptor_loss	1.0000
6:158017202:A:AG	acceptor_gain	1.0000
6:158017202:A:C	acceptor_loss	1.0000
6:158017203:G:GG	acceptor_gain	1.0000
6:158017203:G:GT	acceptor_loss	1.0000
6:158017291:G:GA	donor_loss	1.0000
6:158017291:G:GG	donor_gain	1.0000
6:158017292:T:A	donor_loss	1.0000
6:158017293:GAG:G	donor_loss	1.0000
6:158033677:GCAG:G	donor_gain	1.0000
6:158033681:G:GG	donor_gain	1.0000
6:158033681:GTG:G	donor_loss	1.0000
6:158033682:T:A	donor_loss	1.0000
6:158044590:G:GT	donor_gain	1.0000
6:158059256:GGCAC:G	acceptor_gain	1.0000
6:158059351:AAGGT:A	donor_loss	1.0000
6:158059352:AGGT:A	donor_loss	1.0000
6:158059353:GGTAA:G	donor_loss	1.0000
6:158059354:GTAA:G	donor_loss	1.0000
6:158059355:T:G	donor_loss	1.0000
6:158063788:A:AG	acceptor_gain	1.0000

AlphaMissense

9785 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:158076731:T:A	W800R	1.000
6:158076731:T:C	W800R	1.000
6:158068689:A:T	E587V	0.999
6:158071724:C:A	A688D	0.999
6:158071748:G:C	R696P	0.999
6:158074613:T:A	W723R	0.999
6:158074613:T:C	W723R	0.999
6:158074623:A:T	D726V	0.999
6:158074630:C:A	N728K	0.999
6:158074630:C:G	N728K	0.999
6:158074634:C:A	R730S	0.999
6:158076674:A:G	K781E	0.999
6:158076676:G:C	K781N	0.999
6:158076676:G:T	K781N	0.999
6:158076719:C:A	R796S	0.999
6:158078277:C:G	H855D	0.999
6:158066527:T:A	W537R	0.998
6:158066527:T:C	W537R	0.998
6:158066532:C:A	N538K	0.998
6:158066532:C:G	N538K	0.998
6:158066590:T:A	W558R	0.998
6:158066590:T:C	W558R	0.998
6:158068701:T:C	L591S	0.998
6:158069565:T:C	L611P	0.998
6:158071653:C:A	N664K	0.998
6:158071653:C:G	N664K	0.998
6:158071654:A:G	K665E	0.998
6:158071656:G:C	K665N	0.998
6:158071656:G:T	K665N	0.998
6:158071711:A:C	S684R	0.998

dbSNP variants (sampled 300 via entrez): RS1000040832 (6:157998995 ACAAG>A), RS1000041016 (6:158077577 T>A,C), RS1000066682 (6:157996847 G>T), RS1000104651 (6:158023707 T>C), RS1000118555 (6:158060059 C>T), RS1000153582 (6:158039920 C>A,T), RS1000174981 (6:157993196 A>G), RS1000234179 (6:158072077 T>G), RS1000259595 (6:158006188 C>A,T), RS1000322591 (6:158043607 A>G), RS1000324466 (6:158029759 G>A), RS1000379166 (6:158074822 T>A), RS1000405476 (6:158060228 G>A,T), RS1000412958 (6:158011920 C>T), RS1000446677 (6:157998176 G>A)

Disease associations

OMIM: gene MIM:609410 | disease phenotypes: MIM:156000

GenCC curated gene-disease

Mondo (1): Meniere disease (MONDO:0007972)

Orphanet (1): NON RARE IN EUROPE: Menière disease (Orphanet:45360)

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001616_6	Cannabis use (initiation)	7.000000e-06
GCST003127_10	Lipoprotein (a) levels	4.000000e-10
GCST005580_111	Intraocular pressure	3.000000e-09
GCST006019_29	Gamma glutamyl transferase levels	1.000000e-21
GCST011349_5	Gamma glutamyl transferase levels	6.000000e-19
GCST012442_40	Age-related hearing impairment	8.000000e-14
GCST90002401_544	Platelet distribution width	6.000000e-16

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006925	lipoprotein A measurement
EFO:0004695	intraocular pressure measurement
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0007984	platelet component distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008575	Meniere Disease	C09.218.568.217.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523129 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 87,432 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1201303	PYRVINIUM	4	1,797
CHEMBL790	CHLORHEXIDINE	4	85,053
CHEMBL3348861	AMPELOPSIN	2	582

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Inositol polyphosphate phosphatases

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
example 15 [WO2015079413]	Inhibition	6.06	pIC50

ChEMBL bioactivities

66 potent at pChembl≥5 of 72 total, top 29 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.06	IC50	874	nM	CHEMBL509624
5.97	IC50	1075	nM	CHEMBL4472624
5.91	IC50	1240	nM	CHEMBL4457836
5.90	IC50	1250	nM	PYRVINIUM
5.78	IC50	1670	nM	CHEMBL4514986
5.73	IC50	1870	nM	CHEMBL4574176
5.73	IC50	1870	nM	CHEMBL4456090
5.70	IC50	1980	nM	CHEMBL4465983
5.70	IC50	1980	nM	CHEMBL4469371
5.70	IC50	1980	nM	CHEMBL4575159
5.66	IC50	2190	nM	CHEMBL4471098
5.66	IC50	2190	nM	CHEMBL4577306
5.57	IC50	2710	nM	CHEMBL4451084
5.55	IC50	2840	nM	CHEMBL452764
5.54	IC50	2880	nM	EPICATECHIN GALLATE
5.53	IC50	2940	nM	CHEMBL3236511
5.50	IC50	3170	nM	CHEMBL4437511
5.50	IC50	3170	nM	AMPELOPSIN
5.47	IC50	3400	nM	CHEMBL4536358
5.46	IC50	3440	nM	CHEMBL4471702
5.45	IC50	3520	nM	CHEMBL4541313
5.45	IC50	3520	nM	CHEMBL4551186
5.43	IC50	3750	nM	CHEMBL84333
5.22	IC50	6020	nM	CHEMBL4580754
5.22	IC50	6020	nM	CHEMBL4467655
5.22	IC50	6020	nM	CHEMBL4590432
5.18	IC50	6650	nM	OXYRESVERATROL
5.12	IC50	7530	nM	CHEMBL522251
5.00	IC50	1e+04	nM	CHLORHEXIDINE

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	6
methylmercuric chloride	increases expression, affects cotreatment	4
bisphenol A	affects methylation, affects cotreatment, decreases expression	2
mercuric bromide	increases expression, affects cotreatment	2
Acetaminophen	decreases expression, increases expression	2
Dexamethasone	decreases expression, affects cotreatment	2
Estradiol	increases expression, affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Smoke	increases expression	2
Tetrachlorodibenzodioxin	affects expression, decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Cyclosporine	decreases expression, decreases methylation, increases expression	2
Aflatoxin B1	increases expression, increases methylation	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
trichostatin A	increases expression	1
cypermethrin	decreases expression	1
sodium arsenite	affects methylation	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	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
belinostat	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4420451	Binding	Inhibition of C-Myc/DDK-tagged human recombinant SYNJ2 expressed in HEK293T cells assessed as reduction in 5’-phosphatase activity incubated for 8 mins using fluorescently-labeled PI(3,4)P2 probe and Tapp1 PH-domain as detector protein by f	Synaptojanin-2 inhibitors for use in the treatment of cancer

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2I0	Abcam HeLa SYNJ2 KO	Cancer cell line	Female
CVCL_TR35	HAP1 SYNJ2 (-) 1	Cancer cell line	Male
CVCL_TR36	HAP1 SYNJ2 (-) 2	Cancer cell line	Male
CVCL_TR37	HAP1 SYNJ2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01574313	PHASE4	COMPLETED	Effect of Stellate Ganglion Block on Meniere’s Disease
NCT02529475	PHASE4	TERMINATED	Evaluation of Inner Ear and Brain Structures With Contrast-enhanced MRI in Healthy Subjects (HYDROPS)
NCT04815187	PHASE4	ACTIVE_NOT_RECRUITING	Repurposed Use of Allergic Rhinitis and Allergic Asthma Drug to Reduce Vertigo and Hearing Loss in Meniere’s Disease
NCT03664674	PHASE3	COMPLETED	Phase 3 Study of OTO-104 in Subjects With Unilateral Meniere’s Disease
NCT04677972	PHASE3	COMPLETED	SPI-1005 for the Treatment of Meniere’s Disease
NCT05851508	PHASE3	RECRUITING	The Effecttiveness of Intratympanic Methylprednisolon Injections Compared to Placebo in the Treatment of Vertigo Attacks in Meniere’s Disease
NCT05420350	PHASE2	UNKNOWN	Lamotrigine and Bupropion for Meniere’s Disease
NCT06544434	PHASE2	RECRUITING	Laser Acupuncture for Meniere Disease
NCT04674735	PHASE1	WITHDRAWN	Safety of APSLXR in Patients Presenting Vertigo of Vestibular Origin or Meniere’s Disease
NCT04218123	PHASE2/PHASE3	COMPLETED	Assessing the Efficacy of a Serotonin and Norepinephrine Reuptake Inhibitor for Improving Meniere’s Disease Outcomes
NCT04766853	PHASE1/PHASE2	COMPLETED	Verification of the Efficacy/safety of the Intratympanic Drug Delivery for Hearing Loss
NCT04794842	EARLY_PHASE1	UNKNOWN	Comparing Topical Tetracaine Drops to Topical Focal Phenol for Local Anesthesia During Intratympanic Steroid Injection
NCT00599560	Not specified	COMPLETED	Vasopressin and V2 Receptor in Meniere’s Disease
NCT02371798	Not specified	WITHDRAWN	Unilateral Meniere Disease: Can Double Dose Gadolinium and Delayed Imaging Make the Diagnosis?
NCT03520322	Not specified	TERMINATED	A Study of a Mastoid Device in Subjects With Ménière’s Disease
NCT03795675	Not specified	ACTIVE_NOT_RECRUITING	CI Following VS Removal or Labyrinthectomy
NCT04370366	Not specified	RECRUITING	Imaging of Endolymphatic Hydrops at 7T MRI
NCT04569175	Not specified	COMPLETED	Non Enhanced Labyrinth Imaging for the Detection of Endolymphatic Hydrops in Meniere’s Disease NELI Study
NCT04686695	Not specified	COMPLETED	Transcutaneous Auricular Vagus Nerve Stimulation Treatment on Meniere Disease
NCT04835688	Not specified	UNKNOWN	Ventilation Tube Insertion for Unilateral Menière’s Disease
NCT04902963	Not specified	COMPLETED	What is the Tympanic Membrane Healing Time After Insertion of a Gelfoam PE Tube?
NCT04935970	Not specified	UNKNOWN	Metabolic Disorders and Vertigo
NCT05322538	Not specified	NOT_YET_RECRUITING	Menier’s Disease - Bone Density Study
NCT05328895	Not specified	COMPLETED	Transcutaneous Auricular Vagus Nerve Stimulation for Meniere Disease
NCT05424302	Not specified	RECRUITING	Effect of Peripheral Vestibular Disease Location on Outcomes Following Home-based Virtual Reality Vestibular Therapy
NCT05582148	Not specified	UNKNOWN	Meniere Disease and Hearing Aids
NCT05844657	Not specified	COMPLETED	Comprehensive Evaluation in Patients With Meniere’s Disease
NCT05960786	Not specified	COMPLETED	Treating the Symptoms of Vertigo in a Real-world Setting Using the OtoBand
NCT06278129	Not specified	UNKNOWN	Evaluation of the Diagnostic and Prognostic Efficacy of MRI in Acute Sensorineural Hearing Loss and Ménière’s Disease
NCT06544590	Not specified	COMPLETED	Transcutaneous Auricular Vagus Nerve Stimulation for Meniere Disease
NCT07272473	Not specified	RECRUITING	Effects of Cervical Mobilization on Dizziness, Balance, and Joint Position Sense in Patients With Meniere’s Disease