SYN3

Summary

SYN3 (synapsin III, HGNC:11496) is a protein-coding gene on chromosome 22q12.3, encoding Synapsin-3 (O14994). May be involved in the regulation of neurotransmitter release and synaptogenesis.

This gene is a member of the synapsin gene family. Synapsins encode neuronal phosphoproteins which associate with the cytoplasmic surface of synaptic vesicles. Family members are characterized by common protein domains, and they are implicated in synaptogenesis and the modulation of neurotransmitter release, suggesting a potential role in several neuropsychiatric diseases. The protein encoded by this gene shares the synapsin family domain model, with domains A, C, and E exhibiting the highest degree of conservation. The protein contains a unique domain J, located between domains C and E. Based on this gene’s localization to 22q12.3, a possible schizophrenia susceptibility locus, and the established neurobiological roles of the synapsins, this family member may represent a candidate gene for schizophrenia. The TIMP3 gene is located within an intron of this gene and is transcribed in the opposite direction. Alternative splicing of this gene results in multiple splice variants that encode different isoforms.

Source: NCBI Gene 8224 — RefSeq curated summary.

At a glance

• GWAS associations: 25
• Clinical variants (ClinVar): 358 total — 5 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_003490

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11496
Approved symbol	SYN3
Name	synapsin III
Location	22q12.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000185666
Ensembl biotype	protein_coding
OMIM	602705
Entrez	8224

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 4 protein_coding_CDS_not_defined, 4 retained_intron, 3 protein_coding

ENST00000358763, ENST00000412575, ENST00000441821, ENST00000459990, ENST00000461446, ENST00000462268, ENST00000467095, ENST00000467824, ENST00000468922, ENST00000472027, ENST00000483062

RefSeq mRNA: 7 — MANE Select: NM_003490 NM_001135774, NM_001369907, NM_001369908, NM_001369909, NM_001369910, NM_003490, NM_133633

CCDS: CCDS13908

Canonical transcript exons

ENST00000358763 — 14 exons

Exon	Start	End
ENSE00001292222	32596674	32596736
ENSE00001304263	32868966	32869125
ENSE00001315501	32541571	32541713
ENSE00001324487	32931390	32931481
ENSE00001528635	32507820	32513824
ENSE00001528637	33006352	33006824
ENSE00001528638	33058292	33058381
ENSE00001602975	32538036	32538110
ENSE00001781645	32533793	32533895
ENSE00003488779	32864915	32865004
ENSE00003540980	32518043	32518334
ENSE00003557278	32527918	32528005
ENSE00003674220	32528874	32529008
ENSE00003790863	32980645	32980702

Expression profiles

Bgee: expression breadth ubiquitous, 176 present calls, max score 85.34.

FANTOM5 (CAGE): breadth broad, TPM avg 2.7810 / max 124.0099, expressed in 330 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193768	1.6388	260
193766	0.8187	216
193751	0.1054	55
193765	0.0952	46
193767	0.0489	27
193764	0.0280	9
193762	0.0190	7
193752	0.0151	5
193753	0.0120	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.34	gold quality
cortical plate	UBERON:0005343	83.03	gold quality
primary visual cortex	UBERON:0002436	82.84	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.17	gold quality
prefrontal cortex	UBERON:0000451	78.58	gold quality
right testis	UBERON:0004534	77.96	gold quality
occipital lobe	UBERON:0002021	77.87	gold quality
Brodmann (1909) area 23	UBERON:0013554	77.74	gold quality
left testis	UBERON:0004533	77.27	gold quality
postcentral gyrus	UBERON:0002581	76.78	gold quality
frontal cortex	UBERON:0001870	75.48	gold quality
cerebellar vermis	UBERON:0004720	75.40	gold quality
neocortex	UBERON:0001950	75.10	gold quality
testis	UBERON:0000473	74.83	gold quality
right frontal lobe	UBERON:0002810	74.65	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	74.42	gold quality
middle temporal gyrus	UBERON:0002771	74.23	gold quality
sural nerve	UBERON:0015488	74.20	gold quality
parietal lobe	UBERON:0001872	74.14	gold quality
superior frontal gyrus	UBERON:0002661	74.10	gold quality
Brodmann (1909) area 9	UBERON:0013540	73.95	gold quality
cingulate cortex	UBERON:0003027	73.12	gold quality
cerebral cortex	UBERON:0000956	73.09	gold quality
anterior cingulate cortex	UBERON:0009835	73.02	gold quality
ganglionic eminence	UBERON:0004023	72.30	gold quality
diaphragm	UBERON:0001103	72.18	gold quality
telencephalon	UBERON:0001893	71.90	gold quality
entorhinal cortex	UBERON:0002728	71.44	gold quality
secondary oocyte	CL:0000655	71.27	gold quality
amygdala	UBERON:0001876	70.95	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	1170.32
E-ENAD-17	yes	27.56
E-ANND-3	no	5.07

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP63

miRNA regulators (miRDB)

74 targeting SYN3, 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-1252-5P	100.00	69.80	2774
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-4743-3P	99.62	68.12	2095

Literature-anchored findings (GeneRIF, showing 18)

• Evidence is not in favor of a large effect of synapsin III gene in the pathogenesis of schizophrenia. (PMID:11840510)
• A missense polymorphism, S470N, was identified in the synapsin III gene and appeared more frequently in individuals with schizophrenia. The site affected by the polymorphism, Ser470, was determined to be a substrate for mitogen-activated protein kinase. (PMID:14732590)
• Supports a role for synapsin III in a subset of African American patients with schizophrenia. (PMID:15900227)
• A trend towards significance was detected when the synapsin III -196A allele distribution was analyzed in Caucasian patients with schizophrenia and a cohort of subjects from the Czech Republic with bipolar disorder. (PMID:16511335)
• No evidence that the synapsin III locus as a major susceptibility locus contributing to attention deficit hyperactivity disorder. (PMID:17413450)
• the C/C genotype in rs133946 and the G/G genotype in rs133945 could be protecting factors against multiple sclerosis in the Basque population. (PMID:18755822)
• The variation in SYN III methylation studied is 1) not related to schizophrenia in the population sample or a monozygotic twin pair discordant for schizophrenia and 2) not related to the mRNA level of SYN IIIa in different human brain regions (PMID:19102774)
• Both the association studies and expression studies didn’t support a major role for SYN3 in the susceptibility of schizophrenia in Irish and Chinese populations. (PMID:19766700)
• This protein has been found differentially expressed in thalami from patients with schizophrenia. (PMID:20471030)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• A significant difference was determined between attention deficit hyperactivity disorder and synapsin III gene -631 C>G polymorphism compared to the control group. (PMID:23768104)
• The variations of MnSOD (rs4880) and SYN III (rs3788470, rs3827336, rs5998557) were not major risk factors for PD among Chinese, at least in our study populations (PMID:24586301)
• These findings support a reciprocal modulatory interaction of alpha-syn and synapsin III in the regulation of dopamine neuron synaptic function. (PMID:25967550)
• Syn-3 may mimic Syn-1A in the ability to bind and modulate Cavs, but preferring Cav2.3 to perhaps participate in triggering fusion of newcomer insulin SGs during second-phase GSIS. (PMID:26848587)
• These findings contribute to previous work showing dysregulation of Synapsins, particularly SYN2, in mood disorders and improve our understanding of the regulatory mechanisms that precipitate these changes likely leading to the BD or MDD phenotype. (PMID:27515700)
• Synapsin III is a crucial alpha-synuclein interactant and a key component of Lewy bodies fibrils in the brain of patients affected by Parkinson’s disease. (PMID:29330884)
• Investigation of possible associations of the BDNF, SNAP-25 and SYN III genes with the neurocognitive measures: BDNF and SNAP-25 genes might be involved in attention domain, SYN III gene in executive function. (PMID:35077325)
• Molecular and in silico analyses of SYN III gene variants in autism spectrum disorder. (PMID:37166614)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Syn3	ENSMUSG00000059602
rattus_norvegicus	Syn3	ENSRNOG00000026866

Paralogs (2): SYN1 (ENSG00000008056), SYN2 (ENSG00000157152)

Protein

Protein identifiers

Synapsin-3 — O14994 (reviewed: O14994)

Alternative names: Synapsin III

All UniProt accessions (3): A6ZJ82, O14994, Q4TT46

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in the regulation of neurotransmitter release and synaptogenesis.

Subunit / interactions. Interacts with CAPON.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle. Synaptic vesicle membrane.

Tissue specificity. Neuron specific. Detected predominantly in brain.

Post-translational modifications. Phosphorylation at Ser-9 dissociates synapsins from synaptic vesicles.

Domain organisation. The A region binds phospholipids with a preference for negatively charged species.

Miscellaneous. Regulated by calcium. Calcium inhibits ATP binding to the C-domain.

Similarity. Belongs to the synapsin family.

RefSeq proteins (7): NP_001129246, NP_001356836, NP_001356837, NP_001356838, NP_001356839, NP_003481, NP_598344 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001359	Synapsin	Family
IPR013815	ATP_grasp_subdomain_1	Homologous_superfamily
IPR016185	PreATP-grasp_dom_sf	Homologous_superfamily
IPR019735	Synapsin_CS	Conserved_site
IPR019736	Synapsin_P_site	PTM
IPR020897	Synapsin_pre-ATP-grasp_dom	Domain
IPR020898	Synapsin_ATP-bd_dom	Domain

Pfam: PF02078, PF02750, PF10581

UniProt features (53 total): strand 16, helix 11, modified residue 8, region of interest 7, compositionally biased region 6, turn 3, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2P0A	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14994-F1	73.63	0.51

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 (8): 9, 455, 462, 470, 475, 481, 484, 541

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-181429	Serotonin Neurotransmitter Release Cycle
R-HSA-212676	Dopamine Neurotransmitter Release Cycle
R-HSA-112310	Neurotransmitter release cycle
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System

MSigDB gene sets: 135 (showing top): GOBP_SYNAPTIC_VESICLE_LOCALIZATION, HNF3ALPHA_Q6, GOBP_VESICLE_LOCALIZATION, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_CELL_JUNCTION_ORGANIZATION, REACTOME_DOPAMINE_NEUROTRANSMITTER_RELEASE_CYCLE, MARTIN_NFKB_TARGETS_UP, MARTIN_VIRAL_GPCR_SIGNALING_UP, MODULE_99, GOBP_SECRETION, GOBP_SIGNAL_RELEASE, GOBP_SYNAPTIC_SIGNALING, GOBP_REGULATION_OF_SYNAPTIC_TRANSMISSION_GABAERGIC

GO Biological Process (7): neurotransmitter secretion (GO:0007269), regulation of synaptic transmission, GABAergic (GO:0032228), synapse organization (GO:0050808), synaptic vesicle clustering (GO:0097091), chemical synaptic transmission (GO:0007268), modulation of chemical synaptic transmission (GO:0050804), synaptic vesicle cycle (GO:0099504)

GO Molecular Function (3): ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (8): synaptic vesicle (GO:0008021), postsynaptic density (GO:0014069), synaptic vesicle membrane (GO:0030672), extrinsic component of synaptic vesicle membrane (GO:0098850), glutamatergic synapse (GO:0098978), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Neurotransmitter release cycle	2
Transmission across Chemical Synapses	1
Neuronal System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
presynapse	3
chemical synaptic transmission	2
establishment of localization in cell	2
neurotransmitter transport	1
signal release from synapse	1
modulation of chemical synaptic transmission	1
synaptic transmission, GABAergic	1
cell junction organization	1
synaptic vesicle localization	1
synaptic vesicle cycle	1
anterograde trans-synaptic signaling	1
regulation of trans-synaptic signaling	1
vesicle-mediated transport in synapse	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
exocytic vesicle	1
asymmetric synapse	1
postsynaptic specialization	1
synaptic vesicle	1
exocytic vesicle membrane	1
synaptic vesicle membrane	1
extrinsic component of organelle membrane	1
synapse	1
cellular anatomical structure	1
cytoplasm	1
intracellular vesicle	1
cell junction	1

Protein interactions and networks

STRING

1578 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYN3	DLG4	P78352	852
SYN3	RIC8B	Q9NVN3	840
SYN3	MARCKS	P29966	814
SYN3	SLC17A7	Q9P2U7	803
SYN3	GRIA1	P42261	800
SYN3	SNAP25	P13795	774
SYN3	SYP	P08247	755
SYN3	SLC32A1	Q9H598	749
SYN3	STXBP5	Q5T5C0	718
SYN3	CALML4	Q96GE6	713
SYN3	ERI3	O43414	704
SYN3	MAP1B	P46821	697
SYN3	SYT1	P21579	693
SYN3	GAP43	P17677	685
SYN3	SNCA	P37840	681

IntAct

10 interactions, top by confidence:

A	B	Type	Score
SYN3	SYN2	psi-mi:“MI:0915”(physical association)	0.560
SYN3	CFAP418	psi-mi:“MI:0915”(physical association)	0.370
SYNGAP1	IGLON5	psi-mi:“MI:0914”(association)	0.350
GPM6A	KIF2A	psi-mi:“MI:0914”(association)	0.350
ZNF248	SYN3	psi-mi:“MI:0914”(association)	0.350
DUSP2	SYN3	psi-mi:“MI:0914”(association)	0.350
VCP	SHTN1	psi-mi:“MI:0914”(association)	0.350
VCP	FAM171A2	psi-mi:“MI:0914”(association)	0.350
SYN3	GART	psi-mi:“MI:0914”(association)	0.350

BioGRID (13): SYN3 (Affinity Capture-MS), SYN3 (Two-hybrid), SYN3 (Two-hybrid), SYN3 (Two-hybrid), MORF4L1 (Two-hybrid), SYN3 (Affinity Capture-Western), SYN3 (Reconstituted Complex), SYN3 (Affinity Capture-MS), SYN3 (Affinity Capture-MS), SYN2 (Affinity Capture-MS), SYN3 (Affinity Capture-MS), SYN3 (Two-hybrid), SYN3 (Affinity Capture-MS)

ESM2 similar proteins: A7Z019, B3M301, B4NBP4, F1MH24, F1SPM8, G5EBZ8, O13166, O14994, O42469, O62255, O62732, O70441, O88935, O95835, P09951, P0C1X8, P12252, P17599, P17600, P51531, P51532, P93755, Q09345, Q14693, Q24546, Q2LC84, Q2M2I8, Q2ULU3, Q3TKT4, Q3UHJ0, Q4WHP3, Q5R8Z4, Q63537, Q64332, Q66624, Q6C3D7, Q6DIC0, Q6QM28, Q75DK7, Q8BYR2

Diamond homologs: O14994, O62732, O70441, O88935, P09951, P17599, P17600, Q24546, Q63537, Q64332, Q6QM28, Q8JZP2, Q92777

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
CDK1	up-regulates	SYN3	phosphorylation
MAPK3	up-regulates	SYN3	phosphorylation
SYN3	down-regulates	Synaptic_vesicle_exocytosis
PKA	“down-regulates activity”	SYN3	phosphorylation
SYN3	“up-regulates activity”	ACTB	binding
SYN3	“up-regulates activity”	Actin_cytoskeleton_reorganization	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	3
Uncertain significance	202
Likely benign	74
Benign	42

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
12677	NM_000362.5(TIMP3):c.572A>G (p.Tyr191Cys)	Pathogenic
1351499	NM_000362.5(TIMP3):c.542A>G (p.His181Arg)	Pathogenic
3249712	NM_000362.5(TIMP3):c.545A>G (p.Tyr182Cys)	Pathogenic
3249777	NM_000362.5(TIMP3):c.530A>G (p.Tyr177Cys)	Pathogenic
375384	NM_003490.4(SYN3):c.1444_1445delinsTT (p.Pro482Leu)	Pathogenic
1068059	NM_000362.5(TIMP3):c.584A>G (p.Tyr195Cys)	Likely pathogenic
12679	NM_000362.5(TIMP3):c.565G>T (p.Gly189Cys)	Likely pathogenic
4685575	NM_000362.5(TIMP3):c.489T>A (p.Cys163Ter)	Likely pathogenic

SpliceAI

4813 predictions. Top by Δscore:

Variant	Effect	Δscore
22:32518041:A:AC	donor_gain	1.0000
22:32518042:C:CC	donor_gain	1.0000
22:32528904:T:TA	donor_gain	1.0000
22:32533775:C:CA	donor_gain	1.0000
22:32541567:TCACA:T	donor_loss	1.0000
22:32541568:CACAT:C	donor_loss	1.0000
22:32541569:A:AC	donor_gain	1.0000
22:32541569:AC:A	donor_loss	1.0000
22:32541570:C:CG	donor_gain	1.0000
22:32541570:CA:C	donor_gain	1.0000
22:32541570:CAT:C	donor_gain	1.0000
22:32541570:CATG:C	donor_gain	1.0000
22:32541570:CATGT:C	donor_gain	1.0000
22:32541575:AAG:A	donor_gain	1.0000
22:32541710:TGAT:T	acceptor_gain	1.0000
22:32541711:GATC:G	acceptor_loss	1.0000
22:32541713:TC:T	acceptor_loss	1.0000
22:32541714:C:A	acceptor_loss	1.0000
22:32541714:C:CC	acceptor_gain	1.0000
22:32541716:G:C	acceptor_gain	1.0000
22:32802123:G:GA	donor_loss	1.0000
22:32802123:G:GG	donor_gain	1.0000
22:32802124:TAAG:T	donor_loss	1.0000
22:32849441:T:A	acceptor_gain	1.0000
22:32849447:T:TA	acceptor_gain	1.0000
22:32849447:TGCA:T	acceptor_loss	1.0000
22:32849449:CAG:C	acceptor_loss	1.0000
22:32849450:A:AG	acceptor_gain	1.0000
22:32849450:A:C	acceptor_loss	1.0000
22:32849450:AGT:A	acceptor_gain	1.0000

AlphaMissense

3806 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:32533836:A:T	V351D	1.000
22:32533885:A:G	W335R	1.000
22:32533885:A:T	W335R	1.000
22:32538086:C:A	W314C	1.000
22:32538086:C:G	W314C	1.000
22:32538088:A:G	W314R	1.000
22:32538088:A:T	W314R	1.000
22:32513713:A:C	F574L	0.999
22:32513713:A:T	F574L	0.999
22:32513715:A:G	F574L	0.999
22:32513726:A:G	L570P	0.999
22:32533840:C:G	A350P	0.999
22:32533871:G:C	C339W	0.999
22:32538066:G:T	A321D	0.999
22:32538083:C:A	K315N	0.999
22:32538083:C:G	K315N	0.999
22:32538085:T:C	K315E	0.999
22:32538107:T:A	R307S	0.999
22:32538107:T:G	R307S	0.999
22:32538108:C:G	R307T	0.999
22:32541577:G:T	A304D	0.999
22:32864958:A:G	F223S	0.999
22:32513701:G:C	F578L	0.998
22:32513701:G:T	F578L	0.998
22:32513703:A:G	F578L	0.998
22:32513714:A:C	F574C	0.998
22:32513714:A:G	F574S	0.998
22:32533800:A:T	I363N	0.998
22:32533830:G:T	A353D	0.998
22:32533831:C:G	A353P	0.998

dbSNP variants (sampled 300 via entrez): RS1000008344 (22:33004455 T>C), RS1000015737 (22:32512181 G>A,T), RS1000025703 (22:32909739 T>C), RS1000035223 (22:32795070 T>A,G), RS1000038720 (22:32564440 A>G), RS1000041933 (22:32837334 C>A,G,T), RS1000042876 (22:32843282 G>A,T), RS1000057698 (22:33052693 T>C), RS1000062395 (22:32931804 A>G), RS1000065103 (22:33003139 C>T), RS1000068926 (22:32525336 C>T), RS1000069254 (22:32718459 G>A), RS1000076959 (22:32763240 G>A,T), RS1000078742 (22:32718821 C>T), RS1000088716 (22:32511861 G>A)

Disease associations

OMIM: gene MIM:602705 | disease phenotypes: MIM:136900, MIM:264420

GenCC curated gene-disease

Mondo (4): Sorsby fundus dystrophy (MONDO:0007640), inherited retinal dystrophy (MONDO:0019118), fundus dystrophy, pseudoinflammatory, recessive form (MONDO:0009918), retinal disorder (MONDO:0005283)

Orphanet (2): Sorsby fundus dystrophy (Orphanet:59181), OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000556	Retinal dystrophy

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST000652_1	Age-related macular degeneration	1.000000e-11
GCST000817_174	Height	3.000000e-10
GCST001263_24	Height	5.000000e-07
GCST002647_173	Height	2.000000e-17
GCST002702_93	Height	2.000000e-07
GCST003219_51	Advanced age-related macular degeneration	1.000000e-24
GCST005576_5	Intracranial aneurysm	3.000000e-06
GCST005580_49	Intraocular pressure	2.000000e-12
GCST005580_87	Intraocular pressure	4.000000e-11
GCST006103_7	Interleukin-6 levels	5.000000e-06
GCST006136_12	Alzheimer’s disease progression score	2.000000e-06
GCST006291_93	Spherical equivalent or myopia (age of diagnosis)	4.000000e-09
GCST006394_63	Intraocular pressure	3.000000e-12
GCST006412_132	Intraocular pressure	1.000000e-10
GCST006979_199	Heel bone mineral density	5.000000e-12
GCST007692_86	Chronic obstructive pulmonary disease	8.000000e-09
GCST008150_9	Triglyceride levels	2.000000e-07
GCST008169_2	Benign prostatic hyperplasia	5.000000e-07
GCST008169_8	Benign prostatic hyperplasia	5.000000e-07
GCST008839_175	Height	5.000000e-43
GCST009391_541	Metabolite levels	8.000000e-06
GCST009725_38	Intraocular pressure	3.000000e-12
GCST010002_81	Refractive error	6.000000e-13
GCST010266_18	Femoral neck bone mineral density and trunk fat mass adjusted by trunk lean mass	6.000000e-07
GCST010267_4	Trunk fat mass adjusted for trunk lean mass	9.000000e-08

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:1001492	atrophic macular degeneration
EFO:0004695	intraocular pressure measurement
EFO:0004810	interleukin-6 measurement
EFO:0006514	Alzheimer’s disease biomarker measurement
EFO:0004847	age at onset
EFO:0009270	heel bone mineral density
EFO:0004530	triglyceride measurement
EFO:0010528	quinolinic acid measurement
EFO:0007785	femoral neck bone mineral density

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658
C564992	Fundus Dystrophy, Pseudoinflammatory, Of Sorsby (supp.)
C535828	Pseudoinflammatory fundus dystrophy, Finnish type (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9621532	SYN3		0.00	0

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, increases expression	2
Benzo(a)pyrene	affects methylation	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	increases expression	1
dicrotophos	increases expression	1
bisphenol A	increases methylation	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects expression, affects response to substance	1
arsenite	decreases methylation	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	increases methylation	1
2-palmitoylglycerol	increases expression	1
bisphenol S	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic Trioxide	decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Methapyrilene	affects methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Thiram	increases expression	1
Valproic Acid	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01955135	PHASE4	COMPLETED	Anesthesia for Retinopathy of Prematurity
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT01373476	PHASE2	COMPLETED	Multicentre, Randomized, Controlled Trial of Qideng Mingmu Capsule in The Treatment of Diabetic Retinopathy
NCT01793090	PHASE2	COMPLETED	EPI-743 in Cobalamin C Defect: Effects on Visual and Neurological Impairment
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer
NCT02983305	Not specified	COMPLETED	Optical Head-Mounted Display Technology for Low Vision Rehabilitation
NCT03592017	Not specified	COMPLETED	Performance of Long-wavelength Autofluorescence Imaging
NCT03662386	Not specified	TERMINATED	Prospective Analysis of Genotype-phenotype Correlations Observed in a Large Cohort of Patients With Hereditary Retinal Dystrophies - GEPHIRD
NCT03691168	Not specified	UNKNOWN	Multi-center Observation of the Natural Course of Inherited Retinal Dystrophies
NCT03843840	Not specified	COMPLETED	Dual Wavelength OCT
NCT03853252	Not specified	COMPLETED	iPS Cells of Patients for Models of Retinal Dystrophies
NCT05130385	Not specified	UNKNOWN	High Resolution Optical Coherence Tomography
NCT05294978	Not specified	RECRUITING	EyeConic: Qualification for Cone-Optogenetics
NCT05573984	Not specified	ACTIVE_NOT_RECRUITING	Natural History of PRPF31 Mutation-Associated Retinal Dystrophy
NCT05793515	Not specified	COMPLETED	Mechanisms of Inherited Retinal Dystrophies Using Whole Genome Sequencing and in Vitro and in Vivo Models
NCT05820100	Not specified	COMPLETED	Observational Study to Assess the Reliability and Validity of the MLYMT and MLSDT
NCT05976139	Not specified	RECRUITING	Micropulsed Laser in Patients With Macular Oedema in Retinal Dystrophies
NCT06162585	Not specified	ACTIVE_NOT_RECRUITING	Non-Interventional Long Term Follow-up Study of Participants Previously Enrolled in the RESTORE Study
NCT06177977	Not specified	RECRUITING	SS-HH-OCT as a Novel Diagnostic Modality for Early-Onset Retinal Dystrophies (EORDs)
NCT06375239	Not specified	RECRUITING	Observational Study to Assess Endpoint Operational Feasibility & Measurement Properties in Patients with Retinal Degeneration
NCT06908161	Not specified	NOT_YET_RECRUITING	Functional Assessments in Vision Impairment
NCT07085533	Not specified	RECRUITING	Natural History Study of Inherited Retinal Diseases