SYNGR3

Summary

SYNGR3 (synaptogyrin 3, HGNC:11501) is a protein-coding gene on chromosome 16p13.3, encoding Synaptogyrin-3 (O43761). May play a role in regulated exocytosis.

This gene encodes an integral membrane protein. The exact function of this protein is unclear, but studies of a similar murine protein suggest that it is a synaptic vesicle protein that also interacts with the dopamine transporter. The gene product belongs to the synaptogyrin gene family.

Source: NCBI Gene 9143 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 39 total — 1 pathogenic
• MANE Select transcript: NM_004209

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11501
Approved symbol	SYNGR3
Name	synaptogyrin 3
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000127561
Ensembl biotype	protein_coding
OMIM	603927
Entrez	9143

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 retained_intron

ENST00000248121, ENST00000562045, ENST00000563869, ENST00000564642, ENST00000568896, ENST00000873156

RefSeq mRNA: 1 — MANE Select: NM_004209 NM_004209

CCDS: CCDS10456

Canonical transcript exons

ENST00000248121 — 4 exons

Exon	Start	End
ENSE00000873687	1992863	1994275
ENSE00001261389	1989970	1990201
ENSE00003517889	1991974	1992211
ENSE00003560017	1992636	1992778

Expression profiles

Bgee: expression breadth ubiquitous, 203 present calls, max score 99.11.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.7048 / max 235.0036, expressed in 1145 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152159	8.2025	925
152162	2.3626	411
152160	0.0708	30
152161	0.0688	36

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	99.11	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.81	gold quality
superior frontal gyrus	UBERON:0002661	98.14	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.08	gold quality
orbitofrontal cortex	UBERON:0004167	97.94	gold quality
pons	UBERON:0000988	97.79	gold quality
primary visual cortex	UBERON:0002436	97.61	gold quality
entorhinal cortex	UBERON:0002728	97.57	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.49	gold quality
frontal pole	UBERON:0002795	97.45	gold quality
right frontal lobe	UBERON:0002810	97.41	gold quality
frontal cortex	UBERON:0001870	97.39	gold quality
frontal lobe	UBERON:0016525	97.39	gold quality
Brodmann (1909) area 10	UBERON:0013541	97.36	gold quality
prefrontal cortex	UBERON:0000451	97.29	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.19	gold quality
superior vestibular nucleus	UBERON:0007227	97.14	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.14	gold quality
substantia nigra pars compacta	UBERON:0001965	97.09	gold quality
hypothalamus	UBERON:0001898	97.08	gold quality
postcentral gyrus	UBERON:0002581	97.08	gold quality
endothelial cell	CL:0000115	96.92	gold quality
parietal lobe	UBERON:0001872	96.92	gold quality
neocortex	UBERON:0001950	96.85	gold quality
cingulate cortex	UBERON:0003027	96.79	gold quality
anterior cingulate cortex	UBERON:0009835	96.78	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.68	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.53	gold quality
occipital lobe	UBERON:0002021	96.40	gold quality
cerebellar hemisphere	UBERON:0002245	96.34	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	6.72
E-MTAB-7303	no	1350.50
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

89 targeting SYNGR3, 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-3120-5P	100.00	65.56	965
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-379-3P	99.69	69.60	1524

Literature-anchored findings (GeneRIF, showing 5)

• This study identifies the mouse homolog, synaptogyrin 3, as a synaptic vesicle protein. (PMID:14755516)
• This study demonstrates the interaction of the mouse homolog, synaptogyrin 3, with the dopamine transporter (DAT). (PMID:19357284)
• Transcriptional Regulation of the Synaptic Vesicle Protein Synaptogyrin-3 (SYNGR3) Gene: The Effects of NURR1 on Its Expression. (PMID:35409005)
• Tumor Cell Extrinsic Synaptogyrin 3 Expression as a Diagnostic and Prognostic Biomarker in Head and Neck Cancer. (PMID:36148399)
• In vivo overexpression of synaptogyrin-3 promotes striatal synaptic dopamine uptake in LRRK2[R1441G] mutant mouse model of Parkinson’s disease. (PMID:36624932)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	syngr3a	ENSDARG00000014871
danio_rerio	syngr3b	ENSDARG00000025034
mus_musculus	Syngr3	ENSMUSG00000007021
rattus_norvegicus	Syngr3	ENSRNOG00000012620

Paralogs (3): SYNGR1 (ENSG00000100321), SYNGR4 (ENSG00000105467), SYNGR2 (ENSG00000108639)

Protein

Protein identifiers

Synaptogyrin-3 — O43761 (reviewed: O43761)

All UniProt accessions (4): O43761, H3BNA6, H3BPJ5, H3BQ28

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in regulated exocytosis. May indirectly regulate the activity of the plasma membrane dopamine transporter SLC6A3 and thereby regulate dopamine transport back from the synaptic cleft into the presynaptic terminal.

Subunit / interactions. Interacts (via N-terminus) with SLC6A3 (via N-terminus). May interact with VMAT2.

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

Tissue specificity. Expressed in brain and placenta.

Similarity. Belongs to the synaptogyrin family.

RefSeq proteins (1): NP_004200* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008253	Marvel	Domain
IPR016579	Synaptogyrin	Family

Pfam: PF01284

UniProt features (9 total): transmembrane region 4, chain 1, domain 1, region of interest 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43761-F1	80.95	0.54

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 (1): 1

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 179 (showing top): RNGTGGGC_UNKNOWN, GOBP_NEUROTRANSMITTER_UPTAKE, GOBP_POSITIVE_REGULATION_OF_TRANSPORTER_ACTIVITY, JOHANSSON_GLIOMAGENESIS_BY_PDGFB_DN, GOBP_NEUROTRANSMITTER_TRANSPORT, CREBP1_Q2, TGACCTY_ERR1_Q2, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_CELL_CELL_SIGNALING, CREB_Q4, BROWNE_HCMV_INFECTION_24HR_UP, GOBP_EXOCYTOSIS, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP

GO Biological Process (5): regulation of synaptic vesicle priming (GO:0010807), substantia nigra development (GO:0021762), positive regulation of transporter activity (GO:0032411), regulated exocytosis (GO:0045055), regulation of neurotransmitter uptake (GO:0051580)

GO Molecular Function (2): SH2 domain binding (GO:0042169), protein binding (GO:0005515)

GO Cellular Component (6): synaptic vesicle (GO:0008021), membrane (GO:0016020), synaptic vesicle membrane (GO:0030672), neuromuscular junction (GO:0031594), cytoplasmic vesicle (GO:0031410), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
synaptic vesicle priming	1
regulation of protein-containing complex assembly	1
midbrain development	1
neural nucleus development	1
transporter activity	1
positive regulation of molecular function	1
positive regulation of transport	1
exocytosis	1
neurotransmitter uptake	1
regulation of neurotransmitter transport	1
protein domain specific binding	1
binding	1
exocytic vesicle	1
presynapse	1
cellular anatomical structure	1
synaptic vesicle	1
exocytic vesicle membrane	1
synapse	1
cytoplasm	1
intracellular vesicle	1
cell junction	1

Protein interactions and networks

STRING

1309 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYNGR3	SLC6A3	Q01959	924
SYNGR3	SYP	P08247	725
SYNGR3	SYT1	P21579	667
SYNGR3	VAMP2	P19065	663
SYNGR3	SV2A	Q7L0J3	644
SYNGR3	SNCA	P37840	627
SYNGR3	PICK1	Q9NRD5	590
SYNGR3	TGFB1I1	O43294	497
SYNGR3	MAPT	P10636	489
SYNGR3	SYNPR	Q8TBG9	474
SYNGR3	SLC18A2	Q05940	449
SYNGR3	GAPDH	P00354	445
SYNGR3	STX1A	Q16623	439
SYNGR3	SNAP25	P13795	427
SYNGR3	RAB3A	P20336	412

IntAct

80 interactions, top by confidence:

A	B	Type	Score
SYNGR3	SH3GLB1	psi-mi:“MI:0915”(physical association)	0.720
SH3GLB1	SYNGR3	psi-mi:“MI:0915”(physical association)	0.720
SYNGR3	SPG21	psi-mi:“MI:0915”(physical association)	0.560
SYNGR3	PNKP	psi-mi:“MI:0915”(physical association)	0.560
SYNGR3	TTPA	psi-mi:“MI:0915”(physical association)	0.560
SYNGR3	EHHADH	psi-mi:“MI:0915”(physical association)	0.560
SYNGR3	NDRG4	psi-mi:“MI:0915”(physical association)	0.560
SYNGR3	MPP1	psi-mi:“MI:0915”(physical association)	0.560
SYNGR3	ARFIP1	psi-mi:“MI:0915”(physical association)	0.560
SYNGR3	GAD2	psi-mi:“MI:0915”(physical association)	0.560
HSBP1L1	SYNGR3	psi-mi:“MI:0915”(physical association)	0.560
SYNGR3	ACSF2	psi-mi:“MI:0915”(physical association)	0.560
SYNGR3	PLIN3	psi-mi:“MI:0915”(physical association)	0.560
SYNGR3	MIDN	psi-mi:“MI:0915”(physical association)	0.560
PRKCA	SYNGR3	psi-mi:“MI:0915”(physical association)	0.560
SYNGR3	YWHAG	psi-mi:“MI:0915”(physical association)	0.560
SYNGR3	SETDB1	psi-mi:“MI:0915”(physical association)	0.560
KAT5	SYNGR3	psi-mi:“MI:0915”(physical association)	0.560
LMO3	SYNGR3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (46): SYNGR3 (Affinity Capture-MS), SYNGR3 (Affinity Capture-MS), SYNGR3 (Affinity Capture-MS), SYNGR3 (Affinity Capture-MS), SYNGR3 (Two-hybrid), SYNGR3 (Two-hybrid), SYNGR3 (Two-hybrid), SYNGR3 (Two-hybrid), SYNGR3 (Two-hybrid), SYNGR3 (Two-hybrid), MPP1 (Two-hybrid), GAD2 (Two-hybrid), TTPA (Two-hybrid), ARFIP1 (Two-hybrid), ACSF2 (Two-hybrid)

ESM2 similar proteins: A2VE58, A3KQ86, A6H7B0, A7E3W5, A8MWL6, B2RZ87, O43759, O43760, O43761, O54980, O55100, O55101, O76735, O95473, P07825, P08247, P0DI73, P20488, P22831, P47987, P79826, Q08AU7, Q08DL4, Q28793, Q2YDD6, Q5EBF8, Q5R703, Q5RER2, Q5XGR0, Q5XIT3, Q5YJC1, Q62277, Q62876, Q642A2, Q6RW13, Q7JYV2, Q7TQJ1, Q8BGN8, Q8R191, Q8TBG9

Diamond homologs: A2VE58, A7E3W5, A8MWL6, O43759, O43760, O43761, O54980, O55100, O55101, O76735, O95473, Q2YDD6, Q5R703, Q62876, Q7JYV2, Q8R191, Q9Z1L2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	32
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1459269	NC_000016.9:g.(?2003468)(2126543_?)del	Pathogenic

SpliceAI

648 predictions. Top by Δscore:

Variant	Effect	Δscore
16:1990200:GG:G	donor_gain	1.0000
16:1990201:GG:G	donor_gain	1.0000
16:1990202:G:GG	donor_gain	1.0000
16:1990203:T:A	donor_loss	1.0000
16:1992774:GCTGG:G	donor_gain	1.0000
16:1992775:C:G	donor_gain	1.0000
16:1992777:GG:G	donor_gain	1.0000
16:1992778:GG:G	donor_gain	1.0000
16:1992779:G:GG	donor_gain	1.0000
16:1992780:T:A	donor_loss	1.0000
16:1992861:A:G	acceptor_loss	1.0000
16:1992861:AGGT:A	acceptor_gain	1.0000
16:1992862:GGT:G	acceptor_gain	1.0000
16:1992862:GGTG:G	acceptor_gain	1.0000
16:1990204:GAGTG:G	donor_loss	0.9900
16:1992210:AGGTG:A	donor_loss	0.9900
16:1992211:G:GC	donor_loss	0.9900
16:1992212:GTGGG:G	donor_loss	0.9900
16:1992213:T:G	donor_loss	0.9900
16:1992632:GCA:G	acceptor_loss	0.9900
16:1992633:CA:C	acceptor_loss	0.9900
16:1992634:A:AG	acceptor_gain	0.9900
16:1992635:G:GG	acceptor_gain	0.9900
16:1992635:GGA:G	acceptor_gain	0.9900
16:1992775:CTGG:C	donor_gain	0.9900
16:1992858:C:CA	acceptor_gain	0.9900
16:1992861:A:AG	acceptor_gain	0.9900
16:1992861:AG:A	acceptor_gain	0.9900
16:1992862:G:GG	acceptor_gain	0.9900
16:1992862:GG:G	acceptor_gain	0.9900

AlphaMissense

1468 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:1992056:T:C	F61S	0.996
16:1992755:A:C	S153R	0.996
16:1992757:C:A	S153R	0.996
16:1992757:C:G	S153R	0.996
16:1992773:A:C	S159R	0.996
16:1992775:C:A	S159R	0.996
16:1992775:C:G	S159R	0.996
16:1992665:T:C	F123L	0.995
16:1992667:C:A	F123L	0.995
16:1992667:C:G	F123L	0.995
16:1992688:G:C	W130C	0.995
16:1992688:G:T	W130C	0.995
16:1992653:T:A	W119R	0.994
16:1992653:T:C	W119R	0.994
16:1992211:G:A	G113R	0.993
16:1992211:G:C	G113R	0.993
16:1992776:T:A	W160R	0.993
16:1992776:T:C	W160R	0.993
16:1992049:T:C	C59R	0.992
16:1992636:G:A	G113E	0.992
16:1992056:T:G	F61C	0.991
16:1992077:G:A	C68Y	0.991
16:1992097:G:C	G75R	0.991
16:1992175:C:A	R101S	0.991
16:1992668:T:C	C124R	0.991
16:1991981:C:A	S36Y	0.990
16:1992049:T:A	C59S	0.990
16:1992050:G:A	C59Y	0.990
16:1992050:G:C	C59S	0.990
16:1992098:G:A	G75D	0.990

dbSNP variants (sampled 300 via entrez): RS1000711983 (16:1992324 G>A,T), RS1000976998 (16:1992833 G>A,T), RS1001374114 (16:1994492 G>GTTT), RS1001532463 (16:1989601 G>A,T), RS1001661328 (16:1994773 C>T), RS1001739073 (16:1992121 G>A,C,T), RS1002780657 (16:1993170 G>A), RS1003285887 (16:1988893 G>A), RS1003607175 (16:1990461 A>G), RS1003786557 (16:1994393 G>C), RS1003894189 (16:1992901 G>A), RS1004025522 (16:1988450 C>G), RS1004062564 (16:1990714 T>G), RS1004265882 (16:1992751 C>T), RS1004558419 (16:1991033 C>T)

Disease associations

OMIM: gene MIM:603927 | disease phenotypes: MIM:613254

GenCC curated gene-disease

Mondo (1): tuberous sclerosis 2 (MONDO:0013199)

Orphanet (1): Tuberous sclerosis complex (Orphanet:805)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566021	Tuberous Sclerosis 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	3
Cyclosporine	decreases expression, increases expression	3
mercuric bromide	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Valproic Acid	increases methylation, affects expression, increases expression	2
Aflatoxin B1	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, increases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects cotreatment, affects response to substance	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
azoxystrobin	decreases expression	1
entinostat	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
ICG 001	increases expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, decreases expression	1
picoxystrobin	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Vorinostat	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02201212	PHASE2	COMPLETED	Everolimus for Cancer With TSC1 or TSC2 Mutation
NCT05103358	PHASE2	ACTIVE_NOT_RECRUITING	Phase 2 Basket Trial of Nab-sirolimus in Patients With Malignant Solid Tumors With Pathogenic Alterations in TSC1/TSC2 Genes (PRECISION 1)
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT03817515	Not specified	APPROVED_FOR_MARKETING	Expanded Access for ABI-009 in Patients With Advanced PEComa and Patients With a Malignancy With Relevant Genetic Mutations or mTOR Pathway Activation