INSYN1

Summary

INSYN1 (inhibitory synaptic factor 1, HGNC:33753) is a protein-coding gene on chromosome 15q24.1, encoding Inhibitory synaptic factor 1 (Q2T9L4). Component of the protein machinery at the inhibitory synapses, probably acting as a scaffold.

Predicted to be involved in inhibitory postsynaptic potential. Predicted to be located in synapse. Predicted to be active in GABA-ergic synapse and postsynaptic density.

Source: NCBI Gene 388135 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 3 total
• MANE Select transcript: NM_001039614

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33753
Approved symbol	INSYN1
Name	inhibitory synaptic factor 1
Location	15q24.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC131524, LOC388135
Ensembl gene	ENSG00000205363
Ensembl biotype	protein_coding
OMIM	617128
Entrez	388135

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000558834, ENST00000559817, ENST00000569673, ENST00000929676, ENST00000970607, ENST00000970608

RefSeq mRNA: 5 — MANE Select: NM_001039614 NM_001039614, NM_001303254, NM_001384351, NM_001384352, NM_001384353

CCDS: CCDS32289

Canonical transcript exons

ENST00000569673 — 3 exons

Exon	Start	End
ENSE00001482628	73735458	73740642
ENSE00002591981	73750975	73751697
ENSE00002597830	73752110	73753351

Expression profiles

Bgee: expression breadth ubiquitous, 205 present calls, max score 97.17.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3160 / max 32.1754, expressed in 485 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150861	1.3160	485

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	97.17	gold quality
lower esophagus mucosa	UBERON:0035834	97.12	gold quality
left ventricle myocardium	UBERON:0006566	96.72	gold quality
prefrontal cortex	UBERON:0000451	96.71	gold quality
right frontal lobe	UBERON:0002810	96.22	gold quality
anterior cingulate cortex	UBERON:0009835	96.06	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.80	gold quality
hypothalamus	UBERON:0001898	95.58	gold quality
ganglionic eminence	UBERON:0004023	95.49	gold quality
amygdala	UBERON:0001876	95.46	gold quality
heart left ventricle	UBERON:0002084	95.46	gold quality
putamen	UBERON:0001874	95.45	gold quality
nucleus accumbens	UBERON:0001882	95.33	gold quality
right atrium auricular region	UBERON:0006631	95.27	gold quality
cardiac ventricle	UBERON:0002082	95.22	gold quality
substantia nigra	UBERON:0002038	95.13	gold quality
cardiac atrium	UBERON:0002081	95.08	gold quality
caudate nucleus	UBERON:0001873	94.95	gold quality
midbrain	UBERON:0001891	94.67	gold quality
frontal cortex	UBERON:0001870	94.57	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.43	gold quality
neocortex	UBERON:0001950	94.34	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.27	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.21	gold quality
ventral tegmental area	UBERON:0002691	93.29	gold quality
cerebral cortex	UBERON:0000956	93.02	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.75	gold quality
cortical plate	UBERON:0005343	92.69	gold quality
upper arm skin	UBERON:0004263	92.54	silver quality
substantia nigra pars compacta	UBERON:0001965	92.45	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

123 targeting INSYN1, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1273H-5P	99.77	66.32	2471

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	insyn1	ENSDARG00000026247
mus_musculus	Insyn1	ENSMUSG00000066607
rattus_norvegicus	Insyn1	ENSRNOG00000068374

Paralogs (1): PRR16 (ENSG00000184838)

Protein

Protein identifiers

Inhibitory synaptic factor 1 — Q2T9L4 (reviewed: Q2T9L4)

All UniProt accessions (2): Q2T9L4, H0YKG6

UniProt curated annotations — full annotation on UniProt →

Function. Component of the protein machinery at the inhibitory synapses, probably acting as a scaffold. Inhibitory synapses dampen neuronal activity through postsynaptic hyperpolarization. This synaptic inhibition is fundamental for the functioning of the central nervous system, shaping and orchestrating the flow of information through neuronal networks to generate a precise neural code.

Subunit / interactions. Interacts with GPHN.

Subcellular location. Postsynaptic density.

Similarity. Belongs to the INSYN1 family.

RefSeq proteins (5): NP_001034703, NP_001290183, NP_001371280, NP_001371281, NP_001371282 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027997	Largen/INSYN1	Family

Pfam: PF15252

UniProt features (9 total): compositionally biased region 4, region of interest 3, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2T9L4-F1	62.59	0.16

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 52 (showing top): GOBP_CELL_CELL_SIGNALING, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_REGULATION_OF_POSTSYNAPTIC_MEMBRANE_POTENTIAL, GOBP_SYNAPTIC_SIGNALING, GOCC_POSTSYNAPSE, GOBP_REGULATION_OF_MEMBRANE_POTENTIAL, GOCC_SYNAPSE, GOBP_SYNAPSE_ORGANIZATION, CHEMNITZ_RESPONSE_TO_PROSTAGLANDIN_E2_DN, DUAN_PRDM5_TARGETS, GOBP_INHIBITORY_POSTSYNAPTIC_POTENTIAL, DELACROIX_RAR_BOUND_ES, GOBP_POSTSYNAPTIC_SPECIALIZATION_ORGANIZATION, GOBP_POSTSYNAPSE_ORGANIZATION, GOCC_GABA_ERGIC_SYNAPSE

GO Biological Process (3): inhibitory postsynaptic potential (GO:0060080), postsynaptic specialization organization (GO:0099084), chemical synaptic transmission, postsynaptic (GO:0099565)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): postsynaptic density (GO:0014069), GABA-ergic synapse (GO:0098982), synapse (GO:0045202), postsynaptic specialization (GO:0099572)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
postsynapse	2
regulation of postsynaptic membrane potential	1
chemical synaptic transmission, postsynaptic	1
organelle organization	1
postsynapse organization	1
cell surface receptor signaling pathway	1
chemical synaptic transmission	1
nervous system process	1
binding	1
asymmetric synapse	1
postsynaptic specialization	1
synapse	1
cell junction	1
organelle	1

Protein interactions and networks

STRING

274 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
INSYN1	GPHN	Q9NQX3	807
INSYN1	INSYN2A	Q6ZSG2	715
INSYN1	IQSEC3	Q9UPP2	660
INSYN1	NLGN2	Q8NFZ4	611
INSYN1	FAM187A	A6NFU0	600
INSYN1	ARHGEF9	O43307	578
INSYN1	LHFPL4	Q7Z7J7	496
INSYN1	ARHGAP32	A7KAX9	452
INSYN1	LHFPL3	Q86UP9	450
INSYN1	EVL	Q9UI08	434
INSYN1	DTNB	O60941	430
INSYN1	SLITRK3	O94933	422
INSYN1	CLPTM1	O96005	416
INSYN1	TUBGCP4	Q9UGJ1	413
INSYN1	ITM2C	Q9NQX7	410

IntAct

42 interactions, top by confidence:

A	B	Type	Score
INSYN1	WASHC3	psi-mi:“MI:0915”(physical association)	0.670
INSYN1	MCRS1	psi-mi:“MI:0915”(physical association)	0.670
SNAPIN	INSYN1	psi-mi:“MI:0915”(physical association)	0.670
INSYN1	BORCS6	psi-mi:“MI:0915”(physical association)	0.670
INSYN1	BLOC1S6	psi-mi:“MI:0915”(physical association)	0.630
BLOC1S6	INSYN1	psi-mi:“MI:0915”(physical association)	0.630
DTNB	INSYN1	psi-mi:“MI:0915”(physical association)	0.560
INSYN1	C19orf25	psi-mi:“MI:0915”(physical association)	0.560
GABARAPL2	INSYN1	psi-mi:“MI:0915”(physical association)	0.560
INSYN1	ABI2	psi-mi:“MI:0915”(physical association)	0.560
INSYN1	PBX3	psi-mi:“MI:0915”(physical association)	0.560
INSYN1	CCDC146	psi-mi:“MI:0915”(physical association)	0.560
INSYN1	H1-4	psi-mi:“MI:0915”(physical association)	0.400
INSYN1	PPP1CC	psi-mi:“MI:0915”(physical association)	0.370
INSYN1	CCDC85C	psi-mi:“MI:0914”(association)	0.350
TRAF3IP1	INSYN1	psi-mi:“MI:0915”(physical association)	0.000
DTNB	INSYN1	psi-mi:“MI:0915”(physical association)	0.000
BLOC1S6	INSYN1	psi-mi:“MI:0915”(physical association)	0.000
C19orf25	INSYN1	psi-mi:“MI:0915”(physical association)	0.000
WASHC3	INSYN1	psi-mi:“MI:0915”(physical association)	0.000
GABARAPL2	INSYN1	psi-mi:“MI:0915”(physical association)	0.000
MCRS1	INSYN1	psi-mi:“MI:0915”(physical association)	0.000
SNAPIN	INSYN1	psi-mi:“MI:0915”(physical association)	0.000
ABI2	INSYN1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (173): C15orf59 (Two-hybrid), C15orf59 (Two-hybrid), C15orf59 (Two-hybrid), C15orf59 (Two-hybrid), C15orf59 (Two-hybrid), C15orf59 (Two-hybrid), C15orf59 (Two-hybrid), C15orf59 (Two-hybrid), C15orf59 (Two-hybrid), C15orf59 (Two-hybrid), C15orf59 (Two-hybrid), C15orf59 (Proximity Label-MS), TNIK (Affinity Capture-MS), CORO1A (Affinity Capture-MS), LOC81691 (Affinity Capture-MS)

ESM2 similar proteins: A0JNG6, A2AKB4, A7YWL5, B0BN13, O35181, O43734, O70142, O70240, O88286, O88566, P0DPB3, P0DPB4, P56975, P70298, P86174, P97303, Q00IB7, Q1LY51, Q2M3C6, Q2T9L4, Q3TY60, Q498S6, Q4V7B1, Q568Z1, Q5HZN9, Q5JTD0, Q5SYB0, Q5U5E5, Q5VT97, Q69ZB8, Q6PG95, Q6UXB0, Q6ZU67, Q76N89, Q80YE4, Q86XD5, Q8BWU3, Q8BZB3, Q8CD60, Q8N365

Diamond homologs: A7YWL5, B0BN13, Q1L899, Q2T9L4, Q569H4, Q5PQ25, Q8CD60, A3KMN5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

555 predictions. Top by Δscore:

Variant	Effect	Δscore
15:73750971:TTA:T	donor_loss	1.0000
15:73750972:TA:T	donor_loss	1.0000
15:73750973:A:C	donor_loss	1.0000
15:73750973:ACCT:A	donor_gain	1.0000
15:73750973:ACCTC:A	donor_gain	1.0000
15:73750974:C:CT	donor_loss	1.0000
15:73750974:CCTC:C	donor_gain	1.0000
15:73750974:CCTCC:C	donor_gain	1.0000
15:73740648:C:CT	acceptor_gain	0.9900
15:73740649:A:T	acceptor_gain	0.9900
15:73750973:A:AC	donor_gain	0.9900
15:73750974:C:CC	donor_gain	0.9900
15:73750974:CCT:C	donor_gain	0.9900
15:73750977:C:A	donor_gain	0.9900
15:73750989:TGGCC:T	donor_gain	0.9900
15:73750997:T:TA	donor_gain	0.9900
15:73752105:CTCA:C	donor_loss	0.9900
15:73752106:TCA:T	donor_loss	0.9900
15:73752107:CA:C	donor_loss	0.9900
15:73752108:A:AC	donor_gain	0.9900
15:73752109:C:CA	donor_loss	0.9900
15:73752109:C:CC	donor_gain	0.9900
15:73740161:T:TA	donor_gain	0.9800
15:73740173:T:TA	donor_gain	0.9800
15:73740639:CCAC:C	acceptor_gain	0.9800
15:73740640:CACC:C	acceptor_gain	0.9800
15:73741957:C:CT	donor_gain	0.9800
15:73741958:T:TT	donor_gain	0.9800
15:73750988:TTGGC:T	donor_gain	0.9800
15:73750992:C:CT	donor_gain	0.9800

AlphaMissense

1914 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:73740235:G:C	F188L	1.000
15:73740235:G:T	F188L	1.000
15:73740237:A:G	F188L	1.000
15:73751003:A:G	L43P	1.000
15:73740236:A:G	F188S	0.999
15:73740620:A:G	L60P	0.999
15:73750982:A:G	L50P	0.999
15:73751003:A:T	L43H	0.999
15:73751012:A:G	L40P	0.999
15:73751024:A:G	L36P	0.999
15:73740236:A:C	F188C	0.998
15:73751024:A:T	L36H	0.998
15:73740216:G:C	H195D	0.997
15:73740219:A:C	Y194D	0.997
15:73740559:G:C	S80R	0.997
15:73740559:G:T	S80R	0.997
15:73740561:T:G	S80R	0.997
15:73740629:A:C	I57S	0.997
15:73740629:A:T	I57N	0.997
15:73750991:G:T	A47D	0.997
15:73750992:C:G	A47P	0.997
15:73751012:A:T	L40H	0.997
15:73740230:T:A	D190V	0.996
15:73740232:A:C	S189R	0.996
15:73740232:A:T	S189R	0.996
15:73740234:T:G	S189R	0.996
15:73750982:A:T	L50Q	0.996
15:73740214:A:C	H195Q	0.995
15:73740214:A:T	H195Q	0.995
15:73740471:A:G	W110R	0.995

dbSNP variants (sampled 300 via entrez): RS1000059499 (15:73747377 T>C), RS1000334936 (15:73740854 C>T), RS1000475013 (15:73735216 G>A,C), RS1000508744 (15:73739863 ATATATT>A), RS1000674615 (15:73744343 G>A), RS1000793314 (15:73750586 T>C), RS1000917347 (15:73754148 G>A), RS1001227787 (15:73753241 G>A,C), RS1001283811 (15:73747021 G>A,C), RS1001293895 (15:73747260 T>C), RS1001369830 (15:73754331 T>A), RS1001421007 (15:73753639 C>A,T), RS1001786545 (15:73735645 T>C), RS1001870510 (15:73754057 G>A), RS1001899993 (15:73738161 G>A)

Disease associations

OMIM: gene MIM:617128 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002726_4	Glucose homeostasis traits	7.000000e-08
GCST006461_19	Self-reported risk-taking behaviour	4.000000e-07
GCST007277_20	Tourette syndrome	7.000000e-06
GCST007325_124	General risk tolerance (MTAG)	3.000000e-11
GCST008103_138	Bipolar disorder	2.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004471	insulin sensitivity measurement
EFO:0008579	risk-taking behaviour

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sotorasib	affects cotreatment, increases expression	1
sodium arsenite	increases expression	1
jinfukang	affects cotreatment, increases expression	1
trametinib	increases expression, affects cotreatment	1
NVP-BKM120	affects cotreatment, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Lead	affects expression	1
Progesterone	decreases expression	1
Silicon Dioxide	increases expression	1
Tretinoin	increases expression	1
Triclosan	increases expression	1
Valproic Acid	affects expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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