INSYN2A

Summary

INSYN2A (inhibitory synaptic factor 2A, HGNC:33859) is a protein-coding gene on chromosome 10q26.2, encoding Inhibitory synaptic factor 2A (Q6ZSG2). 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 642938 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 10 total
• MANE Select transcript: NM_001039762

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33859
Approved symbol	INSYN2A
Name	inhibitory synaptic factor 2A
Location	10q26.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ45557
Ensembl gene	ENSG00000188916
Ensembl biotype	protein_coding
OMIM	617129
Entrez	642938

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000424811, ENST00000522781, ENST00000614311, ENST00000939797, ENST00000962069

RefSeq mRNA: 1 — MANE Select: NM_001039762 NM_001039762

CCDS: CCDS31312

Canonical transcript exons

ENST00000522781 — 6 exons

Exon	Start	End
ENSE00001765945	127153852	127153923
ENSE00002109327	127175212	127176400
ENSE00002122564	127192605	127192730
ENSE00002124059	127135430	127138020
ENSE00002135801	127176877	127177139
ENSE00003846353	127195997	127196591

Expression profiles

Bgee: expression breadth ubiquitous, 143 present calls, max score 78.14.

FANTOM5 (CAGE): breadth broad, TPM avg 0.5956 / max 49.5963, expressed in 230 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
111984	0.2739	135
111983	0.1762	79
111985	0.1455	71

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.14	gold quality
cortical plate	UBERON:0005343	78.00	gold quality
nucleus accumbens	UBERON:0001882	69.24	gold quality
buccal mucosa cell	CL:0002336	69.06	silver quality
caudate nucleus	UBERON:0001873	68.56	gold quality
putamen	UBERON:0001874	68.17	gold quality
hypothalamus	UBERON:0001898	65.87	gold quality
lateral globus pallidus	UBERON:0002476	64.98	gold quality
ganglionic eminence	UBERON:0004023	64.38	gold quality
prefrontal cortex	UBERON:0000451	63.96	gold quality
colonic epithelium	UBERON:0000397	63.51	silver quality
amygdala	UBERON:0001876	62.98	gold quality
anterior cingulate cortex	UBERON:0009835	62.17	gold quality
substantia nigra	UBERON:0002038	62.06	gold quality
calcaneal tendon	UBERON:0003701	61.60	gold quality
endothelial cell	CL:0000115	61.58	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	61.23	gold quality
pigmented layer of retina	UBERON:0001782	60.38	silver quality
midbrain	UBERON:0001891	59.61	gold quality
neocortex	UBERON:0001950	59.30	gold quality
lower lobe of lung	UBERON:0008949	59.30	silver quality
primary visual cortex	UBERON:0002436	59.26	gold quality
Brodmann (1909) area 9	UBERON:0013540	58.82	gold quality
forebrain	UBERON:0001890	58.79	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	58.37	gold quality
frontal cortex	UBERON:0001870	58.12	gold quality
brain	UBERON:0000955	57.88	gold quality
cerebral cortex	UBERON:0000956	57.70	gold quality
tendon	UBERON:0000043	57.24	gold quality
temporal lobe	UBERON:0001871	56.78	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

184 targeting INSYN2A, 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-6867-5P	100.00	82.21	3464
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-3613-3P	100.00	76.36	7965
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-5692A	100.00	74.40	6850
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-493-5P	99.96	72.47	2382
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163

Literature-anchored findings (GeneRIF, showing 1)

• Further refining the critical region of 10q26 microdeletion syndrome: A possible involvement of INSYN2 and NPS in the cognitive phenotype. (PMID:34252586)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	INSYN2A	ENSDARG00000107296
danio_rerio	insyn2ab	ENSDARG00000107576
mus_musculus	Insyn2a	ENSMUSG00000073805
rattus_norvegicus	Insyn2a	ENSRNOG00000033881

Paralogs (1): INSYN2B (ENSG00000204767)

Protein

Protein identifiers

Inhibitory synaptic factor 2A — Q6ZSG2 (reviewed: Q6ZSG2)

All UniProt accessions (1): Q6ZSG2

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 INSYN2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6ZSG2-1	1	yes
Q6ZSG2-2	2

RefSeq proteins (1): NP_001034851* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029337	INSYN2	Family

Pfam: PF15265

UniProt features (11 total): region of interest 3, compositionally biased region 3, chain 1, sequence variant 1, coiled-coil region 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZSG2-F1	54.57	0.11

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): 177

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 89 (showing top): GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_POSTSYNAPTIC_MEMBRANE_POTENTIAL, GOBP_SYNAPTIC_SIGNALING, GOCC_POSTSYNAPSE, GOBP_REGULATION_OF_MEMBRANE_POTENTIAL, GOCC_SYNAPSE, KOYAMA_SEMA3B_TARGETS_DN, GOBP_INHIBITORY_POSTSYNAPTIC_POTENTIAL, GOCC_NEURON_TO_NEURON_SYNAPSE, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, ZNF513_TARGET_GENES, MIR153_5P, MIR3662, MIR6867_5P, MIR548AJ_3P_MIR548X_3P

GO Biological Process (1): inhibitory postsynaptic potential (GO:0060080)

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

GO Cellular Component (2): postsynaptic density (GO:0014069), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of postsynaptic membrane potential	1
chemical synaptic transmission, postsynaptic	1
binding	1
asymmetric synapse	1
postsynaptic specialization	1
cell junction	1

Protein interactions and networks

STRING

478 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
INSYN2A	INSYN1	Q2T9L4	715
INSYN2A	EVL	Q9UI08	432
INSYN2A	IQSEC3	Q9UPP2	431
INSYN2A	AGPAT4	Q9NRZ5	429
INSYN2A	ARHGAP32	A7KAX9	428
INSYN2A	LRTM2	Q8N967	406
INSYN2A	DCAF10	Q5QP82	385
INSYN2A	KIAA1614	Q5VZ46	378
INSYN2A	CCDC60	Q8IWA6	372
INSYN2A	GFOD2	Q3B7J2	369
INSYN2A	TIGD3	Q6B0B8	369
INSYN2A	ANKRD18A	Q8IVF6	366
INSYN2A	TMPRSS6	Q8IU80	363
INSYN2A	ZNF541	Q9H0D2	356
INSYN2A	ZNF396	Q96N95	356

IntAct

12 interactions, top by confidence:

A	B	Type	Score
TP53BP2	INSYN2A	psi-mi:“MI:0915”(physical association)	0.560
HSF2BP	INSYN2A	psi-mi:“MI:0915”(physical association)	0.560
INSYN2A	BACH2	psi-mi:“MI:0915”(physical association)	0.560
INSYN2A	CHUK	psi-mi:“MI:0914”(association)	0.530
INSYN2A	NOP56	psi-mi:“MI:0914”(association)	0.350
INSYN2A	TP53BP2	psi-mi:“MI:0915”(physical association)	0.000
INSYN2A	BACH2	psi-mi:“MI:0915”(physical association)	0.000
INSYN2A	HSF2BP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (59): RUNDC1 (Affinity Capture-MS), PRUNE (Affinity Capture-MS), EFTUD1 (Affinity Capture-MS), STX5 (Affinity Capture-MS), STAT2 (Affinity Capture-MS), LRBA (Affinity Capture-MS), IQSEC1 (Affinity Capture-MS), USP4 (Affinity Capture-MS), IKBKG (Affinity Capture-MS), CHUK (Affinity Capture-MS), C2orf44 (Affinity Capture-MS), C17orf70 (Affinity Capture-MS), SECISBP2L (Affinity Capture-MS), AP5B1 (Affinity Capture-MS), MTR (Affinity Capture-MS)

ESM2 similar proteins: A0P8Z5, B0KYV5, B1WC58, B2RYR0, F1LR10, F6SNN2, O75128, O75410, P51826, P61590, P61591, P61592, P61593, P61594, Q3USH1, Q501R9, Q5IFK1, Q5PQK4, Q5R8C5, Q5SU73, Q5SWA1, Q5U5Q9, Q6NZF1, Q6P1D7, Q6P7W0, Q6PJW8, Q6Y685, Q6ZSG2, Q6ZVT6, Q7TT79, Q80XI1, Q80XJ2, Q80YR6, Q86T90, Q8BFU3, Q8C9B9, Q8IY92, Q8IYW5, Q8ND24, Q8NEM0

Diamond homologs: A6NMK8, Q3USH1, Q6GQV1, Q6ZSG2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1677 predictions. Top by Δscore:

Variant	Effect	Δscore
10:127138016:CCACA:C	acceptor_gain	1.0000
10:127138017:CACAC:C	acceptor_gain	1.0000
10:127138019:CA:C	acceptor_gain	1.0000
10:127177141:T:C	acceptor_gain	1.0000
10:127195991:GCTTA:G	donor_loss	1.0000
10:127195994:TAC:T	donor_loss	1.0000
10:127195996:C:T	donor_loss	1.0000
10:127138017:CACA:C	acceptor_gain	0.9900
10:127138021:C:CA	acceptor_loss	0.9900
10:127138021:C:CC	acceptor_gain	0.9900
10:127175206:ACAT:A	donor_loss	0.9900
10:127175208:ATACC:A	donor_loss	0.9900
10:127175209:T:TG	donor_loss	0.9900
10:127175210:AC:A	donor_gain	0.9900
10:127175210:ACCCT:A	donor_loss	0.9900
10:127175211:C:CA	donor_loss	0.9900
10:127175211:CC:C	donor_gain	0.9900
10:127175229:T:A	donor_gain	0.9900
10:127176398:TTCCT:T	acceptor_loss	0.9900
10:127176400:CCTGC:C	acceptor_loss	0.9900
10:127176401:C:A	acceptor_loss	0.9900
10:127176402:T:A	acceptor_loss	0.9900
10:127176408:C:CT	acceptor_gain	0.9900
10:127176409:A:T	acceptor_gain	0.9900
10:127177141:T:TC	acceptor_gain	0.9900
10:127178944:A:C	donor_gain	0.9900
10:127192603:A:AC	donor_gain	0.9900
10:127192604:C:CC	donor_gain	0.9900
10:127195996:CCTT:C	donor_gain	0.9900
10:127175210:A:AC	donor_gain	0.9800

AlphaMissense

3125 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:127153863:A:C	C415W	1.000
10:127153864:C:T	C415Y	1.000
10:127153865:A:G	C415R	1.000
10:127153880:A:G	C410R	1.000
10:127153889:A:G	C407R	1.000
10:127175239:A:G	L386S	1.000
10:127175248:A:T	I383N	1.000
10:127175260:A:G	L379P	1.000
10:127138005:A:C	F424L	0.999
10:127138005:A:T	F424L	0.999
10:127138006:A:G	F424S	0.999
10:127138007:A:G	F424L	0.999
10:127138009:T:A	D423V	0.999
10:127138012:A:G	L422P	0.999
10:127153858:A:T	I417N	0.999
10:127153864:C:A	C415F	0.999
10:127153864:C:G	C415S	0.999
10:127153865:A:T	C415S	0.999
10:127153869:A:C	S413R	0.999
10:127153869:A:T	S413R	0.999
10:127153871:T:G	S413R	0.999
10:127153878:G:C	C410W	0.999
10:127153879:C:G	C410S	0.999
10:127153879:C:T	C410Y	0.999
10:127153880:A:T	C410S	0.999
10:127153887:A:C	C407W	0.999
10:127153888:C:A	C407F	0.999
10:127153888:C:G	C407S	0.999
10:127153888:C:T	C407Y	0.999
10:127153889:A:T	C407S	0.999

dbSNP variants (sampled 300 via entrez): RS1000042798 (10:127169157 C>T), RS1000058451 (10:127149118 T>C), RS1000096551 (10:127162748 C>T), RS1000137185 (10:127180783 G>T), RS1000170598 (10:127162955 C>T), RS1000268279 (10:127195150 A>G), RS1000321769 (10:127156155 A>G), RS1000323015 (10:127198334 T>C), RS1000339144 (10:127149388 G>A), RS1000368574 (10:127145804 A>G), RS1000449964 (10:127185759 G>A), RS1000481927 (10:127191984 C>G,T), RS1000568644 (10:127138354 T>C), RS1000568917 (10:127155795 C>T), RS1000585025 (10:127185962 C>A,T)

Disease associations

OMIM: gene MIM:617129 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010396_127	Gut microbiota (bacterial taxa, hurdle binary method)	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
tobacco tar	decreases reaction, increases expression	1
diallyl disulfide	decreases reaction, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
nutlin 3	increases expression, affects cotreatment	1
abrine	decreases expression	1
MRK 003	decreases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Camptothecin	increases expression	1
Cisplatin	increases expression, affects cotreatment	1
Dactinomycin	affects cotreatment, increases expression	1
Doxorubicin	increases expression	1
Estradiol	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases methylation	1
Valproic Acid	increases methylation	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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