CPLX3

Summary

CPLX3 (complexin 3, HGNC:27652) is a protein-coding gene on chromosome 15q24.1, encoding Complexin-3 (Q8WVH0). Complexin that regulates SNARE protein complex-mediated synaptic vesicle fusion.

Predicted to enable SNARE binding activity. Predicted to be involved in modulation of chemical synaptic transmission; regulation of synaptic vesicle fusion to presynaptic active zone membrane; and synaptic vesicle exocytosis. Predicted to act upstream of or within regulation of neurotransmitter secretion. Predicted to be located in cytosol; plasma membrane; and synapse. Predicted to be part of SNARE complex. Predicted to be active in several cellular components, including photoreceptor ribbon synapse; presynaptic active zone membrane; and synaptic vesicle membrane.

Source: NCBI Gene 594855 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 26 total
• MANE Select transcript: NM_001030005

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27652
Approved symbol	CPLX3
Name	complexin 3
Location	15q24.1
Locus type	gene with protein product
Status	Approved
Aliases	CPX-III
Ensembl gene	ENSG00000213578
Ensembl biotype	protein_coding
OMIM	609585
Entrez	594855

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000395018

RefSeq mRNA: 1 — MANE Select: NM_001030005 NM_001030005

CCDS: CCDS32294

Canonical transcript exons

ENST00000395018 — 3 exons

Exon	Start	End
ENSE00001520338	74826627	74826867
ENSE00002588170	74830130	74831802
ENSE00003519594	74828034	74828121

Expression profiles

Bgee: expression breadth broad, 96 present calls, max score 95.52.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.6580 / max 435.7598, expressed in 124 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
147737	1.6255	124
147736	0.0325	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
spleen	UBERON:0002106	95.52	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.38	gold quality
cerebellar hemisphere	UBERON:0002245	92.62	gold quality
cerebellar cortex	UBERON:0002129	92.47	gold quality
cerebellum	UBERON:0002037	92.32	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.81	gold quality
prostate gland	UBERON:0002367	89.69	gold quality
right atrium auricular region	UBERON:0006631	88.01	gold quality
apex of heart	UBERON:0002098	85.14	gold quality
prefrontal cortex	UBERON:0000451	82.12	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.83	gold quality
frontal cortex	UBERON:0001870	79.83	gold quality
anterior cingulate cortex	UBERON:0009835	79.46	gold quality
temporal lobe	UBERON:0001871	79.12	gold quality
amygdala	UBERON:0001876	78.99	gold quality
right frontal lobe	UBERON:0002810	76.84	gold quality
cerebral cortex	UBERON:0000956	76.12	gold quality
superior frontal gyrus	UBERON:0002661	76.01	gold quality
lower esophagus mucosa	UBERON:0035834	75.46	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	75.41	gold quality
Brodmann (1909) area 9	UBERON:0013540	74.80	gold quality
brain	UBERON:0000955	74.30	gold quality
primary visual cortex	UBERON:0002436	73.13	gold quality
saliva-secreting gland	UBERON:0001044	70.82	gold quality
minor salivary gland	UBERON:0001830	70.79	gold quality
putamen	UBERON:0001874	70.06	gold quality
right testis	UBERON:0004534	69.46	gold quality
pituitary gland	UBERON:0000007	69.12	gold quality
left testis	UBERON:0004533	68.96	gold quality
caudate nucleus	UBERON:0001873	68.56	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	1673.68
E-MTAB-11121	yes	1319.28
E-GEOD-137537	yes	21.31
E-ANND-3	no	0.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

90 targeting CPLX3, 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-7110-3P	100.00	73.18	2486
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306

Literature-anchored findings (GeneRIF, showing 1)

• CPX acts sequentially on assembling SNAREpins, first facilitating zippering by nearly doubling the distance at which v- and t-SNAREs can engage and then clamping them into a half-zippered fusion-incompetent state. (PMID:21785413)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	cplx3a	ENSDARG00000062508
danio_rerio	cplx3b	ENSDARG00000089486
		ENSDARG00000099196
mus_musculus	Cplx3	ENSMUSG00000039714
rattus_norvegicus	Cplx3	ENSRNOG00000019317
drosophila_melanogaster	cpx	FBGN0041605
caenorhabditis_elegans		WBGENE00010520
caenorhabditis_elegans	cpx-1	WBGENE00022271

Paralogs (3): CPLX2 (ENSG00000145920), CPLX4 (ENSG00000166569), CPLX1 (ENSG00000168993)

Protein

Protein identifiers

Complexin-3 — Q8WVH0 (reviewed: Q8WVH0)

Alternative names: Complexin III

All UniProt accessions (2): A0A384N6F4, Q8WVH0

UniProt curated annotations — full annotation on UniProt →

Function. Complexin that regulates SNARE protein complex-mediated synaptic vesicle fusion. Required for the maintenance of synaptic ultrastructure in the adult retina. Positively regulates synaptic transmission through synaptic vesicle availability and exocytosis of neurotransmitters at photoreceptor ribbon synapses in the retina. Suppresses tonic photoreceptor activity and baseline ’noise’ by suppression of Ca(2+) vesicle tonic release and the facilitation of evoked synchronous and asynchronous Ca(2+) vesicle release.

Subunit / interactions. Binds to the SNARE core complex containing SNAP25, VAMP2 and STX1A.

Subcellular location. Synapse. Cell membrane.

Post-translational modifications. Farnesylation mediates presynaptic targeting.

Similarity. Belongs to the complexin/synaphin family.

RefSeq proteins (1): NP_001025176* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008849	Synaphin	Family

Pfam: PF05835

UniProt features (10 total): region of interest 2, compositionally biased region 2, chain 1, propeptide 1, coiled-coil region 1, modified residue 1, lipid moiety-binding region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WVH0-F1	75.95	0.23

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): 155, 155

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 115 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_REGULATION_OF_VESICLE_FUSION, GOBP_VESICLE_LOCALIZATION, GOBP_VESICLE_ORGANIZATION, GOBP_INSULIN_SECRETION, GOBP_MEMBRANE_FUSION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_VESICLE_TARGETING, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_HORMONE_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_MEMBRANE_DOCKING, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_EXOCYTOSIS

GO Biological Process (9): visual perception (GO:0007601), synaptic vesicle exocytosis (GO:0016079), insulin secretion (GO:0030073), regulation of synaptic vesicle fusion to presynaptic active zone membrane (GO:0031630), regulation of neurotransmitter secretion (GO:0046928), modulation of chemical synaptic transmission (GO:0050804), obsolete synaptic vesicle tethering involved in synaptic vesicle exocytosis (GO:0099069), neurotransmitter transport (GO:0006836), exocytosis (GO:0006887)

GO Molecular Function (3): SNARE binding (GO:0000149), neurotransmitter transmembrane transporter activity (GO:0005326), syntaxin binding (GO:0019905)

GO Cellular Component (9): cytosol (GO:0005829), synaptic vesicle membrane (GO:0030672), SNARE complex (GO:0031201), terminal bouton (GO:0043195), presynaptic active zone membrane (GO:0048787), photoreceptor ribbon synapse (GO:0098684), plasma membrane (GO:0005886), membrane (GO:0016020), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
neurotransmitter secretion	2
presynapse	2
cytoplasm	2
cellular anatomical structure	2
sensory perception of light stimulus	1
regulated exocytosis	1
establishment of localization in cell	1
vesicle-mediated transport in synapse	1
synaptic vesicle cycle	1
signal release from synapse	1
protein secretion	1
peptide hormone secretion	1
regulation of vesicle fusion	1
synaptic vesicle fusion to presynaptic active zone membrane	1
regulation of synaptic vesicle membrane organization	1
modulation of chemical synaptic transmission	1
regulation of neurotransmitter transport	1
regulation of secretion by cell	1
chemical synaptic transmission	1
regulation of trans-synaptic signaling	1
transport	1
vesicle-mediated transport	1
secretion by cell	1
vesicle fusion to plasma membrane	1
protein binding	1
neurotransmitter transport	1
transmembrane transporter activity	1
SNARE binding	1
synaptic vesicle	1
exocytic vesicle membrane	1
membrane protein complex	1
axon terminus	1
presynaptic membrane	1
presynaptic active zone	1
synaptic membrane	1
ribbon synapse	1
membrane	1
cell periphery	1
cell junction	1

Protein interactions and networks

STRING

1006 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CPLX3	VAMP1	P23763	866
CPLX3	SNAP25	P13795	830
CPLX3	STX1A	Q16623	805
CPLX3	STX3	Q13277	676
CPLX3	CPLX1	O14810	665
CPLX3	NXPH4	O95158	559
CPLX3	MOXD1	Q6UVY6	548
CPLX3	LPAR1	P78351	478
CPLX3	NR4A2	P43354	463
CPLX3	SYT6	Q5T7P8	452
CPLX3	HTR1D	P28221	412
CPLX3	LAMP5	Q9UJQ1	391
CPLX3	CCN2	P29279	384
CPLX3	PLCXD2	Q0VAA5	380
CPLX3	GSG1L	Q6UXU4	369

IntAct

5 interactions, top by confidence:

A	B	Type	Score
CPLX3	CIAO1	psi-mi:“MI:0914”(association)	0.530
CPLX3	CUTA	psi-mi:“MI:0915”(physical association)	0.400
CPLX3	ATE1	psi-mi:“MI:0914”(association)	0.350

BioGRID (40): DUSP14 (Affinity Capture-MS), SIRT5 (Affinity Capture-MS), ACPP (Affinity Capture-MS), VSIG8 (Affinity Capture-MS), LYG2 (Affinity Capture-MS), PKP3 (Affinity Capture-MS), CIAO1 (Affinity Capture-MS), OTUB2 (Affinity Capture-MS), SERPINB5 (Affinity Capture-MS), DSG4 (Affinity Capture-MS), GNB2 (Affinity Capture-MS), HEPHL1 (Affinity Capture-MS), FHL2 (Affinity Capture-MS), ARL8B (Affinity Capture-MS), SELENBP1 (Affinity Capture-MS)

ESM2 similar proteins: A0MZ67, A1L260, A2AMM0, A2VDA9, A4IGC3, A5PJI6, A9C3W3, B1PRL5, B9EKI3, O35711, O35867, O54724, O76878, O94876, O95810, P34609, P55326, P70302, P83093, P84903, P85125, Q0IIE0, Q13586, Q29EP6, Q32PN7, Q58CP9, Q5BKX8, Q5FWS6, Q63918, Q66H98, Q674X7, Q69ZS8, Q69ZZ6, Q6NZI2, Q6P0R8, Q6P402, Q7T019, Q8CJ96, Q8K2Q9, Q8MJK1

Diamond homologs: Q0IIE0, Q7Z7G2, Q80WM3, Q8R1B5, Q8WVH0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

933 predictions. Top by Δscore:

Variant	Effect	Δscore
15:74826860:G:GT	donor_gain	1.0000
15:74826863:GAGAA:G	donor_gain	1.0000
15:74826865:G:GT	donor_gain	1.0000
15:74826865:GAA:G	donor_gain	1.0000
15:74826866:AA:A	donor_gain	1.0000
15:74826868:G:GG	donor_gain	1.0000
15:74828119:AAGG:A	donor_loss	1.0000
15:74828120:AGG:A	donor_loss	1.0000
15:74828121:GGTAA:G	donor_loss	1.0000
15:74828122:GT:G	donor_loss	1.0000
15:74828123:T:A	donor_loss	1.0000
15:74826864:AGAA:A	donor_gain	0.9900
15:74826865:GAAGT:G	donor_loss	0.9900
15:74826866:AAGTG:A	donor_loss	0.9900
15:74826867:AG:A	donor_loss	0.9900
15:74826868:G:A	donor_loss	0.9900
15:74826869:T:G	donor_loss	0.9900
15:74828122:G:GG	donor_gain	0.9900
15:74830125:TTCA:T	acceptor_loss	0.9900
15:74830128:A:AC	acceptor_loss	0.9900
15:74830128:A:AG	acceptor_gain	0.9900
15:74830128:AGAAC:A	acceptor_gain	0.9900
15:74830129:G:GT	acceptor_gain	0.9900
15:74830129:GA:G	acceptor_gain	0.9900
15:74830129:GAAC:G	acceptor_gain	0.9900
15:74830129:GAACG:G	acceptor_gain	0.9900
15:74826838:G:GT	donor_gain	0.9800
15:74826872:G:GG	donor_gain	0.9800
15:74830126:TCAGA:T	acceptor_gain	0.9800
15:74830127:CAGAA:C	acceptor_gain	0.9800

AlphaMissense

1034 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:74828099:G:C	R77P	0.995
15:74828114:T:C	L82P	0.994
15:74828075:G:C	R69P	0.992
15:74828077:G:C	A70P	0.992
15:74828068:G:C	A67P	0.991
15:74828106:A:C	K79N	0.991
15:74828106:A:T	K79N	0.991
15:74828042:G:C	R58P	0.990
15:74828084:T:C	L72P	0.989
15:74828087:G:C	R73P	0.989
15:74828096:T:C	F76S	0.987
15:74828108:A:C	Y80S	0.987
15:74828107:T:G	Y80D	0.986
15:74828078:C:A	A70D	0.985
15:74830139:G:C	D88H	0.985
15:74828086:C:G	R73G	0.982
15:74828104:A:G	K79E	0.982
15:74828107:T:C	Y80H	0.981
15:74828108:A:G	Y80C	0.979
15:74828098:C:G	R77G	0.978
15:74828105:A:T	K79I	0.977
15:74828099:G:T	R77L	0.976
15:74828114:T:A	L82Q	0.973
15:74826717:T:A	V5E	0.971
15:74828069:C:A	A67E	0.971
15:74830200:T:C	M108T	0.971
15:74826855:T:C	L51P	0.970
15:74830191:T:C	L105P	0.970
15:74826729:T:A	V9E	0.968
15:74830139:G:T	D88Y	0.967

dbSNP variants (sampled 300 via entrez): RS1000166146 (15:74828130 G>A), RS1000562940 (15:74826455 G>C), RS1000642636 (15:74827888 G>T), RS1000933654 (15:74826820 G>A), RS1000950751 (15:74828399 C>A,G), RS1000960420 (15:74828233 T>C), RS1001370171 (15:74827816 C>A), RS1001865254 (15:74832110 C>G,T), RS1001943064 (15:74827110 G>A,T), RS1001954445 (15:74826764 G>A), RS1002802863 (15:74831717 A>G), RS1002988006 (15:74826382 G>A), RS1003062707 (15:74831466 A>G), RS1003066805 (15:74826079 G>T), RS1003361937 (15:74825680 C>T)

Disease associations

OMIM: gene MIM:609585 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000394_3	Diastolic blood pressure	1.000000e-23
GCST001032_3	Caffeine consumption	6.000000e-07
GCST001215_2	Coffee consumption	7.000000e-09
GCST007094_195	Diastolic blood pressure	3.000000e-29
GCST007098_37	Diastolic blood pressure	4.000000e-06
GCST007098_38	Diastolic blood pressure	5.000000e-06
GCST007099_204	Systolic blood pressure	1.000000e-16
GCST010083_302	Hemoglobin levels	1.000000e-13

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0004330	coffee consumption
EFO:0006335	systolic blood pressure
EFO:0004509	hemoglobin measurement

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
Resveratrol	affects cotreatment, decreases expression	2
abrine	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Copper	affects cotreatment, decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	increases expression	1
Ethinyl Estradiol	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Thalidomide	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases methylation	1
1-Methyl-4-phenylpyridinium	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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