CPLX4

Summary

CPLX4 (complexin 4, HGNC:24330) is a protein-coding gene on chromosome 18q21.32, encoding Complexin-4 (Q7Z7G2). Complexin that regulates SNARE protein complex-mediated synaptic vesicle fusion.

This gene likely encodes a member of the complexin family. The encoded protein may be involved in synaptic vesicle exocytosis.

Source: NCBI Gene 339302 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 17 total
• MANE Select transcript: NM_181654

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24330
Approved symbol	CPLX4
Name	complexin 4
Location	18q21.32
Locus type	gene with protein product
Status	Approved
Aliases	CPX-IV
Ensembl gene	ENSG00000166569
Ensembl biotype	protein_coding
OMIM	609586
Entrez	339302

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000299721, ENST00000587244

RefSeq mRNA: 1 — MANE Select: NM_181654 NM_181654

CCDS: CCDS11973

Canonical transcript exons

ENST00000299721 — 3 exons

Exon	Start	End
ENSE00001104260	59312685	59312772
ENSE00001104263	59318296	59318649
ENSE00001104265	59295402	59296925

Expression profiles

Bgee: expression breadth broad, 18 present calls, max score 81.23.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.2702 / max 2378.9175, expressed in 19 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
172193	1.3741	14
172192	0.5667	10
172194	0.3294	12

Top tissues by expression

114 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	81.23	gold quality
cerebellar cortex	UBERON:0002129	58.31	gold quality
cerebellum	UBERON:0002037	58.29	gold quality
cerebellar hemisphere	UBERON:0002245	57.98	gold quality
right hemisphere of cerebellum	UBERON:0014890	57.73	gold quality
islet of Langerhans	UBERON:0000006	50.24	gold quality
colonic epithelium	UBERON:0000397	46.24	gold quality
sural nerve	UBERON:0015488	40.96	gold quality
bone marrow cell	CL:0002092	40.74	gold quality
ventricular zone	UBERON:0003053	40.10	gold quality
pancreas	UBERON:0001264	39.29	gold quality
granulocyte	CL:0000094	37.20	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
skeletal muscle tissue	UBERON:0001134	36.37	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
apex of heart	UBERON:0002098	35.40	gold quality
bone marrow	UBERON:0002371	35.23	gold quality
tonsil	UBERON:0002372	35.13	gold quality
muscle tissue	UBERON:0002385	34.51	gold quality
body of pancreas	UBERON:0001150	33.59	gold quality
lymph node	UBERON:0000029	32.80	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	32.63	silver quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
leukocyte	CL:0000738	32.08	gold quality
endometrium	UBERON:0001295	32.02	gold quality
monocyte	CL:0000576	31.89	gold quality
blood	UBERON:0000178	30.91	gold quality
brain	UBERON:0000955	30.87	gold quality
calcaneal tendon	UBERON:0003701	30.86	gold quality
prefrontal cortex	UBERON:0000451	30.30	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	30.30
E-ANND-3	yes	3.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

65 targeting CPLX4, 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-6873-3P	100.00	71.42	2626
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-593-5P	99.34	69.50	965
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-1264	99.25	66.81	1317

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	cplx4b	ENSDARG00000059486
danio_rerio	cplx4a	ENSDARG00000059978
mus_musculus	Cplx4	ENSMUSG00000024519
rattus_norvegicus	Cplx4	ENSRNOG00000016928
drosophila_melanogaster	cpx	FBGN0041605
caenorhabditis_elegans		WBGENE00010520
caenorhabditis_elegans	cpx-1	WBGENE00022271

Paralogs (3): CPLX2 (ENSG00000145920), CPLX1 (ENSG00000168993), CPLX3 (ENSG00000213578)

Protein

Protein identifiers

Complexin-4 — Q7Z7G2 (reviewed: Q7Z7G2)

Alternative names: Complexin IV

All UniProt accessions (2): Q7Z7G2, K7EM04

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. Weakly binds to the SNARE core complex containing SNAP25, VAMP2 and STX1A.

Subcellular location. Synapse. Cell membrane.

Post-translational modifications. Farnesylation mediates presynaptic targeting and is important for function in neurotransmitter release.

Similarity. Belongs to the complexin/synaphin family.

RefSeq proteins (1): NP_857637* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008849	Synaphin	Family

Pfam: PF05835

UniProt features (6 total): chain 1, propeptide 1, region of interest 1, compositionally biased region 1, modified residue 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z7G2-F1	74.26	0.19

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): 157, 157

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 72 (showing top): GOBP_REGULATION_OF_VESICLE_FUSION, GOBP_VESICLE_ORGANIZATION, GOBP_MEMBRANE_FUSION, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_EXOCYTOSIS, GOBP_VESICLE_FUSION_TO_PLASMA_MEMBRANE, GOBP_ORGANELLE_MEMBRANE_FUSION, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOBP_REGULATION_OF_NEUROTRANSMITTER_TRANSPORT, GOBP_SECRETION, GOBP_SIGNAL_RELEASE, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION

GO Biological Process (7): visual perception (GO:0007601), synaptic vesicle exocytosis (GO:0016079), 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), neurotransmitter transport (GO:0006836), exocytosis (GO:0006887)

GO Molecular Function (3): SNARE binding (GO:0000149), syntaxin binding (GO:0019905), protein binding (GO:0005515)

GO Cellular Component (5): plasma membrane (GO:0005886), SNARE complex (GO:0031201), terminal bouton (GO:0043195), membrane (GO:0016020), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
neurotransmitter secretion	2
presynapse	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
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
SNARE binding	1
binding	1
membrane	1
cell periphery	1
cytoplasm	1
membrane protein complex	1
axon terminus	1
cellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

652 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CPLX4	VAMP1	P23763	806
CPLX4	STX1A	Q16623	714
CPLX4	SNAP25	P13795	713
CPLX4	CPLX1	O14810	641
CPLX4	P84086	P84086	605
CPLX4	SNPH	O15079	499
CPLX4	STARD6	P59095	498
CPLX4	CCDC68	Q9H2F9	463
CPLX4	DMXL2	Q8TDJ6	457
CPLX4	RIMS2	Q9UQ26	454
CPLX4	ABHD14A	Q9BUJ0	436
CPLX4	PHACTR1	Q9C0D0	422
CPLX4	CRX	O43186	410
CPLX4	MAPK4	P31152	403
CPLX4	KCNV2	Q8TDN2	397

IntAct

281 interactions, top by confidence:

A	B	Type	Score
PLN	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
UBIAD1	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
TMEM203	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
YIPF6	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
RTP2	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
DEFB127	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
TMEM218	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
SELENOK	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
GRM2	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
TMEM60	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
PLPP4	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
TMEM120B	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
PPGB	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
CYP4F2	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
TMEM86A	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
MAL	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
TMEM19	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
CYBC1	CPLX4	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (117): SPTB (Affinity Capture-MS), EFHD1 (Affinity Capture-MS), IPPK (Affinity Capture-MS), CPLX4 (Affinity Capture-MS), CBX5 (Affinity Capture-MS), MAPK3 (Affinity Capture-MS), MICU2 (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), CPLX4 (Two-hybrid), CPLX4 (Two-hybrid), CPLX4 (Two-hybrid), CPLX4 (Two-hybrid), CPLX4 (Two-hybrid), CPLX4 (Two-hybrid)

ESM2 similar proteins: B7ZWR6, C4NYP8, D2K8N5, D4A2Y9, O13797, O17453, O82143, P0CT30, P34453, P55034, Q09289, Q0IIE0, Q0P5B1, Q12118, Q16891, Q19951, Q28DG7, Q29Q26, Q2KIS3, Q3SZD1, Q4WTC0, Q5TYV0, Q5XIR9, Q5ZJI9, Q60415, Q60PP8, Q7K2G1, Q7Z7G2, Q80WM3, Q86DS1, Q8CAQ8, Q8CH02, Q8GT66, Q8IWZ8, Q8R1B5, Q8VCI5, Q8VDI7, Q8WVH0, Q92968, Q93YR3

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

268 predictions. Top by Δscore:

Variant	Effect	Δscore
18:59296922:CACT:C	acceptor_gain	1.0000
18:59296928:A:C	acceptor_gain	1.0000
18:59318294:A:AC	donor_gain	1.0000
18:59318295:C:CC	donor_gain	1.0000
18:59318295:CTT:C	donor_gain	1.0000
18:59296921:TCACT:T	acceptor_gain	0.9900
18:59296922:CACTC:C	acceptor_gain	0.9900
18:59296924:CT:C	acceptor_gain	0.9900
18:59296925:TC:T	acceptor_loss	0.9900
18:59296926:C:CC	acceptor_gain	0.9900
18:59296926:C:T	acceptor_loss	0.9900
18:59296930:G:C	acceptor_gain	0.9900
18:59296930:G:GC	acceptor_gain	0.9900
18:59318295:CTTCT:C	donor_gain	0.9900
18:59296924:CTCTA:C	acceptor_gain	0.9800
18:59296925:TCTAT:T	acceptor_gain	0.9800
18:59296928:A:AC	acceptor_gain	0.9800
18:59312678:GTCTT:G	donor_loss	0.9800
18:59312679:TCTTA:T	donor_loss	0.9800
18:59312680:CTTA:C	donor_loss	0.9800
18:59312681:TTA:T	donor_loss	0.9800
18:59312682:TACCT:T	donor_loss	0.9800
18:59312683:A:C	donor_loss	0.9800
18:59312684:C:A	donor_loss	0.9800
18:59296923:ACT:A	acceptor_gain	0.9700
18:59296926:C:G	acceptor_gain	0.9700
18:59298351:A:AC	donor_gain	0.9700
18:59298352:C:CC	donor_gain	0.9700
18:59298351:ACATC:A	donor_gain	0.9600
18:59298352:CATCC:C	donor_gain	0.9600

AlphaMissense

1096 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:59312707:C:G	R78T	0.997
18:59312718:T:A	R74S	0.997
18:59312718:T:G	R74S	0.997
18:59296756:G:T	A142D	0.996
18:59312706:T:A	R78S	0.996
18:59312706:T:G	R78S	0.996
18:59312707:C:A	R78I	0.996
18:59312710:A:G	L77P	0.996
18:59312719:C:G	R74T	0.996
18:59312730:C:A	R70S	0.996
18:59312730:C:G	R70S	0.996
18:59296916:C:G	D89H	0.995
18:59312692:A:G	L83P	0.995
18:59312738:C:G	A68P	0.994
18:59296757:C:G	A142P	0.993
18:59312719:C:A	R74I	0.993
18:59312722:A:G	L73P	0.993
18:59312728:G:T	A71E	0.993
18:59312729:C:G	A71P	0.992
18:59296864:A:G	L106P	0.990
18:59312731:C:G	R70T	0.990
18:59312763:T:A	R59S	0.990
18:59312763:T:G	R59S	0.990
18:59312700:T:A	K80N	0.989
18:59312700:T:G	K80N	0.989
18:59312699:A:C	Y81D	0.988
18:59312737:G:T	A68E	0.988
18:59312720:T:C	R74G	0.987
18:59312731:C:A	R70M	0.987
18:59312702:T:C	K80E	0.986

dbSNP variants (sampled 300 via entrez): RS1000051832 (18:59310766 T>A), RS1000120215 (18:59303822 G>A), RS1000165791 (18:59310062 C>T), RS1000242913 (18:59316948 G>A), RS1000474080 (18:59314646 A>AT), RS1000536209 (18:59297491 G>T), RS1000713741 (18:59315113 G>A), RS1000801067 (18:59299731 C>T), RS1000835974 (18:59316640 T>G), RS1000936494 (18:59299984 C>T), RS1001031988 (18:59304889 C>A,G,T), RS1001110224 (18:59296104 A>G), RS1001232411 (18:59320130 G>C), RS1001415829 (18:59296334 T>C), RS1001475848 (18:59297269 C>A,T)

Disease associations

OMIM: gene MIM:609586 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003837_8	Chronotype	7.000000e-10
GCST003838_8	Morning vs. evening chronotype	1.000000e-06
GCST006976_20	Macular thickness	7.000000e-24
GCST008309_7	Cardiac troponin-I levels	1.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010071	cardiac troponin I measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, affects response to substance, increases expression	1
CGP 52608	increases reaction, affects binding	1
bisphenol S	increases methylation	1
Fulvestrant	affects cotreatment, increases methylation	1
Benzo(a)pyrene	increases methylation	1
Lead	affects expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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