CPLX2

Summary

CPLX2 (complexin 2, HGNC:2310) is a protein-coding gene on chromosome 5q35.2, encoding Complexin-2 (Q6PUV4). Negatively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons.

Proteins encoded by the complexin/synaphin gene family are cytosolic proteins that function in synaptic vesicle exocytosis. These proteins bind syntaxin, part of the SNAP receptor. The protein product of this gene binds to the SNAP receptor complex and disrupts it, allowing transmitter release. Two transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 10814 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 11 total
• GTEx eGene: eQTL in 6 tissues, sQTL in 1 (q < 0.05)
• Constraint (gnomAD): pLI 0.70 (intermediate), LOEUF 0.68 (unconstrained)
• MANE Select transcript: NM_001008220

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2310
Approved symbol	CPLX2
Name	complexin 2
Location	5q35.2
Locus type	gene with protein product
Status	Approved
Aliases	CPX-2, DKFZp547D155
Ensembl gene	ENSG00000145920
Ensembl biotype	protein_coding
OMIM	605033
Entrez	10814

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 19 protein_coding, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000393745

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1, TSL 4: 7

ENST00000393745, ENST00000359546, ENST00000502265, ENST00000506642, ENST00000509837, ENST00000512824, ENST00000514150, ENST00000515025, ENST00000515094, ENST00000515502, ENST00000899625, ENST00000899626, ENST00000899627, ENST00000899628, ENST00000899629, ENST00000899630, ENST00000971154, ENST00001114342, ENST00001114343, ENST00001138043

RefSeq mRNA: 2 — MANE Select: NM_001008220 NM_001008220, NM_006650

CCDS: CCDS4396

Canonical transcript exons

ENST00000393745 — 4 exons

Exon	Start	End
ENSE00000973070	175878908	175879083
ENSE00001129358	175878652	175878770
ENSE00002024679	175871578	175871705
ENSE00002062090	175879848	175884021

Expression profiles

Bgee: expression breadth ubiquitous, 173 present calls, max score 99.51.

FANTOM5 (CAGE): breadth broad, TPM avg 16.2384 / max 1449.7150, expressed in 226 samples.

Highest expression (Bgee): hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex, frontal lobe, amygdala.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CPLX2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 6 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

7 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Pancreas	eqtl	1.6e-05	-0.29	5:175919694:T:C
Brain Cerebellar Hemisphere	eqtl	1.3e-02	+0.14	5:175880883:T:C
Pituitary	eqtl	3.9e-02	+0.13	5:175944019:G:T
Cells Cultured fibroblasts	eqtl	4.1e-02	-0.44	5:175736291:T:C
Skin Not Sun Exposed Suprapubic	eqtl	4.4e-02	+0.89	5:175001587:T:A
Testis	eqtl	4.6e-02	+0.41	5:176035330:T:C
Pancreas	sqtl	4.8e-02	-0.42	5:176640057:T:C

FANTOM5 promoters

showing 10 of 29 alternative TSS:

Promoter ID	TPM avg	Samples expressed
60383	8.0841	167
60375	1.5744	130
60384	1.3448	116
60381	1.0763	112
60370	0.8956	106
60382	0.7277	109
60373	0.4011	98
60371	0.2671	88
60385	0.2292	77
60394	0.1848	49

Top tissues by expression

showing 100 of 283 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	99.51	gold quality
cerebellar hemisphere	UBERON:0002245	99.39	gold quality
cerebellar cortex	UBERON:0002129	99.26	gold quality
right frontal lobe	UBERON:0002810	99.06	gold quality
amygdala	UBERON:0001876	97.54	gold quality
cerebellum	UBERON:0002037	97.44	gold quality
caudate nucleus	UBERON:0001873	97.15	gold quality
cingulate cortex	UBERON:0003027	96.70	gold quality
anterior cingulate cortex	UBERON:0009835	96.70	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.68	gold quality
prefrontal cortex	UBERON:0000451	96.44	gold quality
nucleus accumbens	UBERON:0001882	96.18	gold quality
Ammon’s horn	UBERON:0001954	95.95	gold quality
temporal lobe	UBERON:0001871	95.93	gold quality
postcentral gyrus	UBERON:0002581	95.92	gold quality
putamen	UBERON:0001874	95.32	gold quality
entorhinal cortex	UBERON:0002728	95.27	gold quality
neocortex	UBERON:0001950	94.97	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.89	gold quality
frontal cortex	UBERON:0001870	94.87	gold quality
primary visual cortex	UBERON:0002436	94.84	gold quality
cortical plate	UBERON:0005343	94.67	gold quality
telencephalon	UBERON:0001893	94.58	gold quality
cerebral cortex	UBERON:0000956	94.57	gold quality
parietal lobe	UBERON:0001872	94.38	gold quality
superior frontal gyrus	UBERON:0002661	94.04	gold quality
forebrain	UBERON:0001890	93.74	gold quality
brain	UBERON:0000955	93.50	gold quality
central nervous system	UBERON:0001017	93.15	gold quality
middle temporal gyrus	UBERON:0002771	93.13	gold quality
adenohypophysis	UBERON:0002196	92.55	gold quality
ganglionic eminence	UBERON:0004023	92.22	gold quality
pituitary gland	UBERON:0000007	92.09	gold quality
occipital lobe	UBERON:0002021	91.55	gold quality
islet of Langerhans	UBERON:0000006	91.50	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.40	gold quality
substantia nigra	UBERON:0002038	88.84	gold quality
substantia nigra pars compacta	UBERON:0001965	88.70	gold quality
hypothalamus	UBERON:0001898	88.54	gold quality
midbrain	UBERON:0001891	87.50	gold quality
corpus epididymis	UBERON:0004359	86.89	gold quality
substantia nigra pars reticulata	UBERON:0001966	86.54	gold quality
endothelial cell	CL:0000115	85.83	silver quality
cerebellar vermis	UBERON:0004720	85.29	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	85.24	gold quality
spinal cord	UBERON:0002240	82.73	gold quality
pancreas	UBERON:0001264	78.21	gold quality
lateral globus pallidus	UBERON:0002476	78.06	gold quality
ventricular zone	UBERON:0003053	77.39	gold quality
pons	UBERON:0000988	77.21	gold quality
embryo	UBERON:0000922	75.52	gold quality
ventral tegmental area	UBERON:0002691	75.31	gold quality
paraflocculus	UBERON:0005351	73.39	silver quality
body of pancreas	UBERON:0001150	73.15	gold quality
superior vestibular nucleus	UBERON:0007227	72.90	gold quality
globus pallidus	UBERON:0001875	72.11	silver quality
cauda epididymis	UBERON:0004360	71.59	gold quality
medial globus pallidus	UBERON:0002477	71.52	silver quality
Brodmann (1909) area 10	UBERON:0013541	70.94	gold quality
sperm	CL:0000019	70.83	gold quality
endometrium epithelium	UBERON:0004811	70.81	gold quality
corpus callosum	UBERON:0002336	70.74	gold quality
middle frontal gyrus	UBERON:0002702	70.65	gold quality
adult organism	UBERON:0007023	70.57	gold quality
dorsal root ganglion	UBERON:0000044	69.69	gold quality
medulla oblongata	UBERON:0001896	69.59	gold quality
muscle layer of sigmoid colon	UBERON:0035805	69.40	gold quality
male germ cell	CL:0000015	69.21	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	68.13	gold quality
trigeminal ganglion	UBERON:0001675	68.10	gold quality
colonic epithelium	UBERON:0000397	66.78	silver quality
sigmoid colon	UBERON:0001159	66.28	gold quality
body of stomach	UBERON:0001161	65.05	gold quality
dorsal plus ventral thalamus	UBERON:0001897	64.57	silver quality
subthalamic nucleus	UBERON:0001906	64.13	silver quality
oocyte	CL:0000023	63.97	gold quality
lateral nuclear group of thalamus	UBERON:0002736	63.93	silver quality
caput epididymis	UBERON:0004358	63.64	silver quality
stomach	UBERON:0000945	63.31	gold quality
inferior vagus X ganglion	UBERON:0005363	63.23	silver quality
rectum	UBERON:0001052	62.84	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	62.80	gold quality
lower esophagus muscularis layer	UBERON:0035833	62.49	gold quality
apex of heart	UBERON:0002098	62.35	gold quality
epithelium of nasopharynx	UBERON:0001951	62.26	gold quality
lower esophagus	UBERON:0013473	62.26	gold quality
colon	UBERON:0001155	62.17	gold quality
nasal cavity epithelium	UBERON:0005384	62.07	gold quality
parotid gland	UBERON:0001831	61.90	gold quality
large intestine	UBERON:0000059	61.48	gold quality
left testis	UBERON:0004533	61.32	gold quality
vastus lateralis	UBERON:0001379	61.30	gold quality
fundus of stomach	UBERON:0001160	61.04	gold quality
quadriceps femoris	UBERON:0001377	60.93	gold quality
myocardium	UBERON:0002349	60.55	gold quality
intestine	UBERON:0000160	60.40	gold quality
pancreatic ductal cell	CL:0002079	60.30	silver quality
cartilage tissue	UBERON:0002418	60.17	gold quality
transverse colon	UBERON:0001157	60.13	gold quality
testis	UBERON:0000473	60.06	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	26.11
E-GEOD-81547	yes	21.94
E-GEOD-84465	yes	6.75
E-ANND-3	yes	3.09

HPA expression

RNA tissue specificity: Group enriched

57 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Postcentral gyrus	tissue	751.9
Caudate putamen	tissue	687.2
Putamen	tissue	686.6
Hippocampus	tissue	680.2	medium
Basal ganglia	tissue	616.6	medium
Frontal cortex	tissue	491.3
Cerebellum	tissue	464.6	medium
Cerebral cortex	tissue	462.8	high
Occipital cortex	tissue	462.8
Temporal cortex	tissue	447.8
Somatosensory cortex	tissue	442.6
Motor cortex	tissue	415.9
Insular cortex	tissue	407.9
Hippocampal formation	tissue	387.0
Prefrontal cortex	tissue	368.8
Ventral forebrain	tissue	364.8
Entorhinal cortex	tissue	357.4
Retrosplenial and cingulate cortex	tissue	334.1
Amygdala	tissue	321.5
Retrosplenial cortex	tissue	317.8
Substantia nigra	tissue	259.0
Septum	tissue	207.6
Pons	tissue	169.6
Nucleus accumbens	tissue	142.4
Locus coeruleus	tissue	139.6
Epididymis	tissue	121.4	not detected
Thalamus	tissue	117.6
Midbrain	tissue	117.4
Medulla oblongata	tissue	113.0
Superior colliculi	tissue	107.6
Olfactory bulb	tissue	105.5
Spinal cord	tissue	85.9
Hypothalamus	tissue	67.0
Periaqueductal gray	tissue	65.0
Pituitary gland	tissue	60.1
Corpus callosum	tissue	54.2
Adrenal gland	tissue	26.7	high
Retina	tissue	18.0
Choroid plexus	tissue	16.0
Pancreas	tissue	8.5	medium
Stomach 1	tissue	4.7	low
Testis	tissue	2.8	medium
Duodenum	tissue	1.9	not detected
Colon	tissue	1.6	low
Small intestine	tissue	1.5	not detected
Rectum	tissue	1.3	low
Lung	tissue	1.2	not detected
Appendix	tissue	0.9	not detected
Adipose tissue	tissue	0.6	not detected
Vagina	tissue	0.3	not detected
Smooth muscle	tissue	0.3	not detected
Skin 1	tissue	0.1	not detected
Esophagus	tissue	0.1	not detected
Parathyroid gland	tissue	0.1	not detected
Urinary bladder	tissue	0.1	not detected
Kidney	tissue	0.1	low
Thymus	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Hippocampus, CA3 (792.8), Posterior cingulate cortex (737.0), Hippocampus, CA1 (725.0), Precentral gyrus (706.2), Dentate gyrus (657.0).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CPLX2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 230 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-1229-3P	99.97	66.49	906
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-493-5P	99.96	72.47	2382
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-1-3P	99.93	72.35	1914

Functional genomics

gnomAD constraint: pLI 0.7, LOEUF 0.683, missense Z 1.04 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000393745 — one region, missense o/e 0.79.

Literature-anchored findings (GeneRIF, showing 11)

• role in synaptic vesicle exocytosis (PMID:12058476)
• altered immunoreactivity of this protein in prefrontal cortex in severe mental illness (PMID:12082566)
• in huntingtin mutation, the decline in neurotransmitter release is a direct consequence of complexin II depletion (PMID:12807877)
• In schizophrenia, complexin II was reduced in dorsolateral prefrontal cortex and superior temporal cortex. The impairment of synaptic transmission may contribute to the dysfunction of cortical neural circuits that characterises the disorder. (PMID:15653259)
• CX2 level increased between the fetal and the 6-10 years groups and then plateaued (PMID:18240322)
• Then results indicated that CPLX2 may be involved in the etiology of schizophrenia and one of its potential biological mechanisms by studying the effects of CPLX2 risk variants on working memory load-dependent neural activity in a frontoparietal network. (PMID:25297695)
• CPLX2 rs1366116*T variant represents a risk factor of schizophrenia, and , at the same time, CPLX2 rs3892909*T variant is protective against schizophrenia (study performed in Armenians). (PMID:25564026)
• These results suggested that CPLX2 participated in synaptic taste transduction. (PMID:25692331)
• This study demonstrated that complexin-II differentially influence cognitive function in early and late stages of Alzheimer’s disease. (PMID:27866231)
• CPLX2 Regulates Ferroptosis and Apoptosis Through NRF2 Pathway in Human Hepatocellular Carcinoma Cells. (PMID:36107387)
• CPLX2 is a novel tumor suppressor and improves the prognosis in glioma. (PMID:38427133)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cplx2	ENSMUSG00000025867
rattus_norvegicus	Cplx2	ENSRNOG00000000105
drosophila_melanogaster	cpx	FBGN0041605
caenorhabditis_elegans		WBGENE00010520
caenorhabditis_elegans	cpx-1	WBGENE00022271

Paralogs (3): CPLX4 (ENSG00000166569), CPLX1 (ENSG00000168993), CPLX3 (ENSG00000213578)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:104726) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 25 distinct phenotype terms.

Mouse phenotype (MP)	Records
impaired coordination	2
abnormal spatial learning	2
reduced long-term potentiation	2
abnormal anxiety-related response	1
abnormal locomotor behavior	1
decreased locomotor activity	1
abnormal gait	1
short stride length	1
decreased exploration in new environment	1
abnormal grooming behavior	1
decreased grooming behavior	1
abnormal whisker trimming behavior	1
increased startle reflex	1
abnormal posture	1
limb grasping	1
abnormal learning/memory/conditioning	1
abnormal fear/anxiety-related behavior	1
abnormal motor capabilities/coordination/movement	1
decreased vertical activity	1
increased thigmotaxis	1
novel environmental response-related retropulsion	1
tail dragging	1
abnormal spatial reference memory	1
induced hyperactivity	1
decreased hippocampus volume	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	P84088	100.0%	Diamond
Macaca fascicularis	Q4R4N1	99.3%	Diamond
Caenorhabditis briggsae	Q60PP8	96.5%	Diamond
Narke japonica	O42105	90.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
THOC3-AS1	ncRNA	105377745
HRH2	protein-coding	3274
THOC3	protein-coding	84321
SFXN1	protein-coding	94081

Protein

Protein identifiers

Complexin-2 — Q6PUV4 (reviewed: Q6PUV4)

Alternative names: Complexin II, Synaphin-1

All UniProt accessions (6): D6R960, D6RBA5, D6RDN3, D6RGY3, D6RI05, Q6PUV4

UniProt curated annotations — full annotation on UniProt →

Function. Negatively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons. Positively regulates a late step in exocytosis of various cytoplasmic vesicles, such as synaptic vesicles and other secretory vesicles. Also involved in mast cell exocytosis.

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

Subcellular location. Cytoplasm. Cytosol. Presynapse. Nucleus. Perikaryon.

Tissue specificity. Nervous system. In hippocampus and cerebellum, expressed mainly by excitatory neurons. Down-regulated in brain cortex from patients suffering from Huntington disease, bipolar disorder or major depression. Down-regulated in cerebellum from patients with schizophrenia.

Similarity. Belongs to the complexin/synaphin family.

RefSeq proteins (2): NP_001008221, NP_006641 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008849	Synaphin	Family

Pfam: PF05835

UniProt features (6 total): region of interest 2, chain 1, coiled-coil region 1, compositionally biased region 1, modified residue 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6PUV4-F1	71.01	0.18

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles

Antibody reliability (HPA): IH supported · IF uncertain

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)

Type	Positions
Phosphoserine	93

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 254 (showing top): GOBP_REGULATION_OF_VESICLE_FUSION, GOBP_VESICLE_ORGANIZATION, AAGCCAT_MIR135A_MIR135B, GOBP_MEMBRANE_FUSION, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GGGTGGRR_PAX4_03, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_CELL_CELL_SIGNALING, GOBP_MEMBRANE_DOCKING, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, NFKB_Q6, PATIL_LIVER_CANCER, GOBP_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE

GO Biological Process (10): nervous system development (GO:0007399), synaptic vesicle exocytosis (GO:0016079), regulation of exocytosis (GO:0017157), cell differentiation (GO:0030154), regulation of synaptic vesicle fusion to presynaptic active zone membrane (GO:0031630), positive regulation of synaptic plasticity (GO:0031915), mast cell degranulation (GO:0043303), modulation of chemical synaptic transmission (GO:0050804), neurotransmitter transport (GO:0006836), exocytosis (GO:0006887)

GO Molecular Function (5): SNARE binding (GO:0000149), syntaxin-1 binding (GO:0017075), calcium-dependent protein binding (GO:0048306), protein binding (GO:0005515), syntaxin binding (GO:0019905)

GO Cellular Component (14): nucleus (GO:0005634), cytosol (GO:0005829), dendrite (GO:0030425), SNARE complex (GO:0031201), terminal bouton (GO:0043195), perikaryon (GO:0043204), calyx of Held (GO:0044305), synaptobrevin 2-SNAP-25-syntaxin-1a-complexin II complex (GO:0070033), synaptobrevin 2-SNAP-25-syntaxin-3-complexin complex (GO:0070554), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), neuronal cell body (GO:0043025), synapse (GO:0045202), presynapse (GO:0098793)

GO top-level categories

46 GO namespaces:

Category	Terms
cellular anatomical structure	4
synapse	3
presynapse	2
protein binding	2
cytoplasm	2
axon terminus	2
SNARE complex	2
system development	1
animal gross anatomical part developmental process	1
neurotransmitter secretion	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
exocytosis	1
regulation of vesicle-mediated transport	1
regulation of secretion by cell	1
cellular developmental process	1
regulation of vesicle fusion	1
synaptic vesicle fusion to presynaptic active zone membrane	1
regulation of synaptic vesicle membrane organization	1
regulation of synaptic plasticity	1
mast cell activation involved in immune response	1
mast cell mediated immunity	1
lysosome localization	1
leukocyte degranulation	1
establishment of organelle localization	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
syntaxin binding	1
calcium ion binding	1
binding	1
SNARE binding	1
intracellular membrane-bounded organelle	1
neuron projection	1
dendritic tree	1
membrane protein complex	1
neuronal cell body	1
somatodendritic compartment	1
cell body	1
cell junction	1

Protein interactions and networks

IntAct

Human interaction partners of CPLX2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

9 partners by confidence:

Partner	Interaction type	MIscore	Records
MYG1	physical association	0.560	3
NDRG4	physical association	0.560	3
PBX3	physical association	0.560	3
TSFM	physical association	0.560	3
DEGS1	association	0.530	2
CPLX1	association	0.530	1
PTCHD1	physical association	0.370	1
ETS1	physical association	0.000	1
PCBD1	physical association	0.000	1

BioGRID (31 interactions; top human partners by supporting records): CPLX1 (Affinity Capture-MS; 3 records), ANKRD13C (Affinity Capture-MS; 2 records), DEGS1 (Affinity Capture-MS; 2 records), RAP1A (Affinity Capture-MS; 2 records), SCCPDH (Affinity Capture-MS; 2 records), APP (Reconstituted Complex), C12orf10 (Two-hybrid), DBN1 (Cross-Linking-MS (XL-MS)), DHX16 (Affinity Capture-MS), FAM21A (Affinity Capture-MS), HDAC2 (Cross-Linking-MS (XL-MS)), INF2 (Affinity Capture-MS), NDRG4 (Two-hybrid), PBX3 (Two-hybrid), PHF6 (Affinity Capture-MS)

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
★ SNARE complex (CPLX2, SNAP25, STX1a, VAMP2)	4	CPLX2, SNAP25, STX1A, VAMP2

Disease & clinical

Genetic variants

Variant evidence for CPLX2: 11 ClinVar records (0 pathogenic / likely pathogenic); 3 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	0
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 29 predictions of 281):

Position(s)	Effect	Δscore	Sites
5:175878650–175878651	acceptor_loss	1.0000	6
5:175878771–175878772	donor_loss	1.0000	5
5:175878894	acceptor_gain	1.0000
5:175878903	acceptor_gain	1.0000
5:175878906–175878907	acceptor_loss	1.0000	4
5:175878907	acceptor_gain	1.0000
5:175879079	donor_gain	1.0000
5:175879084–175879085	donor_loss	1.0000	4
5:175879846–175879847	acceptor_loss	1.0000	5
5:175871697	donor_gain	0.9900

AlphaMissense

628 missense substitutions predicted likely pathogenic (of 883 scored), across 126 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M19	9	0.933	0.998
D15	8	0.987	0.996
F3	8	0.978	0.999
D68	8	0.950	0.993
D27	8	0.939	0.975
S93	8	0.912	0.996
D130	8	0.860	0.976
D118	8	0.856	0.979
F132	8	0.854	0.994
H52	7	0.991	0.998
E56	7	0.989	0.997
E60	7	0.989	0.998
C105	7	0.966	0.993
I66	7	0.958	0.999
Q7	7	0.954	0.982
E45	7	0.948	0.987
Q64	7	0.933	0.998
K6	7	0.927	0.996
M55	7	0.925	0.984
E47	7	0.827	0.968

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Papillary Cell Carcinoma (TCGA)	unfavorable	5.52e-06
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.000209

Disease associations

OMIM: gene MIM:605033 | disease phenotypes:

GWAS associations

3 associations:

Study	Trait	p-value
GCST007576_335	Chronotype	2e-8
GCST001762_917	Obesity-related traits	3e-7
GCST002498_2	Age-related nuclear cataracts	1e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0008328	chronotype measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression, decreases methylation	2
dicrotophos	increases expression	1
propionaldehyde	decreases expression	1
bisphenol A	affects expression	1
beta-lapachone	increases expression	1
arsenite	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
licochalcone B	increases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Ethanol	decreases expression	1
Allergens	increases expression	1
Amiodarone	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	increases abundance, increases expression	1
Diazinon	increases methylation	1
Dimethyl Sulfoxide	decreases expression	1
Ivermectin	decreases expression	1
Lipopolysaccharides	affects expression, affects response to substance	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Testosterone	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases methylation	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.