CPLX1

Chr 4AR

complexin 1

Also known as: CPX-I, CPX1, DEE63, EIEE63

NCBI Gene: 10815ENSG00000168993UniProt: O14810

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. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 63MIM #617976
AR
251
ClinVar variants
146
Pathogenic / LP
0.82
pLI score
0
Active trials
Clinical Summary— CPLX1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.82) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
146 Pathogenic / Likely Pathogenic· 65 VUS of 251 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.52LOEUF
pLI 0.825
Z-score 2.22
OE 0.00 (0.00–0.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.35Z-score
OE missense 1.11 (0.94–1.32)
93 obs / 83.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.52)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.11 (0.94–1.32)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.42
0≤1.21.6
LoF obs/exp: 0 / 5.7Missense obs/exp: 93 / 83.9Syn Z: -1.98

ClinVar Variant Classifications

251 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic138
Likely Pathogenic8
VUS65
Likely Benign36
Benign3
Conflicting1
138
Pathogenic
8
Likely Pathogenic
65
VUS
36
Likely Benign
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
138
0
138
Likely Pathogenic
1
0
7
0
8
VUS
0
37
28
0
65
Likely Benign
0
1
15
20
36
Benign
0
0
3
0
3
Conflicting
—1
Total13819120251

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CPLX1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
COMPLEXIN 1; CPLX1
MIM #605032 · *

Developmental and epileptic encephalopathy 63

MIM #617976

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease.
Karaca E et al.·Neuron
2015
Identification of CPLX1 expression as a potential prognostic marker in colorectal cancer.
Jin L et al.·Mol Cell Probes
2025
Transcriptomic profiling on localized gastric cancer identified CPLX1 as a gene promoting malignant phenotype of gastric cancer and a predictor of recurrence after surgery and subsequent chemotherapy.
Tanaka H et al.·J Gastroenterol
2022
Variants in CPLX1 in two families with autosomal-recessive severe infantile myoclonic epilepsy and ID.
Redler S et al.·Eur J Hum Genet
2017
Generation of iPSC lines (KAIMRCi003A, KAIMRCi003B) from a Saudi patient with Dravet syndrome carrying homozygous mutation in the CPLX1 gene and heterozygous mutation in SCN9A.
Alowaysi M et al.·Hum Cell
2024
Increased complexin-1 and decreased miR-185 expression levels in Behçet's disease with and without neurological involvement.
Uğurel E et al.·Neurol Sci
2016
Cortical Proteins Associated With Cognitive Resilience in Community-Dwelling Older Persons.
Yu L et al.·JAMA Psychiatry
2020
Distinct Epileptogenic Mechanisms Associated with Seizures in Wolf-Hirschhorn Syndrome.
Corrêa T et al.·Mol Neurobiol
2022Functional
Microarray and FISH-based genotype-phenotype analysis of 22 Japanese patients with Wolf-Hirschhorn syndrome.
Shimizu K et al.·Am J Med Genet A
2014Cohort
Convex combination sequence kernel association test for rare-variant studies.
Posner DC et al.·Genet Epidemiol
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools