CPLX1

Chr 4AR

complexin 1

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

The protein binds to the SNAP receptor complex and disrupts it to allow neurotransmitter release from synaptic vesicles. Biallelic mutations cause developmental and epileptic encephalopathy 63, inherited in an autosomal recessive pattern. Loss-of-function mutations likely disrupt synaptic transmission by impairing neurotransmitter release.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 0.521 OMIM phenotype
Clinical SummaryCPLX1
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.82) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.52LOEUF
pLI 0.825
Z-score 2.22
OE 0.00 (0.000.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
-0.35Z-score
OE missense 1.11 (0.941.32)
93 obs / 83.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.00 (0.000.52)
00.351.4
Missense OE1.11 (0.941.32)
00.61.4
Synonymous OE1.42
01.21.6
LoF obs/exp: 0 / 5.7Missense obs/exp: 93 / 83.9Syn Z: -1.98
DN
0.6261th %ile
GOF
0.6931th %ile
LOF
0.51top 25%

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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