CPLX1

Chr 4AR

complexin 1

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

NCBI Gene: 10815 ENSG00000168993 UniProt: O14810 OMIM: 605032

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 63MIM #617976

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Developmental and epileptic encephalopathy 63; no ClinGen or GenCC tier

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.52

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

-0.35Z-score

OE missense 1.11 (0.94–1.32)

93 obs / 83.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.52)

0≤0.351.4

Missense OE?1.11 (0.94–1.32)

0≤0.61.4

Synonymous OE?1.42

0≤1.21.6

LoF obs/exp: 0 / 5.7Missense obs/exp: 93 / 83.9Syn Z: -1.98

Background carrier burden — how many people carry a rare variant somewhere in CPLX1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 460

251 rare PASS variants

Rare truncating (LoF)

1 in 11,000

27 rare PASS variants

Rare synonymous (reference)

1 in 440

91 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CPLX1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 530	1 in 9,500
South Asian	~43k	1 in 530	≈ 1 in 22,000
Remaining (unassigned)	~30k	1 in 350	≈ 1 in 15,000
European (Finnish)	~27k	1 in 4,300	≈ 1 in 13,000
Admixed American	~22k	1 in 350	≈ 1 in 22,000
African / African American	~21k	1 in 350	≈ 1 in 5,600
East Asian	~20k	1 in 360	≈ 1 in 6,600
Ashkenazi Jewish	~13k	1 in 720	none seen
Middle Eastern	~2,883	1 in 470	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓