CPLX3

Chr 15

complexin 3

Also known as: CPX-III, CPXIII, Nbla11589

NCBI Gene: 594855 ENSG00000213578 UniProt: Q8WVH0 OMIM: 609585

Predicted to enable SNARE binding activity. Predicted to be involved in modulation of chemical synaptic transmission; regulation of synaptic vesicle fusion to presynaptic active zone membrane; and synaptic vesicle tethering involved in synaptic vesicle exocytosis. Predicted to act upstream of or within regulation of neurotransmitter secretion. Predicted to be located in cytosol; plasma membrane; and synapse. Predicted to be part of SNARE complex. Predicted to be active in terminal bouton. [provided by Alliance of Genome Resources, Jun 2026]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

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

0.85

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.85LOEUF

pLI 0.240

Z-score 1.84

OE 0.27 (0.11–0.85)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.51Z-score

OE missense 0.85 (0.71–1.02)

81 obs / 95.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.27 (0.11–0.85)

0≤0.351.4

Missense OE?0.85 (0.71–1.02)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 2 / 7.4Missense obs/exp: 81 / 95.1Syn Z: 0.31

Background carrier burden — how many people carry a rare variant somewhere in CPLX3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 320

190 rare PASS variants

Rare truncating (LoF)

1 in 4,500

26 rare PASS variants

Rare synonymous (reference)

1 in 1,200

78 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CPLX3. 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 390	1 in 6,600
South Asian	~43k	1 in 440	1 in 1,600
Remaining (unassigned)	~30k	1 in 250	1 in 3,800
European (Finnish)	~27k	1 in 1,300	none seen
Admixed American	~22k	1 in 470	≈ 1 in 11,000
African / African American	~21k	1 in 500	1 in 3,900
East Asian	~20k	1 in 210	≈ 1 in 20,000
Ashkenazi Jewish	~13k	≈ 1 in 13,000	none seen
Middle Eastern	~2,880	1 in 280	none seen

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 ↓