CPLX4

Chr 18

complexin 4

Also known as: CPX-IV, CPXIV

NCBI Gene: 339302 ENSG00000166569 UniProt: Q7Z7G2 OMIM: 609586

The encoded protein regulates SNARE-mediated synaptic vesicle fusion and is specifically required for maintaining synaptic ultrastructure and neurotransmitter release at photoreceptor ribbon synapses in the retina. Mutations cause autosomal recessive cone-rod dystrophy, a progressive retinal degeneration affecting both cone and rod photoreceptors. The gene shows low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

This gene likely encodes a member of the complexin family. The encoded protein may be involved in synaptic vesicle exocytosis. [provided by RefSeq, Jan 2009]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.71

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.71LOEUF

pLI 0.000

Z-score 0.18

OE 0.92 (0.50–1.71)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.06Z-score

OE missense 0.98 (0.82–1.18)

83 obs / 84.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.92 (0.50–1.71)

0≤0.351.4

Missense OE?0.98 (0.82–1.18)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 6 / 6.5Missense obs/exp: 83 / 84.5Syn Z: 0.22

Background carrier burden — how many people carry a rare variant somewhere in CPLX4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 250

225 rare PASS variants

Rare truncating (LoF)

1 in 4,000

44 rare PASS variants

Rare synonymous (reference)

1 in 390

65 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CPLX4. 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 260	1 in 3,900
South Asian	~43k	1 in 170	1 in 3,400
Remaining (unassigned)	~30k	1 in 200	1 in 5,600
European (Finnish)	~27k	1 in 730	none seen
Admixed American	~22k	1 in 300	none seen
African / African American	~21k	1 in 180	1 in 2,100
East Asian	~20k	1 in 300	≈ 1 in 4,200
Ashkenazi Jewish	~13k	1 in 1,000	≈ 1 in 12,000
Middle Eastern	~2,884	1 in 310	≈ 1 in 650

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): 2 of 3 coding exons well covered in gnomAD exomes; exon 2 marginal. Genomes: all 3.? see exons ↓