PCNX3

Chr 11

pecanex 3

Also known as: PCNXL3

NCBI Gene: 399909 ENSG00000197136 UniProt: Q9H6A9 OMIM: 617657

The PCNX3 protein is predicted to be located in cellular membranes. Mutations cause neurodevelopmental disorders, though the specific phenotypic spectrum is not well-characterized in the provided data. This gene is highly constrained against loss-of-function variants, suggesting that mutations likely follow an autosomal dominant inheritance pattern.

OMIM ResearchSummary from RefSeq

Predicted to be located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

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

0.23

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.23LOEUF

pLI 1.000

Z-score 7.57

OE 0.14 (0.09–0.23)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.04Z-score

OE missense 0.76 (0.72–0.80)

962 obs / 1266.1 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.14 (0.09–0.23)

0≤0.351.4

Missense OE?0.76 (0.72–0.80)

0≤0.61.4

Synonymous OE?1.19

0≤1.21.6

LoF obs/exp: 13 / 90.9Missense obs/exp: 962 / 1266.1Syn Z: -3.52

Background carrier burden — how many people carry a rare variant somewhere in PCNX3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 22

2,564 rare PASS variants

Rare truncating (LoF)

1 in 1,500

142 rare PASS variants

Rare synonymous (reference)

1 in 26

1,414 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PCNX3. 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 27	1 in 1,900
South Asian	~43k	1 in 22	1 in 1,700
Remaining (unassigned)	~30k	1 in 24	1 in 1,600
European (Finnish)	~27k	1 in 41	1 in 770
Admixed American	~22k	1 in 25	1 in 840
African / African American	~21k	1 in 21	1 in 1,600
East Asian	~20k	1 in 25	1 in 3,200
Ashkenazi Jewish	~13k	1 in 84	1 in 1,100
Middle Eastern	~2,884	1 in 28	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 35 coding exons well covered in gnomAD exomes and genomes.? see exons ↓