NPIPA5

Chr 16

nuclear pore complex interacting protein family member A5

Also known as: NPIP

NCBI Gene: 100288332 ENSG00000183793 UniProt: E9PKD4

The NPIPA5 protein is a nuclear pore complex-interacting protein involved in nucleocytoplasmic transport regulation. Mutations cause autosomal recessive intellectual disability with developmental delay and seizures. This gene shows low constraint against loss-of-function variants, consistent with a recessive inheritance pattern.

Research

ResearchGenerating clinical summary…

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

1.86

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.86LOEUF

pLI 0.108

Z-score 0.27

OE 0.75 (0.23–1.86)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.95Z-score

OE missense 1.62 (1.40–1.86)

128 obs / 79.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.75 (0.23–1.86)

0≤0.351.4

Missense OE?1.62 (1.40–1.86)

0≤0.61.4

Synonymous OE?1.42

0≤1.21.6

LoF obs/exp: 1 / 1.3Missense obs/exp: 128 / 79.2Syn Z: -1.92

Background carrier burden — how many people carry a rare variant somewhere in NPIPA5?

gnomAD v4 · ~727k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 69

187 rare PASS variants

Rare truncating (LoF)

1 in 400

44 rare PASS variants

Rare synonymous (reference)

1 in 150

77 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NPIPA5. 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 110	1 in 600
South Asian	~43k	1 in 92	1 in 230
Remaining (unassigned)	~30k	1 in 61	none seen
European (Finnish)	~23k	1 in 180	≈ 1 in 7,600
Admixed American	~22k	1 in 68	1 in 920
African / African American	~21k	1 in 70	1 in 1,200
East Asian	~20k	1 in 130	≈ 1 in 18,000
Ashkenazi Jewish	~13k	1 in 110	1 in 840
Middle Eastern	~2,572	1 in 310	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.