NPIPA1

Chr 16

nuclear pore complex interacting protein family member A1

Also known as: NPIP, NPIPA, morpheus

NCBI Gene: 9284 ENSG00000183426 UniProt: Q9UND3 OMIM: 606406

The protein is predicted to function in mRNA and protein transport as part of the nuclear pore complex within the nuclear membrane. Currently, no established human diseases have been associated with NPIPA1 mutations in the medical literature. The gene shows tolerance to loss-of-function variants with a low constraint score (pLI 0.32, LOEUF 1.85).

OMIM ResearchSummary from RefSeq

Predicted to be involved in mRNA transport and protein transport. Predicted to be located in nuclear membrane. Predicted to be part of nuclear pore. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.85

Clinical Summary— NPIPA1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.85LOEUF

pLI 0.322

Z-score 0.57

OE 0.00 (0.00–1.85)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.66Z-score

OE missense 1.24 (1.03–1.50)

75 obs / 60.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.85)

0≤0.351.4

Missense OE?1.24 (1.03–1.50)

0≤0.61.4

Synonymous OE?1.21

0≤1.21.6

LoF obs/exp: 0 / 0.4Missense obs/exp: 75 / 60.6Syn Z: -0.82

This gene — mechanism propensity

0.7034th %ile

GOF

0.73top 25%

LOF

0.4726th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.