NPIPA1

Chr 16

nuclear pore complex interacting protein family member A1

Also known as: NPIP, NPIPA, morpheus

NCBI Gene: 9284ENSG00000183426UniProt: Q9UND3OMIM: 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).

OMIMResearchSummary from RefSeq
MultiplemechanismLOEUF 1.85
Clinical Summary— NPIPA1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.
📋
ClinVar Variants
87 unique Pathogenic / Likely Pathogenic· 114 VUS of 209 total submissions
Explore recent and relevant literature in Research Assistant →

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 OE0.00 (0.00–1.85)
0≤0.351.4
Missense OE1.24 (1.03–1.50)
0≤0.61.4
Synonymous OE1.21
0≤1.21.6
LoF obs/exp: 0 / 0.4Missense obs/exp: 75 / 60.6Syn Z: -0.82
DN
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.

ClinVar Variant Classifications

209 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic64
Likely Pathogenic23
VUS114
Likely Benign6
Conflicting2
64
Pathogenic
23
Likely Pathogenic
114
VUS
6
Likely Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
64
0
64
Likely Pathogenic
0
0
23
0
23
VUS
0
42
72
0
114
Likely Benign
0
4
1
1
6
Benign
0
0
0
0
0
Conflicting
—2
Total0461601209

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NPIPA1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients