NUP58

Chr 13

nucleoporin 58

Also known as: NUP45, NUPL1, PRO2463

This protein is a component of the nuclear pore complex that regulates trafficking of molecules across the nuclear membrane. Mutations cause autosomal dominant or autosomal recessive neurodevelopmental disorders with intellectual disability, developmental delay, and seizures. The gene is highly constrained against loss-of-function variants, indicating intolerance to protein-disrupting mutations.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.35
Clinical SummaryNUP58
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.93). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
33 unique Pathogenic / Likely Pathogenic· 77 VUS of 136 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.35LOEUF
pLI 0.927
Z-score 4.27
OE 0.16 (0.090.35)
Highly constrained

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

Missense Constraint
1.06Z-score
OE missense 0.83 (0.750.92)
254 obs / 306.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.16 (0.090.35)
00.351.4
Missense OE0.83 (0.750.92)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 5 / 30.4Missense obs/exp: 254 / 306.0Syn Z: -0.72
DN
0.5280th %ile
GOF
0.3194th %ile
LOF
0.70top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.35

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

136 submitted variants in ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic2
VUS77
Likely Benign1
Benign1
31
Pathogenic
2
Likely Pathogenic
77
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
31
0
31
Likely Pathogenic
0
0
2
0
2
VUS
0
74
3
0
77
Likely Benign
0
1
0
0
1
Benign
0
0
0
1
1
Total075361112

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

View in ClinVar →

Protein Context — Lollipop Plot

NUP58 · 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

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗