NUP188

Chr 9AR

nucleoporin 188

Also known as: KIAA0169, SANDSTEF, hNup188

NCBI Gene: 23511ENSG00000095319UniProt: Q5SRE5OMIM: 615587

This protein is a component of the nuclear pore complex required for trafficking across the nuclear envelope and proper protein transport into the nucleus. Mutations cause Sandestig-Stefanova syndrome, which is inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variants, suggesting an essential cellular role.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.301 OMIM phenotype
Clinical Summary— NUP188
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Gene-Disease Validity (ClinGen)
sandestig-stefanova syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.95). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
50 unique Pathogenic / Likely Pathogenic· 303 VUS of 496 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.30LOEUF
pLI 0.954
Z-score 7.29
OE 0.20 (0.14–0.30)
Highly constrained

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

Missense Constraint
1.12Z-score
OE missense 0.90 (0.85–0.95)
881 obs / 980.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.20 (0.14–0.30)
0≤0.351.4
Missense OE0.90 (0.85–0.95)
0≤0.61.4
Synonymous OE1.05
0≤1.21.6
LoF obs/exp: 20 / 97.9Missense obs/exp: 881 / 980.0Syn Z: -0.73
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongNUP188-related neurodegeneration, cataracts and facial dysmorphismsLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.3892th %ile
GOF
0.4184th %ile
LOF
0.66top 25%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

496 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic38
Likely Pathogenic12
VUS303
Likely Benign62
Benign25
Conflicting3
38
Pathogenic
12
Likely Pathogenic
303
VUS
62
Likely Benign
25
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
0
30
0
38
Likely Pathogenic
10
0
2
0
12
VUS
2
284
16
1
303
Likely Benign
0
20
6
36
62
Benign
0
1
13
11
25
Conflicting
—3
Total203056748443

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

View in ClinVar →

Protein Context — Lollipop Plot

NUP188 · 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
Bi-allelic Loss-of-Function Variants in NUP188 Cause a Recognizable Syndrome Characterized by Neurologic, Ocular, and Cardiac Abnormalities.
Muir AM et al.·Am J Hum Genet
2020
Nucleoporin 188 as a Predictive Biomarker of Poor Prognosis in Muscle-invasive Bladder Cancer.
Zheng M et al.·Anticancer Res
2025
A Novel Homozygous Splice Variant in the NUP188 Gene Causing Sandestig-Stefanova Syndrome in a Saudi Patient.
Almalki F et al.·Am J Med Genet A
2026Case report
Single nucleotide variant in Nucleoporin 107 may be predictive of sensitivity to chemotherapy in patients with ovarian cancer.
Alanee S et al.·Pharmacogenet Genomics
2017Cohort
Whole Exome Sequencing Identifies Truncating Variants in Nuclear Envelope Genes in Patients With Cardiovascular Disease.
Haskell GT et al.·Circ Cardiovasc Genet
2017Cohort
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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