NUP88

Chr 17AR

nucleoporin 88

Also known as: FADS4

NCBI Gene: 4927ENSG00000108559UniProt: Q99567

The nuclear pore complex is a massive structure that extends across the nuclear envelope, forming a gateway that regulates the flow of macromolecules between the nucleus and the cytoplasm. Nucleoporins, a family of 50 to 100 proteins, are the main components of the nuclear pore complex in eukaryotic cells. The protein encoded by this gene belongs to the nucleoporin family and is associated with the oncogenic nucleoporin CAN/Nup214 in a dynamic subcomplex. This protein is also overexpressed in a large number of malignant neoplasms and precancerous dysplasias. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

Primary Disease Associations & Inheritance

Fetal akinesia deformation sequence 4MIM #618393
AR
176
ClinVar variants
26
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— NUP88
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
26 Pathogenic / Likely Pathogenic· 123 VUS of 176 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.69LOEUF
pLI 0.000
Z-score 3.18
OE 0.47 (0.33–0.69)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.53Z-score
OE missense 1.07 (0.99–1.16)
436 obs / 406.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.47 (0.33–0.69)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.07 (0.99–1.16)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 20 / 42.3Missense obs/exp: 436 / 406.2Syn Z: -0.23

ClinVar Variant Classifications

176 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic1
VUS123
Likely Benign16
Benign11
25
Pathogenic
1
Likely Pathogenic
123
VUS
16
Likely Benign
11
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
24
0
25
Likely Pathogenic
0
0
1
0
1
VUS
0
115
7
1
123
Likely Benign
0
9
4
3
16
Benign
0
1
6
4
11
Total0126428176

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

View in ClinVar →

Protein Context — Lollipop Plot

NUP88 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Fetal akinesia deformation sequence 4

MIM #618393

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Overexpression of the nucleoporin Nup88 stimulates migration and invasion of HeLa cells.
Makise M et al.·Histochem Cell Biol
2021
The role of vimentin in the tumor marker Nup88-dependent multinucleated phenotype.
Makise M et al.·BMC Cancer
2018
Centrosome and ciliary abnormalities in fetal akinesia deformation sequence human fibroblasts.
Jühlen R et al.·Sci Rep
2020
Nup88 mRNA overexpression is associated with high aggressiveness of breast cancer.
Agudo D et al.·Int J Cancer
2004
Nup88 expression is associated with myometrial invasion in endometrial carcinoma.
Schneider J et al.·Int J Gynecol Cancer
2010
Identification and genomic analysis of pedigrees with exceptional longevity identifies candidate rare variants.
Miller JB et al.·Neurobiol Dis
2020
Oncogenic potential of nucleoporins in non-hematological cancers: recent update beyond chromosome translocation and gene fusion.
Roy A et al.·J Cancer Res Clin Oncol
2019Review
Pathogenic Variants in NUP214 Cause "Plugged" Nuclear Pore Channels and Acute Febrile Encephalopathy.
Fichtman B et al.·Am J Hum Genet
2019
A novel, nuclear pore-associated, widely distributed molecule overexpressed in oncogenesis and development.
Gould VE et al.·Am J Pathol
2000
Circulating estradiol defines the tumor phenotype in menopausal breast cancer patients.
Schneider J et al.·Maturitas
2009Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Breast Cancer Female

Vascular Supply Identification, Lesion Extension and Search for Tumor Similarity at a Distance by VTM in Breast Cancer

NOT YET RECRUITING
NCT06045572Phase NAGalzu Institute of Research, Teaching, Science and Applied TechnologyStarted 2026-06-01
VTM examination and breast biopsy

External Resources

Links to major genomics databases and tools