NUP62

Chr 19AR

nucleoporin 62

Also known as: IBSN, SNDI, p62

NCBI Gene: 23636ENSG00000213024UniProt: P37198

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 are the main components of the nuclear pore complex in eukaryotic cells. The protein encoded by this gene is a member of the FG-repeat containing nucleoporins and is localized to the nuclear pore central plug. This protein associates with the importin alpha/beta complex which is involved in the import of proteins containing nuclear localization signals. Multiple transcript variants of this gene encode a single protein isoform. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Striatonigral degeneration, infantileMIM #271930
AR
UniProtInfantile striatonigral degeneration
269
ClinVar variants
12
Pathogenic / LP
0.95
pLI score· haploinsufficient
0
Active trials
Clinical Summary— NUP62
🧬
Gene-Disease Validity (ClinGen)
Leigh syndrome · ARDisputed

Disputed — evidence questions this relationship

⚡
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.
📋
ClinVar Variants
12 Pathogenic / Likely Pathogenic· 166 VUS of 269 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.32LOEUF
pLI 0.950
Z-score 2.85
OE 0.00 (0.00–0.32)
Highly constrained

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

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.
0.01Z-score
OE missense 1.00 (0.91–1.10)
304 obs / 304.3 exp
Tolerant

Mild missense constraint

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.0.00 (0.00–0.32)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.00 (0.91–1.10)
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.1.15
0≤1.21.6
LoF obs/exp: 0 / 9.4Missense obs/exp: 304 / 304.3Syn Z: -1.37

ClinVar Variant Classifications

269 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic3
VUS166
Likely Benign72
Benign14
Conflicting5
9
Pathogenic
3
Likely Pathogenic
166
VUS
72
Likely Benign
14
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
8
0
9
Likely Pathogenic
0
0
3
0
3
VUS
0
146
20
0
166
Likely Benign
0
4
0
68
72
Benign
0
4
1
9
14
Conflicting
—5
Total01553277269

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

View in ClinVar →

Protein Context — Lollipop Plot

NUP62 · protein map & ClinVar variants

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

Gene2Phenotype Curations

NUP62-related infantile striatonigral degeneration

strong
ARUndeterminedUncertain
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Striatonigral degeneration, infantile

MIM #271930

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — NUP62
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Exploring NUP62's role in cancer progression, tumor immunity, and treatment response: insights from multi-omics analysis.
Chen L et al.·Front Immunol
2025
Nuclear import receptors are recruited by FG-nucleoporins to rescue hallmarks of TDP-43 proteinopathy.
Khalil B et al.·Mol Neurodegener
2022
Alternative pre-mRNA processing regulates cell-type specific expression of the IL4l1 and NUP62 genes.
Wiemann S et al.·BMC Biol
2005Review
Interactions between FUS and the C-terminal Domain of Nup62 are Sufficient for their Co-phase Separation into Amorphous Assemblies.
Kumar MS et al.·J Mol Biol
2023
Recessive NUP54 Variants Underlie Early-Onset Dystonia with Striatal Lesions.
Harrer P et al.·Ann Neurol
2023
Role for NUP62 depletion and PYK2 redistribution in dendritic retraction resulting from chronic stress.
Kinoshita Y et al.·Proc Natl Acad Sci U S A
2014
Nucleoporin 62 and Ca(2+)/calmodulin dependent kinase kinase 2 regulate androgen receptor activity in castrate resistant prostate cancer cells.
Karacosta LG et al.·Prostate
2016
Nuclear Pore Complex 62 Promotes Metastasis of Gastric Cancer by Regulating Wnt/β-Catenin and TGF-β Signaling Pathways.
Wang H et al.·J Environ Pathol Toxicol Oncol
2021
A three-gene expression score for predicting clinical benefit to anti-PD-1 blockade in advanced renal cell carcinoma.
Betancor YZ et al.·Front Immunol
2024
Dual targeting of AMRC12 and Malassezia globosa disrupts MYC liquid condensates-driven nuclear pore complex biogenesis in neuroblastoma.
Hu A et al.·Theranostics
2026
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools