NUP62

Chr 19

nucleoporin 62

Also known as: IBSN, SNDI, p62

NCBI Gene: 23636 ENSG00000213024 UniProt: P37198

The protein is an essential component of the nuclear pore complex that regulates transport of macromolecules between the nucleus and cytoplasm, and also plays a role in mitotic cell cycle progression by regulating centrosome segregation and spindle orientation. Mutations cause infantile striatonigral degeneration with autosomal recessive inheritance. The gene is highly constrained against loss-of-function variants (pLI 0.95, LOEUF 0.32), consistent with the severe early-onset neurodegeneration affecting the basal ganglia.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.32

Clinical Summary— NUP62

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Gene-Disease Validity (ClinGen)

Leigh syndrome · ARDisputed

Disputed — evidence questions this relationship

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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

1 unique Pathogenic / Likely Pathogenic· 160 VUS of 255 total submissions

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GeneReview available — NUP62

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

0.01Z-score

OE missense 1.00 (0.91–1.10)

304 obs / 304.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.32)

0≤0.351.4

Missense OE?1.00 (0.91–1.10)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 0 / 9.4Missense obs/exp: 304 / 304.3Syn Z: -1.37

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongNUP62-related infantile striatonigral degenerationOTHERAR

This gene — mechanism propensity

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

0.3892th %ile

GOF

0.2398th %ile

LOF

0.74top 10%

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

255 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS160

Likely Benign72

Benign14

Conflicting5

Likely Pathogenic

160

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	1	0	0	1
VUS	1	158	1	0	160
Likely Benign	0	4	0	68	72
Benign	0	5	0	9	14
Conflicting	—				5
Total	1	168	1	77	252

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap NUP62 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →