NUP62

Chr 19AR

nucleoporin 62

Also known as: IBSN, SNDI, p62

NCBI Gene: 23636 ENSG00000213024 UniProt: P37198 OMIM: 605815

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 OMIM 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 OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Striatonigral degeneration, infantileMIM #271930

UniProtInfantile striatonigral degeneration

Clinical highlights

Gene–disease validity (ClinGen)

Disputed · Leigh syndrome · AR · ClinGen 2020

evidence questions this relationship

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.32

LOEUF· LoF intol.

LOF

Mechanism· predicted

📖

GeneReview available — NUP62

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

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

Background carrier burden — how many people carry a rare variant somewhere in NUP62?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 72

693 rare PASS variants

Rare truncating (LoF)

1 in 890

12 rare PASS variants

Rare synonymous (reference)

1 in 110

326 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NUP62. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 100	1 in 2,600
South Asian	~43k	1 in 120	1 in 2,700
Remaining (unassigned)	~30k	1 in 96	1 in 580
European (Finnish)	~27k	1 in 340	≈ 1 in 6,500
Admixed American	~22k	1 in 91	1 in 740
African / African American	~21k	1 in 54	1 in 2,400
East Asian	~20k	1 in 120	1 in 1,300
Ashkenazi Jewish	~13k	1 in 420	none seen
Middle Eastern	~2,884	1 in 76	≈ 1 in 2,800

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓