NUP54

Chr 4AR

nucleoporin 54

Also known as: DYT37

NCBI Gene: 53371 ENSG00000138750 UniProt: Q7Z3B4 OMIM: 607607

NUP54 encodes a nucleoporin that is a component of the nuclear pore complex required for trafficking of molecules across the nuclear membrane. Mutations cause autosomal recessive dystonia 37, an early-onset dystonia with striatal lesions. The gene shows high constraint against loss-of-function variants (LOEUF 0.454), suggesting intolerance to reduced protein levels.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The nuclear envelope creates distinct nuclear and cytoplasmic compartments in eukaryotic cells. It consists of two concentric membranes perforated by nuclear pores, large protein complexes that form aqueous channels to regulate the flow of macromolecules between the nucleus and the cytoplasm. These complexes are composed of at least 100 different polypeptide subunits, many of which belong to the nucleoporin family. This gene encodes a member of the phe-gly (FG) repeat-containing nucleoporin subset. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2013]

OMIM ResearchGenerating clinical summary…

ARLOEUF 0.451 OMIM phenotype

Clinical Summary— NUP54

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.

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ClinVar Variants

4 unique Pathogenic / Likely Pathogenic· 44 VUS of 75 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.45LOEUF

pLI 0.216

Z-score 3.78

OE 0.24 (0.14–0.45)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.14Z-score

OE missense 0.62 (0.55–0.71)

161 obs / 257.9 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.24 (0.14–0.45)

0≤0.351.4

Missense OE?0.62 (0.55–0.71)

0≤0.61.4

Synonymous OE?0.81

0≤1.21.6

LoF obs/exp: 7 / 29.0Missense obs/exp: 161 / 257.9Syn Z: 1.41

ClinVar Variant Classifications

75 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

VUS44

Likely Benign3

Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	4	0	4
Likely Pathogenic	0	0	0
VUS	44	0	44
Likely Benign	2	1	3
Benign	0	0	0
Total	50	1	51

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

View in ClinVar →

23 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap NUP54 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →