NUP54

Chr 4AR

nucleoporin 54

Also known as: DYT37

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 0.451 OMIM phenotype
Clinical SummaryNUP54
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
📋
ClinVar Variants
26 unique Pathogenic / Likely Pathogenic· 51 VUS of 104 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.45LOEUF
pLI 0.216
Z-score 3.78
OE 0.24 (0.140.45)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.14Z-score
OE missense 0.62 (0.550.71)
161 obs / 257.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.24 (0.140.45)
00.351.4
Missense OE0.62 (0.550.71)
00.61.4
Synonymous OE0.81
01.21.6
LoF obs/exp: 7 / 29.0Missense obs/exp: 161 / 257.9Syn Z: 1.41

ClinVar Variant Classifications

104 submitted variants in ClinVar

Classification Summary

Pathogenic26
VUS51
Likely Benign3
26
Pathogenic
51
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
4
22
0
26
Likely Pathogenic
0
0
0
0
0
VUS
0
44
7
0
51
Likely Benign
0
2
0
1
3
Benign
0
0
0
0
0
Total05029180

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

View in ClinVar →

Protein Context — Lollipop Plot

NUP54 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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