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Mendeliome

Gene: NUP54

Amber List (moderate evidence)

NUP54 (nucleoporin 54)
EnsemblGeneIds (GRCh38): ENSG00000138750
EnsemblGeneIds (GRCh37): ENSG00000138750
OMIM: 607607, Gene2Phenotype
NUP54 is in 2 panels

1 review

Hazel Phillimore (Victorian Clinical Genetics Services)

I don't know

From PMID: 36333996.; Harrer, P. et al. (2022) Ann Neurol. doi: 10.1002/ana.26544.

Three patients from unrelated families with dystonia and/or Leigh(-like) syndromes, with biallelic variants in NUP54, in the C-terminal protein region that interacts with NUP62. Onset was between 12 months and 5 years. All had progressive neurological deterioration with dystonia, ataxia, dysarthria, dysphagia, hypotonia.

Patient / Family A (consanguineous) was homozygous for c.1073T>G p.(Ile358Ser).

Patient / Family B was compound heterozygous for c.1073T>G p.(Ile358Ser) and c.1126A>G p.(Lys376Glu).

Patient / Family C was compound heterozygosity for c.1410_1412del p.(Gln471del) and two missense variants c.1414G>A, p.(Glu472Lys); c.1420C>T, p.(Leu474Phe)

The phenotypes were similar to those of NUP62 including early-onset dystonia with dysphagic choreoathetosis, and T2-hyperintense lesions in striatum.

Brain MRIs showed T2/FLAIR hyperintensities in the dorsal putamina.

Western blots showing reduced expression of NUP54 and its interaction partners NUP62/NUP58 in patient fibroblasts.
Sources: Literature
Created: 1 Dec 2022, 3:56 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia

Publications

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Dystonia 37, early-onset, with striatal lesions, MIM# 620427
  • Early onset dystonia
  • progressive neurological deterioration
  • ataxia
  • dysarthria
  • dysphagia
  • hypotonia
OMIM
607607
Clinvar variants
Variants in NUP54
Penetrance
None
Publications
Panels with this gene

History Filter Activity

28 Jun 2023, Gel status: 2

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: NUP54 were changed from Striatonigral degeneration, MONDO:0003122, NUP54-related; Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia to Dystonia 37, early-onset, with striatal lesions, MIM# 620427; Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia

1 Dec 2022, Gel status: 2

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: nup54 has been classified as Amber List (Moderate Evidence).

1 Dec 2022, Gel status: 2

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: NUP54 were changed from Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia to Striatonigral degeneration, MONDO:0003122, NUP54-related; Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia

1 Dec 2022, Gel status: 2

Set mode of pathogenicity

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of pathogenicity for gene: NUP54 was changed from None to None

1 Dec 2022, Gel status: 2

Set mode of pathogenicity

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of pathogenicity for gene: NUP54 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to None

1 Dec 2022, Gel status: 2

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: nup54 has been classified as Amber List (Moderate Evidence).

1 Dec 2022, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set mode of pathogenicity

Hazel Phillimore (Victorian Clinical Genetics Services)

gene: NUP54 was added gene: NUP54 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NUP54 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NUP54 were set to PMID: 36333996 Phenotypes for gene: NUP54 were set to Early onset dystonia; progressive neurological deterioration; ataxia; dysarthria; dysphagia; hypotonia Mode of pathogenicity for gene: NUP54 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: NUP54 was set to AMBER