Childhood onset hereditary spastic paraplegia
Gene: KPNA3

KPNA3 (karyopherin subunit alpha 3)
EnsemblGeneIds (GRCh38): ENSG00000102753
EnsemblGeneIds (GRCh37): ENSG00000102753
OMIM: 601892, Gene2Phenotype
KPNA3 is in 2 panels

3 reviews

Mafalda Gomes (Genomics England Curator)

The mode of inheritance of this gene has been updated to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.
Created: 1 Feb 2023, 2:55 p.m. | Last Modified: 1 Feb 2023, 2:55 p.m.

Panel Version: 3.9

Created: 1 Feb 2023, 2:55 p.m.
Last Modified: 1 Feb 2023, 2:55 p.m.
Panel version: 3.9

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Promoting this gene from grey to amber with a recommendation of GREEN rating following GMS review.
Created: 5 Aug 2022, 9:44 p.m. | Last Modified: 5 Aug 2022, 9:44 p.m.

Panel Version: 2.144

As the reviewer state, Shob et al 2021 (PMID: 34564892) report 8 individuals from 5 families affected by an early-onset (first year of life) pure HSP and bearing heterozygous variants in KPNA3 identified by trio WES. 5 different missense variants were detected, which could be identified as either de novo or inherited and segregating with HSP within the family. In Individual 8, 2 independent de novo KPNA3 variants (ie, p.Leu328Met and p.Pro415Leu) were identified, and it couldn't be determined whether 1 variant alone or both variants were causing the disease. 1 patient showed also presented with a delay in speech development and intellectual disability, but was found to carry an additional maternally inherited PURA variant (p.Arg169Cys), classified as likely pathogenic. Functional characterization of the protein variants showed that the proteins exhibited a variable pattern of altered expression level, subcellular distribution, and protein interaction.
Created: 5 Aug 2022, 9:42 p.m. | Last Modified: 5 Aug 2022, 9:42 p.m.

Panel Version: 2.140

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
autosomal dominant pure spastic paraplegia, MONDO:0015088

Publications

34564892

Created: 5 Aug 2022, 9:42 p.m.
Last Modified: 5 Aug 2022, 9:42 p.m.
Panel version: 2.140

Dmitrijs Rots (Children's Clinical University Hospital)

Green List (high evidence)

8 reported families with de novo missense variants, that segregates with pure HSP with infantile onset and some functional data PMID: 34564892
Sources: Literature
Created: 25 Oct 2021, 5:56 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Infantile onset spastic paraplegia; developmental delay

Publications

PMID: 34564892

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

Created: 25 Oct 2021, 5:56 a.m.

Panel version: 2.84

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Sources

NHS GMS
Expert Review Green

Phenotypes

autosomal dominant pure spastic paraplegia, MONDO:0015088

OMIM

601892

Clinvar variants

Variants in KPNA3

Penetrance

unknown

Publications

34564892

Mode of Pathogenicity

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

Panels with this gene

History Filter Activity

1 Feb 2023, Gel status: 3

Removed Tag

Mafalda Gomes (Genomics England Curator)

Tag Q3_22_rating was removed from gene: KPNA3.

1 Feb 2023, Gel status: 3

Added New Source, Added New Source, Status Update

Mafalda Gomes (Genomics England Curator)

Source Expert Review Green was added to KPNA3. Source NHS GMS was added to KPNA3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

5 Aug 2022, Gel status: 2