Hereditary spastic paraplegia

Gene: ATP13A2

Green List (high evidence)

ATP13A2 (ATPase 13A2)
EnsemblGeneIds (GRCh38): ENSG00000159363
EnsemblGeneIds (GRCh37): ENSG00000159363
OMIM: 610513, Gene2Phenotype
ATP13A2 is in 19 panels

3 reviews

Rebecca Foulger (Genomics England curator)

Comment on mode of inheritance: Biallelic MOI supported by PMID:28137957 and OMIM.
Created: 8 Jan 2019, 12:06 p.m.
Comment on list classification: Updating rating from Red to Green based on literature evidence. ATP13A2 was added to panel and rated Red by Chris Buxton (Bristol NHS) although he provides evidence of 3 unrelated cases in PMID:28137957. PMID:27217339 (Kara et al 2016) provides evidence of an additional case. Therefore sufficient (4) unrelated cases to support diagnostic rating, and ATP13A2 is associated with Spastic paraplegia 78, autosomal recessive, 617225 in OMIM.
Created: 8 Jan 2019, 12:06 p.m.
In a 46-year-old man (proband 41), born of consanguineous Pakistani parents, with AR spastic paraplegia, Kara et al. (2016, PMID:27217339) identified a homozygous 3-bp deletion (c.3020_3022del, NM_001141974.2), resulting in an in-frame deletion (Phe1007del).
Created: 8 Jan 2019, 12:05 p.m.
Estrada-Cuzcano (2017, 28137957) examined a Bulgarian family with 3 siblings affected by complicated hereditary spastic paraplegia, and identified a homozygous p.Thr512Ile (c.1535C>T) variant in ATP13A2. Further analysis of 795 index cases with HSP and related disorders revealed 2 additional families carrying truncating biallelic variants in ATP13A2. They also provide biochemical evidence that disease-causing variants can affect the catalytic autophosphorylation activity of ATP13A2.
Created: 8 Jan 2019, 12:05 p.m.

Sarah Leigh (Genomics England Curator)

Comment on list classification: This gene is awaiting curator evaluation and rating.
Created: 19 Dec 2018, 2:11 p.m.

Chris Buxton (North Bristol NHS Trust)

Red List (low evidence)

Estrada-Cuzcano (2017, 28137957). Biallelic LoF varaints cause complicated hereditary spastic paraplegia.
Exome study identified biallelic missense . Further analysis of 795 HSP /erlated disorders identified 2 families with truncating ATP13A2 variants. Some supportive functional studies.
Clin: Adult-onset lower-limb predominant spastic paraparesis
Sources: Literature
Created: 28 Nov 2018, 9:59 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Adult-onset lower-limb predominant spastic paraparesis

Publications

History Filter Activity

8 Jan 2019, Gel status: 3

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: ATP13A2 were changed from Adult-onset lower-limb predominant spastic paraparesis to Adult-onset lower-limb predominant spastic paraparesis; Spastic paraplegia 78, autosomal recessive, 617225; complicated hereditary spastic paraplegia

8 Jan 2019, Gel status: 3

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: ATP13A2 were set to 28137957

8 Jan 2019, Gel status: 3

Set mode of inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for gene: ATP13A2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal

8 Jan 2019, Gel status: 3

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: atp13a2 has been classified as Green List (High Evidence).

19 Dec 2018, Gel status: 1

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: atp13a2 has been classified as Red List (Low Evidence).

28 Nov 2018, Gel status: 0

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

Chris Buxton (North Bristol NHS Trust)

gene: ATP13A2 was added gene: ATP13A2 was added to Hereditary spastic paraplegia. Sources: Literature Mode of inheritance for gene: ATP13A2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATP13A2 were set to 28137957 Phenotypes for gene: ATP13A2 were set to Adult-onset lower-limb predominant spastic paraparesis Penetrance for gene: ATP13A2 were set to unknown Review for gene: ATP13A2 was set to RED