Research panel - Severe Paediatric Disorders
Gene: SPAST

SPAST (spastin)
EnsemblGeneIds (GRCh38): ENSG00000021574
EnsemblGeneIds (GRCh37): ENSG00000021574
OMIM: 604277, Gene2Phenotype
SPAST is in 9 panels

2 reviews

Sarah Leigh (Genomics England Curator)

Comment on publications: PMID: 39731306 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Created: 12 Mar 2025, 4:42 p.m. | Last Modified: 12 Mar 2025, 4:42 p.m.

Panel Version: 1.210

Numerous heterozygous SPAST variants have been associated with Spastic paraplegia 4, autosomal dominant (OMIM:182601). PMID: 39731306 reports five homozygous SPAST variants in nine individuals from six families with spastic paraplegia and neurodegeneration. Amongst the homozygous children, all had lower limb spasticity, 5/6 had upper limb spasticity and 3/6 had severe intellectual disability. Evidence of consanguinity was evident in five of the families and the parents of the homozygous children were heterozygous for the SPAST variant found in the child, these carrier parents were asymptomatic in all but one the families studied.
Created: 12 Mar 2025, 4:35 p.m. | Last Modified: 12 Mar 2025, 4:35 p.m.

Panel Version: 1.209

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Created: 12 Mar 2025, 4:35 p.m.
Last Modified: 12 Mar 2025, 4:35 p.m.
Panel version: 1.209

Louise Daugherty (Genomics England Curator)

I don't know

Initial gene list (NGC_genelist-20190823_GREEN_dis_moi_forCuration_20200211.xlsx) collated by Dr Courtney French (University of Cambridge University Hospital NHS Foundation), Dr Karyn Megy (Clinical Feedback Lead, NIHR BioResource - Rare Diseases Study, University of Cambridge University Hospital NHS Foundation), Dr Alba Sanchis-Juan (NIHR BioResource - Rare Diseases Study, University of Cambridge University Hospital NHS Foundation) and Lucy Raymond (Professor of Medical Genetics and Neurodevelopment, University of Cambridge University Hospital NHS Foundation). Submitted to the PanelApp resource January 2020 on behalf of the Next Generation Children Project, Addenbrookes' Hospital, Cambridge. Gene Symbol submitted: SPAST; Recommended initial gene rating: Green List (high evidence); Phenotypes: Spastic paraplegia 4, autosomal dominant, 182601 (3); Mode of inheritance: Autosomal dominant
Created: 20 Feb 2020, 5:26 p.m. | Last Modified: 20 Feb 2020, 5:26 p.m.

Panel Version: 0.12

Created: 20 Feb 2020, 5:26 p.m.
Last Modified: 20 Feb 2020, 5:26 p.m.
Panel version: 0.12

Details

Mode of Inheritance

BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Sources

Next Generation Children Project
Expert Review Green
Expert list

Phenotypes

Spastic paraplegia 4, autosomal dominant, OMIM:182601
hereditary spastic paraplegia 4, MONDO:0008438

OMIM

604277

Clinvar variants

Variants in SPAST

Penetrance

None

Publications

Panels with this gene

History Filter Activity

12 Mar 2025, Gel status: 3

Set mode of inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for gene: SPAST was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

12 Mar 2025, Gel status: 3

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: SPAST were set to 30847515

14 Mar 2023, Gel status: 3

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: SPAST were changed from Spastic paraplegia 4, autosomal dominant, 182601 to Spastic paraplegia 4, autosomal dominant, OMIM:182601; hereditary spastic paraplegia 4, MONDO:0008438

20 Feb 2020, Gel status: 3