Developmental Brain Disorder Gene Database

Missense Gene

Gene

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Missense

SPAST

HGNC:11233 (protein-coding gene)

spastin

Unique Cases:: 26

Disorders:: ID, ASD, EP, ADHD, CP

Last Updated:: January 4, 2024

Gene Summary:

Gene Function: ATP-dependent microtubule severing protein that specifically recognizes and cuts microtubules that are polyglutamylated (PubMed:11809724, PubMed:15716377, PubMed:16219033, PubMed:17389232, PubMed:20530212, PubMed:22637577, PubMed:26875866). Preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (PubMed:26875866). Seve... (Source: Uniprot)

Previous symbols: SPG4

Alias symbols: FSP2, ADPSP, KIAA1083

Chromosomal Location: 2p22.3

Genomic Coordinates: GRCh37:chr2:32288680-32382706; GRCh38:chr2:32063551-32157637

Associated Disorders: Intellectual Disability, Autism, Epilepsy, Attention Deficit Hyperactivity Disorder, Cerebral Palsy

Predictive Scores:

HI Score (Decipher): 9.51

pLI (gnomAD): 1.00

LOEUF (gnomAD): 0.22

Classifications from External Sources:

SFARI Score (SFARI): 1

DDG2P Classification (DDG2P): No Classification

ClinGen Classification (ClinGen): No Classification

GenCC Classification (GenCC): Strong2 Moderate1 Supportive1 Definitive2

Cases:

Publications:

Matthews AM et. al., Atypical cerebral palsy: genomics analysis enables precision medicine., Genet Med, 2019

Balicza P et. al., Comprehensive Analysis of Rare Variants of 101 Autism-Linked Genes in a Hungarian Cohort of Autism Spectrum Disorder Patients., Front Genet, 2019

Mei H et. al., Genetic Spectrum Identified by Exome Sequencing in a Chinese Pediatric Cerebral Palsy Cohort., J Pediatr, 2022

Li N et. al., In-depth analysis reveals complex molecular aetiology in a cohort of idiopathic cerebral palsy., Brain, 2022

Rosello M et. al., Hidden etiology of cerebral palsy: genetic and clinical heterogeneity and efficient diagnosis by next-generation sequencing., Pediatr Res, 2021

Zouvelou V et. al., The genetic etiology in cerebral palsy mimics: The results from a Greek tertiary care center., Eur J Paediatr Neurol, 2019

Takezawa Y et. al., Genomic analysis identifies masqueraders of full-term cerebral palsy., Ann Clin Transl Neurol, 2018

McMichael G et. al., Whole-exome sequencing points to considerable genetic heterogeneity of cerebral palsy., Mol Psychiatry, 2015

Chopra M et. al., Mendelian etiologies identified with whole exome sequencing in cerebral palsy., Ann Clin Transl Neurol, 2022

Zech M et. al., Monogenic variants in dystonia: an exome-wide sequencing study., Lancet Neurol, 2020

Jin SC et. al., Mutations disrupting neuritogenesis genes confer risk for cerebral palsy., Nat Genet, 2020

Moreno-De-Luca A et. al., Molecular Diagnostic Yield of Exome Sequencing in Patients With Cerebral Palsy., JAMA, 2021

External References:

NCBI: Gene

Integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.

NCBI: Gene

Gene Reviews

An international point-of-care resource for busy clinicians, provides clinically relevant and medically actionable information for inherited conditions in a standardized journal-style format, covering diagnosis, management, and genetic counseling for patients and their families.

Gene Reviews

DECIPHER

DECIPHER (DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources) is an interactive web-based database which incorporates a suite of tools designed to aid the interpretation of genomic variants. DECIPHER enhances clinical diagnosis by retrieving information from a variety of bioinformatics resources relevant to the variant found in the patient.

DECIPHER

SFARI

SFARI Gene is an evolving online database designed to permit quick entrée into the genetics of autism, and to help researchers track the ever-expanding genetic risk factors that emerge in the literature.

SFARI

ClinGen

ClinGen is a National Institutes of Health (NIH)-funded resource dedicated to building an authoritative central resource that defines the clinical relevance of genes and variants for use in precision medicine and research.

ClinGen

GenCC

The GenCC DB provides information pertaining to the validity of gene-disease relationships, with a current focus on Mendelian diseases.

GenCC

gnomAD

The Genome Aggregation Database (gnomAD) is a resource developed by an international coalition of investigators, with the goal of aggregating and harmonizing both exome and genome sequencing data from a wide variety of large-scale sequencing projects, and making summary data available for the wider scientific community.