SPAST spastin [Homo sapiens (human)] - Gene

Summary

Official Symbol: SPASTprovided by HGNC
Official Full Name: spastinprovided by HGNC
Primary source: HGNC:HGNC:11233
See related: Ensembl:ENSG00000021574 MIM:604277; Vega:OTTHUMG00000128455
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: FSP2; SPG4; ADPSP
Summary: This gene encodes a member of the AAA (ATPases associated with a variety of cellular activities) protein family. Members of this protein family share an ATPase domain and have roles in diverse cellular processes including membrane trafficking, intracellular motility, organelle biogenesis, protein folding, and proteolysis. The use of alternative translational initiation sites in this gene results in a single transcript variant that can produce isoforms that differ in the length of their N-terminus and which thereby differ in the efficiency of their export from the nucleus to the cytoplasm. In addition, alternative splicing results in multiple transcript variants that encode isoforms that differ in other protein regions as well. One isoform of this gene has been shown to be a microtubule-severing enzyme that regulates microtubule abundance, mobility, and plus-end distribution. Mutations in this gene cause the most frequent form of autosomal dominant spastic paraplegia 4. [provided by RefSeq, May 2018]
Expression: Ubiquitous expression in brain (RPKM 7.7), testis (RPKM 5.2) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 2p22.3

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	2	NC_000002.12 (32063551..32157637)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (32288660..32382706)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

The findings suggest a mechanism for neurodegeneration in hereditary spastic paraplegia whereby SPAST mutations indirectly lead to impaired peroxisome transport and oxidative stress.
Title: Mechanism of impaired microtubule-dependent peroxisome trafficking and oxidative stress in SPAST-mutated cells from patients with Hereditary Spastic Paraplegia.
study to explore the novel SPAST splice site donor variant, c.1004+3A>C in spastic paraplegia type 4; Exon 6 is skipped out by the variant, leading to premature termination of translation, p.Gly290Trpfs*5; measurement of SPAST transcripts in lymphocytes demonstrated reduction through nonsense-mediated mRNA decay
Title: Spastic paraplegia type 4: A novel SPAST splice site donor mutation and expansion of the phenotype variability.
Two novel mutations in gene SPG4 in patients with autosomal dominant spastic paraplegia
Title: [Two novel mutations in gene SPG4 in patients with autosomal dominant spastic paraplegia].
The N184X mutation triggers the reinitiation of translation at a third start codon in SPAST, resulting in synthesis of a novel M187 spastin isoform that is able to sever microtubules.
Title: Truncating mutations of <i>SPAST</i> associated with hereditary spastic paraplegia indicate greater accumulation and toxicity of the M1 isoform of spastin.
Our data reveal a high rate of complex cases (25%), with psychiatric disorders among the most common comorbidity (10% of all SPASTpatients). Further, we identify a genotype-phenotype correlation between patients carrying loss-of-function mutations in SPAST and the presence of psychiatric disorders.
Title: Truncating mutations in <i>SPAST</i> patients are associated with a high rate of psychiatric comorbidities in hereditary spastic paraplegia.
Variants in SPAST and KIF5A were the most common causes of autosomal dominant hereditary spastic paraplegia in Greece.
Title: Hereditary spastic paraplegia in Greece: characterisation of a previously unexplored population using next-generation sequencing.
Two distinct Alu insertion-associated deletions in the SPAST gene cause hereditary spastic paraplegia type SPG4.
Title: A polymorphic Alu insertion that mediates distinct disease-associated deletions.
The data of this study confirmed the genetic heterogeneity of childhood-onset pure HSP, with SPG4/SPAST and SPG3A/ATL1 being the most frequent forms.
Title: A series of Greek children with pure hereditary spastic paraplegia: clinical features and genetic findings.
We report the first genetic study of uncomplicated HSP patients from the Czech Republic. We found broad mutation spectrum in 13 from the 17 coding exons and adjacent regions of the SPAST gene. We detected 21 novel presumably pathogenic mutations. The high frequency of SPAST mutations was found only in familial patients.
Title: SPAST mutation spectrum and familial occurrence among Czech patients with pure hereditary spastic paraplegia.
This study demonstrted that the most frequently affected gene was SPAST with pathogenic or likely pathogenic mutations in hereditary spastic paraplegia.
Title: Genetic background of the hereditary spastic paraplegia phenotypes in Hungary - An analysis of 58 probands.

Submit: New GeneRIF Correction See all GeneRIFs (130)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Spastic paraplegia 4, autosomal dominant MedGen: C1866855 OMIM: 182601 GeneReviews: Spastic Paraplegia 4	Compare labs

NHGRI GWAS Catalog

Description
Novel gene variants predict serum levels of the cytokines IL-18 and IL-1ra in older adults. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of spastin (SPAST) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D8S2279 (e-PCR)
- UniSTS:473907

RH103789 (e-PCR)
- UniSTS:98114

RH94043 (e-PCR)
- UniSTS:83572

SHGC-32499 (e-PCR)
- UniSTS:2171

G31531 (e-PCR)
- UniSTS:8957

Homology

Homologs of the SPAST gene: The SPAST gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, C.elegans, A.thaliana, rice, and frog.
Orthologs from Annotation Pipeline: 223 organisms have orthologs with human gene SPAST
The Hierarchical Catalog of Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
ATPase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
alpha-tubulin binding	IPI Inferred from Physical Interaction more info	PubMed
beta-tubulin binding	IDA Inferred from Direct Assay more info	PubMed
beta-tubulin binding	IPI Inferred from Physical Interaction more info	PubMed
microtubule binding	IDA Inferred from Direct Assay more info	PubMed
microtubule-severing ATPase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
microtubule-severing ATPase activity	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein-containing complex binding	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
ER to Golgi vesicle-mediated transport	IMP Inferred from Mutant Phenotype more info	PubMed
anterograde axonal transport	ISS Inferred from Sequence or Structural Similarity more info
axonal transport of mitochondrion	ISS Inferred from Sequence or Structural Similarity more info
cell differentiation	IEA Inferred from Electronic Annotation more info
cytokinetic process	IMP Inferred from Mutant Phenotype more info	PubMed
cytoplasmic microtubule organization	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cytoskeleton-dependent cytokinesis	TAS Traceable Author Statement more info	PubMed
exit from mitosis	IMP Inferred from Mutant Phenotype more info	PubMed
membrane fission	IMP Inferred from Mutant Phenotype more info	PubMed
metabolic process	IEA Inferred from Electronic Annotation more info
microtubule bundle formation	IDA Inferred from Direct Assay more info	PubMed
microtubule severing	IDA Inferred from Direct Assay more info	PubMed
microtubule severing	IMP Inferred from Mutant Phenotype more info	PubMed
microtubule severing	TAS Traceable Author Statement more info	PubMed
mitotic cytokinesis	IMP Inferred from Mutant Phenotype more info	PubMed
mitotic spindle disassembly	IMP Inferred from Mutant Phenotype more info	PubMed
nervous system development	IEA Inferred from Electronic Annotation more info
nuclear envelope reassembly	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of cytokinesis	IMP Inferred from Mutant Phenotype more info	PubMed
protein hexamerization	IDA Inferred from Direct Assay more info	PubMed
protein homooligomerization	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
colocalizes_with ESCRT III complex	TAS Traceable Author Statement more info	PubMed
axon cytoplasm	IEA Inferred from Electronic Annotation more info
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytoplasmic vesicle	IDA Inferred from Direct Assay more info	PubMed
cytosol	IDA Inferred from Direct Assay more info
colocalizes_with endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
endoplasmic reticulum membrane	IEA Inferred from Electronic Annotation more info
colocalizes_with endosome	IDA Inferred from Direct Assay more info	PubMed
extracellular exosome	HDA more info	PubMed
lipid droplet	IEA Inferred from Electronic Annotation more info
microtubule	IEA Inferred from Electronic Annotation more info
colocalizes_with microtubule cytoskeleton	IDA Inferred from Direct Assay more info	PubMed
microtubule organizing center	IEA Inferred from Electronic Annotation more info
midbody	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with midbody	IDA Inferred from Direct Assay more info	PubMed
midbody	IMP Inferred from Mutant Phenotype more info	PubMed
nuclear membrane	IMP Inferred from Mutant Phenotype more info	PubMed
nucleoplasm	IDA Inferred from Direct Assay more info
nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nucleus	IDA Inferred from Direct Assay more info	PubMed
perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info
spindle	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: spastin

Names: spastic paraplegia 4 (autosomal dominant; spastin); spastic paraplegia 4 protein

NP_055761.2

EC 3.6.4.3

NP_955468.1

EC 3.6.4.3

XP_005264573.1

EC 3.6.4.3

XP_011531369.1

EC 3.6.4.3

XP_016860266.1

EC 3.6.4.3

XP_016860267.1

EC 3.6.4.3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008730.1 RefSeqGene

Range

5001..99027

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_714

mRNA and Protein(s)

NM_001363823.1 → NP_001350752.1 spastin isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1, which results in a shorter isoform (3), compared to isoform 1. This variant is also predicted to use an alternate, in-frame, downstream translation initiation site to encode an even shorter isoform.

Source sequence(s)

AL121655, AL121658
NM_001363875.1 → NP_001350804.1 spastin isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (4) has multiple differences in the coding region, compared to variant 1. It encodes a shorter isoform (4), compared to isoform 1. This variant is also predicted to use an alternate, in-frame, downstream translation initiation site to encode an even shorter isoform.

Source sequence(s)

AL121655, AL121658

Consensus CDS

CCDS86830.1
NM_014946.3 → NP_055761.2 spastin isoform 1

See identical proteins and their annotated locations for NP_055761.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1; also known as M1). It also encodes a shorter isoform (M87) from an alternate, in-frame, downstream translation initiation site.

Source sequence(s)

AA830062, AB029006, AJ246001, BG532310

Consensus CDS

CCDS1778.1

UniProtKB/Swiss-Prot

Q9UBP0

UniProtKB/TrEMBL

E5KRP5

Related

ENSP00000480893.1, ENST00000615843.4

Conserved Domains (2) summary

COG0464
Location:311 → 597

SpoVK; AAA+-type ATPase, SpoVK/Ycf46/Vps4 family [Cell wall/membrane/envelope biogenesis, Cell cycle control, cell division, chromosome partitioning, Signal transduction mechanisms]

cd02679
Location:116 → 195

MIT_spastin; MIT: domain contained within Microtubule Interacting and Trafficking molecules. This MIT domain sub-family is found in the AAA protein spastin, a probable ATPase involved in the assembly or function of nuclear protein complexes; spastins might also be ...
NM_199436.1 → NP_955468.1 spastin isoform 2

See identical proteins and their annotated locations for NP_955468.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame segment of the coding region, compared to variant 1. It encodes a shorter isoform (2), compared to isoform 1. This variant is also predicted to use an alternate, in-frame, downstream translation initiation site to encode an even shorter isoform.

Source sequence(s)

AA830062, AB029006, BG532310

Consensus CDS

CCDS1779.1

UniProtKB/Swiss-Prot

Q9UBP0

UniProtKB/TrEMBL

E5KRP6

Related

ENSP00000495015.1, OTTHUMP00000158570, ENST00000646571.1, OTTHUMT00000250252

Conserved Domains (2) summary

COG0464
Location:279 → 565

SpoVK; AAA+-type ATPase, SpoVK/Ycf46/Vps4 family [Cell wall/membrane/envelope biogenesis, Cell cycle control, cell division, chromosome partitioning, Signal transduction mechanisms]

cd02679
Location:116 → 195

MIT_spastin; MIT: domain contained within Microtubule Interacting and Trafficking molecules. This MIT domain sub-family is found in the AAA protein spastin, a probable ATPase involved in the assembly or function of nuclear protein complexes; spastins might also be ...

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000002.12 Reference GRCh38.p12 Primary Assembly

Range

32063551..32157637

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011533067.2 → XP_011531369.1 spastin isoform X3

See identical proteins and their annotated locations for XP_011531369.1

Conserved Domains (2) summary

COG0464
Location:311 → 547

SpoVK; AAA+-type ATPase, SpoVK/Ycf46/Vps4 family [Cell wall/membrane/envelope biogenesis, Cell cycle control, cell division, chromosome partitioning, Signal transduction mechanisms]

cd02679
Location:116 → 195

MIT_spastin; MIT: domain contained within Microtubule Interacting and Trafficking molecules. This MIT domain sub-family is found in the AAA protein spastin, a probable ATPase involved in the assembly or function of nuclear protein complexes; spastins might also be ...
XM_017004778.2 → XP_016860267.1 spastin isoform X4

Related

ENSP00000495478.1, ENST00000642751.1
XM_017004777.2 → XP_016860266.1 spastin isoform X2

Related

ENSP00000493827.1, ENST00000642455.1
XM_005264516.5 → XP_005264573.1 spastin isoform X1

See identical proteins and their annotated locations for XP_005264573.1

Related

ENSP00000482496.2, ENST00000621856.2

Conserved Domains (2) summary

COG0464
Location:310 → 596

SpoVK; AAA+-type ATPase, SpoVK/Ycf46/Vps4 family [Cell wall/membrane/envelope biogenesis, Cell cycle control, cell division, chromosome partitioning, Signal transduction mechanisms]

cd02679
Location:116 → 194

MIT_spastin; MIT: domain contained within Microtubule Interacting and Trafficking molecules. This MIT domain sub-family is found in the AAA protein spastin, a probable ATPase involved in the assembly or function of nuclear protein complexes; spastins might also be ...