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
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
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Genomic context

Location:: 2p22.3

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
109.20201120	current	GRCh38.p13 (GCF_000001405.39)	2	NC_000002.12 (32063551..32157637)
105.20201022	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (32288625..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 Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Clinical Characterization of 2 Siblings with a Homozygous SPAST Variant.
Title: Clinical Characterization of 2 Siblings with a Homozygous SPAST Variant.
[Identification of SPAST gene variant in a pedigree affected with hereditary spastic paraplegia type 4].
Title: [Identification of SPAST gene variant in a pedigree affected with hereditary spastic paraplegia type 4].
Mutational Spectrum of Spast (Spg4) and Atl1 (Spg3a) Genes In Russian Patients With Hereditary Spastic Paraplegia.
Title: Mutational Spectrum of Spast (Spg4) and Atl1 (Spg3a) Genes In Russian Patients With Hereditary Spastic Paraplegia.
Structure of spastin bound to a glutamate-rich peptide implies a hand-over-hand mechanism of substrate translocation.
Title: Structure of spastin bound to a glutamate-rich peptide implies a hand-over-hand mechanism of substrate translocation.
Novel mutations in the SPAST gene cause hereditary spastic paraplegia.
Title: Novel mutations in the SPAST gene cause hereditary spastic paraplegia.
Spastin modulates transcripts levels and subcellular location of Seipin and REEP1. Spastin and its partners coordinate lipid droplet dispersion and ER.
Title: Spastin mutations impair coordination between lipid droplet dispersion and reticulum.
A novel role for ESCRT-III proteins and spastin in regulating polarised membrane traffic.
Title: ESCRT-III-associated proteins and spastin inhibit protrudin-dependent polarised membrane traffic.
identified novel variants in two patients. We have also identified two novel mutations in the SPAST group
Title: High diagnostic yield and novel variants in very late-onset spasticity.
M1 Spastin's dual roles in tethering lipid droplets (LDs) to peroxisomes and in recruiting ESCRT-III components to LD-peroxisome contact sites for fatty acid (FA) trafficking may underlie the pathogenesis of diseases associated with defective FA metabolism
Title: Spastin tethers lipid droplets to peroxisomes and directs fatty acid trafficking through ESCRT-III.
This study presents a family with spastic paraplegia due to a novel mutation c.1390GT(p.Glu464Term) in SPAST gene
Title: Case report on novel mutation in SPAST gene in Polish family with spastic paraplegia.

Submit: New GeneRIF Correction See all GeneRIFs (149)

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
Novel gene variants predict serum levels of the cytokines IL-18 and IL-1ra in older adults. GeneReviews: Not available
Spastic paraplegia 4, autosomal dominant MedGen: C1866855 OMIM: 182601 GeneReviews: Spastic Paraplegia 4	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2019-09-25) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2019-09-25) ClinGen Genome Curation PagePubMed

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: 333 organisms have orthologs with human gene SPAST
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
isomerase activity	IEA Inferred from Electronic Annotation more info
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
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
axonogenesis	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
endoplasmic reticulum to Golgi vesicle-mediated transport	IMP Inferred from Mutant Phenotype 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
nuclear envelope reassembly	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of cytokinesis	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of microtubule depolymerization	IEA Inferred from Electronic Annotation more info
protein hexamerization	IDA Inferred from Direct Assay more info	PubMed
protein homooligomerization	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
axon cytoplasm	IEA Inferred from Electronic Annotation more info
centrosome	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
integral component of membrane	IEA Inferred from Electronic Annotation more info
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
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_001350752.1

EC 5.6.1.1

NP_001350804.1

EC 5.6.1.1

NP_001364888.1

EC 5.6.1.1

NP_055761.2

EC 5.6.1.1

NP_955468.1

EC 5.6.1.1

XP_011531369.1

EC 5.6.1.1

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_001363823.2 → 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

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 ...
NM_001363875.2 → 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

Related

ENSP00000493827.1, ENST00000642455.1

Conserved Domains (2) summary

COG0464
Location:278 → 564

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 ...
NM_001377959.1 → NP_001364888.1 spastin isoform 5

Status: REVIEWED

Source sequence(s)

AL121655, AL121658

Related

ENSP00000495478.1, ENST00000642751.1
NM_014946.4 → 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)

AJ246001, AL121655, AL121658

Consensus CDS

CCDS1778.1

UniProtKB/Swiss-Prot

Q9UBP0

UniProtKB/TrEMBL

E5KRP5

Related

ENSP00000320885.3, ENST00000315285.8

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_199436.2 → 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)

AL121655, AL121658, BC150260

Consensus CDS

CCDS1779.1

UniProtKB/Swiss-Prot

Q9UBP0

UniProtKB/TrEMBL

E5KRP6

Related

ENSP00000495015.1, ENST00000646571.1

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 Updated Annotation Release 109.20201120

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

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000002.12 Reference GRCh38.p13 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 ...