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; AllianceGenome:HGNC:11233
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
110	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (32063556..32157637)
110	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (32111981..32206198)
105.20220307	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?

The enhanced association between mutant CHMP2B and spastin is a novel pathological link between frontotemporal dementia and hereditary spastic paraplegias.
Title: The enhanced association between mutant CHMP2B and spastin is a novel pathological link between frontotemporal dementia and hereditary spastic paraplegias.
Anticipation Can Be More Common in Hereditary Spastic Paraplegia with SPAST Mutations Than It Appears.
Title: Anticipation Can Be More Common in Hereditary Spastic Paraplegia with <i>SPAST</i> Mutations Than It Appears.
Modeling gain-of-function and loss-of-function components of SPAST-based hereditary spastic paraplegia using transgenic mice.
Title: Modeling gain-of-function and loss-of-function components of SPAST-based hereditary spastic paraplegia using transgenic mice.
Genetic, structural and clinical analysis of spastic paraplegia 4.
Title: Genetic, structural and clinical analysis of spastic paraplegia 4.
A Novel SPAST Mutation Results in Spastin Accumulation and Defects in Microtubule Dynamics.
Title: A Novel SPAST Mutation Results in Spastin Accumulation and Defects in Microtubule Dynamics.
Amplifying the spectrum of SPAST gene mutations.
Title: Amplifying the spectrum of SPAST gene mutations.
Different fusion tags affect the activity of ubiquitin overexpression on spastin protein stability.
Title: Different fusion tags affect the activity of ubiquitin overexpression on spastin protein stability.
Evidence of mosaicism in SPAST variant carriers in four French families.
Title: Evidence of mosaicism in SPAST variant carriers in four French families.
Spastin recovery in hereditary spastic paraplegia by preventing neddylation-dependent degradation.
Title: Spastin recovery in hereditary spastic paraplegia by preventing neddylation-dependent degradation.
Microtubule-dependent and independent roles of spastin in lipid droplet dispersion and biogenesis.
Title: Microtubule-dependent and independent roles of spastin in lipid droplet dispersion and biogenesis.

Submit: New GeneRIF Correction See all GeneRIFs (160)

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
Hereditary spastic paraplegia 4 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

EBI GWAS Catalog

Description
Novel gene variants predict serum levels of the cytokines IL-18 and IL-1ra in older adults. EBI GWAS Catalog EBI GWAS 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: 446 organisms have orthologs with human gene SPAST
Orthologs

Gene Ontology Provided by GOA

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

Process	Evidence Code	Pubs
involved_in anterograde axonal transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in axonal transport of mitochondrion	ISS Inferred from Sequence or Structural Similarity more info
involved_in axonogenesis	IEA Inferred from Electronic Annotation more info
involved_in cytokinetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cytoskeleton-dependent cytokinesis	TAS Traceable Author Statement more info	PubMed
involved_in endoplasmic reticulum to Golgi vesicle-mediated transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in exit from mitosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in membrane fission	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in metabolic process	IEA Inferred from Electronic Annotation more info
involved_in microtubule bundle formation	IDA Inferred from Direct Assay more info	PubMed
involved_in microtubule severing	IDA Inferred from Direct Assay more info	PubMed
involved_in microtubule severing	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in microtubule severing	TAS Traceable Author Statement more info	PubMed
involved_in mitotic cytokinesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitotic nuclear membrane reassembly	TAS Traceable Author Statement more info
involved_in mitotic spindle disassembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in nuclear membrane reassembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cytokinesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of microtubule depolymerization	IEA Inferred from Electronic Annotation more info
involved_in protein hexamerization	IDA Inferred from Direct Assay more info	PubMed
involved_in protein homooligomerization	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in axon	IDA Inferred from Direct Assay more info	PubMed
located_in axon cytoplasm	IEA Inferred from Electronic Annotation more info
located_in centrosome	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasmic vesicle	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
colocalizes_with endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	IEA Inferred from Electronic Annotation more info
colocalizes_with endosome	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
located_in lipid droplet	IEA Inferred from Electronic Annotation more info
located_in microtubule	IEA Inferred from Electronic Annotation more info
colocalizes_with microtubule cytoskeleton	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with midbody	IDA Inferred from Direct Assay more info	PubMed
located_in midbody	IDA Inferred from Direct Assay more info	PubMed
located_in midbody	IMP Inferred from Mutant Phenotype more info	PubMed
located_in nuclear membrane	IMP Inferred from Mutant Phenotype more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in spindle pole	IDA Inferred from Direct Assay more info	PubMed

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

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

Consensus CDS

CCDS92732.1

UniProtKB/TrEMBL

A0A2U3TZR0

Related

ENSP00000482496.2, ENST00000621856.2

Conserved Domains (4) summary

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 ...

pfam09336
Location:579 → 611

Vps4_C; Vps4 C terminal oligomerization domain

pfam17862
Location:532 → 586

AAA_lid_3; AAA+ lid domain

cd19524
Location:342 → 505

RecA-like_spastin; ATPase domain of spastin
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

UniProtKB/TrEMBL

A0A2R8Y4I8

Related

ENSP00000493827.1, ENST00000642455.1

Conserved Domains (4) summary

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 ...

pfam09336
Location:547 → 579

Vps4_C; Vps4 C terminal oligomerization domain

pfam17862
Location:500 → 554

AAA_lid_3; AAA+ lid domain

cd19524
Location:310 → 473

RecA-like_spastin; ATPase domain of spastin
NM_001377959.1 → NP_001364888.1 spastin isoform 5

Status: REVIEWED

Source sequence(s)

AL121655, AL121658

Related

ENSP00000495478.1, ENST00000642751.1

Conserved Domains (2) summary

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 ...

cd19524
Location:311 → 474

RecA-like_spastin; ATPase domain of spastin
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, Q9UPR9

UniProtKB/TrEMBL

E5KRP5

Related

ENSP00000320885.3, ENST00000315285.9

Conserved Domains (4) summary

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 ...

pfam09336
Location:580 → 612

Vps4_C; Vps4 C terminal oligomerization domain

pfam17862
Location:533 → 587

AAA_lid_3; AAA+ lid domain

cd19524
Location:343 → 506

RecA-like_spastin; ATPase domain of spastin
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 (4) summary

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 ...

pfam09336
Location:548 → 580

Vps4_C; Vps4 C terminal oligomerization domain

pfam17862
Location:501 → 555

AAA_lid_3; AAA+ lid domain

cd19524
Location:311 → 474

RecA-like_spastin; ATPase domain of spastin