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    SPAST spastin [ Homo sapiens (human) ]

    Gene ID: 6683, updated on 26-Jan-2024

    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
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See SPAST in Genome Data Viewer
    Location:
    2p22.3
    Exon count:
    17
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (32063556..32157637)
    RS_2023_10 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_000002.12Genomic Context describing neighboring genes Neighboring gene NANOG hESC enhancer GRCh37_chr2:32111667-32112574 Neighboring gene mediator of cell motility 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11332 Neighboring gene MPRA-validated peak3645 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15554 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:32209277-32209778 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:32209779-32210278 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:32225693-32226193 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11333 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11334 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11335 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11336 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:32236012-32236171 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15555 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15556 Neighboring gene dpy-30 histone methyltransferase complex regulatory subunit Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15557 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:32288537-32289337 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11339 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:32392253-32392769 Neighboring gene SLC30A6 divergent transcript Neighboring gene MPRA-validated peak3647 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15558 Neighboring gene solute carrier family 30 member 6 Neighboring gene DEAD-box helicase 50 pseudogene 1

    Genomic regions, transcripts, and products

    Expression

    • 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

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    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

    HIV-1 interactions

    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

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • KIAA1083

    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 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

    Preferred Names
    spastin
    Names
    spastic paraplegia 4 (autosomal dominant; spastin)
    spastic paraplegia 4 protein
    NP_001350752.1
    NP_001350804.1
    NP_001364888.1
    NP_055761.2
    NP_955468.1

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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

    1. NG_008730.1 RefSeqGene

      Range
      5001..99027
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_714

    mRNA and Protein(s)

    1. NM_001363823.2NP_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
      A0A2R8YGN6, A0A2U3TZR0
      Related
      ENSP00000482496.2, ENST00000621856.2
      Conserved Domains (4) summary
      cd02679
      Location:116194
      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:579611
      Vps4_C; Vps4 C terminal oligomerization domain
      pfam17862
      Location:532586
      AAA_lid_3; AAA+ lid domain
      cd19524
      Location:342505
      RecA-like_spastin; ATPase domain of spastin
    2. NM_001363875.2NP_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, A0A2R8YGN6
      Related
      ENSP00000493827.1, ENST00000642455.1
      Conserved Domains (4) summary
      cd02679
      Location:116194
      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:547579
      Vps4_C; Vps4 C terminal oligomerization domain
      pfam17862
      Location:500554
      AAA_lid_3; AAA+ lid domain
      cd19524
      Location:310473
      RecA-like_spastin; ATPase domain of spastin
    3. NM_001377959.1NP_001364888.1  spastin isoform 5

      Status: REVIEWED

      Source sequence(s)
      AL121655, AL121658
      UniProtKB/TrEMBL
      A0A2R8YFW8
      Related
      ENSP00000495478.1, ENST00000642751.1
      Conserved Domains (2) summary
      cd02679
      Location:116195
      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:311474
      RecA-like_spastin; ATPase domain of spastin
    4. NM_014946.4NP_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
      A7E2A7, Q9UBP0, Q9UPR9
      UniProtKB/TrEMBL
      A0A2R8YGN6, E5KRP5
      Related
      ENSP00000320885.3, ENST00000315285.9
      Conserved Domains (4) summary
      cd02679
      Location:116195
      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:580612
      Vps4_C; Vps4 C terminal oligomerization domain
      pfam17862
      Location:533587
      AAA_lid_3; AAA+ lid domain
      cd19524
      Location:343506
      RecA-like_spastin; ATPase domain of spastin
    5. NM_199436.2NP_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/TrEMBL
      A0A2R8YGN6, E5KRP6
      Related
      ENSP00000495015.1, ENST00000646571.1
      Conserved Domains (4) summary
      cd02679
      Location:116195
      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:548580
      Vps4_C; Vps4 C terminal oligomerization domain
      pfam17862
      Location:501555
      AAA_lid_3; AAA+ lid domain
      cd19524
      Location:311474
      RecA-like_spastin; ATPase domain of spastin

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      32063556..32157637
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      32111981..32206198
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)