LOCUS       NM_014946               5268 bp    mRNA    linear   PRI 12-OCT-2024
DEFINITION  Homo sapiens spastin (SPAST), transcript variant 1, mRNA.
ACCESSION   NM_014946
VERSION     NM_014946.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 5268)
  AUTHORS   Elert-Dobkowska,E., Stepniak,I., Radziwonik-Fraczyk,W., Jahic,A.,
            Beetz,C. and Sulek,A.
  TITLE     SPAST Intragenic CNVs Lead to Hereditary Spastic Paraplegia via a
            Haploinsufficiency Mechanism
  JOURNAL   Int J Mol Sci 25 (9), 5008 (2024)
   PUBMED   38732227
  REMARK    GeneRIF: SPAST Intragenic CNVs Lead to Hereditary Spastic
            Paraplegia via a Haploinsufficiency Mechanism.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 5268)
  AUTHORS   Aiken,J. and Holzbaur,E.L.F.
  TITLE     Spastin locally amplifies microtubule dynamics to pattern the axon
            for presynaptic cargo delivery
  JOURNAL   Curr Biol 34 (8), 1687-1704 (2024)
   PUBMED   38554708
  REMARK    GeneRIF: Spastin locally amplifies microtubule dynamics to pattern
            the axon for presynaptic cargo delivery.
REFERENCE   3  (bases 1 to 5268)
  AUTHORS   Wang,J., Wu,Y., Dong,H., Ji,Y., Zhang,L., Liu,Y., Liu,Y., Gao,X.,
            Jia,Y. and Wang,X.
  TITLE     A novel truncated variant in SPAST results in spastin accumulation
            and defects in microtubule dynamics
  JOURNAL   BMC Med Genomics 16 (1), 321 (2023)
   PUBMED   38066582
  REMARK    GeneRIF: A novel truncated variant in SPAST results in spastin
            accumulation and defects in microtubule dynamics.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 5268)
  AUTHORS   Chen,X., Li,X., Tan,Y., Yang,D., Lu,L., Deng,Y. and Xu,R.
  TITLE     Identification of c.1495C > T mutation in SPAST gene in a family of
            Han Chinese with hereditary spastic paraplegia
  JOURNAL   Neurosci Lett 812, 137399 (2023)
   PUBMED   37473796
  REMARK    GeneRIF: Identification of c.1495C > T mutation in SPAST gene in a
            family of Han Chinese with hereditary spastic paraplegia.
REFERENCE   5  (bases 1 to 5268)
  AUTHORS   Santorelli,F.M., Patrono,C., Fortini,D., Tessa,A., Comanducci,G.,
            Bertini,E., Pierallini,A., Amabile,G.A. and Casali,C.
  TITLE     Intrafamilial variability in hereditary spastic paraplegia
            associated with an SPG4 gene mutation
  JOURNAL   Neurology 55 (5), 702-705 (2000)
   PUBMED   10980739
REFERENCE   6  (bases 1 to 5268)
  AUTHORS   Fonknechten,N., Mavel,D., Byrne,P., Davoine,C.S., Cruaud,C.,
            Bonsch,D., Samson,D., Coutinho,P., Hutchinson,M., McMonagle,P.,
            Burgunder,J.M., Tartaglione,A., Heinzlef,O., Feki,I., Deufel,T.,
            Parfrey,N., Brice,A., Fontaine,B., Prud'homme,J.F., Weissenbach,J.,
            Durr,A. and Hazan,J.
  TITLE     Spectrum of SPG4 mutations in autosomal dominant spastic paraplegia
  JOURNAL   Hum Mol Genet 9 (4), 637-644 (2000)
   PUBMED   10699187
  REMARK    Erratum:[Hum Mol Genet. 2005 Feb 1;14(3):461. Boentsch, D
            [corrected to Bonsch, D]]
REFERENCE   7  (bases 1 to 5268)
  AUTHORS   Hazan,J., Fonknechten,N., Mavel,D., Paternotte,C., Samson,D.,
            Artiguenave,F., Davoine,C.S., Cruaud,C., Durr,A., Wincker,P.,
            Brottier,P., Cattolico,L., Barbe,V., Burgunder,J.M.,
            Prud'homme,J.F., Brice,A., Fontaine,B., Heilig,B. and
            Weissenbach,J.
  TITLE     Spastin, a new AAA protein, is altered in the most frequent form of
            autosomal dominant spastic paraplegia
  JOURNAL   Nat Genet 23 (3), 296-303 (1999)
   PUBMED   10610178
REFERENCE   8  (bases 1 to 5268)
  AUTHORS   Hazan,J., Davoine,C.S., Mavel,D., Fonknechten,N., Paternotte,C.,
            Fizames,C., Cruaud,C., Samson,D., Muselet,D., Vega-Czarny,N.,
            Brice,A., Gyapay,G., Heilig,R., Fontaine,B. and Weissenbach,J.
  TITLE     A fine integrated map of the SPG4 locus excludes an expanded CAG
            repeat in chromosome 2p-linked autosomal dominant spastic
            paraplegia
  JOURNAL   Genomics 60 (3), 309-319 (1999)
   PUBMED   10493830
REFERENCE   9  (bases 1 to 5268)
  AUTHORS   Hedera,P.
  TITLE     Hereditary Spastic Paraplegia Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301682
REFERENCE   10 (bases 1 to 5268)
  AUTHORS   Parodi,L., Rydning,S.L., Tallaksen,C. and Durr,A.
  TITLE     Spastic Paraplegia 4
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301339
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL121655.1, AJ246001.1 and
            AL121658.4.
            
            On Jan 22, 2020 this sequence version replaced NM_014946.3.
            
            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].
            
            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.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR14038197.503723.1,
                                           SRR11853564.15189.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000315285.9/ ENSP00000320885.3
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-151               AL121655.1         69754-69904
            152-3414            AJ246001.1         1-3263
            3415-5268           AL121658.4         83270-85123
FEATURES             Location/Qualifiers
     source          1..5268
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2p22.3"
     gene            1..5268
                     /gene="SPAST"
                     /gene_synonym="ADPSP; FSP2; SPG4"
                     /note="spastin"
                     /db_xref="GeneID:6683"
                     /db_xref="HGNC:HGNC:11233"
                     /db_xref="MIM:604277"
     exon            1..691
                     /gene="SPAST"
                     /gene_synonym="ADPSP; FSP2; SPG4"
                     /inference="alignment:Splign:2.1.0"
     CDS             277..2127
                     /gene="SPAST"
                     /gene_synonym="ADPSP; FSP2; SPG4"
                     /EC_number="5.6.1.1"
                     /note="isoform 1 is encoded by transcript variant 1;
                     spastic paraplegia 4 (autosomal dominant; spastin);
                     spastic paraplegia 4 protein"
                     /codon_start=1
                     /product="spastin isoform 1"
                     /protein_id="NP_055761.2"
                     /db_xref="CCDS:CCDS1778.1"
                     /db_xref="GeneID:6683"
                     /db_xref="HGNC:HGNC:11233"
                     /db_xref="MIM:604277"
                     /translation="MNSPGGRGKKKGSGGASNPVPPRPPPPCLAPAPPAAGPAPPPES
                     PHKRNLYYFSYPLFVGFALLRLVAFHLGLLFVWLCQRFSRALMAAKRSSGAAPAPASA
                     SAPAPVPGGEAERVRVFHKQAFEYISIALRIDEDEKAGQKEQAVEWYKKGIEELEKGI
                     AVIVTGQGEQCERARRLQAKMMTNLVMAKDRLQLLEKMQPVLPFSKSQTDVYNDSTNL
                     ACRNGHLQSESGAVPKRKDPLTHTSNSLPRSKTVMKTGSAGLSGHHRAPSYSGLSMVS
                     GVKQGSGPAPTTHKGTPKTNRTNKPSTPTTATRKKKDLKNFRNVDSNLANLIMNEIVD
                     NGTAVKFDDIAGQDLAKQALQEIVILPSLRPELFTGLRAPARGLLLFGPPGNGKTMLA
                     KAVAAESNATFFNISAASLTSKYVGEGEKLVRALFAVARELQPSIIFIDEVDSLLCER
                     REGEHDASRRLKTEFLIEFDGVQSAGDDRVLVMGATNRPQELDEAVLRRFIKRVYVSL
                     PNEETRLLLLKNLLCKQGSPLTQKELAQLARMTDGYSGSDLTALAKDAALGPIRELKP
                     EQVKNMSASEMRNIRLSDFTESLKKIKRSVSPQTLEAYIRWNKDFGDTTV"
     exon            692..778
                     /gene="SPAST"
                     /gene_synonym="ADPSP; FSP2; SPG4"
                     /inference="alignment:Splign:2.1.0"
     exon            779..862
                     /gene="SPAST"
                     /gene_synonym="ADPSP; FSP2; SPG4"
                     /inference="alignment:Splign:2.1.0"
     exon            863..958
                     /gene="SPAST"
                     /gene_synonym="ADPSP; FSP2; SPG4"
                     /inference="alignment:Splign:2.1.0"
     exon            959..1146
                     /gene="SPAST"
                     /gene_synonym="ADPSP; FSP2; SPG4"
                     /inference="alignment:Splign:2.1.0"
     exon            1147..1280
                     /gene="SPAST"
                     /gene_synonym="ADPSP; FSP2; SPG4"
                     /inference="alignment:Splign:2.1.0"
     exon            1281..1374
                     /gene="SPAST"
                     /gene_synonym="ADPSP; FSP2; SPG4"
                     /inference="alignment:Splign:2.1.0"
     exon            1375..1449
                     /gene="SPAST"
                     /gene_synonym="ADPSP; FSP2; SPG4"
                     /inference="alignment:Splign:2.1.0"
     exon            1450..1521
                     /gene="SPAST"
                     /gene_synonym="ADPSP; FSP2; SPG4"
                     /inference="alignment:Splign:2.1.0"
     exon            1522..1597
                     /gene="SPAST"
                     /gene_synonym="ADPSP; FSP2; SPG4"
                     /inference="alignment:Splign:2.1.0"
     exon            1598..1689
                     /gene="SPAST"
                     /gene_synonym="ADPSP; FSP2; SPG4"
                     /inference="alignment:Splign:2.1.0"
     exon            1690..1769
                     /gene="SPAST"
                     /gene_synonym="ADPSP; FSP2; SPG4"
                     /inference="alignment:Splign:2.1.0"
     exon            1770..1812
                     /gene="SPAST"
                     /gene_synonym="ADPSP; FSP2; SPG4"
                     /inference="alignment:Splign:2.1.0"
     exon            1813..1892
                     /gene="SPAST"
                     /gene_synonym="ADPSP; FSP2; SPG4"
                     /inference="alignment:Splign:2.1.0"
     exon            1893..1963
                     /gene="SPAST"
                     /gene_synonym="ADPSP; FSP2; SPG4"
                     /inference="alignment:Splign:2.1.0"
     exon            1964..2004
                     /gene="SPAST"
                     /gene_synonym="ADPSP; FSP2; SPG4"
                     /inference="alignment:Splign:2.1.0"
     exon            2005..5268
                     /gene="SPAST"
                     /gene_synonym="ADPSP; FSP2; SPG4"
                     /inference="alignment:Splign:2.1.0"
     regulatory      5251..5256
                     /regulatory_class="polyA_signal_sequence"
                     /gene="SPAST"
                     /gene_synonym="ADPSP; FSP2; SPG4"
                     /note="hexamer: AATAAA"
     polyA_site      5268
                     /gene="SPAST"
                     /gene_synonym="ADPSP; FSP2; SPG4"
                     /note="major polyA site"
ORIGIN      
        1 gcggccgccg ctgggagcca ccaggcggcg gagaggacag cgacaggaag ggaggggccc
       61 gagccaccga ctgcaggagg agaaggggtt gtgctcctgg ccgaggaagg agaaaggggc
      121 ggggccggcg ggcagcgtgc ggcagtgcgg agctcctgag accggcgggc acacgggggt
      181 ctgtggcccc cgccgtagca gtggctgccg ccgtcgcttg gttcccgtcg gtctgcggga
      241 ggcgggttat ggcggcggcg gcagtgagag ctgtgaatga attctccggg tggacgaggg
      301 aagaagaaag gctccggcgg cgccagcaac ccggtgcctc ccaggcctcc gcccccttgc
      361 ctggcccccg cccctcccgc cgccgggccg gcccctccgc ccgagtcgcc gcataagcgg
      421 aacctgtact atttctccta cccgctgttt gtaggcttcg cgctgctgcg tttggtcgcc
      481 ttccacctgg ggctcctctt cgtgtggctc tgccagcgct tctcccgcgc cctcatggca
      541 gccaagagga gctccggggc cgcgccagca cctgcctcgg cctcggcccc ggcgccggtg
      601 ccgggcggcg aggccgagcg cgtccgagtc ttccacaaac aggccttcga gtacatctcc
      661 attgccctgc gcatcgatga ggatgagaaa gcaggacaga aggagcaagc tgtggaatgg
      721 tataagaaag gtattgaaga actggaaaaa ggaatagctg ttatagttac aggacaaggt
      781 gaacagtgtg aaagagctag acgccttcaa gctaaaatga tgactaattt ggttatggcc
      841 aaggaccgct tacaacttct agagaagatg caaccagttt tgccattttc caagtcacaa
      901 acggacgtct ataatgacag tactaacttg gcatgccgca atggacatct ccagtcagaa
      961 agtggagctg ttccaaaaag aaaagacccc ttaacacaca ctagtaattc actgcctcgt
     1021 tcaaaaacag ttatgaaaac tggatctgca ggcctttcag gccaccatag agcacctagt
     1081 tacagtggtt tatccatggt ttctggagtg aaacagggat ctggtcctgc tcctaccact
     1141 cataagggta ctccgaaaac aaataggaca aataaacctt ctacccctac aactgctact
     1201 cgtaagaaaa aagacttgaa gaattttagg aatgtggaca gcaaccttgc taaccttata
     1261 atgaatgaaa ttgtggacaa tggaacagct gttaaatttg atgatatagc tggtcaagac
     1321 ttggcaaaac aagcattgca agaaattgtt attcttcctt ctctgaggcc tgagttgttc
     1381 acagggctta gagctcctgc cagagggctg ttactctttg gtccacctgg gaatgggaag
     1441 acaatgctgg ctaaagcagt agctgcagaa tcgaatgcaa ccttctttaa tataagtgct
     1501 gcaagtttaa cttcaaaata cgtgggagaa ggagagaaat tggtgagggc tctttttgct
     1561 gtggctcgag aacttcaacc ttctataatt tttatagatg aagttgatag ccttttgtgt
     1621 gaaagaagag aaggggagca cgatgctagt agacgcctaa aaactgaatt tctaatagaa
     1681 tttgatggtg tacagtctgc tggagatgac agagtacttg taatgggtgc aactaatagg
     1741 ccacaagagc ttgatgaggc tgttctcagg cgtttcatca aacgggtata tgtgtcttta
     1801 ccaaatgagg agacaagact acttttgctt aaaaatctgt tatgtaaaca aggaagtcca
     1861 ttgacccaaa aagaactagc acaacttgct agaatgactg atggatactc aggaagtgac
     1921 ctaacagctt tggcaaaaga tgcagcactg ggtcctatcc gagaactaaa accagaacag
     1981 gtgaagaata tgtctgccag tgagatgaga aatattcgat tatctgactt cactgaatcc
     2041 ttgaaaaaaa taaaacgcag cgtcagccct caaactttag aagcgtacat acgttggaac
     2101 aaggactttg gagataccac tgtttaagga aatacctttg taaacctgca gaacatttta
     2161 cttaaaagag gaaacacaag atcttcaatg aacgtcatcg gctacagaaa cagcctaagt
     2221 ttacaggact ttttagagtc ttacatattt gtgcaccaaa cttgaagatg aaccagaaaa
     2281 cagacttaaa caaaatatac aatgcaaatg taattttttg ttgtttaagg ccttgccttg
     2341 atggtcacag ttatcccaat ggacactaag ttagagcaca acaaaacctg attctggtct
     2401 tctttaccaa tataatcata atgtaaataa taatttgtat attgtgttgc agatgaaagt
     2461 attccaggaa cagtgaatgg tagaagacac aagaacattt gtttgtttgt cttctgatgt
     2521 tttttcttaa aatagtaatt tctcctactt ttcttttcta ctgttgtctt aactacaggt
     2581 gattggaatg ccaaacactc ttaagtttat tttctttttt cgttttataa attcagtgtg
     2641 ccaaatgaaa cttttttcct aagtaactgt aataggaaaa agtttatttt gagagtttct
     2701 tcttcataaa tctacagaca ttaaacaatt gttgtgttct ttttaccttt tatttttcta
     2761 ttaccttgct accaaacagt ttagatagca atataatagc aaaaaagcaa atatggtaaa
     2821 atagagaagg tttgaaggtt tgagttactc tgtcatataa catgtagatc agtcttcatg
     2881 tgacctgcag tatttttttt tctaatgtat ttgtcagaaa tctgttgtag actgttaact
     2941 tcttcctgat ggaatttatt ttctgcaaga attattctga tatttaagag agccaatttt
     3001 aactgctgtg aaaatgtttc cagtgcaaga gaagggaaat actaggaact aagacatttc
     3061 taatttattg cttattactt tcttaatttt acaggataat tataagcaag tggaactacc
     3121 atcttttatt cttaataatt attaatccct tcaatgaaac tttaaaaaaa ctgaattttt
     3181 atacatggca tacatttttc tagttccttc tgcttgcttt attaactcaa aagttctagt
     3241 tctagtctgt tgatctgcct tttgttctcc caaaatgtac agtaattcca tttgtttgta
     3301 taaatatgcc tggattttca ttataaaaat gtcattgtag ggagtagaga ctcatatcat
     3361 ggccttttaa atattgtaat aaaggcaaat agatatttgc ccttagttta ctggttaaaa
     3421 gtttgtttac agaacttttc tctggtgctt aaatgatgct atgtaaaatg tcatgagtgg
     3481 aaagaatatt tgtagtagta acaagaattt ttcatttagg aaagatttct taggttttga
     3541 aagaatacat taaaataaaa aacttgcccc tactaggtaa gaactttata atgaagacat
     3601 acattcttct taattttact cttgctcttg ttaaagattt gtttgaatat agaagatgca
     3661 tgatttctgg gttttttttt ttttttgaga cagagtttcg ctcttgttgc ccaggctgga
     3721 gtgcaatggc gcaatctcga ctcaccacaa cctccgcctc ccaggttcaa gcaattctcc
     3781 tgcctcagcc tcccgagtag ctgggattac aggcatgcgc cactacccca gctaattttg
     3841 tatttttagt agagatgggg tttctccatg ttggtcaggc tggtcttgaa ctcctgacct
     3901 caggtgatcc gcctgcctcg gcctcccaaa gtgctgggat tacaggcata agccactgcg
     3961 cccagccaga agatgcatga tttcttagga tcatatgctg tttgtagcca taaggtaaat
     4021 catgtctctt ccaatcatga ctttggaact ccctgaataa taaaaatgag agttgagata
     4081 aataggggaa aaaaaatttt tttcaagcca gagctatgca tatgttaggt gatgggtagt
     4141 atccctttaa ggtctcaaac attacaacat caattatgaa atactgataa cgaaaggtag
     4201 taatgaaata tatatgatga aaagaattga gaagttctaa attaagacat ttcagttaag
     4261 ctcataaaat ttcattgttt tcatttaaaa gattaacgtt attgatactt ggataactgg
     4321 ctaatcatat taaaggacta tgtggttcca gctcaacttt taatatattg tctcctttaa
     4381 aactatcatg gttataattc tattgggaaa gacttttaga taacaaagat ttcaaatgtt
     4441 aaaagagata aaagtcaggt taatactatc ttaaacactg agtcagaaaa tcattactgt
     4501 atagaagttg ctttcctgat caagtctgaa cttcagctag tgctagagaa ctattttcta
     4561 tgacttaact ctaaccaagt tttattttaa gctgtttctt tgatagaagg gccatgaaaa
     4621 tagagtaatg atatagtagg agataaggga ttggtttggt ctttttcaat aaagatagaa
     4681 gttgctgaag ttttctgaat taataatgac ttagattgtg accttttaga ttcggtgttg
     4741 agctctgtgt tgtattactt cctaaaagat aatgcttaaa cattaagcat tagtgtgctc
     4801 ttcatgttaa tatggcagag ttttgtaaac taaattaaaa cttactgata tattggactt
     4861 tgagccaagg gaaagaatga gtactatctt tccagatatc ttaagggtaa aagcttattc
     4921 taagacagtc tgtccattga gaatattaga tttctgactt gcaaatatgt ttgtactcca
     4981 gaagaattag aggaaaagca gatactagaa ttctaattta attacatata cagccgtctt
     5041 tgtttatagt gtagaattct ttatattttg tacaaaaact aattcttttg gtaaaatgaa
     5101 ccatttacag ttcggttttg gactctgagt caaaggattt tcctttaaat gcttgtctca
     5161 attttagtct ggtcttttgt acttttcttc agaagaaatg aattaaaggg tacagttgca
     5221 taaagtgggt ttttatccta atgtattgga aataaatgat aaacttta
//
