LOCUS       NM_021076               3795 bp    mRNA    linear   PRI 03-AUG-2024
DEFINITION  Homo sapiens neurofilament heavy chain (NEFH), mRNA.
ACCESSION   NM_021076
VERSION     NM_021076.4
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 3795)
  AUTHORS   Runge,K., Balla,A., Fiebich,B.L., Maier,S.J., von Zedtwitz,K.,
            Nickel,K., Dersch,R., Domschke,K., Tebartz van Elst,L. and
            Endres,D.
  TITLE     Neurodegeneration Markers in the Cerebrospinal Fluid of 100
            Patients with Schizophrenia Spectrum Disorder
  JOURNAL   Schizophr Bull 49 (2), 464-473 (2023)
   PUBMED   36200879
  REMARK    GeneRIF: Neurodegeneration Markers in the Cerebrospinal Fluid of
            100 Patients with Schizophrenia Spectrum Disorder.
REFERENCE   2  (bases 1 to 3795)
  AUTHORS   Theunissen,F., Anderton,R.S., Mastaglia,F.L., James,I., Bedlack,R.
            and Akkari,P.A.
  TITLE     Intronic NEFH variant is associated with reduced risk for sporadic
            ALS and later age of disease onset
  JOURNAL   Sci Rep 12 (1), 14739 (2022)
   PUBMED   36042248
  REMARK    GeneRIF: Intronic NEFH variant is associated with reduced risk for
            sporadic ALS and later age of disease onset.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 3795)
  AUTHORS   Ando,M., Higuchi,Y., Okamoto,Y., Yuan,J., Yoshimura,A., Takei,J.,
            Taniguchi,T., Hiramatsu,Y., Sakiyama,Y., Hashiguchi,A.,
            Matsuura,E., Nakagawa,H., Sonoda,K., Yamashita,T., Tamura,A.,
            Terasawa,H., Mitsui,J., Ishiura,H., Tsuji,S. and Takashima,H.
  TITLE     An NEFH founder mutation causes broad phenotypic spectrum in
            multiple Japanese families
  JOURNAL   J Hum Genet 67 (7), 399-403 (2022)
   PUBMED   35091664
  REMARK    GeneRIF: An NEFH founder mutation causes broad phenotypic spectrum
            in multiple Japanese families.
REFERENCE   4  (bases 1 to 3795)
  AUTHORS   Pipis,M., Cortese,A., Polke,J.M., Poh,R., Vandrovcova,J., Laura,M.,
            Skorupinska,M., Jacquier,A., Juntas-Morales,R., Latour,P.,
            Petiot,P., Sole,G., Fromes,Y., Shah,S., Blake,J., Choi,B.O.,
            Chung,K.W., Stojkovic,T., Rossor,A.M. and Reilly,M.M.
  TITLE     Charcot-Marie-Tooth disease type 2CC due to NEFH variants causes a
            progressive, non-length-dependent, motor-predominant phenotype
  JOURNAL   J Neurol Neurosurg Psychiatry 93 (1), 48-56 (2022)
   PUBMED   34518334
  REMARK    GeneRIF: Charcot-Marie-Tooth disease type 2CC due to NEFH variants
            causes a progressive, non-length-dependent, motor-predominant
            phenotype.
REFERENCE   5  (bases 1 to 3795)
  AUTHORS   Bohnert,S., Wirth,C., Schmitz,W., Trella,S., Monoranu,C.M.,
            Ondruschka,B. and Bohnert,M.
  TITLE     Myelin basic protein and neurofilament H in postmortem
            cerebrospinal fluid as surrogate markers of fatal traumatic brain
            injury
  JOURNAL   Int J Legal Med 135 (4), 1525-1535 (2021)
   PUBMED   33895854
  REMARK    GeneRIF: Myelin basic protein and neurofilament H in postmortem
            cerebrospinal fluid as surrogate markers of fatal traumatic brain
            injury.
REFERENCE   6  (bases 1 to 3795)
  AUTHORS   Collard,J.F., Cote,F. and Julien,J.P.
  TITLE     Defective axonal transport in a transgenic mouse model of
            amyotrophic lateral sclerosis
  JOURNAL   Nature 375 (6526), 61-64 (1995)
   PUBMED   7536898
REFERENCE   7  (bases 1 to 3795)
  AUTHORS   Figlewicz,D.A., Krizus,A., Martinoli,M.G., Meininger,V., Dib,M.,
            Rouleau,G.A. and Julien,J.P.
  TITLE     Variants of the heavy neurofilament subunit are associated with the
            development of amyotrophic lateral sclerosis
  JOURNAL   Hum Mol Genet 3 (10), 1757-1761 (1994)
   PUBMED   7849698
REFERENCE   8  (bases 1 to 3795)
  AUTHORS   Srinivasan,J., Hays,A.P., Thomas,F.P., Sadiq,S.A., Barth,K.H.,
            Liem,R., Mena,M.A., DeYebenes,J.G. and Latov,N.
  TITLE     Autoantigens in human neuroblastoma cells
  JOURNAL   J Neuroimmunol 26 (1), 43-50 (1990)
   PUBMED   1688443
REFERENCE   9  (bases 1 to 3795)
  AUTHORS   Chin,T.K., Harding,S.E. and Eagles,P.A.
  TITLE     Characterization of two proteolytically derived soluble
            polypeptides from the neurofilament triplet components NFM and NFH
  JOURNAL   Biochem J 264 (1), 53-60 (1989)
   PUBMED   2557834
REFERENCE   10 (bases 1 to 3795)
  AUTHORS   Lees,J.F., Shneidman,P.S., Skuntz,S.F., Carden,M.J. and
            Lazzarini,R.A.
  TITLE     The structure and organization of the human heavy neurofilament
            subunit (NF-H) and the gene encoding it
  JOURNAL   EMBO J 7 (7), 1947-1955 (1988)
   PUBMED   3138108
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC000035.2 and AF203032.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 17, 2019 this sequence version replaced NM_021076.3.
            
            Summary: Neurofilaments are type IV intermediate filament
            heteropolymers composed of light, medium, and heavy chains.
            Neurofilaments comprise the axoskeleton and functionally maintain
            neuronal caliber. They may also play a role in intracellular
            transport to axons and dendrites. This gene encodes the heavy
            neurofilament protein. This protein is commonly used as a biomarker
            of neuronal damage and susceptibility to amyotrophic lateral
            sclerosis (ALS) has been associated with mutations in this gene.
            [provided by RefSeq, Oct 2008].
            
            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 :: AF203032.1, BC073969.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1968540
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000310624.7/ ENSP00000311997.6
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-45                AC000035.2         18941-18985
            46-2009             AF203032.1         1-1964
            2010-3695           AC000035.2         28328-30013
            3696-3795           AC000035.2         30014-30113
FEATURES             Location/Qualifiers
     source          1..3795
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="22"
                     /map="22q12.2"
     gene            1..3795
                     /gene="NEFH"
                     /gene_synonym="CMT2CC; NFH"
                     /note="neurofilament heavy chain"
                     /db_xref="GeneID:4744"
                     /db_xref="HGNC:HGNC:7737"
                     /db_xref="MIM:162230"
     exon            1..928
                     /gene="NEFH"
                     /gene_synonym="CMT2CC; NFH"
                     /inference="alignment:Splign:2.1.0"
     CDS             46..3108
                     /gene="NEFH"
                     /gene_synonym="CMT2CC; NFH"
                     /note="neurofilament, heavy polypeptide 200kDa;
                     neurofilament triplet H protein; NF-H; 200 kDa
                     neurofilament protein"
                     /codon_start=1
                     /product="neurofilament heavy polypeptide"
                     /protein_id="NP_066554.2"
                     /db_xref="CCDS:CCDS13858.1"
                     /db_xref="GeneID:4744"
                     /db_xref="HGNC:HGNC:7737"
                     /db_xref="MIM:162230"
                     /translation="MMSFGGADALLGAPFAPLHGGGSLHYALARKGGAGGTRSAAGSS
                     SGFHSWTRTSVSSVSASPSRFRGAGAASSTDSLDTLSNGPEGCMVAVATSRSEKEQLQ
                     ALNDRFAGYIDKVRQLEAHNRSLEGEAAALRQQQAGRSAMGELYEREVREMRGAVLRL
                     GAARGQLRLEQEHLLEDIAHVRQRLDDEARQREEAEAAARALARFAQEAEAARVDLQK
                     KAQALQEECGYLRRHHQEEVGELLGQIQGSGAAQAQMQAETRDALKCDVTSALREIRA
                     QLEGHAVQSTLQSEEWFRVRLDRLSEAAKVNTDAMRSAQEEITEYRRQLQARTTELEA
                     LKSTKDSLERQRSELEDRHQADIASYQEAIQQLDAELRNTKWEMAAQLREYQDLLNVK
                     MALDIEIAAYRKLLEGEECRIGFGPIPFSLPEGLPKIPSVSTHIKVKSEEKIKVVEKS
                     EKETVIVEEQTEETQVTEEVTEEEEKEAKEEEGKEEEGGEEEEAEGGEEETKSPPAEE
                     AASPEKEAKSPVKEEAKSPAEAKSPEKEEAKSPAEVKSPEKAKSPAKEEAKSPPEAKS
                     PEKEEAKSPAEVKSPEKAKSPAKEEAKSPAEAKSPEKAKSPVKEEAKSPAEAKSPVKE
                     EAKSPAEVKSPEKAKSPTKEEAKSPEKAKSPEKEEAKSPEKAKSPVKAEAKSPEKAKS
                     PVKAEAKSPEKAKSPVKEEAKSPEKAKSPVKEEAKSPEKAKSPVKEEAKTPEKAKSPV
                     KEEAKSPEKAKSPEKAKTLDVKSPEAKTPAKEEARSPADKFPEKAKSPVKEEVKSPEK
                     AKSPLKEDAKAPEKEIPKKEEVKSPVKEEEKPQEVKVKEPPKKAEEEKAPATPKTEEK
                     KDSKKEEAPKKEAPKPKVEEKKEPAVEKPKESKVEAKKEEAEDKKKVPTPEKEAPAKV
                     EVKEDAKPKEKTEVAKKEPDDAKAKEPSKPAEKKEAAPEKKDTKEEKAKKPEEKPKTE
                     AKAKEDDKTLSKEPSKPKAEKAEKSSSTDQKDSKPPEKATEDKAAKGK"
     exon            929..1128
                     /gene="NEFH"
                     /gene_synonym="CMT2CC; NFH"
                     /inference="alignment:Splign:2.1.0"
     exon            1129..1253
                     /gene="NEFH"
                     /gene_synonym="CMT2CC; NFH"
                     /inference="alignment:Splign:2.1.0"
     exon            1254..3795
                     /gene="NEFH"
                     /gene_synonym="CMT2CC; NFH"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3667..3672
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NEFH"
                     /gene_synonym="CMT2CC; NFH"
                     /note="hexamer: AATAAA"
     polyA_site      3695
                     /gene="NEFH"
                     /gene_synonym="CMT2CC; NFH"
                     /note="major polyA site"
ORIGIN      
        1 gcagtgcctc ccgccccgtc ccggcctcgc gcacctgctc aggccatgat gagcttcggc
       61 ggcgcggacg cgctgctggg cgccccgttc gcgccgctgc atggcggcgg cagcctccac
      121 tacgcgctag cccgaaaggg tggcgcaggc gggacgcgct ccgccgctgg ctcctccagc
      181 ggcttccact cgtggacacg gacgtccgtg agctccgtgt ccgcctcgcc cagccgcttc
      241 cgtggcgcag gcgccgcctc aagcaccgac tcgctggaca cgctgagcaa cgggccggag
      301 ggctgcatgg tggcggtggc cacctcacgc agtgagaagg agcagctgca ggcgctgaac
      361 gaccgcttcg ccgggtacat cgacaaggtg cggcagctgg aggcgcacaa ccgcagcctg
      421 gagggcgagg ctgcggcgct gcggcagcag caggcgggcc gctccgctat gggcgagctg
      481 tacgagcgcg aggtccgcga gatgcgcggc gcggtgctgc gcctgggcgc ggcgcgcggt
      541 cagctacgcc tggagcagga gcacctgctc gaggacatcg cgcacgtgcg ccagcgccta
      601 gacgacgagg cccggcagcg agaggaggcc gaggcggcgg cccgcgcgct ggcgcgcttc
      661 gcgcaggagg ccgaggcggc gcgcgtggac ctgcagaaga aggcgcaggc gctgcaggag
      721 gagtgcggct acctgcggcg ccaccaccag gaagaggtgg gcgagctgct cggccagatc
      781 cagggctccg gcgccgcgca ggcgcagatg caggccgaga cgcgcgacgc cctgaagtgc
      841 gacgtgacgt cggcgctgcg cgagattcgc gcgcagcttg aaggccacgc ggtgcagagc
      901 acgctgcagt ccgaggagtg gttccgagtg aggctggacc gactgtcgga ggcagccaag
      961 gtgaacacag acgctatgcg ctcagcgcag gaggagataa ctgagtaccg gcgtcagctg
     1021 caggccagga ccacagagct ggaggcactg aaaagcacca aggactcact ggagaggcag
     1081 cgctctgagc tggaggaccg tcatcaggcc gacattgcct cctaccagga agccattcag
     1141 cagctggacg ctgagctgag gaacaccaag tgggagatgg ccgcccagct gcgagaatac
     1201 caggacctgc tcaatgtcaa gatggctctg gatatagaga tagccgctta cagaaaactc
     1261 ctggaaggtg aagagtgtcg gattggcttt ggcccaattc ctttctcgct tccagaagga
     1321 ctccccaaaa ttccctctgt gtccactcac ataaaggtga aaagcgaaga gaagatcaaa
     1381 gtggtggaga agtctgagaa agaaactgtg attgtggagg aacagacaga ggagacccaa
     1441 gtgactgaag aagtgactga agaagaggag aaagaggcca aagaggagga gggcaaggag
     1501 gaagaagggg gtgaagaaga ggaggcagaa gggggagaag aagaaacaaa gtctccccca
     1561 gcagaagagg ctgcatcccc agagaaggaa gccaagtcac cagtaaagga agaggcaaag
     1621 tcaccggctg aggccaagtc cccagagaag gaggaagcaa aatccccagc cgaagtcaag
     1681 tcccctgaga aggccaagtc tccagcaaag gaagaggcaa agtcaccgcc tgaggccaag
     1741 tccccagaga aggaggaagc aaaatctcca gctgaggtca agtcccccga gaaggccaag
     1801 tccccagcaa aggaagaggc aaagtcaccg gctgaggcca agtctccaga gaaggccaag
     1861 tccccagtga aggaagaagc aaagtcaccg gctgaggcca agtccccagt gaaggaagaa
     1921 gcaaaatctc cagctgaggt caagtccccg gaaaaggcca agtctccaac gaaggaggaa
     1981 gcaaagtccc ctgagaaggc caagtcccca gagaaggaag aggccaagtc ccctgagaag
     2041 gccaagtccc cagtgaaggc agaagcaaag tcccctgaga aggccaagtc cccagtgaag
     2101 gcagaagcaa agtcccctga gaaggccaag tccccagtga aggaagaagc aaagtcccct
     2161 gagaaggcca agtccccagt gaaggaagaa gcaaagtccc ctgagaaggc caagtcccca
     2221 gtgaaggaag aagcaaagac ccccgagaag gccaagtccc cagtgaagga agaagctaag
     2281 tccccagaga aggccaagtc cccagagaag gccaagactc ttgatgtgaa gtctccagaa
     2341 gccaagactc cagcgaagga ggaagcaagg tcccctgcag acaaattccc tgaaaaggcc
     2401 aaaagccctg tcaaggagga ggtcaagtcc ccagagaagg cgaaatctcc cctgaaggag
     2461 gatgccaagg cccctgagaa ggagatccca aaaaaggaag aggtgaagtc cccagtgaag
     2521 gaggaggaga agccccagga ggtgaaagtc aaagagcccc caaagaaggc agaggaagag
     2581 aaagcccctg ccacaccaaa aacagaggag aagaaggaca gcaagaaaga ggaggcaccc
     2641 aagaaggagg ctccaaagcc caaggtggag gagaagaagg aacctgctgt cgaaaagccc
     2701 aaagaatcca aagttgaagc caagaaggaa gaggctgaag ataagaaaaa agtccccacc
     2761 ccagagaagg aggctcctgc caaggtggag gtgaaggaag acgctaaacc caaagaaaag
     2821 acagaggtag ccaagaagga accagatgat gccaaggcca aggaacccag caaaccagca
     2881 gagaagaagg aggcagcacc ggagaaaaaa gacaccaagg aggagaaggc caagaagcct
     2941 gaggagaaac ccaagacaga ggccaaagcc aaggaagatg acaagaccct ctcaaaagag
     3001 cctagcaagc ctaaggcaga aaaggctgaa aaatcctcca gcacagacca aaaagacagc
     3061 aagcctccag agaaggccac agaagacaag gccgccaagg ggaagtaagg cagggagaaa
     3121 ggaacatccg gaacagccaa agaaactcag aagagtcccg gagctcaagg atcagagtaa
     3181 cacaattttc actttttctg tctttatgta agaagaaact gcttagatga cggggcctcc
     3241 ttcttcaaac aggaatttct gttagcaata tgttagcaag agagggcact cccaggcccc
     3301 tgcccccagg ccctccccag gcgatggaca attatgatag cttatgtagc tgaatgtgat
     3361 acatgccgaa tgccacacgt aaacacttga ctataaaaac tgcccccctc ctttccaaat
     3421 aagtgcattt attgcctcta tgtgcaactg acagatgacc gcaataatga atgagcagtt
     3481 agaaatacat tatgcttgag atgtcttaac ctattcccaa atgccttctg ttttccaaag
     3541 gagtggtcaa gcccttgccc agagctctct attctggaag agcggtccag gtggggccgg
     3601 ggactggcca ctgaattatg ccagggcgca ctttccactg gagttcactt tcaattgctt
     3661 ctgtgcaata aaaccaagtg cttataaaat gaaaatgttg ctgctgttat tctctttccc
     3721 tgggaaggct gggggcaggg caggggaggt ctggatgtga caccccagac tgcatgggac
     3781 tgagcaagca tcagt
//
