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    OTOF otoferlin [ Homo sapiens (human) ]

    Gene ID: 9381, updated on 5-May-2013
    Official Symbol
    OTOFprovided by HGNC
    Official Full Name
    otoferlinprovided by HGNC
    Primary source
    HGNC:8515
    See related
    Ensembl:ENSG00000115155; HPRD:04727; MIM:603681; Vega:OTTHUMG00000096977
    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
    AUNB1; DFNB6; DFNB9; NSRD9; FER1L2
    Summary
    Mutations in this gene are a cause of neurosensory nonsyndromic recessive deafness, DFNB9. The short form of the encoded protein has 3 C2 domains, a single carboxy-terminal transmembrane domain found also in the C. elegans spermatogenesis factor FER-1 and human dysferlin, while the long form has 6 C2 domains. The homology suggests that this protein may be involved in vesicle membrane fusion. Several transcript variants encoding multiple isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
    Location :
    2p23.1
    Sequence :
    Chromosome: 2; NC_000002.11 (26680071..26781566, complement)
    See OTOF in Epigenomics, MapViewer

    Chromosome 2 - NC_000002.11Genomic Context describing neighboring genes Neighboring gene G protein-coupled receptor 113 Neighboring gene ethanolaminephosphotransferase 1 (CDP-ethanolamine-specific) Neighboring gene dynein regulatory complex subunit 1 homolog (Chlamydomonas) Neighboring gene chromosome 2 open reading frame 70 Neighboring gene calcium and integrin binding family member 4

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    Deafness, autosomal recessive 9

    Summary from GeneReviews: OTOF-Related Deafness Go to GeneReviews

    Disease Characteristics
    OTOF-related deafness (DFNB9 nonsyndromic hearing loss) is characterized by two phenotypes: prelingual nonsyndromic hearing loss and, less frequently, temperature-sensitive nonsyndromic auditory neuropathy (TS-NSAN). The nonsyndromic hearing loss is bilateral severe-to-profound congenital deafness. In the first one or two years of life, OTOF-related deafness can appear to be an auditory neuropathy based on electrophysiologic testing in which auditory brain stem responses (ABRs) are absent and otoacoustic emissions (OAEs) are present. However, with time OAEs disappear and electrophysiologic testing is more consistent with a cochlear defect. The distinction between auditory neuropathy and a cochlear defect is important as cochlear implants may be of marginal value in persons with auditory neuropathy. TS-NSAN characterized by normal-to-mild hearing loss in the absence of fever and significant hearing loss ranging from severe-to-profound in the presence of fever. When the fever resolves, hearing returns to normal.
    Diagnosis Testing
    The diagnosis of OTOF-related deafness is suspected based on clinical findings, including results of ABR if in the early stages. The diagnosis is confirmed by molecular genetic testing of OTOF, the gene encoding the protein otoferlin. OTOF is the only gene known to be associated with this condition.
    Genetic Counseling
    OTOF-related deafness is inherited in an autosomal recessive manner. At conception, each sib of an individual with OTOF-related deafness has a 25% chance of having OTOF-related deafness, a 50% chance of being a carrier, and a 25% chance of being unaffected and not a carrier. Heterozygotes (carriers) are asymptomatic. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the deafness-causing mutations in a family are known.
    References

    Summary from GeneReviews: Deafness and Hereditary Hearing Loss Overview Go to GeneReviews

    Disease Characteristics
    Hereditary hearing loss and deafness may be conductive, sensorineural, or a combination of both; syndromic (associated with malformations of the external ear or other organs or with medical problems involving other organ systems) or nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems); and prelingual (before language develops) or postlingual (after language develops).
    Diagnosis Testing
    Genetic forms of hearing loss must be distinguished from acquired (non-genetic) causes of hearing loss. The genetic forms of hearing loss are diagnosed by otologic, audiologic, and physical examination, family history, ancillary testing (e.g., CT examination of the temporal bone), and molecular genetic testing. Molecular genetic testing, available in clinical laboratories for many types of syndromic and nonsyndromic deafness, plays a prominent role in diagnosis and genetic counseling.
    Genetic Counseling
    Hereditary hearing loss can be inherited in an autosomal dominant, autosomal recessive, or X-linked recessive manner, as well as by mitochondrial inheritance. Genetic counseling and risk assessment depend on accurate determination of the specific genetic diagnosis. In the absence of a specific diagnosis, empiric recurrence risk figures, coupled with GJB2 and GJB6 molecular genetic testing results, can be used for genetic counseling.
    References
    Products Interactant Other Gene Complex Source Pubs Description
    BioGRID:114782 BioGRID:118159 STK39    BioGRID  PubMed Two-hybrid 

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    calcium ion binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    molecular_function ND
    No biological Data available
    more info
     
    Process Evidence Code Pubs
    cellular membrane fusion TAS
    Traceable Author Statement
    more info
    PubMed 
    sensory perception of sound IEA
    Inferred from Electronic Annotation
    more info
     
    synaptic vesicle exocytosis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    Component Evidence Code Pubs
    basolateral plasma membrane IEA
    Inferred from Electronic Annotation
    more info
     
    cell junction IEA
    Inferred from Electronic Annotation
    more info
     
    cytosol TAS
    Traceable Author Statement
    more info
    PubMed 
    endoplasmic reticulum membrane IEA
    Inferred from Electronic Annotation
    more info
     
    integral to membrane IEA
    Inferred from Electronic Annotation
    more info
     
    synaptic vesicle membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    Preferred Names
    otoferlin
    Names
    otoferlin
    fer-1-like protein 2
    otoferlin transcript variant 46-48

    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_009937.1 RefSeqGene

      Range
      5001..106496
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_004802.3NP_004793.2  otoferlin isoform b

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR and coding region compared to variant 1. The resulting isoform (b, also called 'short form 1') has a shorter N-terminus and lacks a segment compared to isoform a.
      Source sequence(s)
      AC093378, AF107403, AF183187
      Consensus CDS
      CCDS1726.1
      UniProtKB/Swiss-Prot
      Q9HC10
      Related
      ENSP00000345137, OTTHUMP00000122454, ENST00000338581, OTTHUMT00000214048
      Conserved Domains (4) summary
      pfam08150
      Location:95172
      Blast Score: 345
      FerB; FerB (NUC096) domain
      cd04017
      Location:213350
      Blast Score: 595
      C2D_Ferlin; C2 domain fourth repeat in Ferlin
      cd04037
      Location:726849
      Blast Score: 582
      C2E_Ferlin; C2 domain fifth repeat in Ferlin
      cd08374
      Location:9661099
      Blast Score: 611
      C2F_Ferlin; C2 domain sixth repeat in Ferlin
    2. NM_194248.2NP_919224.1  otoferlin isoform a

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).
      Source sequence(s)
      AC093378, AF183185, AF183187
      Consensus CDS
      CCDS1725.1
      UniProtKB/Swiss-Prot
      Q9HC10
      Related
      ENSP00000272371, OTTHUMP00000122453, ENST00000272371, OTTHUMT00000214047
      Conserved Domains (8) summary
      pfam08150
      Location:842919
      Blast Score: 349
      FerB; FerB (NUC096) domain
      pfam08151
      Location:339410
      Blast Score: 326
      FerI; FerI (NUC094) domain
      cd04011
      Location:251362
      Blast Score: 556
      C2B_Ferlin; C2 domain second repeat in Ferlin
      cd04017
      Location:9601097
      Blast Score: 598
      C2D_Ferlin; C2 domain fourth repeat in Ferlin
      cd04018
      Location:418567
      Blast Score: 727
      C2C_Ferlin; C2 domain third repeat in Ferlin
      cd04037
      Location:14931616
      Blast Score: 581
      C2E_Ferlin; C2 domain fifth repeat in Ferlin
      cd08373
      Location:3130
      Blast Score: 456
      C2A_Ferlin; C2 domain first repeat in Ferlin
      cd08374
      Location:17331866
      Blast Score: 610
      C2F_Ferlin; C2 domain sixth repeat in Ferlin
    3. NM_194322.2NP_919303.1  otoferlin isoform c

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (c, also called 'short form 2') has a shorter and distinct C-terminus compared to isoform a.
      Source sequence(s)
      AC093378, AF183186, AF183187
      Consensus CDS
      CCDS46241.1
      UniProtKB/Swiss-Prot
      Q9HC10
      Related
      ENSP00000383906, OTTHUMP00000200815, ENST00000402415, OTTHUMT00000324492
      Conserved Domains (4) summary
      pfam08150
      Location:152229
      Blast Score: 345
      FerB; FerB (NUC096) domain
      cd04017
      Location:270407
      Blast Score: 595
      C2D_Ferlin; C2 domain fourth repeat in Ferlin
      cd04037
      Location:803926
      Blast Score: 582
      C2E_Ferlin; C2 domain fifth repeat in Ferlin
      cd08374
      Location:10431176
      Blast Score: 611
      C2F_Ferlin; C2 domain sixth repeat in Ferlin
    4. NM_194323.2NP_919304.1  otoferlin isoform d

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR and coding region, as well as in the 3' coding region, compared to variant 1. The resulting isoform (d) has a shorter N-terminus and a distinct C-terminus compared to isoform a.
      Source sequence(s)
      AC093378, AF183185, AF183187
      Consensus CDS
      CCDS1724.1
      UniProtKB/Swiss-Prot
      Q9HC10
      Related
      ENSP00000344521, OTTHUMP00000122455, ENST00000339598, OTTHUMT00000214049
      Conserved Domains (4) summary
      pfam08150
      Location:95172
      Blast Score: 345
      FerB; FerB (NUC096) domain
      cd04017
      Location:213350
      Blast Score: 596
      C2D_Ferlin; C2 domain fourth repeat in Ferlin
      cd04037
      Location:726849
      Blast Score: 582
      C2E_Ferlin; C2 domain fifth repeat in Ferlin
      cd08374
      Location:9661099
      Blast Score: 611
      C2F_Ferlin; C2 domain sixth repeat in Ferlin

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

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

    Reference GRCh37.p10 Primary Assembly

    Genomic

    1. NC_000002.11 Reference GRCh37.p10 Primary Assembly

      Range
      26680071..26781566, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000134.1 Alternate HuRef

      Range
      26419277..26520993, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.0

    Genomic

    1. NC_018913.1 Alternate CHM1_1.0

      Range
      26602915..26704362, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

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