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    OTOF otoferlin [ Homo sapiens (human) ]

    Gene ID: 9381, updated on 10-Dec-2024

    Summary

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    Official Symbol
    OTOFprovided by HGNC
    Official Full Name
    otoferlinprovided by HGNC
    Primary source
    HGNC:HGNC:8515
    See related
    Ensembl:ENSG00000115155 MIM:603681; AllianceGenome:HGNC:8515
    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]
    Expression
    Low expression observed in reference dataset See more
    Orthologs
    mouse all
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    Genomic context

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    See OTOF in Genome Data Viewer
    Location:
    2p23.3
    Exon count:
    48
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (26457203..26558756, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (26495826..26597899, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (26680071..26781624, complement)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene adhesion G protein-coupled receptor F3 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:26568936-26569703 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15471 Neighboring gene selenoprotein I Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15472 Neighboring gene dynein regulatory complex subunit 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:26680500-26681070 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:26681071-26681640 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:26683329-26684034 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr2:26685720-26686919 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15473 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:26703326-26703826 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:26704893-26705698 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:26712674-26712916 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15474 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11274 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:26728504-26729004 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:26734217-26735140 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:26744163-26744328 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:26759696-26760624 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:26760625-26761553 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:26765926-26766660 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:26780985-26781778 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:26781779-26782571 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:26785229-26785729 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:26788976-26789481 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:26799126-26799700 Neighboring gene ciliary microtubule inner protein 2C Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:26813715-26814459 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:26814460-26815203 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:26821036-26821536 Neighboring gene calcium and integrin binding family member 4 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:26856058-26856598

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. OTOF-Related Deafness. Adam MP, et al. , 1993. PMID 20301429
    2. Recurrent variants in OTOF are significant contributors to prelingual nonsydromic hearing loss in Saudi patients. Almontashiri NAM, et al. Genet Med, 2018 Apr. PMID 29048421, Free PMC Article
    3. Novel compound heterozygous mutations in the OTOF Gene identified by whole-exome sequencing in auditory neuropathy spectrum disorder. Tang F, et al. BMC Med Genet, 2017 Mar 23. PMID 28335750, Free PMC Article
    4. A novel missense mutation in the C2C domain of otoferlin causes profound hearing impairment in an Omani family with auditory neuropathy. Al-Wardy NM, et al. Saudi Med J, 2016 Oct. PMID 27652356, Free PMC Article
    5. High frequency of OTOF mutations in Chinese infants with congenital auditory neuropathy spectrum disorder. Zhang QJ, et al. Clin Genet, 2016 Sep. PMID 26818607

    See all (78) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. A splice-site variant (c.3289-1G>T) in OTOF underlies profound hearing loss in a Pakistani kindred.
      Title: A splice-site variant (c.3289-1G>T) in OTOF underlies profound hearing loss in a Pakistani kindred.
    2. [The updates of the ACMG variant interpretation guidelines affect the pathogenicity determination of OTOF gene variations in patients with auditory neuropathy].
      Title: [The updates of the ACMG variant interpretation guidelines affect the pathogenicity determination of OTOF gene variations in patients with auditory neuropathy].
    3. Predicting the Impact of OTOF Gene Missense Variants on Auditory Neuropathy Spectrum Disorder.
      Title: Predicting the Impact of OTOF Gene Missense Variants on Auditory Neuropathy Spectrum Disorder.
    4. Loss-of-function mutations in MYO15A and OTOF cause non-syndromic hearing loss in two Yemeni families.
      Title: Loss-of-function mutations in MYO15A and OTOF cause non-syndromic hearing loss in two Yemeni families.
    5. Intronic OTOF mutation causes an atypical splicing defect resulting in auditory neuropathy spectrum disorder.
      Title: Intronic OTOF mutation causes an atypical splicing defect resulting in auditory neuropathy spectrum disorder.
    6. Hearing of Otof-deficient mice restored by trans-splicing of N- and C-terminal otoferlin.
      Title: Hearing of Otof-deficient mice restored by trans-splicing of N- and C-terminal otoferlin.
    7. Membrane Protein OTOF Is a Type I Interferon-Induced Entry Inhibitor of HIV-1 in Macrophages.
      Title: Membrane Protein OTOF Is a Type I Interferon-Induced Entry Inhibitor of HIV-1 in Macrophages.
    8. Detailed clinical features and genotype-phenotype correlation in an OTOF-related hearing loss cohort in Japan.
      Title: Detailed clinical features and genotype-phenotype correlation in an OTOF-related hearing loss cohort in Japan.
    9. Cochlear Synaptopathy due to Mutations in OTOF Gene May Result in Stable Mild Hearing Loss and Severe Impairment of Speech Perception.
      Title: Cochlear Synaptopathy due to Mutations in OTOF Gene May Result in Stable Mild Hearing Loss and Severe Impairment of Speech Perception.
    10. The natural history of OTOF-related auditory neuropathy spectrum disorders: a multicenter study.
      Title: The natural history of OTOF-related auditory neuropathy spectrum disorders: a multicenter study.
    Submit: New GeneRIF Correction See all GeneRIFs (61)

    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
    Autosomal recessive nonsyndromic hearing loss 9
    MedGen: C1832828 OMIM: 601071 GeneReviews: OTOF-Related Deafness, Genetic Hearing Loss Overview
    		not available

    EBI GWAS Catalog

    Description
    Genome-wide association study of monoamine metabolite levels in human cerebrospinal fluid.
    EBI GWAS Catalog
    Genome-wide association study of periodontal pathogen colonization.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables calcium ion binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables calcium ion binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Process Evidence Code Pubs
    involved_in membrane fusion TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of neurotransmitter secretion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in sensory perception of sound IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in synaptic vesicle exocytosis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    located_in Golgi membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in basolateral plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cell projection IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in endoplasmic reticulum membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in presynaptic membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in synaptic vesicle membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in synaptic vesicle membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  

    General protein information

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    Preferred Names
    otoferlin
    Names
    fer-1-like family member 2
    fer-1-like protein 2

    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

    1. NG_009937.1 RefSeqGene

      Range
      4943..106496
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001287489.2 → NP_001274418.1  otoferlin isoform e

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) lacks an alternate in-frame exon in the 3' coding region and uses a downstream stop codon compared to variant 1. It encodes isoform e which has a distinct C-terminus compared to isoform 1.
      Source sequence(s)
      AC093378, AC108070, AF183185, AF183187, AK296272
      Consensus CDS
      CCDS74497.1
      UniProtKB/Swiss-Prot
      Q9HC10
      Related
      ENSP00000385255.3, ENST00000403946.7
      Conserved Domains (9) summary
      cd04011
      Location:251 → 362
      C2B_Ferlin; C2 domain second repeat in Ferlin
      cd04017
      Location:960 → 1097
      C2D_Ferlin; C2 domain fourth repeat in Ferlin
      cd04018
      Location:418 → 567
      C2C_Ferlin; C2 domain third repeat in Ferlin
      cd04037
      Location:1493 → 1616
      C2E_Ferlin; C2 domain fifth repeat in Ferlin
      cd08373
      Location:3 → 130
      C2A_Ferlin; C2 domain first repeat in Ferlin
      cd08374
      Location:1733 → 1866
      C2F_Ferlin; C2 domain sixth repeat in Ferlin
      pfam08150
      Location:842 → 917
      FerB; FerB (NUC096) domain
      pfam08151
      Location:360 → 410
      FerI; FerI (NUC094) domain
      pfam16165
      Location:1876 → 1994
      Ferlin_C; Ferlin C-terminus

    2. NM_004802.4 → NP_004793.2  otoferlin isoform b

      See identical proteins and their annotated locations for NP_004793.2

      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/TrEMBL
      A0A2U3TZT7
      Related
      ENSP00000345137.6, ENST00000338581.10
      Conserved Domains (6) summary
      cd04017
      Location:213 → 350
      C2D_Ferlin; C2 domain fourth repeat in Ferlin
      cd04037
      Location:726 → 849
      C2E_Ferlin; C2 domain fifth repeat in Ferlin
      cd08374
      Location:966 → 1099
      C2F_Ferlin; C2 domain sixth repeat in Ferlin
      pfam08150
      Location:96 → 170
      FerB; FerB (NUC096) domain
      pfam16165
      Location:1109 → 1195
      Ferlin_C; Ferlin C-terminus
      cl14603
      Location:396 → 473
      C2; C2 domain

    3. NM_194248.3 → NP_919224.1  otoferlin isoform a

      See identical proteins and their annotated locations for NP_919224.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).
      Source sequence(s)
      AC093378, AC108070, AF183185, AF183187
      Consensus CDS
      CCDS1725.1
      UniProtKB/Swiss-Prot
      B4DJX0, B5MCC1, B9A0H6, Q53R90, Q9HC08, Q9HC09, Q9HC10, Q9Y650
      Related
      ENSP00000272371.2, ENST00000272371.7
      Conserved Domains (10) summary
      cd04011
      Location:251 → 362
      C2B_Ferlin; C2 domain second repeat in Ferlin
      cd04017
      Location:960 → 1097
      C2D_Ferlin; C2 domain fourth repeat in Ferlin
      cd04018
      Location:418 → 567
      C2C_Ferlin; C2 domain third repeat in Ferlin
      cd04037
      Location:1493 → 1616
      C2E_Ferlin; C2 domain fifth repeat in Ferlin
      cd08373
      Location:3 → 130
      C2A_Ferlin; C2 domain first repeat in Ferlin
      cd08374
      Location:1733 → 1866
      C2F_Ferlin; C2 domain sixth repeat in Ferlin
      pfam08150
      Location:843 → 917
      FerB; FerB (NUC096) domain
      pfam08151
      Location:360 → 410
      FerI; FerI (NUC094) domain
      pfam16165
      Location:1876 → 1962
      Ferlin_C; Ferlin C-terminus
      cl14603
      Location:1143 → 1220
      C2; C2 domain

    4. NM_194322.3 → NP_919303.1  otoferlin isoform c

      See identical proteins and their annotated locations for NP_919303.1

      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
      UniProtKB/TrEMBL
      A0A2U3TZT7
      Related
      ENSP00000383906.4, ENST00000402415.8
      Conserved Domains (6) summary
      cd04017
      Location:270 → 407
      C2D_Ferlin; C2 domain fourth repeat in Ferlin
      cd04037
      Location:803 → 926
      C2E_Ferlin; C2 domain fifth repeat in Ferlin
      cd08374
      Location:1043 → 1176
      C2F_Ferlin; C2 domain sixth repeat in Ferlin
      pfam08150
      Location:153 → 227
      FerB; FerB (NUC096) domain
      pfam16165
      Location:1186 → 1272
      Ferlin_C; Ferlin C-terminus
      cl14603
      Location:453 → 530
      C2; C2 domain

    5. NM_194323.3 → NP_919304.1  otoferlin isoform d

      See identical proteins and their annotated locations for NP_919304.1

      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/TrEMBL
      A0A2U3TZT7
      Related
      ENSP00000344521.3, ENST00000339598.8
      Conserved Domains (6) summary
      cd04017
      Location:213 → 350
      C2D_Ferlin; C2 domain fourth repeat in Ferlin
      cd04037
      Location:726 → 849
      C2E_Ferlin; C2 domain fifth repeat in Ferlin
      cd08374
      Location:966 → 1099
      C2F_Ferlin; C2 domain sixth repeat in Ferlin
      pfam08150
      Location:96 → 170
      FerB; FerB (NUC096) domain
      pfam16165
      Location:1109 → 1225
      Ferlin_C; Ferlin C-terminus
      cl14603
      Location:396 → 473
      C2; C2 domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    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
      26457203..26558756 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      26495826..26597899 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9HC10.3 GenPept UniProtKB/Swiss-Prot:Q9HC10

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