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Otof otoferlin [ Mus musculus (house mouse) ]

Gene ID: 83762, updated on 11-Apr-2024

Summary

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Official Symbol
Otofprovided by MGI
Official Full Name
otoferlinprovided by MGI
Primary source
MGI:MGI:1891247
See related
Ensembl:ENSMUSG00000062372 AllianceGenome:MGI:1891247
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Mus musculus
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Summary
Enables AP-2 adaptor complex binding activity and calcium ion binding activity. Involved in synaptic vesicle priming. Located in endoplasmic reticulum; presynaptic active zone membrane; and synaptic vesicle membrane. Is expressed in brain; pons mantle layer; and rest of cerebellum ventricular layer. Used to study autosomal recessive nonsyndromic deafness 9. Human ortholog(s) of this gene implicated in autosomal recessive nonsyndromic deafness 9. Orthologous to human OTOF (otoferlin). [provided by Alliance of Genome Resources, Apr 2022]
Expression
Biased expression in CNS E18 (RPKM 4.0), cortex adult (RPKM 3.4) and 9 other tissues See more
Orthologs
human all
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Genomic context

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See Otof in Genome Data Viewer
Location:
5 B1; 5 16.48 cM
Exon count:
49
Annotation release Status Assembly Chr Location
RS_2024_02 current GRCm39 (GCF_000001635.27) 5 NC_000071.7 (30524410..30620073, complement)
108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 5 NC_000071.6 (30367066..30462730, complement)

Chromosome 5 - NC_000071.7Genomic Context describing neighboring genes Neighboring gene selenoprotein I Neighboring gene predicted gene 16288 Neighboring gene CapStarr-seq enhancer MGSCv37_chr5:30645501-30645684 Neighboring gene dynein regulatory complex subunit 1 Neighboring gene STARR-seq mESC enhancer starr_12752 Neighboring gene ciliary microtubule inner protein 2C Neighboring gene calcium and integrin binding family member 4 Neighboring gene predicted gene, 40272

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: Mouse ENCODE transcriptome data
  • Description: RNA profiling data sets generated by the Mouse ENCODE project.
  • BioProject: PRJNA66167
  • Publication: PMID 25409824
  • Analysis date: n/a

Bibliography

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Related articles in PubMed

  1. Apoptosis of type I spiral ganglion neuron cells in Otof-mutant mice. Tsuzuki N, et al. Neurosci Lett, 2023 Apr 23. PMID 36914046
  2. Impaired Hearing and Altered Subplate Circuits During the First and Second Postnatal Weeks of Otoferlin-Deficient Mice. Mukherjee D, et al. Cereb Cortex, 2022 Jun 16. PMID 34849612, Free PMC Article
  3. Otoferlin Is Required for Proper Synapse Maturation and for Maintenance of Inner and Outer Hair Cells in Mouse Models for DFNB9. Stalmann U, et al. Front Cell Neurosci, 2021. PMID 34335185, Free PMC Article
  4. Viral Transfer of Mini-Otoferlins Partially Restores the Fast Component of Exocytosis and Uncovers Ultrafast Endocytosis in Auditory Hair Cells of Otoferlin Knock-Out Mice. Tertrais M, et al. J Neurosci, 2019 May 1. PMID 30833506, Free PMC Article
  5. Disruption of Otoferlin Alters the Mode of Exocytosis at the Mouse Inner Hair Cell Ribbon Synapse. Takago H, et al. Front Mol Neurosci, 2018. PMID 30687007, Free PMC Article

See all (62) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Apoptosis of type I spiral ganglion neuron cells in Otof-mutant mice.
    Title: Apoptosis of type I spiral ganglion neuron cells in Otof-mutant mice.
  2. Impaired Hearing and Altered Subplate Circuits During the First and Second Postnatal Weeks of Otoferlin-Deficient Mice.
    Title: Impaired Hearing and Altered Subplate Circuits During the First and Second Postnatal Weeks of Otoferlin-Deficient Mice.
  3. Altered Gap Junction Network Topography in Mouse Models for Human Hereditary Deafness.
    Title: Altered Gap Junction Network Topography in Mouse Models for Human Hereditary Deafness.
  4. Study shows the viral expression of truncated forms of otoferlin can partially rescue the fast and transient release component of exocytosis in mouse hair cells lacking otoferlin, yet cannot sustain exocytosis after long repeated stimulation.
    Title: Viral Transfer of Mini-Otoferlins Partially Restores the Fast Component of Exocytosis and Uncovers Ultrafast Endocytosis in Auditory Hair Cells of Otoferlin Knock-Out Mice.
  5. Otoferlin thus functions as a Ca(2+) sensor, setting the rates of primed vesicle fusion with the presynaptic plasma membrane and synaptic vesicle pool replenishment in the inner hair cell active zone.
    Title: Otoferlin acts as a Ca(2+) sensor for vesicle fusion and vesicle pool replenishment at auditory hair cell ribbon synapses.
  6. Furthermore, this F-actin mesh network attached to the synaptic ribbons directly influences the efficiency of otoferlin-dependent exocytosis and its sensitivity to intracellular hydrostatic pressure.
    Title: A synaptic F-actin network controls otoferlin-dependent exocytosis in auditory inner hair cells.
  7. Mice that carry a mutation in a calcium binding domain of Otoferlin, the putative calcium sensor at hair cell synapses, have normal distortion product otoacoustic emissions (DPOAEs), but auditory brain stem responses (ABRs) are absent.
    Title: Synaptic transmission between end bulbs of Held and bushy cells in the cochlear nucleus of mice with a mutation in Otoferlin.
  8. a direct role for otoferlin in exocytosis and modulation of calcium-dependent membrane fusion
    Title: Calcium regulates molecular interactions of otoferlin with soluble NSF attachment protein receptor (SNARE) proteins required for hair cell exocytosis.
  9. The analysis of otoferlin knockout mice gave the 1st insights into its function in inner hair cell calcium-dependent exocytosis & type-i vestibular hair cells. Review.
    Title: Otoferlin: a multi-C2 domain protein essential for hearing.
  10. Co-localization studies revealed an overlap of Ergic2 and Otoferlin signals in IHCs and neurons of cerebral cortical layer I making Ergic2 the promising binding candidate
    Title: Ergic2, a brain specific interacting partner of Otoferlin.
Submit: New GeneRIF Correction See all GeneRIFs (21)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics  (MGI)

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC183613

Gene Ontology Provided by MGI

Function Evidence Code Pubs
enables AP-2 adaptor complex binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables AP-2 adaptor complex binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables calcium ion binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables calcium ion binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein-containing complex binding ISO
Inferred from Sequence Orthology
more info
  
Process Evidence Code Pubs
involved_in plasma membrane organization IBA
Inferred from Biological aspect of Ancestor
more info
  
acts_upstream_of_or_within sensory perception of sound ISO
Inferred from Sequence Orthology
more info
 PubMed 
acts_upstream_of_or_within startle response ISO
Inferred from Sequence Orthology
more info
 PubMed 
involved_in synaptic vesicle exocytosis EXP
Inferred from Experiment
more info
 PubMed 
involved_in synaptic vesicle exocytosis IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of_or_within synaptic vesicle exocytosis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in synaptic vesicle exocytosis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in synaptic vesicle priming IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in synaptic vesicle priming IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in synaptic vesicle priming IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
located_in Golgi apparatus IEA
Inferred from Electronic Annotation
more info
  
located_in apical part of cell ISO
Inferred from Sequence Orthology
more info
  
located_in basal part of cell ISO
Inferred from Sequence Orthology
more info
  
located_in cell projection IEA
Inferred from Electronic Annotation
more info
  
located_in clathrin-sculpted glutamate transport vesicle membrane TAS
Traceable Author Statement
more info
  
is_active_in cochlear hair cell ribbon synapse EXP
Inferred from Experiment
more info
 PubMed 
is_active_in cochlear hair cell ribbon synapse IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in cochlear hair cell ribbon synapse IMP
Inferred from Mutant Phenotype
more info
 PubMed 
located_in cytoplasmic vesicle IEA
Inferred from Electronic Annotation
more info
  
located_in endoplasmic reticulum IDA
Inferred from Direct Assay
more info
 PubMed 
located_in membrane IEA
Inferred from Electronic Annotation
more info
  
located_in plasma membrane IEA
Inferred from Electronic Annotation
more info
  
is_active_in presynaptic active zone membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in presynaptic active zone membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in synapse IEA
Inferred from Electronic Annotation
more info
  
is_active_in synaptic vesicle membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in synaptic vesicle membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in synaptic vesicle membrane IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
otoferlin
Names
fer-1-like protein 2
protein pachanga

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.

mRNA and Protein(s)

  1. NM_001100395.1 → NP_001093865.1  otoferlin isoform 1

    See identical proteins and their annotated locations for NP_001093865.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) contains multiple coding region differences resulting in different 3' coding region and 3' UTR, compared to variant 2. It encodes isoform 1, which is shorter and has a distinct C-terminus, compared to isoform 2.
    Source sequence(s)
    AC157761, AK033317, AK046460, AK147256
    Consensus CDS
    CCDS51452.1
    UniProtKB/TrEMBL
    A0A0R4J1K2, B7ZN98
    Related
    ENSMUSP00000110395.3, ENSMUST00000114747.9
    Conserved Domains (10) summary
    cd04011
    Location:265 → 376
    C2B_Ferlin; C2 domain second repeat in Ferlin
    cd04017
    Location:974 → 1111
    C2D_Ferlin; C2 domain fourth repeat in Ferlin
    cd04018
    Location:432 → 581
    C2C_Ferlin; C2 domain third repeat in Ferlin
    cd04037
    Location:1488 → 1611
    C2E_Ferlin; C2 domain fifth repeat in Ferlin
    cd08373
    Location:3 → 130
    C2A_Ferlin; C2 domain first repeat in Ferlin
    cd08374
    Location:1728 → 1861
    C2F_Ferlin; C2 domain sixth repeat in Ferlin
    pfam08150
    Location:857 → 931
    FerB; FerB (NUC096) domain
    pfam08151
    Location:374 → 424
    FerI; FerI (NUC094) domain
    pfam16165
    Location:1871 → 1987
    Ferlin_C; Ferlin C-terminus
    cl14603
    Location:1157 → 1234
    C2; C2 domain

  2. NM_001286421.1 → NP_001273350.1  otoferlin isoform 3

    Status: VALIDATED

    Description
    Transcript Variant: This variant (3) uses an alternate in-frame splice site in the 3' coding region, compared to variant 2. It encodes isoform 3, which is shorter than isoform 2.
    Source sequence(s)
    AK033317, AK046460, AK147256
    UniProtKB/TrEMBL
    B7ZN98
    Related
    ENSMUST00000150734.8
    Conserved Domains (10) summary
    cd04011
    Location:250 → 361
    C2B_Ferlin; C2 domain second repeat in Ferlin
    cd04017
    Location:959 → 1096
    C2D_Ferlin; C2 domain fourth repeat in Ferlin
    cd04018
    Location:417 → 566
    C2C_Ferlin; C2 domain third repeat in Ferlin
    cd04037
    Location:1473 → 1596
    C2E_Ferlin; C2 domain fifth repeat in Ferlin
    cd08373
    Location:3 → 130
    C2A_Ferlin; C2 domain first repeat in Ferlin
    cd08374
    Location:1713 → 1846
    C2F_Ferlin; C2 domain sixth repeat in Ferlin
    pfam08150
    Location:842 → 916
    FerB; FerB (NUC096) domain
    pfam08151
    Location:359 → 409
    FerI; FerI (NUC094) domain
    pfam16165
    Location:1856 → 1942
    Ferlin_C; Ferlin C-terminus
    cl14603
    Location:1142 → 1219
    C2; C2 domain

  3. NM_001313767.1 → NP_001300696.1  otoferlin isoform 4

    Status: VALIDATED

    Description
    Transcript Variant: This variant (4) uses an alternate in-frame splice junction in the 3' end and lacks the penultimate exon compared to variant 2. It encodes isoform 4, which lacks an internal segment and has a shorter and distinct C-terminus compared to isoform 2.
    Source sequence(s)
    AC157761, AC175379, AC242405
    UniProtKB/TrEMBL
    A0A2Z2CEU0, B7ZN98
    Conserved Domains (10) summary
    cd04011
    Location:250 → 361
    C2B_Ferlin; C2 domain second repeat in Ferlin
    cd04017
    Location:959 → 1096
    C2D_Ferlin; C2 domain fourth repeat in Ferlin
    cd04018
    Location:417 → 566
    C2C_Ferlin; C2 domain third repeat in Ferlin
    cd04037
    Location:1473 → 1596
    C2E_Ferlin; C2 domain fifth repeat in Ferlin
    cd08373
    Location:3 → 130
    C2A_Ferlin; C2 domain first repeat in Ferlin
    cd08374
    Location:1713 → 1846
    C2F_Ferlin; C2 domain sixth repeat in Ferlin
    pfam08150
    Location:842 → 916
    FerB; FerB (NUC096) domain
    pfam08151
    Location:359 → 409
    FerI; FerI (NUC094) domain
    pfam16165
    Location:1856 → 1972
    Ferlin_C; Ferlin C-terminus
    cl14603
    Location:1142 → 1219
    C2; C2 domain

  4. NM_031875.2 → NP_114081.2  otoferlin isoform 2

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) represents the longest transcript and encodes the longest isoform (2).
    Source sequence(s)
    AC175379, AK033317, AK046460, AK147256
    Consensus CDS
    CCDS19157.1
    UniProtKB/Swiss-Prot
    A3KLM3, B2RWU0, Q8CCE7, Q9ESF1, Q9ESF2
    UniProtKB/TrEMBL
    E9PYR6
    Related
    ENSMUSP00000073803.7, ENSMUST00000074171.10
    Conserved Domains (9) summary
    cd04011
    Location:250 → 361
    C2B_Ferlin; C2 domain second repeat in Ferlin
    cd04017
    Location:959 → 1096
    C2D_Ferlin; C2 domain fourth repeat in Ferlin
    cd04018
    Location:417 → 566
    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 → 916
    FerB; FerB (NUC096) domain
    pfam08151
    Location:359 → 409
    FerI; FerI (NUC094) domain
    pfam16165
    Location:1876 → 1994
    Ferlin_C; Ferlin C-terminus

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

  1. NC_000071.7 Reference GRCm39 C57BL/6J

    Range
    30524410..30620073 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006504206.4 → XP_006504269.1  otoferlin isoform X2

    UniProtKB/Swiss-Prot
    A3KLM3, B2RWU0, Q8CCE7, Q9ESF1, Q9ESF2
    Conserved Domains (9) summary
    cd04011
    Location:250 → 361
    C2B_Ferlin; C2 domain second repeat in Ferlin
    cd04017
    Location:959 → 1096
    C2D_Ferlin; C2 domain fourth repeat in Ferlin
    cd04018
    Location:417 → 566
    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 → 916
    FerB; FerB (NUC096) domain
    pfam08151
    Location:359 → 409
    FerI; FerI (NUC094) domain
    pfam16165
    Location:1876 → 1994
    Ferlin_C; Ferlin C-terminus

  2. XM_006504209.5 → XP_006504272.1  otoferlin isoform X5

    UniProtKB/Swiss-Prot
    A3KLM3, B2RWU0, Q8CCE7, Q9ESF1, Q9ESF2
    Conserved Domains (9) summary
    cd04011
    Location:73 → 184
    C2B_Ferlin; C2 domain second repeat in Ferlin
    cd04017
    Location:782 → 919
    C2D_Ferlin; C2 domain fourth repeat in Ferlin
    cd04018
    Location:240 → 389
    C2C_Ferlin; C2 domain third repeat in Ferlin
    cd04037
    Location:1316 → 1439
    C2E_Ferlin; C2 domain fifth repeat in Ferlin
    cd08374
    Location:1556 → 1689
    C2F_Ferlin; C2 domain sixth repeat in Ferlin
    pfam08150
    Location:665 → 739
    FerB; FerB (NUC096) domain
    pfam08151
    Location:182 → 232
    FerI; FerI (NUC094) domain
    pfam16165
    Location:1699 → 1817
    Ferlin_C; Ferlin C-terminus
    cl14603
    Location:965 → 1042
    C2; C2 domain

  3. XM_017321186.2 → XP_017176675.1  otoferlin isoform X3

    UniProtKB/Swiss-Prot
    A3KLM3, B2RWU0, Q8CCE7, Q9ESF1, Q9ESF2
    Conserved Domains (9) summary
    cd04011
    Location:250 → 361
    C2B_Ferlin; C2 domain second repeat in Ferlin
    cd04017
    Location:959 → 1096
    C2D_Ferlin; C2 domain fourth repeat in Ferlin
    cd04018
    Location:417 → 566
    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 → 916
    FerB; FerB (NUC096) domain
    pfam08151
    Location:359 → 409
    FerI; FerI (NUC094) domain
    pfam16165
    Location:1876 → 1944
    Ferlin_C; Ferlin C-terminus

  4. XM_017321185.2 → XP_017176674.1  otoferlin isoform X1

    UniProtKB/Swiss-Prot
    A3KLM3, B2RWU0, Q8CCE7, Q9ESF1, Q9ESF2
    UniProtKB/TrEMBL
    E9PYR6
    Conserved Domains (9) summary
    cd04011
    Location:250 → 361
    C2B_Ferlin; C2 domain second repeat in Ferlin
    cd04017
    Location:959 → 1096
    C2D_Ferlin; C2 domain fourth repeat in Ferlin
    cd04018
    Location:417 → 566
    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 → 916
    FerB; FerB (NUC096) domain
    pfam08151
    Location:359 → 409
    FerI; FerI (NUC094) domain
    pfam16165
    Location:1876 → 1994
    Ferlin_C; Ferlin C-terminus

  5. XM_006504208.5 → XP_006504271.1  otoferlin isoform X4

    UniProtKB/Swiss-Prot
    A3KLM3, B2RWU0, Q8CCE7, Q9ESF1, Q9ESF2
    Conserved Domains (9) summary
    cd04011
    Location:250 → 361
    C2B_Ferlin; C2 domain second repeat in Ferlin
    cd04017
    Location:959 → 1096
    C2D_Ferlin; C2 domain fourth repeat in Ferlin
    cd04018
    Location:417 → 566
    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 → 916
    FerB; FerB (NUC096) domain
    pfam08151
    Location:359 → 409
    FerI; FerI (NUC094) domain
    pfam16165
    Location:1876 → 1938
    Ferlin_C; Ferlin C-terminus

  6. XM_011240802.3 → XP_011239104.1  otoferlin isoform X6

    Conserved Domains (6) summary
    cd04011
    Location:250 → 361
    C2B_Ferlin; C2 domain second repeat in Ferlin
    cd04017
    Location:959 → 1096
    C2D_Ferlin; C2 domain fourth repeat in Ferlin
    cd04018
    Location:417 → 566
    C2C_Ferlin; C2 domain third repeat in Ferlin
    cd08373
    Location:3 → 130
    C2A_Ferlin; C2 domain first repeat in Ferlin
    pfam08150
    Location:842 → 916
    FerB; FerB (NUC096) domain
    pfam08151
    Location:359 → 409
    FerI; FerI (NUC094) domain

RNA

  1. XR_001784761.3 RNA Sequence

  2. XR_376842.4 RNA Sequence

  3. XR_376841.4 RNA Sequence

Nucleotide Protein Strain
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9ESF1.1 GenPept UniProtKB/Swiss-Prot:Q9ESF1

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