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FLASH GENE
Symbol OTOF contributors: mct/npt/pgu - updated : 13-10-2009
HGNC name otoferlin
HGNC id 8515
Corresponding disease
DFNB9 neurosensory deafness 9
NSRAN non-syndromic recessive auditory neuropathy
Location 2p23.3      Physical location : 26.680.071 - 26.781.566
Synonym name Fer-1-like protein 2
Synonym symbol(s) NSRD9, FER1L2
DNA
TYPE functioning gene
STRUCTURE 101.50 kb     47 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Map pter - D2S2170 - ADCY3 - D2S171 - KHK KHK - D2S2303 - DTNB - KIF3C - HADHA - D2S158 - HADHB - D2S2223 - D2S2350 - CENPA - D2S174 - D2S166 - D2S365 - SNX17 - GCKR - D2S170 - cen
Text see DFNB9
Physical map
ASXL2 2p24.1 additional sex combs like 2 (Drosophila) KIF3C 2p23 kinesin family member 3C LOC391357 2 similar to Ubiquinol-cytochrome C reductase complex 11 kDa protein, mitochondrial precursor (Mitochondrial hinge protein) (Cytochrome C1, nonheme 11 kDa protein) (Complex III subunit VIII) LOC391358 2 similar to hypothetical protein HSPC152 RAB10 2p24.1 RAB10, member RAS oncogene family LOC391359 2 similar to Epithelial membrane protein-2 (EMP-2) (XMP protein) LOC130482 2p24.1 similar to SWI/SNF-related matrix-associated actin-dependent regulator of chromatin e1; mammalian chromatin remodeling complex BRG1-associated factor 57 PPIL1P1 2p23.3 peptidylprolyl isomerase (cyclophilin)-like 1 pseudogene 1 LOC150946 2p24.1 hypothetical protein LOC150946 HADHA 2p23 hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme A thiolase/enoyl-Coenzyme A hydratase (trifunctional protein), alpha subunit HADHB 2p23 hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme A thiolase/enoyl-Coenzyme A hydratase (trifunctional protein), beta subunit GPR113 2p24.1 G protein-coupled receptor 113 KIAA1724 2p24.1 selenoprotein I, 1 MGC16372 2p24.1 CG10958-like OTOF 2p23-p22 otoferlin LOC388936 2 similar to RIKEN cDNA 1700001C02 LOC130106 2p24.1 similar to Calcium and integrin-binding protein 1 (Calmyrin) (DNA-PKcs interacting protein) (Kinase interacting protein) (KIP) (CIB) KCNK3 2p24.1-p23.1 potassium channel, subfamily K, member 3 FLJ20555 CENPA 2p23.1-p22.3 centromere protein A, 17kDa DPYSL5 2p23-p21 dihydropyrimidinase-like 5 MAPRE3 2p23.3-p23.1 microtubule-associated protein, RP/EB family, member 3 FLJ20254 2p23.3 hypothetical protein FLJ20254 FLJ21839 2p23.3 hypothetical protein FLJ21839 EMILIN1 2p23.3-p23.2 elastin microfibril interfacer 1 KHK 2p23.3-p23.2 ketohexokinase (fructokinase) CGREF1 2p23.3 cell growth regulator with EF hand domain 1 ABHD1 2p23.3 abhydrolase domain containing 1 PREB 2p23 prolactin regulatory element binding MGC44505 2p23.3 hypothetical protein MGC44505 LOC391360 2 similar to class II basic helix-loop-helix protein TCF23 SLC5A6 2p23 solute carrier family 5 (sodium-dependent vitamin transporter), member 6
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
30 initiation site 4969 140.5 1230 fetus and some adult tissues 2006 16371502
  • exon 20-48, three C2 domains
  • short form 1
  • 47 initiation site 7171 227 1997 - 2006 16371502
  • exon 18
  • long form
  • 29 initiation site 5123 149 1307 - 2006 16371502
  • start site with additional AA, exons 20-48
  • short form
  • 29 splicing 4771 140.5 1230 cochlea, heart, brain 2006 16371502
    skipping exon 47
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Hearing/Equilibriumearinnervestibule  
    Lymphoid/Immunethymus    
    Nervousbrain    
     spinal cord    
    Reproductivemale systemprostate   
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone   
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    hearing equilibriuminner ear
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text neuroepithelium of utricle, saccule and semicircular canals; inner and outer hair cells, spinal ganglion cells, placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • six C2 domains (C2A-F) homolog to C2 calcium binding domain of protein kinase C,
  • two (C2A-B) not binding Ca2+, a SH3 domain,a single carboxy terminal transmembrane domain
  • a short C terminal extracellular tail
  • HOMOLOGY
    interspecies homolog to C.elegans otoferlin a FER1-like
    Homologene
    FAMILY
  • ferlin family
  • CATEGORY transport
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic,vesicle
    text
  • type II transmembrane protein
  • cytosolic membrane anchored
  • localizing to ribbon-associated synaptic vesicles in hair cells
  • basic FUNCTION
  • multi-C2 domain protein, putatively involved in synaptic vesicular trafficking and vesicle membrane fusion
  • is essential for a late step of synaptic vesicle exocytosis and may act as the major Ca(2+) sensor triggering membrane fusion at the inner hair cell ribbon synapse
  • could be a part of components contributing to trans-Golgi trafficking
  • C2 domain-containing Ca2+-binding protein, implicated as having a role in vesicular release
  • involved in replenishing synaptic vesicles
  • confers the high capacity for vesicle re-supply to the inner hair cell synapse
  • potentially, endowing vesicle supply at the inner hair cell synapse with high Ca2+ sensitivity to enable sufficient vesicle replenishment during weak stimulation
  • ferlins are calcium-sensing proteins and are candidate mediators of vesicle-plasma membrane fusion during myoblast fusion
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • RAB8b/otoferlin complexes may thus play a role within the recycling of endosomes
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Ca2+
  • protein
  • interacts with two main target-SNARE proteins of the hair-cell synaptic complex, syntaxin 1A and SNAP-25, as well as the calcium channel, with the otoferlin C2F and C2D domains of central importance for binding
  • interaction with RAB8B (interaction links otoferlin to this basolateral endocytic and secretory trafficking)
  • interacting with MYO6 (otoferlin and myosin VI are likely to control the topographical development of inner hair cells active zones by appropriate targeting of intracellular compartments to the basolateral inner hair cells membrane)
  • ferlins and EHBP1 may compete for EHD binding to regulate the complex process of exit from the endocytic recycling compartment, translocation to the plasma membrane, and reorganization of the actin cytoskeleton to facilitate the fusion of exocytosed vesicles to the membrane
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) DFNB9 , NSRAN
    related resource Hereditary Hearing Loss Homepage
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Otof(-/-) mice are profoundly deaf, exocytosis in inner hair cells is almost completely abolished, despite normal ribbon synapse morphogenesis and Ca(2+) current