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Aliases for OTOF Gene

Aliases for OTOF Gene

  • Otoferlin 2 3 3 5
  • Fer-1-Like Family Member 2 2 3
  • Fer-1-Like Protein 2 3 4
  • FER1L2 3 4
  • EC 4.2.1.11 56
  • EC 2.7.10.1 56
  • AUNB1 3
  • DFNB6 3
  • NSRD9 3
  • DFNB9 3

External Ids for OTOF Gene

Previous HGNC Symbols for OTOF Gene

  • DFNB9

Previous GeneCards Identifiers for OTOF Gene

  • GC02M026601
  • GC02M026772
  • GC02M026654
  • GC02M026591
  • GC02M026688

Summaries for OTOF Gene

Entrez Gene Summary for OTOF Gene

  • 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]

GeneCards Summary for OTOF Gene

OTOF (Otoferlin) is a Protein Coding gene. Diseases associated with OTOF include Deafness, Autosomal Recessive 9 and Nonsyndromic Deafness. Gene Ontology (GO) annotations related to this gene include calcium ion binding and AP-2 adaptor complex binding. An important paralog of this gene is FER1L6.

UniProtKB/Swiss-Prot for OTOF Gene

  • Key calcium ion sensor involved in the Ca(2+)-triggered synaptic vesicle-plasma membrane fusion and in the control of neurotransmitter release at these output synapses. Interacts in a calcium-dependent manner to the presynaptic SNARE proteins at ribbon synapses of cochlear inner hair cells (IHCs) to trigger exocytosis of neurotransmitter. Also essential to synaptic exocytosis in immature outer hair cells (OHCs). May also play a role within the recycling of endosomes (By similarity).

Gene Wiki entry for OTOF Gene

Additional gene information for OTOF Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for OTOF Gene

Genomics for OTOF Gene

GeneHancer (GH) Regulatory Elements for OTOF Gene

Promoters and enhancers for OTOF Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02I026477 Promoter/Enhancer 1.1 EPDnew Ensembl ENCODE 558.5 +80.6 80580 1.9 CREB1 ATF2 ZBTB17 OTOF DRC1
GH02I026558 Promoter 0.7 EPDnew 550.8 +0.0 19 0.1 ZSCAN4 ZIC2 EZH2 OTOF DRC1
GH02I026717 Enhancer 1.9 VISTA FANTOM5 Ensembl ENCODE dbSUPER 10.8 -163.6 -163557 10.1 HDGF FOXA2 MLX SIN3A DMAP1 YY1 ZNF766 FOS SP5 REST CENPA EIF2B4 GPN1 GTF3C2 CAD KCNK3 SLC35F6 GTF3C2-AS1 NRBP1 C2orf70
GH02I026493 Enhancer 0.6 FANTOM5 17.2 +65.0 64980 0.4 STAT1 POLR2A ZNF512 STAT2 CEBPB PRDM10 ATF2 SPI1 OTOF C2orf70 RAB10 GAREM2 DRC1
GH02I026492 Enhancer 0.8 ENCODE 11.3 +65.8 65750 0.2 HDAC1 MEIS2 PKNOX1 TEAD4 TAL1 TCF12 ZFHX2 CTBP1 ZNF766 GATA2 OTOF C2orf70 DRC1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around OTOF on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the OTOF gene promoter:

Genomic Locations for OTOF Gene

Genomic Locations for OTOF Gene
chr2:26,457,203-26,558,698
(GRCh38/hg38)
Size:
101,496 bases
Orientation:
Minus strand
chr2:26,680,071-26,781,566
(GRCh37/hg19)

Genomic View for OTOF Gene

Genes around OTOF on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
OTOF Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for OTOF Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for OTOF Gene

Proteins for OTOF Gene

  • Protein details for OTOF Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9HC10-OTOF_HUMAN
    Recommended name:
    Otoferlin
    Protein Accession:
    Q9HC10
    Secondary Accessions:
    • B4DJX0
    • B5MCC1
    • B9A0H6
    • Q53R90
    • Q9HC08
    • Q9HC09
    • Q9Y650

    Protein attributes for OTOF Gene

    Size:
    1997 amino acids
    Molecular mass:
    226753 Da
    Cofactor:
    Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
    Quaternary structure:
    • Interacts with SNAP2; the interaction is direct. Interacts with STX1; the interaction is direct. Interacts with RAB8B (By similarity).
    SequenceCaution:
    • Sequence=BAG58982.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Alternative splice isoforms for OTOF Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for OTOF Gene

Selected DME Specific Peptides for OTOF Gene

Q9HC10:
  • EAHELRD
  • LKLPGKR

Post-translational modifications for OTOF Gene

No Post-translational modifications

Domains & Families for OTOF Gene

Gene Families for OTOF Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Plasma proteins
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for OTOF Gene

Suggested Antigen Peptide Sequences for OTOF Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q9HC10

UniProtKB/Swiss-Prot:

OTOF_HUMAN :
  • The N-terminal first 124 residues can be classified as C2 domain, based on their 3D-structure. They are not sufficient for calcium ion or phospholipid binding (By similarity).
  • Belongs to the ferlin family.
Domain:
  • The N-terminal first 124 residues can be classified as C2 domain, based on their 3D-structure. They are not sufficient for calcium ion or phospholipid binding (By similarity).
Family:
  • Belongs to the ferlin family.
genes like me logo Genes that share domains with OTOF: view

Function for OTOF Gene

Molecular function for OTOF Gene

GENATLAS Biochemistry:
otoferlin C elegans a FER1-like homolog,mainly expressed in the cochlear inner hair cells and vestibular type I sensory hair cells,putatively involved in synaptic vesicular trafficking
UniProtKB/Swiss-Prot Function:
Key calcium ion sensor involved in the Ca(2+)-triggered synaptic vesicle-plasma membrane fusion and in the control of neurotransmitter release at these output synapses. Interacts in a calcium-dependent manner to the presynaptic SNARE proteins at ribbon synapses of cochlear inner hair cells (IHCs) to trigger exocytosis of neurotransmitter. Also essential to synaptic exocytosis in immature outer hair cells (OHCs). May also play a role within the recycling of endosomes (By similarity).

Enzyme Numbers (IUBMB) for OTOF Gene

Phenotypes From GWAS Catalog for OTOF Gene

Gene Ontology (GO) - Molecular Function for OTOF Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003674 molecular_function ND --
GO:0005509 calcium ion binding IEA,ISS --
genes like me logo Genes that share ontologies with OTOF: view
genes like me logo Genes that share phenotypes with OTOF: view

Human Phenotype Ontology for OTOF Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for OTOF Gene

MGI Knock Outs for OTOF:

Animal Model Products

Clone Products

No data available for Transcription Factor Targets and HOMER Transcription for OTOF Gene

Localization for OTOF Gene

Subcellular locations from UniProtKB/Swiss-Prot for OTOF Gene

Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane; Single-pass type II membrane protein. Basolateral cell membrane; Single-pass type II membrane protein. Endoplasmic reticulum membrane; Single-pass type II membrane protein. Cell membrane; Single-pass type II membrane protein. Note=Detected at basolateral cell membrane with synaptic vesicles surrounding the ribbon and at the presynaptic plasma membrane in the inner hair cells (IHCs). Colocalizes with GPR25 and RAB8B in inner hair cells (By similarity). {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for OTOF gene
Compartment Confidence
cytosol 5
plasma membrane 4
endoplasmic reticulum 3
mitochondrion 2
peroxisome 1
nucleus 1

Gene Ontology (GO) - Cellular Components for OTOF Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005783 endoplasmic reticulum IEA --
GO:0005789 endoplasmic reticulum membrane IEA --
GO:0005829 cytosol TAS 10192385
GO:0005886 plasma membrane IEA --
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with OTOF: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for OTOF Gene

Pathways & Interactions for OTOF Gene

No Data Available

Gene Ontology (GO) - Biological Process for OTOF Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007605 sensory perception of sound IEA,TAS --
GO:0016079 synaptic vesicle exocytosis IEA,ISS --
GO:0061025 membrane fusion TAS 10192385
genes like me logo Genes that share ontologies with OTOF: view

No data available for Pathways by source and SIGNOR curated interactions for OTOF Gene

Drugs & Compounds for OTOF Gene

No Compound Related Data Available

Transcripts for OTOF Gene

Unigene Clusters for OTOF Gene

Otoferlin:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for OTOF Gene

No ASD Table

Relevant External Links for OTOF Gene

GeneLoc Exon Structure for
OTOF
ECgene alternative splicing isoforms for
OTOF

Expression for OTOF Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for OTOF Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for OTOF Gene

This gene is overexpressed in Brain - Nucleus accumbens (basal ganglia) (x15.4), Brain - Putamen (basal ganglia) (x12.8), and Brain - Caudate (basal ganglia) (x8.7).

Protein differential expression in normal tissues from HIPED for OTOF Gene

This gene is overexpressed in Pancreas (66.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for OTOF Gene



Protein tissue co-expression partners for OTOF Gene

NURSA nuclear receptor signaling pathways regulating expression of OTOF Gene:

OTOF

SOURCE GeneReport for Unigene cluster for OTOF Gene:

Hs.91608

mRNA Expression by UniProt/SwissProt for OTOF Gene:

Q9HC10-OTOF_HUMAN
Tissue specificity: Isoform 1 and isoform 3 are found in adult brain. Isoform 2 is expressed in the fetus and in adult brain, heart, placenta, skeletal muscle and kidney.

Evidence on tissue expression from TISSUES for OTOF Gene

  • Nervous system(4.4)

Phenotype-based relationships between genes and organs from Gene ORGANizer for OTOF Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • nervous
  • skeletal muscle
  • skeleton
Organs:
Head and neck:
  • brain
  • cerebellum
  • cranial nerve
  • ear
  • eye
  • head
  • inner ear
  • middle ear
  • outer ear
  • skull
General:
  • peripheral nerve
  • peripheral nervous system
genes like me logo Genes that share expression patterns with OTOF: view

Orthologs for OTOF Gene

This gene was present in the common ancestor of animals.

Orthologs for OTOF Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia OTOF 33
  • 95.32 (n)
-- 34
  • 25 (a)
ManyToMany
oppossum
(Monodelphis domestica)
Mammalia OTOF 34
  • 93 (a)
OneToOne
dog
(Canis familiaris)
Mammalia OTOF 33 34
  • 91.55 (n)
cow
(Bos Taurus)
Mammalia OTOF 33 34
  • 90.52 (n)
rat
(Rattus norvegicus)
Mammalia Otof 33
  • 88.73 (n)
mouse
(Mus musculus)
Mammalia Otof 33 16 34
  • 88.61 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia OTOF 34
  • 87 (a)
OneToOne
chicken
(Gallus gallus)
Aves OTOF 33 34
  • 78.43 (n)
lizard
(Anolis carolinensis)
Reptilia OTOF 34
  • 75 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia otof 33
  • 74.52 (n)
zebrafish
(Danio rerio)
Actinopterygii OTOF (1 of 2) 34
  • 76 (a)
OneToMany
otof 33 34
  • 72.08 (n)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP000389 33
  • 62.22 (n)
fruit fly
(Drosophila melanogaster)
Insecta CG5747 35
  • 32 (a)
mfr 34
  • 23 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea fer-1 34
  • 20 (a)
ManyToMany
ferl-1 34
  • 15 (a)
ManyToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 55 (a)
OneToOne
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.9502 33
Species where no ortholog for OTOF was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for OTOF Gene

ENSEMBL:
Gene Tree for OTOF (if available)
TreeFam:
Gene Tree for OTOF (if available)

Paralogs for OTOF Gene

Paralogs for OTOF Gene

(2) SIMAP similar genes for OTOF Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with OTOF: view

Variants for OTOF Gene

Sequence variations from dbSNP and Humsavar for OTOF Gene

SNP ID Clin Chr 02 pos Variation AA Info Type
rs1007850280 uncertain-significance, Nonsyndromic Hearing Loss, Recessive 26,457,468(-) A/G/T 3_prime_UTR_variant, genic_downstream_transcript_variant
rs1050733802 uncertain-significance, Nonsyndromic Hearing Loss, Recessive 26,558,635(-) C/T 5_prime_UTR_variant, genic_upstream_transcript_variant, upstream_transcript_variant
rs1057518840 likely-pathogenic, Hearing impairment 26,476,319(-) T/C splice_acceptor_variant
rs1060499805 pathogenic, Deafness, autosomal recessive 9 26,468,468(-) G/A coding_sequence_variant, stop_gained
rs111033330 likely-pathogenic, Nonsyndromic hearing loss and deafness 26,461,897(-) C/A/T coding_sequence_variant, missense_variant

Structural Variations from Database of Genomic Variants (DGV) for OTOF Gene

Variant ID Type Subtype PubMed ID
esv33316 CNV loss 17666407
esv3435082 CNV duplication 20981092
esv3583675 CNV loss 25503493
esv3583676 CNV loss 25503493
nsv1071984 CNV deletion 25765185
nsv1126545 CNV deletion 24896259
nsv455941 CNV loss 19166990
nsv455952 CNV loss 19166990
nsv517800 CNV loss 19592680
nsv581241 CNV loss 21841781
nsv817662 CNV loss 17921354
nsv819195 CNV gain 19587683
nsv953759 CNV deletion 24416366

Variation tolerance for OTOF Gene

Residual Variation Intolerance Score: 92.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 18.47; 98.58% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for OTOF Gene

Human Gene Mutation Database (HGMD)
OTOF
SNPedia medical, phenotypic, and genealogical associations of SNPs for
OTOF

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for OTOF Gene

Disorders for OTOF Gene

MalaCards: The human disease database

(24) MalaCards diseases for OTOF Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
deafness, autosomal recessive 9
  • dfnb9
nonsyndromic deafness
  • nonsyndromic hearing loss
non-syndromic genetic deafness
  • isolated genetic deafness
deafness, autosomal recessive
autosomal recessive non-syndromic sensorineural deafness type dfnb
  • autosomal recessive isolated neurosensory deafness type dfnb
- elite association - COSMIC cancer census association via MalaCards
Search OTOF in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

OTOF_HUMAN
  • Auditory neuropathy, autosomal recessive, 1 (AUNB1) [MIM:601071]: A form of sensorineural hearing loss with absent or severely abnormal auditory brainstem response, in the presence of normal cochlear outer hair cell function and normal otoacoustic emissions. Auditory neuropathies result from a lesion in the area including the inner hair cells, connections between the inner hair cells and the cochlear branch of the auditory nerve, the auditory nerve itself and auditory pathways of the brainstem. In some cases AUNB1 phenotype can be temperature sensitive. {ECO:0000269 PubMed:16371502, ECO:0000269 PubMed:18381613}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Deafness, autosomal recessive, 9 (DFNB9) [MIM:601071]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269 PubMed:10192385, ECO:0000269 PubMed:12127154, ECO:0000269 PubMed:16097006, ECO:0000269 PubMed:16283880, ECO:0000269 PubMed:16371502, ECO:0000269 PubMed:26437881}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for OTOF

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with OTOF: view

No data available for Genatlas for OTOF Gene

Publications for OTOF Gene

  1. A multicenter study on the prevalence and spectrum of mutations in the otoferlin gene (OTOF) in subjects with nonsyndromic hearing impairment and auditory neuropathy. (PMID: 18381613) Rodríguez-Ballesteros M … del Castillo I (Human mutation 2008) 2 3 4 22 44 58
  2. A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness. (PMID: 10192385) Yasunaga S … Petit C (Nature genetics 1999) 2 3 4 22 58
  3. OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele. (PMID: 16371502) Varga R … Kimberling WJ (Journal of medical genetics 2006) 3 4 22 58
  4. Auditory neuropathy in patients carrying mutations in the otoferlin gene (OTOF). (PMID: 14635104) Rodríguez-Ballesteros M … del Castillo I (Human mutation 2003) 3 22 44 58
  5. OTOF encodes multiple long and short isoforms: genetic evidence that the long ones underlie recessive deafness DFNB9. (PMID: 10903124) Yasunaga S … Petit C (American journal of human genetics 2000) 3 4 22 58

Products for OTOF Gene

Sources for OTOF Gene

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