U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

OTOF otoferlin [ Homo sapiens (human) ]

Gene ID: 9381, updated on 11-Apr-2024

Summary

Go to the top of the page Help
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
NEW
Try the new Gene table
Try the new Transcript table

Genomic context

Go to the top of the page Help
Location:
2p23.3
Exon count:
48
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (26457203..26558756, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (26495826..26597899, complement)
105.20220307 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

Go to the top of the page Help

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help
  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the pageHelp

Related articles in PubMed

  1. Intronic OTOF mutation causes an atypical splicing defect resulting in auditory neuropathy spectrum disorder. Mohammadi S, et al. J Genet, 2023. PMID 36988134
  2. Hearing of Otof-deficient mice restored by trans-splicing of N- and C-terminal otoferlin. Tang H, et al. Hum Genet, 2023 Feb. PMID 36383253
  3. Membrane Protein OTOF Is a Type I Interferon-Induced Entry Inhibitor of HIV-1 in Macrophages. Ding H, et al. mBio, 2022 Aug 30. PMID 35862790, Free PMC Article
  4. Detailed clinical features and genotype-phenotype correlation in an OTOF-related hearing loss cohort in Japan. Iwasa YI, et al. Hum Genet, 2022 Apr. PMID 34536124, Free PMC Article
  5. The natural history of OTOF-related auditory neuropathy spectrum disorders: a multicenter study. Thorpe RK, et al. Hum Genet, 2022 Apr. PMID 34424407, Free PMC Article

See all (74) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. The Many Faces of DFNB9: Relating OTOF Variants to Hearing Impairment.
    Title: The Many Faces of DFNB9: Relating OTOF Variants to Hearing Impairment.
  10. [OTOF-related auditory neuropathy spectrum disorder].", trans "Zabolevanie spektra auditornykh neiropatii, obuslovlennoe mutatsiyami v gene otoferlina (OTOF).
    Title: [OTOF-related auditory neuropathy spectrum disorder].
Submit: New GeneRIF Correction See all GeneRIFs (59)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

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

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

Go to the top of the page

Interactions

Go to the top of the page Help
Products Interactant Other Gene Complex Source Pubs Description

General gene information

Go to the top of the page Help

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
  
enables molecular_function ND
No biological Data available
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 
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

Go to the top of the page Help
Preferred Names
otoferlin
Names
fer-1-like family member 2
fer-1-like protein 2

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

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_2023_10

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

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

Chemical Information
Molecular Biology Databases
Research Materials
Tools
Miscellaneous