This gene encodes a transmembrane protein which belongs to the otopetrin domain protein family and is required for the formation of otoconia and otoliths, calcium carbonate biominerals within the inner ear of mammals that are required for the detection of linear acceleration and gravity. This gene modulates purinergic control of intracellular calcium in vestibular supporting ce... See more...

Aliases for OTOP1 Gene

Aliases for OTOP1 Gene

  • Otopetrin 1 2 3 5
  • Proton Channel OTOP1 3 4
  • Otopetrin-1 4
  • HOtop1 4

External Ids for OTOP1 Gene

Previous GeneCards Identifiers for OTOP1 Gene

  • GC04M004183
  • GC04M004255
  • GC04M004308
  • GC04M004241
  • GC04M004126

Summaries for OTOP1 Gene

Entrez Gene Summary for OTOP1 Gene

  • This gene encodes a transmembrane protein which belongs to the otopetrin domain protein family and is required for the formation of otoconia and otoliths, calcium carbonate biominerals within the inner ear of mammals that are required for the detection of linear acceleration and gravity. This gene modulates purinergic control of intracellular calcium in vestibular supporting cells. Naturally occurring mutations in the orthologous mouse gene are associated with nonsyndromic otoconia agenesis and a consequent balance defect. The orthologous mouse gene is also induced in white adipose tissue during obesity. The encoded protein is a component of a counterinflammatory pathway that attenuates obesity-induced adipose tissue inflammation and plays an adaptive role in maintaining metabolic homeostasis in obesity. [provided by RefSeq, Jul 2017]

GeneCards Summary for OTOP1 Gene

OTOP1 (Otopetrin 1) is a Protein Coding gene. Diseases associated with OTOP1 include Benign Paroxysmal Positional Nystagmus and Bestiality. An important paralog of this gene is OTOP2.

UniProtKB/Swiss-Prot Summary for OTOP1 Gene

  • Proton-selective channel that specifically transports protons into cells (PubMed:29371428). Proton channel activity is only weakly-sensitive to voltage (By similarity). Proton-selective channel activity is probably required in cell types that use changes in intracellular pH for cell signaling or to regulate biochemical or developmental processes (PubMed:29371428). In the vestibular system of the inner ear, required for the formation and function of otoconia, which are calcium carbonate crystals that sense gravity and acceleration (By similarity). Probably acts by maintaining the pH appropriate for formation of otoconia (By similarity). Regulates purinergic control of intracellular calcium in vestibular supporting cells (By similarity). May be involved in sour taste perception in sour taste cells by mediating entry of protons within the cytosol (By similarity). Also involved in energy metabolism, by reducing adipose tissue inflammation and protecting from obesity-induced metabolic dysfunction (By similarity).

Additional gene information for OTOP1 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for OTOP1 Gene

Genomics for OTOP1 Gene

GeneHancer (GH) Regulatory Elements for OTOP1 Gene

Promoters and enhancers for OTOP1 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
GH04J003782 Enhancer 0.6 FANTOM5 1.9 +444.4 444357 0.1 POLR2G ZFX TFDP1 POLR2A ZNF48 ZFP69B MIER2 NONO AGO2 RAD21 HSALNG0032491 RGS12 OTOP1 piR-60146-121
GH04J004215 Enhancer 0.7 Ensembl ENCODE dbSUPER 0.4 +10.1 10130 2 FOS KLF1 TMEM128 OR7E99P LYAR OTOP1 piR-55723-006
GH04J004205 Enhancer 0.2 Ensembl 0.4 +21.5 21493 0.8 piR-55723-006 OTOP1
GH04J004202 Enhancer 0.2 Ensembl 0.4 +22.6 22593 0.2 piR-55723-006 OTOP1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around OTOP1 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for OTOP1

Top Transcription factor binding sites by QIAGEN in the OTOP1 gene promoter:
  • AML1a
  • Evi-1
  • Lmo2
  • NCX
  • Pax-2
  • Pax-2a
  • POU2F1
  • POU2F1a

Genomic Locations for OTOP1 Gene

Genomic Locations for OTOP1 Gene
chr4:4,188,803-4,226,894
(GRCh38/hg38)
Size:
38,092 bases
Orientation:
Minus strand
chr4:4,190,530-4,228,621
(GRCh37/hg19)
Size:
38,092 bases
Orientation:
Minus strand

Genomic View for OTOP1 Gene

Genes around OTOP1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
OTOP1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for OTOP1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for OTOP1 Gene

Proteins for OTOP1 Gene

  • Protein details for OTOP1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q7RTM1-OTOP1_HUMAN
    Recommended name:
    Proton channel OTOP1
    Protein Accession:
    Q7RTM1
    Secondary Accessions:
    • A1L476

    Protein attributes for OTOP1 Gene

    Size:
    612 amino acids
    Molecular mass:
    67353 Da
    Quaternary structure:
    No Data Available

neXtProt entry for OTOP1 Gene

Post-translational modifications for OTOP1 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for OTOP1 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for OTOP1 Gene

Domains & Families for OTOP1 Gene

Gene Families for OTOP1 Gene

Human Protein Atlas (HPA):
  • Predicted membrane proteins
  • Transporters

Protein Domains for OTOP1 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for OTOP1 Gene

GenScript: Design optimal peptide antigens:
  • Otopetrin-1 (OTOP1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q7RTM1

UniProtKB/Swiss-Prot:

OTOP1_HUMAN :
  • Belongs to the otopetrin family.
Family:
  • Belongs to the otopetrin family.
genes like me logo Genes that share domains with OTOP1: view

Function for OTOP1 Gene

Molecular function for OTOP1 Gene

UniProtKB/Swiss-Prot Function:
Proton-selective channel that specifically transports protons into cells (PubMed:29371428). Proton channel activity is only weakly-sensitive to voltage (By similarity). Proton-selective channel activity is probably required in cell types that use changes in intracellular pH for cell signaling or to regulate biochemical or developmental processes (PubMed:29371428). In the vestibular system of the inner ear, required for the formation and function of otoconia, which are calcium carbonate crystals that sense gravity and acceleration (By similarity). Probably acts by maintaining the pH appropriate for formation of otoconia (By similarity). Regulates purinergic control of intracellular calcium in vestibular supporting cells (By similarity). May be involved in sour taste perception in sour taste cells by mediating entry of protons within the cytosol (By similarity). Also involved in energy metabolism, by reducing adipose tissue inflammation and protecting from obesity-induced metabolic dysfunction (By similarity).

Gene Ontology (GO) - Molecular Function for OTOP1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0015252 proton channel activity IDA 29371428
genes like me logo Genes that share ontologies with OTOP1: view
genes like me logo Genes that share phenotypes with OTOP1: view

Animal Models for OTOP1 Gene

MGI Knock Outs for OTOP1:

Animal Model Products

CRISPR Products

miRNA for OTOP1 Gene

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for OTOP1

No data available for Enzyme Numbers (IUBMB) , Phenotypes From GWAS Catalog , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for OTOP1 Gene

Localization for OTOP1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for OTOP1 Gene

Cell membrane; Multi-pass membrane protein. Note=Detected in the gelatinous membrane overlying the inner ear macular epithelium. {ECO:0000250 UniProtKB:Q80VM9}.

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 OTOP1 gene
Compartment Confidence
plasma membrane 5
extracellular 1
cytoskeleton 1
mitochondrion 1
peroxisome 1
nucleus 1
cytosol 1

Gene Ontology (GO) - Cellular Components for OTOP1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005887 integral component of plasma membrane IEA,ISS --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with OTOP1: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for OTOP1 Gene

Pathways & Interactions for OTOP1 Gene

PathCards logo

SuperPathways for OTOP1 Gene

No Data Available

Interacting Proteins for OTOP1 Gene

STRING Interaction Network Preview (showing top 2 STRING interactants - click image to see details)
STRING Interaction Network
Selected Interacting proteins: ENSP00000296358 Q7RTM1-OTOP1_HUMAN for OTOP1 Gene via STRING IID

;

Gene Ontology (GO) - Biological Process for OTOP1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006811 ion transport IEA --
GO:0009590 detection of gravity IEA --
GO:0031214 biomineral tissue development IEA --
GO:0032869 cellular response to insulin stimulus IEA,ISS --
GO:0042472 inner ear morphogenesis IEA --
genes like me logo Genes that share ontologies with OTOP1: view

No data available for Pathways by source and SIGNOR curated interactions for OTOP1 Gene

Drugs & Compounds for OTOP1 Gene

(1) Drugs for OTOP1 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Calcium Approved Nutra 7884
genes like me logo Genes that share compounds with OTOP1: view

Transcripts for OTOP1 Gene

mRNA/cDNA for OTOP1 Gene

1 REFSEQ mRNAs :
3 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for OTOP1

Alternative Splicing Database (ASD) splice patterns (SP) for OTOP1 Gene

No ASD Table

Relevant External Links for OTOP1 Gene

GeneLoc Exon Structure for
OTOP1

Expression for OTOP1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for OTOP1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for OTOP1 Gene

This gene is overexpressed in Skin - Not Sun Exposed (Suprapubic) (x9.5), Esophagus - Mucosa (x7.4), and Skin - Sun Exposed (Lower leg) (x7.1).

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for OTOP1

SOURCE GeneReport for Unigene cluster for OTOP1 Gene:

Hs.534544
genes like me logo Genes that share expression patterns with OTOP1: view

No data available for Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt , Evidence on tissue expression from TISSUES and Phenotype-based relationships between genes and organs from Gene ORGANizer for OTOP1 Gene

Orthologs for OTOP1 Gene

This gene was present in the common ancestor of chordates.

Orthologs for OTOP1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia OTOP1 31 30
  • 99.4 (n)
OneToOne
dog
(Canis familiaris)
Mammalia OTOP1 31 30
  • 86.81 (n)
OneToOne
cow
(Bos Taurus)
Mammalia OTOP1 31 30
  • 85.6 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Otop1 30
  • 80.88 (n)
mouse
(Mus musculus)
Mammalia Otop1 17 31 30
  • 80.28 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia OTOP1 31
  • 59 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia OTOP1 31
  • 42 (a)
OneToOne
chicken
(Gallus gallus)
Aves OTOP1 31 30
  • 71.1 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia OTOP1 31
  • 66 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia otop1 30
  • 65.63 (n)
zebrafish
(Danio rerio)
Actinopterygii otop1 30 30
  • 57.71 (n)
OTOP1 31
  • 31 (a)
OneToOne
Species where no ortholog for OTOP1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • 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)
  • fruit fly (Drosophila melanogaster)
  • 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 squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • 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)
  • worm (Caenorhabditis elegans)

Evolution for OTOP1 Gene

ENSEMBL:
Gene Tree for OTOP1 (if available)
TreeFam:
Gene Tree for OTOP1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for OTOP1: view image

Paralogs for OTOP1 Gene

Paralogs for OTOP1 Gene

(2) SIMAP similar genes for OTOP1 Gene using alignment to 1 proteins:

  • OTOP1_HUMAN
genes like me logo Genes that share paralogs with OTOP1: view

Variants for OTOP1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for OTOP1 Gene

SNP ID Clinical significance and condition Chr 04 pos Variation AA Info Type
rs11736799 - p.Val434Met
rs28394859 - p.Ile241Val
rs2916414 - p.Asp309Glu
rs34666677 - p.Lys493Thr
rs35106142 - p.Gln516His

Additional dbSNP identifiers (rs#s) for OTOP1 Gene

Structural Variations from Database of Genomic Variants (DGV) for OTOP1 Gene

Variant ID Type Subtype PubMed ID
dgv5085n100 CNV gain 25217958
dgv5090n100 CNV gain 25217958
esv2726966 CNV deletion 23290073
esv2759219 CNV gain 17122850
esv2763838 CNV gain+loss 21179565
esv34196 OTHER inversion 12058347
esv3599458 CNV loss 21293372
nsv1001885 CNV gain 25217958
nsv1008251 CNV gain 25217958
nsv10436 CNV loss 18304495
nsv1128027 CNV deletion 24896259
nsv469857 CNV gain 16826518
nsv508270 CNV deletion 20534489
nsv517008 CNV gain+loss 19592680
nsv822448 CNV gain 20364138
nsv964026 CNV duplication 23825009
nsv980180 CNV duplication 23825009

Variation tolerance for OTOP1 Gene

Residual Variation Intolerance Score: 88.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.38; 76.97% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for OTOP1 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
OTOP1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for OTOP1 Gene

Disorders for OTOP1 Gene

MalaCards: The human disease database

(4) MalaCards diseases for OTOP1 Gene - From: DISEASES

Disorder Aliases PubMed IDs
benign paroxysmal positional nystagmus
  • bppv
bestiality
  • zoophilia
peripheral vertigo
  • vertigo, peripheral
vestibular disease
  • vertigo, vestibular disorder
- elite association - COSMIC cancer census association via MalaCards
Search OTOP1 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for OTOP1

genes like me logo Genes that share disorders with OTOP1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for OTOP1 Gene

Publications for OTOP1 Gene

  1. Non-syndromic vestibular disorder with otoconial agenesis in tilted/mergulhador mice caused by mutations in otopetrin 1. (PMID: 12651873) Hurle B … Ornitz DM (Human molecular genetics 2003) 2 3 4 54
  2. An evolutionarily conserved gene family encodes proton-selective ion channels. (PMID: 29371428) Tu YH … Liman ER (Science (New York, N.Y.) 2018) 3 4 54
  3. Otopetrin 1 protects mice from obesity-associated metabolic dysfunction through attenuating adipose tissue inflammation. (PMID: 24379350) Wang GX … Lin JD (Diabetes 2014) 3 54
  4. Missense mutations in Otopetrin 1 affect subcellular localization and inhibition of purinergic signaling in vestibular supporting cells. (PMID: 21236346) Kim E … Ornitz DM (Molecular and cellular neurosciences 2011) 3 54
  5. Identification of the Otopetrin Domain, a conserved domain in vertebrate otopetrins and invertebrate otopetrin-like family members. (PMID: 18254951) Hughes I … Ornitz DM (BMC evolutionary biology 2008) 3 54

Products for OTOP1 Gene

Sources for OTOP1 Gene