Details for: TPRN

Gene ID: 286262

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: TPRN

Ensembl ID: ENSG00000176058

Description: taperin

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • colon epithelial cell CL0011108
    CSI 6.36
    rCSI 6.66%
    PRS 95.5
  • cerebellar granule cell CL0001031
    CSI 3.68
    rCSI 5.4%
    PRS 93.77
  • fallopian tube secretory epithelial cell CL4030006
    CSI 3.62
    rCSI 3.48%
    PRS 95.8
  • stem cell CL0000034
    CSI 3.27
    rCSI 3.15%
    PRS 95.33
  • goblet cell CL0000160
    CSI 3.01
    rCSI 2.84%
    PRS 95.4
  • enterocyte of epithelium of large intestine CL0002071
    CSI 2.85
    rCSI 14.99%
    PRS 97.03
  • retinal pigment epithelial cell CL0002586
    CSI 2.8
    rCSI 5.56%
    PRS 94.7
  • choroid plexus epithelial cell CL0000706
    CSI 2.75
    rCSI 4.51%
    PRS 93.49
  • colonocyte CL1000347
    CSI 2.75
    rCSI 3.94%
    PRS 95.37
  • intestine goblet cell CL0019031
    CSI 2.57
    rCSI 2.28%
    PRS 95.37
  • pancreatic acinar cell CL0002064
    CSI 2.52
    rCSI 3.35%
    PRS 97.51
  • transit amplifying cell of colon CL0009011
    CSI 2.45
    rCSI 2.87%
    PRS 97.19
  • BEST4+ enteroycte CL4030026
    CSI 2.39
    rCSI 2.98%
    PRS 96
  • hepatocyte CL0000182
    CSI 2.33
    rCSI 4.17%
    PRS 95.19
  • enterocyte CL0000584
    CSI 1.98
    rCSI 3.2%
    PRS 94.28
  • inhibitory interneuron CL0000498
    CSI 1.93
    rCSI 4.44%
    PRS 91.92
  • colon goblet cell CL0009039
    CSI 1.69
    rCSI 4.03%
    PRS 96.96
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.66
    rCSI 2.94%
    PRS 90.43
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 1.38
    rCSI 3.73%
    PRS 97.3
  • intestinal crypt stem cell of colon CL0009043
    CSI 0.74
    rCSI 5.57%
    PRS 98.24

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [TPRN](/details-gene/286262) (taperin) is a protein-coding gene located on chromosome 9q34.3. Functionally, it is critically involved in the organization and maintenance of stereocilia, the actin-rich mechanosensing organelles of auditory hair cells. Its molecular activities include actin binding and interaction with protein phosphatase 1, where it acts as a docking protein and potential inhibitor ([Link](https://doi.org/10.1242/bio.2011049)). Consistent with this role, mutations in [TPRN](/details-gene/286262) are a known cause of autosomal-recessive nonsyndromic deafness ([Link](https://doi.org/10.1016/j.ajhg.2010.01.030); [Link](https://doi.org/10.1016/j.ajhg.2010.02.003)). While its role in auditory function is well-established, expression data reveals that [TPRN](/details-gene/286262) is also a highly significant gene in non-auditory tissues, showing prominent expression in various epithelial cell types, particularly within the colon and cerebellum. ## Cellular Roles and Expression Landscape The expression profile of [TPRN](/details-gene/286262) suggests a broader function beyond the auditory system, particularly in specialized epithelial and neuronal cells. **Overall**, the gene shows its highest significance in the [colon epithelial cell](/details-cell/CL0011108) (CSI: 6.36), indicating a primary role in the gastrointestinal tract. This is supported by its high significance in related cell types such as [goblet cells](/details-cell/CL0000160), [enterocytes of the large intestine](/details-cell/CL0002071), [colonocytes](/details-cell/CL1000347), and [transit amplifying cells of the colon](/details-cell/CL0009011). This pattern suggests a role in the maintenance, structure, or function of the intestinal lining. Beyond the gut, [TPRN](/details-gene/286262) is also significantly expressed in: * **Neuronal cells**, such as the [cerebellar granule cell](/details-cell/CL0001031) (CSI: 3.68). * **Specialized secretory and barrier epithelial cells**, including [fallopian tube secretory epithelial cells](/details-cell/CL4030006), [retinal pigment epithelial cells](/details-cell/CL0002586), and [choroid plexus epithelial cells](/details-cell/CL0000706). * **Metabolically active cells** like the [pancreatic acinar cell](/details-cell/CL0002064) and [hepatocyte](/details-cell/CL0000182). The collective expression data points to a specialized role for [TPRN](/details-gene/286262) in cells that feature highly organized actin-based structures, such as the microvilli of intestinal cells, which are structurally analogous to the stereocilia of the inner ear. ## Pathways and Molecular Function The known functions of [TPRN](/details-gene/286262) are strongly linked to auditory perception and cellular architecture. * **Biological Processes:** Gene Ontology annotations highlight its critical role in the auditory system, specifically in '[auditory receptor cell stereocilium organization](/details-go/GO:0060088)', '[sensory perception of sound](/details-go/GO:0007605)', and '[stereocilium maintenance](/details-go/GO:0120045)'. These functions are corroborated by Reactome pathways, including '[Sensory perception of sound](/details-reactome/R-HSA-9659379)' and its sub-pathways involving inner and outer hair cells of the cochlea. * **Molecular Function:** At the molecular level, [TPRN](/details-gene/286262) is an '[actin binding](/details-go/GO:0003779)' protein. It is also involved in protein-protein interactions, specifically through '[protein phosphatase 1 binding](/details-go/GO:0008157)', and may exhibit '[protein serine/threonine phosphatase inhibitor activity](/details-go/GO:0004865)'. One study identified it as a docking protein for protein phosphatase one alpha (PP1alpha) ([Link](https://doi.org/10.1242/bio.2011049)). This interaction suggests it may regulate cellular processes by modulating protein phosphorylation status. * **Cellular Component:** It is localized to the '[stereocilium](/details-go/GO:0032420)' and specifically the '[stereocilium base](/details-go/GO:0120044)', where it forms a complex with other proteins to anchor actin filaments to the cell membrane ([Link](https://doi.org/10.1002/cm.21159)). Its presence in the '[microvillus](/details-go/GO:0005902)' is also noted, consistent with its high expression in intestinal epithelial cells. The functional data strongly supports its role in deafness, but the actin-binding and phosphatase-regulating functions are general enough to be applicable in the diverse cell types where it is highly expressed. ## Research Directions The well-defined role of [TPRN](/details-gene/286262) in auditory stereocilia, combined with its high expression in non-auditory epithelial tissues, presents intriguing avenues for future research. The primary question is whether its function in organizing actin-based protrusions is conserved in other cell types. **Proposed Hypotheses:** 1. **Hypothesis 1:** Given its function in stereocilia (specialized microvilli) and its high expression in [colon epithelial cells](/details-cell/CL0011108), [TPRN](/details-gene/286262) is essential for the structural integrity and organization of the brush border microvilli in intestinal [enterocytes](/details-cell/CL0000584), thereby regulating nutrient absorption and barrier function. 2. **Hypothesis 2:** In [cerebellar granule cells](/details-cell/CL0001031), the function of [TPRN](/details-gene/286262) as a PP1alpha docking protein is its primary role. It likely regulates neuronal signaling pathways by localizing phosphatase activity to specific subcellular compartments, potentially influencing synaptic structure or neurotransmission. **Key Experimental Approach:** To test Hypothesis 1, a robust experimental model would be the use of human intestinal organoids. * **Experiment:** Generate [TPRN](/details-gene/286262) knockout (KO) intestinal organoids using CRISPR-Cas9 technology, with isogenic wild-type organoids as a control. * **Analysis:** * Assess microvillar morphology and density using transmission electron microscopy (TEM) and scanning electron microscopy (SEM). * Perform functional assays to measure changes in intestinal barrier integrity (e.g., transepithelial electrical resistance - TEER) and nutrient transporter activity. * Use phosphoproteomics to determine if the loss of [TPRN](/details-gene/286262) alters the phosphorylation status of key cytoskeletal or junctional proteins, consistent with its role as a PP1alpha interactor. **Therapeutic Potential:** The therapeutic relevance of [TPRN](/details-gene/286262) is primarily focused on hereditary deafness. Since mutations typically cause a loss of function, the therapeutic strategy would involve **activation or gene replacement**, such as AAV-mediated gene therapy delivered to the inner ear, to restore protein function in hair cells. However, its significant expression in other vital tissues, including the intestine, liver, and brain, poses a potential challenge for systemic therapies, highlighting the need for targeted delivery systems to avoid off-target effects. Targeting its function in other contexts would require a deeper understanding of its role in potential pathologies of those tissues.

Genular Protein ID: 3594769344

Symbol: TPRN_HUMAN

Name: Taperin

UniProtKB Accession Codes:

Q4KMQ1 B7ZKU5 Q5VSG5 Q5VSG6 Q6IPP2 Q8NCH2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 7 Ensembl 1 ExpressionAtlas 1 GO 11 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 4 Pumba 1 RNAct 1 Reactome 2 RefSeq 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15164053

Title: DNA sequence and analysis of human chromosome 9.

PubMed ID: 15164053

DOI: 10.1038/nature02465

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 17081983

Title: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.

PubMed ID: 17081983

DOI: 10.1016/j.cell.2006.09.026

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 20170899

Title: Targeted capture and next-generation sequencing identifies C9orf75, encoding taperin, as the mutated gene in nonsyndromic deafness DFNB79.

PubMed ID: 20170899

DOI: 10.1016/j.ajhg.2010.01.030

PubMed ID: 20170898

Title: Mutations in TPRN cause a progressive form of autosomal-recessive nonsyndromic hearing loss.

PubMed ID: 20170898

DOI: 10.1016/j.ajhg.2010.02.003

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 21406692

Title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

PubMed ID: 21406692

DOI: 10.1126/scisignal.2001570

PubMed ID: 23213405

Title: Taperin (c9orf75), a mutated gene in nonsyndromic deafness, encodes a vertebrate specific, nuclear localized protein phosphatase one alpha (PP1alpha) docking protein.

PubMed ID: 23213405

DOI: 10.1242/bio.2011049

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24285636

Title: CLIC5 stabilizes membrane-actin filament linkages at the base of hair cell stereocilia in a molecular complex with radixin, taperin, and myosin VI.

PubMed ID: 24285636

DOI: 10.1002/cm.21159

Sequence Information:

  • Length: 711
  • Mass: 75556
  • Checksum: B85D155DF1DD2147
  • Sequence:
    • MAALGRPGSG PRAAVPAWKR EILERKRAKL AALGGGAGPG AAEPEQRVLA ESLGPLRENP 
FMLLEAERRR GGGAAGARLL ERYRRVPGVR ALRADSVLII ETVPGFPPAP PAPGAAQIRA 
AEVLVYGAPP GRVSRLLERF DPPAAPRRRG SPERARPPPP PPPPAPPRPP PAAPSPPAAP 
GPRGGGASPG ARRSDFLQKT GSNSFTVHPR GLHRGAGARL LSNGHSAPEP RAGPANRLAG 
SPPGSGQWKP KVESGDPSLH PPPSPGTPSA TPASPPASAT PSQRQCVSAA TSTNDSFEIR 
PAPKPVMETI PLGDLQARAL ASLRANSRNS FMVIPKSKAS GAPPPEGRQS VELPKGDLGP 
ASPSQELGSQ PVPGGDGAPA LGKSPLEVEA QWAVEEGACP RTATALADRA IRWQRPSSPP 
PFLPAASEEA EPAEGLRVPG LAKNSREYVR PGLPVTFIDE VDSEEAPQAA KLPYLPHPAR 
PLHPARPGCV AELQPRGSNT FTVVPKRKPG TLQDQHFSQA NREPRPREAE EEEASCLLGP 
TLKKRYPTVH EIEVIGGYLA LQKSCLTKAG SSRKKMKISF NDKSLQTTFE YPSESSLEQE 
EEVDQQEEEE EEEEEEEEEE EGSGSEEKPF ALFLPRATFV SSVRPESSRL PEGSSGLSSY 
TPKHSVAFSK WQEQALEQAP REAEPPPVEA MLTPASQNDL SDFRSEPALY F