Details for: PRPH

Gene ID: 5630

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: PRPH

Ensembl ID: ENSG00000135406

Description: peripherin

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • peripheral nervous system neuron CL2000032
    CSI 37.71
    rCSI 51.39%
    PRS 98.67
  • microcirculation associated smooth muscle cell CL0008035
    CSI 8.9
    rCSI 25.78%
    PRS 99.28
  • epithelial cell CL0000066
    CSI 7.82
    rCSI 12.02%
    PRS 96.45
  • neural progenitor cell CL0011020
    CSI 6.27
    rCSI 27.58%
    PRS 95.93
  • type L enteroendocrine cell CL0002279
    CSI 6.09
    rCSI 11.44%
    PRS 99.17
  • basal cell of epidermis CL0002187
    CSI 5.64
    rCSI 10%
    PRS 89.4
  • retina horizontal cell CL0000745
    CSI 5.5
    rCSI 8.38%
    PRS 98.72
  • neuroplacodal cell CL0000032
    CSI 5.01
    rCSI 46.3%
    PRS 97.9
  • vascular associated smooth muscle cell CL0000359
    CSI 4.71
    rCSI 15.27%
    PRS 99.47
  • innate lymphoid cell CL0001065
    CSI 4.68
    rCSI 9.66%
    PRS 96.97
  • retinal ganglion cell CL0000740
    CSI 4.61
    rCSI 10.18%
    PRS 97.53
  • enteric neuron CL0007011
    CSI 4.29
    rCSI 63.48%
    PRS 98.98
  • helper T cell CL0000912
    CSI 3.3
    rCSI 4.67%
    PRS 97.21
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 2.53
    rCSI 3.07%
    PRS 92.23
  • enteroendocrine cell of colon CL0009042
    CSI 2.32
    rCSI 10.87%
    PRS 99.06
  • suprabasal keratinocyte CL4033013
    CSI 2.18
    rCSI 3.56%
    PRS 91.3
  • melanocyte of skin CL1000458
    CSI 1.81
    rCSI 2.46%
    PRS 90.95
  • ON parasol ganglion cell CL4033052
    CSI 1
    rCSI 14.21%
    PRS 97.17
  • OFF midget ganglion cell CL4033047
    CSI 0.65
    rCSI 13.29%
    PRS 97.2
  • ON midget ganglion cell CL4033046
    CSI 0.56
    rCSI 11.47%
    PRS 97.25

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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  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
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    • 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 [PRPH](/details-gene/5630) is a protein-coding gene located on chromosome 12 that encodes peripherin, a type III intermediate filament protein. As a key component of the neuronal cytoskeleton, peripherin provides structural support and integrity, particularly within the axons of neurons. Expression data highlight its profound significance in the [peripheral nervous system neuron](/details-cell/CL2000032), where it serves as a defining molecular marker. Consistent with its critical structural role, mutations in [PRPH](/details-gene/5630) have been clinically associated with neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) ([170710](https://omim.org/entry/170710)), as documented in several studies ([Link](https://doi.org/10.1111/j.1750-3639.2004.tb00066.x), [Link](https://doi.org/10.1074/jbc.m408139200)). ## Cellular Roles and Expression Landscape The expression profile of [PRPH](/details-gene/5630) strongly indicates a specialized function within the nervous system. **Overall**, the gene exhibits its highest significance by a substantial margin in the [peripheral nervous system neuron](/details-cell/CL2000032) (CSI: 37.71), underscoring its role as a principal cytoskeletal element in this cell lineage. This neuronal specificity is further supported by its notable expression in other neural cell types, including [neural progenitor cell](/details-cell/CL0011020), [retina horizontal cell](/details-cell/CL0000745), [retinal ganglion cell](/details-cell/CL0000740), and [enteric neuron](/details-cell/CL0007011). Beyond the nervous system, [PRPH](/details-gene/5630) shows moderate but significant expression in several non-neuronal cell types. These include [microcirculation associated smooth muscle cell](/details-cell/CL0008035), [epithelial cell](/details-cell/CL0000066), and [type L enteroendocrine cell](/details-cell/CL0002279), suggesting that peripherin may contribute to the cytoskeletal architecture in a wider range of cells than previously appreciated, albeit to a lesser extent than in neurons. Minor significance is also observed in certain immune subsets, such as the [helper T cell](/details-cell/CL0000912), though its functional relevance in this context remains to be elucidated. ## Pathways and Molecular Function Functionally, [PRPH](/details-gene/5630) is categorized by its `structural molecule activity` ([GO:0005198](https://www.ebi.ac.uk/QuickGO/term/GO:0005198)) and its capacity for `protein binding` ([GO:0005515](https://www.ebi.ac.uk/QuickGO/term/GO:0005515)). These functions are realized through its assembly into `type iii intermediate filament`s ([GO:0045098](https://www.ebi.ac.uk/QuickGO/term/GO:0045098)), which form a critical part of the cellular scaffold. The subcellular localization of peripherin is highly consistent with its expression pattern and role in neuronal maintenance. Gene Ontology annotations place the protein within the `intermediate filament` network ([GO:0005882](https://www.ebi.ac.uk/QuickGO/term/GO:0005882)) and specifically within key neuronal compartments such as the `axon` ([GO:0030424](https://www.ebi.ac.uk/QuickGO/term/GO:0030424)) and `perikaryon` ([GO:0043204](https://www.ebi.ac.uk/QuickGO/term/GO:0043204)). This localization is essential for maintaining axonal caliber and facilitating the long-distance transport of organelles and molecules, processes that are vital for neuronal survival and function. The disruption of this network by pathogenic mutations is a plausible mechanism for the axonal decay observed in related neurodegenerative diseases ([Link](https://doi.org/10.1007/s00401-012-1063-8)). ## Research Directions The strong association between [PRPH](/details-gene/5630) and neuronal function, combined with its implication in pathology, opens several avenues for future investigation. **Proposed Hypotheses:** 1. Pathogenic mutations in [PRPH](/details-gene/5630), such as those identified in ALS patients ([Link](https://doi.org/10.1016/j.neurobiolaging.2010.02.011)), act in a dominant-negative manner to disrupt the assembly of the entire neurofilament network, leading to impaired axonal transport, cytoskeletal collapse, and eventual motor neuron death. 2. Post-translational modifications, such as the phosphorylation of peripherin by Protein Kinase C epsilon (PKCε) ([Link](https://doi.org/10.1074/jbc.m710436200)), regulate its solubility and filament dynamics. Aberrant kinase activity in stressed neurons could promote the formation of insoluble peripherin aggregates, which contribute to cellular toxicity and disease progression. **Experimental Approach:** To test the first hypothesis, a robust *in vitro* model could be developed. Human induced pluripotent stem cells (iPSCs) from a healthy donor could be differentiated into [peripheral nervous system neuron](/details-cell/CL2000032)s or motor neurons. Using CRISPR-Cas9 genome editing, a known pathogenic frameshift or missense mutation would be introduced into one allele of the [PRPH](/details-gene/5630) gene. Isogenic control lines would be maintained. The impact on the cytoskeleton would be assessed using super-resolution microscopy to visualize the integrity of the peripherin and neurofilament network within axons. Furthermore, axonal transport dynamics could be quantified by live-cell imaging of fluorescently-labeled mitochondria or synaptic vesicles, comparing transport velocity and processivity between mutant and control neurons. **Therapeutic Potential:** As an intracellular structural protein, peripherin is a challenging therapeutic target for conventional antibodies or small molecules. The pathogenic mechanism likely involves a toxic gain-of-function or dominant-negative effect from the mutant protein, rather than a simple loss of function. Therefore, a therapeutic strategy would likely focus on reducing the expression of the mutant allele specifically. This could potentially be achieved using allele-specific antisense oligonucleotides (ASOs) or siRNA delivered to the central nervous system. An alternative approach could involve the development of small molecule chaperones designed to stabilize the peripherin protein, prevent its aggregation, and promote proper filament assembly, thereby mitigating its toxic effects.

Genular Protein ID: 4281680456

Symbol: PERI_HUMAN

Name: Peripherin

UniProtKB Accession Codes:

P41219 Q8N577

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 1 ExpressionAtlas 1 GO 9 Gene3D 3 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 MetOSite 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PIR 1 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 RefSeq 2 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 UniProtKB 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 7806235

Title: The structure of the human peripherin gene (PRPH) and identification of potential regulatory elements.

PubMed ID: 7806235

DOI: 10.1006/geno.1994.1410

PubMed ID: 16541075

Title: The finished DNA sequence of human chromosome 12.

PubMed ID: 16541075

DOI: 10.1038/nature04569

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: 18408015

Title: Protein kinase Cepsilon binds peripherin and induces its aggregation, which is accompanied by apoptosis of neuroblastoma cells.

PubMed ID: 18408015

DOI: 10.1074/jbc.m710436200

PubMed ID: 21088854

Title: Expression of peripherin in human cochlea.

PubMed ID: 21088854

DOI: 10.1007/s00441-010-1081-6

PubMed ID: 23179371

Title: Charcot-Marie-Tooth type 2B disease-causing RAB7A mutant proteins show altered interaction with the neuronal intermediate filament peripherin.

PubMed ID: 23179371

DOI: 10.1007/s00401-012-1063-8

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 15446584

Title: A pathogenic peripherin gene mutation in a patient with amyotrophic lateral sclerosis.

PubMed ID: 15446584

DOI: 10.1111/j.1750-3639.2004.tb00066.x

PubMed ID: 15322088

Title: A frameshift deletion in peripherin gene associated with amyotrophic lateral sclerosis.

PubMed ID: 15322088

DOI: 10.1074/jbc.m408139200

PubMed ID: 20363051

Title: A novel peripherin gene (PRPH) mutation identified in one sporadic amyotrophic lateral sclerosis patient.

PubMed ID: 20363051

DOI: 10.1016/j.neurobiolaging.2010.02.011

Sequence Information:

  • Length: 470
  • Mass: 53651
  • Checksum: 4ABEAB96088719D6
  • Sequence:
    • MSHHPSGLRA GFSSTSYRRT FGPPPSLSPG AFSYSSSSRF SSSRLLGSAS PSSSVRLGSF 
RSPRAGAGAL LRLPSERLDF SMAEALNQEF LATRSNEKQE LQELNDRFAN FIEKVRFLEQ 
QNAALRGELS QARGQEPARA DQLCQQELRE LRRELELLGR ERDRVQVERD GLAEDLAALK 
QRLEEETRKR EDAEHNLVLF RKDVDDATLS RLELERKIES LMDEIEFLKK LHEEELRDLQ 
VSVESQQVQQ VEVEATVKPE LTAALRDIRA QYESIAAKNL QEAEEWYKSK YADLSDAANR 
NHEALRQAKQ EMNESRRQIQ SLTCEVDGLR GTNEALLRQL RELEEQFALE AGGYQAGAAR 
LEEELRQLKE EMARHLREYQ ELLNVKMALD IEIATYRKLL EGEESRISVP VHSFASLNIK 
TTVPEVEPPQ DSHSRKTVLI KTIETRNGEV VTESQKEQRS ELDKSSAHSY

Genular Protein ID: 666805711

Symbol: B3KWQ6_HUMAN

Name: N/A

UniProtKB Accession Codes:

B3KWQ6

Database IDs:

ARBA 2 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 6 Gene3D 3 InterPro 5 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRINTS 1 PROSITE 3 PeptideAtlas 1 Pfam 2 PharmGKB 1 RefSeq 1 RuleBase 1 SAM 2 SMART 1 SUPFAM 1

Citations:

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

Sequence Information:

  • Length: 470
  • Mass: 53681
  • Checksum: 5AB3C6EA698A74A6
  • Sequence:
    • MSHHPSGLRA GFSSTSYRRT FGPPPSLSPG AFSYSSSSRF SSSRLLGSAS PSSSVRLGSF 
RSPRAGAGAL LRLPSERLDF SMAEALNQEF LATRSNEKQE LQELNDRFAN FIEKVRFLEQ 
QNAALRGELS QARGQEPARA DQLCQQELRE LRRELELLGR ERDRVQVERD GLAEDLAALK 
QRLEEETRKR EDAEHNLVLF RKDVDDATLS RLELERKIES LMDEIEFLKK LHEEELRDLQ 
VSVESQQVQQ VEVEATVKPE LTAALRDIRA QYESIATKNL QEAEEWYKSK YADLSDAANR 
NHEALRQAKQ EMNESRRQIQ SLTCEVDGLR GTNEALLRQL RELEEQFALE AGGYQAGAAR 
LEEELRQLKE EMARHLREYQ ELLNVKMALD IEIATYRKLL EGEESRISVP VHSFASLNIK 
TTVPEVEPPQ DSHSRKTVLI KTIETRNGEV VTESQKEQRS ELDKSSAHSY