Details for: PTPRO

Gene ID: 5800

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: PTPRO

Ensembl ID: ENSG00000151490

Description: protein tyrosine phosphatase receptor type O

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • sst GABAergic cortical interneuron CL4023017
    CSI 38.05
    rCSI 49.06%
    PRS 91.57
  • VIP GABAergic cortical interneuron CL4023016
    CSI 37.14
    rCSI 44.36%
    PRS 90.93
  • sncg GABAergic cortical interneuron CL4023015
    CSI 33.99
    rCSI 54.66%
    PRS 91.37
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 29.1
    rCSI 48.84%
    PRS 91.04
  • retinal bipolar neuron CL0000748
    CSI 23.33
    rCSI 43.69%
    PRS 92.47
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 19.39
    rCSI 42.07%
    PRS 89.41
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 17.97
    rCSI 43.67%
    PRS 89.32
  • neuron CL0000540
    CSI 16.94
    rCSI 45.11%
    PRS 88.67
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 16.32
    rCSI 28.82%
    PRS 90.7
  • glioblast CL0000030
    CSI 16.2
    rCSI 25.85%
    PRS 92.68
  • interneuron CL0000099
    CSI 15.34
    rCSI 30.81%
    PRS 94.28
  • L6b glutamatergic cortical neuron CL4023038
    CSI 15
    rCSI 46.88%
    PRS 91.51
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 14.88
    rCSI 17.18%
    PRS 92.51
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 14.49
    rCSI 18.59%
    PRS 94.81
  • cerebellar granule cell CL0001031
    CSI 14.43
    rCSI 21.21%
    PRS 93.93
  • GABAergic amacrine cell CL4030027
    CSI 14.36
    rCSI 49.19%
    PRS 89.1
  • inhibitory interneuron CL0000498
    CSI 14.1
    rCSI 32.55%
    PRS 92.05
  • cerebral cortex neuron CL0010012
    CSI 13.3
    rCSI 54.21%
    PRS 91.93
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 13
    rCSI 16.18%
    PRS 89.46
  • podocyte CL0000653
    CSI 12.8
    rCSI 56.89%
    PRS 96.84
  • H1 horizontal cell CL0004217
    CSI 12.49
    rCSI 49.47%
    PRS 92.93
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 12.45
    rCSI 44.8%
    PRS 89.56
  • Kupffer cell CL0000091
    CSI 11.37
    rCSI 26%
    PRS 97.26
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 11.34
    rCSI 37.28%
    PRS 89.82
  • amacrine cell CL0000561
    CSI 10.78
    rCSI 31.24%
    PRS 92.22
  • neural cell CL0002319
    CSI 10.24
    rCSI 38.65%
    PRS 88.37
  • OFFx cell CL4033036
    CSI 9.81
    rCSI 46.17%
    PRS 89.75
  • flat midget bipolar cell CL4033033
    CSI 9.54
    rCSI 68.2%
    PRS 90.6
  • epithelial cell of proximal tubule CL0002306
    CSI 9.41
    rCSI 22.99%
    PRS 92.83
  • neural crest cell CL0011012
    CSI 9.13
    rCSI 7.21%
    PRS 94.28
  • alveolar macrophage CL0000583
    CSI 8.72
    rCSI 14.36%
    PRS 97.28
  • retina horizontal cell CL0000745
    CSI 8.63
    rCSI 13.15%
    PRS 95.01
  • glutamatergic neuron CL0000679
    CSI 8.33
    rCSI 17.12%
    PRS 89.3
  • H2 horizontal cell CL0004218
    CSI 8.25
    rCSI 41%
    PRS 93.37
  • diffuse bipolar 2 cell CL4033028
    CSI 7.33
    rCSI 56.76%
    PRS 91.75
  • lung interstitial macrophage CL4033043
    CSI 6.55
    rCSI 14.7%
    PRS 99.3
  • dopaminergic neuron CL0000700
    CSI 6.39
    rCSI 36.11%
    PRS 90.64
  • parietal epithelial cell CL1000452
    CSI 6.38
    rCSI 17.04%
    PRS 94.68
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 6.27
    rCSI 16.33%
    PRS 97.84
  • GABAergic neuron CL0000617
    CSI 6.24
    rCSI 20.9%
    PRS 88.87
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 6.21
    rCSI 19.42%
    PRS 92.56
  • serotonergic neuron CL0000850
    CSI 5.94
    rCSI 26.53%
    PRS 87.27
  • diffuse bipolar 3b cell CL4033030
    CSI 5.67
    rCSI 37.61%
    PRS 92.56
  • medium spiny neuron CL1001474
    CSI 5.56
    rCSI 47.94%
    PRS 92.2
  • cerebral cortex endothelial cell CL1001602
    CSI 5.39
    rCSI 9.32%
    PRS 94.57
  • renal interstitial pericyte CL1001318
    CSI 5.16
    rCSI 14.23%
    PRS 96.14
  • diffuse bipolar 1 cell CL4033027
    CSI 4.91
    rCSI 36.9%
    PRS 89.71
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 4.87
    rCSI 8.86%
    PRS 93.45
  • central nervous system neuron CL2000029
    CSI 4.44
    rCSI 32.63%
    PRS 92.87
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 3.9
    rCSI 9.34%
    PRS 90.75
  • retinal ganglion cell CL0000740
    CSI 3.72
    rCSI 8.22%
    PRS 91.35
  • diffuse bipolar 6 cell CL4033032
    CSI 3.41
    rCSI 17.91%
    PRS 90.14
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.89
    rCSI 2.22%
    PRS 98.25
  • glycinergic amacrine cell CL4030028
    CSI 2.76
    rCSI 7.2%
    PRS 92.72
  • starburst amacrine cell CL0004232
    CSI 2.52
    rCSI 21.19%
    PRS 87.63
  • midbrain dopaminergic neuron CL2000097
    CSI 2.43
    rCSI 15.55%
    PRS 92.42
  • OFF-bipolar cell CL0000750
    CSI 2.34
    rCSI 3.2%
    PRS 95.23
  • direct pathway medium spiny neuron CL4023026
    CSI 2.32
    rCSI 55.64%
    PRS 88.66
  • indirect pathway medium spiny neuron CL4023029
    CSI 2.3
    rCSI 55.45%
    PRS 88.41
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 2.23
    rCSI 8.42%
    PRS 90.84
  • Hofbauer cell CL3000001
    CSI 2.16
    rCSI 4.08%
    PRS 98.59
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 1.57
    rCSI 9.21%
    PRS 91.01
  • cerebral cortex pyramidal neuron CL4023111
    CSI 1.56
    rCSI 9.63%
    PRS 96.04
  • ON midget ganglion cell CL4033046
    CSI 0.97
    rCSI 19.7%
    PRS 91.54
  • intestinal crypt stem cell of colon CL0009043
    CSI 0.95
    rCSI 7.17%
    PRS 98.41
  • invaginating midget bipolar cell CL4033034
    CSI 0.9
    rCSI 5.32%
    PRS 90.95
  • OFF midget ganglion cell CL4033047
    CSI 0.82
    rCSI 16.6%
    PRS 91.79

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.

Comma-separated if multiple.
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 [PTPRO](/details-gene/5800), or Protein Tyrosine Phosphatase Receptor Type O, is a protein-coding gene located on chromosome 12. It encodes a receptor-type protein tyrosine phosphatase (PTP) that plays a crucial role in regulating cellular signaling through the dephosphorylation of tyrosine residues. **Overall**, expression data reveals that [PTPRO](/details-gene/5800) is a highly significant gene within the central nervous system, showing prominent expression in a wide array of neuronal subtypes, particularly cortical [interneurons](/details-cell/CL0000099) and [glutamatergic neurons](/details-cell/CL4023040). Functionally, it is implicated in key neurodevelopmental processes such as [axon guidance](/details-go/GO:0007411) and the [regulation of synapse organization](/details-go/GO:0050807). Beyond its neurological roles, [PTPRO](/details-gene/5800) is also essential for proper kidney function, with mutations linked to childhood-onset nephrotic syndrome ([600579](https://omim.org/entry/600579)). ## Cellular Roles and Expression Landscape The expression profile of [PTPRO](/details-gene/5800) firmly establishes it as a key gene in the nervous system. **Overall**, it exhibits exceptionally high significance in various subtypes of cortical inhibitory [neurons](/details-cell/CL0000540), including [sst GABAergic cortical interneurons](/details-cell/CL4023017) (CSI: 38.05), [VIP GABAergic cortical interneurons](/details-cell/CL4023016) (CSI: 37.14), and [sncg GABAergic cortical interneurons](/details-cell/CL4023015) (CSI: 33.99). Its high CSI values in these specific cell types suggest it may serve as a critical marker and functional regulator of interneuron identity and circuit integration. The gene is also significantly expressed in excitatory [neurons](/details-cell/CL0000540), such as [L2/3 intratelencephalic projecting glutamatergic neurons](/details-cell/CL4030059) (CSI: 19.39), and in other neural cell types like the [retinal bipolar neuron](/details-cell/CL0000748) (CSI: 23.33). Furthermore, its presence in developing cells like [neuroblasts](/details-cell/CL0000031) (CSI: 14.49) and in glial-derived tumor cells like [glioblasts](/details-cell/CL0000030) (CSI: 16.20) points to a broader role in neural development and pathology. Although primarily neuronal, an alternatively spliced isoform has been reported in B-lymphoid cells, where it is suggested to promote cell cycle arrest ([Link](https://pubmed.ncbi.nlm.nih.gov/10498613)). ## Pathways and Molecular Function Functionally, [PTPRO](/details-gene/5800) is a transmembrane receptor with intrinsic [protein tyrosine phosphatase activity](/details-go/GO:0004725). Its involvement in the [Signal transduction](/details-reactome/R-HSA-162582) and [Signaling by receptor tyrosine kinases](/details-reactome/R-HSA-9006934) pathways is central to its function. The molecular activities of [PTPRO](/details-gene/5800) are consistent with its observed cellular expression patterns. Its roles in [axon guidance](/details-go/GO:0007411), [negative regulation of neuron projection development](/details-go/GO:0010977), and [regulation of synapse organization](/details-go/GO:0050807) directly support its importance in establishing and maintaining the complex wiring of the nervous system. In addition to its neural functions, [PTPRO](/details-gene/5800) is annotated for processes critical to kidney physiology, including [glomerulus development](/details-go/GO:0032835), [podocyte differentiation](/details-go/GO:0072112), and [slit diaphragm assembly](/details-go/GO:0036060). This dual role is underscored by research demonstrating that disruption of [PTPRO](/details-gene/5800) leads to childhood-onset nephrotic syndrome, likely by impairing the structure and function of the glomerular filtration barrier ([Link](https://doi.org/10.1016/j.ajhg.2011.05.026)). ## Research Directions The data highlights the multifaceted roles of [PTPRO](/details-gene/5800) in both the nervous system and the kidney, providing several avenues for future research. **Proposed Hypotheses:** 1. Given its highly specific and significant expression in diverse cortical [interneuron](/details-cell/CL0000099) subtypes, [PTPRO](/details-gene/5800) likely functions as a subtype-specific regulator of synaptic connectivity. It may control the formation or stability of synapses between specific interneurons and their targets, thereby fine-tuning the excitatory/inhibitory balance in cortical microcircuits. 2. The established link between [PTPRO](/details-gene/5800) mutations and nephrotic syndrome ([Link](https://doi.org/10.1016/j.ajhg.2011.05.026)) suggests that its phosphatase activity is essential for maintaining the integrity of the podocyte slit diaphragm. It is hypothesized that [PTPRO](/details-gene/5800) dephosphorylates key structural proteins (e.g., nephrin or its binding partners) at the slit diaphragm, and loss of this activity leads to structural collapse and proteinuria. **Key Experimental Approach:** To test the first hypothesis regarding the role of [PTPRO](/details-gene/5800) in regulating interneuron synaptic specificity, a conditional knockout mouse model could be employed. By crossing a floxed-[PTPRO](/details-gene/5800) mouse with Cre-driver lines specific for interneuron subtypes (e.g., Sst-Cre or Pvalb-Cre), the gene can be selectively deleted in those populations. Subsequent analysis using a combination of slice electrophysiology (to measure synaptic currents) and high-resolution microscopy (to quantify synapse number and morphology) would reveal deficits in synaptic connectivity and function, directly testing the gene's role in circuit formation. **Therapeutic Potential:** [PTPRO](/details-gene/5800) presents distinct therapeutic possibilities depending on the disease context. For nephrotic syndrome caused by loss-of-function mutations, the goal would be functional restoration. This could potentially be achieved through gene therapy aimed at reintroducing a functional copy of the gene into podocytes or through the development of small-molecule compounds that can activate downstream pathways to compensate for the missing phosphatase activity. In contrast, its expression in [glioblasts](/details-cell/CL0000030) suggests a potential role in cancer. If [PTPRO](/details-gene/5800) is found to act as a tumor suppressor (a common role for PTPs), targeted activators could be beneficial. Conversely, if its activity promotes tumor growth in this context, it could become a target for selective inhibition.

Genular Protein ID: 4196106739

Symbol: PTPRO_HUMAN

Name: Receptor-type tyrosine-protein phosphatase O

UniProtKB Accession Codes:

Q16827 A0AV39 Q13101 Q8IYG3 Q9UBF0 Q9UBT5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 4 CDD 2 CTD 1 ChEBI 4 ChEMBL 1 ChiTaRS 1 DEPOD 1 DMDM 1 DNASU 1 DisGeNET 1 EC 2 EMBL 14 Ensembl 10 EvolutionaryTrace 1 ExpressionAtlas 1 GO 35 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 9 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 2 PDBsum 2 PIR 2 PRINTS 1 PRO 1 PROSITE 4 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 5 RNAct 1 Reactome 1 RefSeq 6 Rhea 3 SABIO-RK 1 SIGNOR 1 SMART 3 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 7753550

Title: Cloning, expression and chromosomal localization of a novel gene for protein tyrosine phosphatase (PTP-U2) induced by various differentiation-inducing agents.

PubMed ID: 7753550

PubMed ID: 7665166

Title: Molecular cloning of cDNAs encoding human GLEPP1, a membrane protein tyrosine phosphatase: characterization of the GLEPP1 protein distribution in human kidney and assignment of the GLEPP1 gene to human chromosome 12p12-p13.

PubMed ID: 7665166

DOI: 10.1006/geno.1995.1021

PubMed ID: 10498613

Title: PTPROt: an alternatively spliced and developmentally regulated B-lymphoid phosphatase that promotes G0/G1 arrest.

PubMed ID: 10498613

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

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: 21722858

Title: Disruption of PTPRO causes childhood-onset nephrotic syndrome.

PubMed ID: 21722858

DOI: 10.1016/j.ajhg.2011.05.026

PubMed ID: 19167335

Title: Large-scale structural analysis of the classical human protein tyrosine phosphatome.

PubMed ID: 19167335

DOI: 10.1016/j.cell.2008.11.038

PubMed ID: 18058037

Title: Structural genomics of protein phosphatases.

PubMed ID: 18058037

DOI: 10.1007/s10969-007-9036-1

Sequence Information:

  • Length: 1216
  • Mass: 138344
  • Checksum: C902B48D1A73BFE1
  • Sequence:
    • MGHLPTGIHG ARRLLPLLWL FVLFKNATAF HVTVQDDNNI VVSLEASDVI SPASVYVVKI 
TGESKNYFFE FEEFNSTLPP PVIFKASYHG LYYIITLVVV NGNVVTKPSR SITVLTKPLP 
VTSVSIYDYK PSPETGVLFE IHYPEKYNVF TRVNISYWEG KDFRTMLYKD FFKGKTVFNH 
WLPGMCYSNI TFQLVSEATF NKSTLVEYSG VSHEPKQHRT APYPPQNISV RIVNLNKNNW 
EEQSGNFPEE SFMRSQDTIG KEKLFHFTEE TPEIPSGNIS SGWPDFNSSD YETTSQPYWW 
DSASAAPESE DEFVSVLPME YENNSTLSET EKSTSGSFSF FPVQMILTWL PPKPPTAFDG 
FHIHIEREEN FTEYLMVDEE AHEFVAELKE PGKYKLSVTT FSSSGSCETR KSQSAKSLSF 
YISPSGEWIE ELTEKPQHVS VHVLSSTTAL MSWTSSQENY NSTIVSVVSL TCQKQKESQR 
LEKQYCTQVN SSKPIIENLV PGAQYQVVIY LRKGPLIGPP SDPVTFAIVP TGIKDLMLYP 
LGPTAVVLSW TRPYLGVFRK YVVEMFYFNP ATMTSEWTTY YEIAATVSLT ASVRIANLLP 
AWYYNFRVTM VTWGDPELSC CDSSTISFIT APVAPEITSV EYFNSLLYIS WTYGDDTTDL 
SHSRMLHWMV VAEGKKKIKK SVTRNVMTAI LSLPPGDIYN LSVTACTERG SNTSMLRLVK 
LEPAPPKSLF AVNKTQTSVT LLWVEEGVAD FFEVFCQQVG SSQKTKLQEP VAVSSHVVTI 
SSLLPATAYN CSVTSFSHDS PSVPTFIAVS TMVTEMNPNV VVISVLAILS TLLIGLLLVT 
LIILRKKHLQ MARECGAGTF VNFASLERDG KLPYNWRRSI FAFLTLLPSC LWTDYLLAFY 
INPWSKNGLK KRKLTNPVQL DDFDAYIKDM AKDSDYKFSL QFEELKLIGL DIPHFAADLP 
LNRCKNRYTN ILPYDFSRVR LVSMNEEEGA DYINANYIPG YNSPQEYIAT QGPLPETRND 
FWKMVLQQKS QIIVMLTQCN EKRRVKCDHY WPFTEEPIAY GDITVEMISE EEQDDWACRH 
FRINYADEMQ DVMHFNYTAW PDHGVPTANA AESILQFVHM VRQQATKSKG PMIIHCSAGV 
GRTGTFIALD RLLQHIRDHE FVDILGLVSE MRSYRMSMVQ TEEQYIFIHQ CVQLMWMKKK 
QQFCISDVIY ENVSKS