PTPRT Gene (Protein Tyrosine Phosphatase Receptor Type T)

PTPRT Gene (Protein Tyrosine Phosphatase Receptor Type T)

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">PTPRT</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>PTPRT</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Protein Tyrosine Phosphatase Receptor Type T</td>
</tr>
<tr>
<td class="label">Alias</td>
<td>RPTPρ, RPTP-Sigma</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>20q12-q13.12</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>5792</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>602706</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000196090</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9Y2P9</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Receptor-type protein tyrosine phosphatase (RPTP) family</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td>[Autism Spectrum Disorder](/diseases/autism-spectrum-disorder), Intellectual Disability, Colorectal Cancer</td>
</tr>
</table>

PTPRT Gene (Protein Tyrosine Phosphatase Receptor Type T)

Overview

PTPRT Gene (Protein Tyrosine Phosphatase Receptor Type T)

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">PTPRT</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>PTPRT</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Protein Tyrosine Phosphatase Receptor Type T</td>
</tr>
<tr>
<td class="label">Alias</td>
<td>RPTPρ, RPTP-Sigma</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>20q12-q13.12</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>5792</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>602706</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000196090</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9Y2P9</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Receptor-type protein tyrosine phosphatase (RPTP) family</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td>[Autism Spectrum Disorder](/diseases/autism-spectrum-disorder), Intellectual Disability, Colorectal Cancer</td>
</tr>
</table>

PTPRT Gene (Protein Tyrosine Phosphatase Receptor Type T)

Overview

PTPRT (Protein Tyrosine Phosphatase Receptor Type T), also known as RPTPρ or RPTP-Sigma, is a member of the receptor protein tyrosine phosphatase (RPTP) family. It is primarily expressed in the nervous system where it plays critical roles in regulating synaptic connectivity, neuronal migration, and axon guidance [[moll1991]](https://pubmed.ncbi.nlm.nih.gov/1725271/). PTPRT functions as a receptor-type phosphatase that dephosphorylates specific substrates involved in neuronal development and synaptic plasticity [[besco2006]](https://pubmed.ncbi.nlm.nih.gov/16533388/).

PTPRT is unique among RPTPs due to its extended extracellular domain and brain-restricted expression pattern. The protein has emerged as an important regulator of neuronal connectivity and has been implicated in neurodevelopmental disorders and cancer.

Function

Structure

PTPRT consists of:

• Extracellular domain: Contains multiple fibronectin type III repeats that mediate cell-cell interactions
• Transmembrane domain: Single pass membrane-spanning region
• Cytoplasmic domain: Contains two tandem tyrosine phosphatase domains (D1 and D2)

Normal Function in the Nervous System

In neurons, PTPRT performs several critical functions:

Synapse Formation and Function
PTPRT localizes to postsynaptic sites and regulates synaptic development [[charette2020]](https://pubmed.ncbi.nlm.nih.gov/32061126/):

• Controls the formation and maintenance of dendritic spines
• Regulates synaptic transmission through modulation of postsynaptic receptors
• Coordinates with presynaptic signaling molecules for proper synaptic alignment

• Regulates growth cone dynamics
• Modulates cytoskeletal organization in response to guidance cues
• Coordinates with intracellular signaling pathways

• Modulates adhesion dynamics during migration
• Interacts with cytoskeletal regulators

• Controls dendritic tree complexity
• Influences spine distribution along dendrites

Signaling Mechanisms

PTPRT dephosphorylates several key substrates:

• Fyn kinase: Regulates Src family kinase activity at synapses
• PSD-95: Modulates synaptic scaffold organization [[yang2013]](https://pubmed.ncbi.nlm.nih.gov/24089054/)
• NMDA receptor subunits: Alters receptor trafficking and function
• Actin cytoskeletal regulators: Controls spine morphology

Disease Associations

Autism Spectrum Disorder

PTPRT mutations are associated with ASD [[farber2011]](https://pubmed.ncbi.nlm.nih.gov/21266527/):

• Loss-of-function variants identified in ASD patients
• Haploinsufficiency may disrupt synaptic development
• Contributes to social behavior and communication deficits
• Synaptic formation deficits observed in PTPRT-deficient neurons [[anderson2015]](https://pubmed.ncbi.nlm.nih.gov/26041908/)

Intellectual Disability

PTPRT variants cause:

• Non-syndromic intellectual disability
• Developmental delay
• Speech and language impairments

Cancer

As a tumor suppressor [[beltran2013]](https://pubmed.ncbi.nlm.nih.gov/23707783/):

• Frequently mutated in colorectal cancers [[chen2018]](https://pubmed.ncbi.nlm.nih.gov/29476153/)
• Loss-of-function mutations promote cell proliferation
• Associated with poor prognosis in some cancers

Neurodegenerative Diseases

Emerging evidence suggests roles in [[park2023]](https://pubmed.ncbi.nlm.nih.gov/37179567/):

• Synaptic dysfunction in Alzheimer's disease
• Axonal degeneration in Parkinson's disease
• Neuronal death in stroke models
• Proteolytic cleavage by ADAM10 and γ-secretase affects its function [[lim2023]](https://doi.org/10.1016/j.jbc.2023.102901)

Expression Patterns

Tissue Distribution

• Primarily neural: Highest expression in brain and nervous system
• Lower expression: Detected in some epithelial tissues
• Developmentally regulated: Expression peaks during embryogenesis

Brain Regional Expression

• Cerebral cortex: Layer 2-6 pyramidal neurons
• Hippocampus: CA1-CA3 pyramidal cells and dentate gyrus granule cells
• Cerebellum: Purkinje cells and granule cells
• Brainstem: Various neuronal populations
• Spinal cord: Motor neurons and interneurons

Subcellular Localization

• Postsynaptic density: Concentrated at excitatory synapses
• Growth cones: Present in developing axons
• Dendritic shafts: Along dendritic processes

Cell-Type Specificity

• Neurons: Primary expression in excitatory glutamatergic neurons
• Astrocytes: Lower expression
• Oligodendrocytes: Limited expression

Therapeutic Implications

Drug Development

PTPRT is being explored as a therapeutic target:

• Inhibitors: Small molecule inhibitors for cancer treatment
• Activators: Compounds that enhance PTPRT function in neurodevelopmental disorders
• Blood-brain barrier considerations: Important for CNS applications

Research Applications

• Biomarkers: PTPRT expression as a marker for synaptic integrity
• Gene therapy: Restoring PTPRT function in neurodevelopmental disorders
• Combination therapies: Targeting PTPRT with other treatments

Interactions and Pathways

Protein Interactions

• Ligands: PTPRT interacts with various cell adhesion molecules
• Substrates: Fyn, PSD-95, NMDA receptors
• Scaffolding proteins: Links to cytoskeletal organizers

Signaling Pathways

• Src family kinases: Regulates Src signaling at synapses
• NMDA receptor signaling: Modulates glutamatergic transmission
• Integrin signaling: Coordinates adhesion and migration

Cross-links

• [PTPRT Protein](/proteins/ptprt-protein) - Corresponding protein page
• [Synaptic Signaling](/mechanisms/synaptic-signaling) - Related mechanism
• [Neuronal Development](/mechanisms/neuronal-development) - Related mechanism
• [Autism Spectrum Disorder](/diseases/autism-spectrum-disorder) - Disease association

References

See Also

• [Neurodegenerative Diseases](/diseases/neurodegeneration)
• [Cell Types - Neurons](/cell-types/neurons)
• [Genes - Index of gene pages](/genes)
• [Proteins - Index of protein pages](/proteins)
• [Mechanisms - Index of mechanism pages](/mechanisms)