PTPRD (protein tyrosine phosphatase, receptor type, D)

2009-01-01   Laavanya Parthasarathi , Raymond L Stallings 

Royal College of Surgeons in Ireland, Childrens Research Centre, Our Ladys Childrens Hospital, Crumlin, Dublin, Ireland





The PTPRD gene is composed of 36 coding sequence exons and a 5 UTR spliced together from 11 non-coding exons.


There are five known transcript variants for PTPRD.
Transcript Variant 1: This variant encodes the longest isoform 1 and is 10078 bp in length (Figure A).
Transcript Variant 2: This variant lacks two separate internal segments within the coding region. It thus encodes a protein that lacks a 9 aa, and a 4 aa internal fragments, as compared to isoform 1 and is 10039 bp in length (Figure C).
Transcript Variant 3: This variant lacks an internal segment within the coding region. It thus encodes a protein that lacks a 9 aa internal fragment, as compared to isoform 1 and is 10051 bp in length (Figure D).
Transcript Variant 4: This variant lacks an internal segment within the coding region. It thus encodes a protein that lacks a 411 aa internal fragment, and has one amino acid change, as compared to isoform 1 and is 8845 bp in length (Figure B).
Transcript Variant 5: This variant omits several exons, and utilizes an alternate exon, in the coding region. The resulting protein (isoform 5) retains the same reading frame and has the same N- and C-terminus as isoform 1. This variant is 8848 bp in length (Figure E).


No pseudogenes have been reported.


Atlas Image
Figure A - E: Illustrates the differences between the known PTPRD isoforms, as described in the text.


Amino acids: 1912.
Molecular Weight: 214760 Da.
The PTPRD gene belongs to the receptor class 2A subfamily of the protein-tyrosine phosphatases. It contains an extracellular region composed of 8 fibronectin type-III domains and 3 Ig-like C2-type (immunoglobulin-like) domains, a single transmembrane segment and two tandem intracytoplasmic tyrosine-protein phosphatase domains.
Molecular Class: Receptor Tyrosine Phosphatase.
Molecular Function: Receptor Signalling Protein Tyrosine Phosphatase Activity.
Biological Process: Cell Communication ; Signal Transduction.


Brain, Kidney.
Multiple isoforms are generated by either alternate splicing or by alternate transcriptional start sites in a tissue specific manner. The predominant isoform in brain has an extended 711 base pair 5 UTR (L isoform), while the isoform (S) expressed in kidney lacks the extended 5 UTR. In addition, the brain isoform is characterized by the absence of exons 14 to 18 corresponding to amino acid residues 568 to 978 of the 4th through 7th fibronectin III-like domain and by the insertion of a 12 base pair mini-exon sequence between exons 23 and 24 (Nair et al., 2008).
The full length PTPRD isoform has an extracellular region containing three Ig-like and eight FN-III like domains connected via a transmembrane peptide to an intracellular region with two PTPase domains (A), whereas another isoform lacks four of the eight FN-III like domains (B). Furthermore, other PTPRD isoforms exist that lack 9 AA within the second Ig-like domain and 4 AA at the junction of the 2nd and 3rd Ig-like domains (C) or 9 AAs within the 5th FN-III like domain (D). The fifth isoform lacks four of the eight FN-III like domains and has mutation in the second Ig-like domain (E). RT-PCR analysis demonstrated that PTPRD isoforms lacking these short peptides are expressed in kidney, whereas isoforms containing these peptides are expressed in the brain (Pulido et al., 1995).


Membrane; Single-pass type I membrane protein.


A cleavage occurs, separating the extracellular domain from the transmembrane segment. This process called ectodomain shedding is thought to be involved in receptor desensitization, signal transduction and/or membrane localization. Plays key role in promoting neurite growth and regulating axon guidance.


PTPRD shares a PTP domain, involved in dephosphorylating phosphorylated tyrosine residues, with the other receptor-like protein tyrosine phosphatases. The human and mouse PTPRD sequences are 93% identical and 95% homologous.

Implicated in

Entity name
Lung Adenocarcinoma
Early evidence for the involvement of PTPRD in lung adenocarcinoma came from the detection of homozygous deletions in both primary tumours and cell lines representing both small cell lung carcinoma and non-small cell lung carcinoma (Cox et al., 2005; Zhao et al., 2005; Sato et al., 2005; Nagayama et al., 2007). In addition, somatically acquired PTPRD mutations were found in 11 out of 188 lung adenocarcinoma samples (Weir et al., 2007). Notably, three of the mutations encode predicated inactivating changes in the tyrosine phosphatase domain. Screening for somatic mutations in 623 candidate genes using 188 primary lung adenocarcinoma tissues also revealed sequence changes in PTPRD (Ding et al., 2008).
Entity name
High resolution a CGH analysis of neuroblastoma (NBL) tumours and cell lines identified homozygous and hemizygous intragenic deletions of the PTPRD gene, implicating the gene as a candidate tumor suppressor gene in this type of cancer (Stallings et al., 2006). In addition, the 5 UTR of PTPRD, consisting of 11 noncoding exons, was found to be aberrantly spliced in > 50% of NBL primary tumors and cell lines (Nair et al., 2008). mRNA levels were determined to be significantly reduced in unfavorable tumour subtypes relative to more favorable tumor subtypes.
Entity name
Squamous Cell Carcinoma
Both homozygous and hemizygous deletions affecting the PTPRD gene have been reported in squamous cell carcinoma (Purdie et al., 2007).
Entity name
Colorectal Carcinoma
PTPRD was found to be somatically mutated in colorectal carcinoma with the sequence changes, R28Q, L276P, V901A (Sjoblom et al., 2006).
Entity name
Glioblastoma Multiforme and Malignant Melanoma
A high frequency of deletions in the PTPRD gene were detected in glioblastoma multiforme (GBM) tumours using Affymetrix 250K single nucleotide polymorphism arrays (Solomon et al., 2008). Missense and nonsense mutations of PTPRD were also identified in a subset of the samples lacking deletions, including an inherited mutation with somatic loss of the wild-type allele. The same group also identified 10 somatically acquired mutations in PTPRD among 7 of 57 melanoma tumors (12%). Ectopic reconstitution of wild-type PTPRD expression in GBM and melanoma cell lines harboring deletions or mutations of the endogenous PTPRD gene led to growth suppression and apoptosis, indicating that this gene functions as a tumour suppressor in multiple forms of cancer (Solomon et al., 2008).
Entity name
Restless Leg Syndrome (RLS)
Genome-wide association study of RLS identified three SNPs within the PTPRD gene in the chromosome 9 linkage region (RLS3) as nominally significant (Winkelmann et al., 2007). PTPRD is identified as the fourth genome-wide significant locus for RLS from the genome wide association study in 2458 affected individuals and 4749 controls from Germany, Austria, Czech Republic and Canada (Schormair et al., 2008).
Entity name
Pediatric Asthma
A whole-genome linkage disequilibrium mapping study for asthma on 190 allergic and nonallergic asthma children in Taiwan revealed that polymorphisms of PTPRD are strongly associated with pediatric bronchial asthma in the Taiwanese population (Shyur et al., 2008).


Pubmed IDLast YearTitleAuthors
163380722006Protein tyrosine-phosphatase expression profiling in gastric cancer tissues.Wu CW et al
123765452002Intra- and intermolecular interactions between intracellular domains of receptor protein-tyrosine phosphatases.Blanchetot C et al
157610582005A survey of homozygous deletions in human cancer genomes.Cox C et al
189489472008Somatic mutations affect key pathways in lung adenocarcinoma.Ding L et al
100801911999Neuroendocrine dysplasia in mice lacking protein tyrosine phosphatase sigma.Elchebly M et al
165071382006Genome-wide review of transcriptional complexity in mouse protein kinases and phosphatases.Forrest AR et al
180343172009Screening of AMP-activated protein kinase alpha2 subunit interacting proteins by bacterial two-hybrid system.Fu QY et al
156840342005Receptor tyrosine phosphatase-dependent cytoskeletal remodeling by the hedgehog-responsive gene MIM/BEG4.Gonzalez-Quevedo R et al
186182262008Genomic changes in progression of low-grade gliomas.Idbaih A et al
122378612002Protein tyrosine phosphatase sigma-deficient mice show aberrant cytoarchitecture and structural abnormalities in the central nervous system.Meathrel K et al
79886771994Developmental regulation of gene expression for the MPTP delta isoforms in the central nervous system and the immune system.Mizuno K et al
176743612007Homozygous deletion scanning of the lung cancer genome at a 100-kb resolution.Nagayama K et al
180503032008Aberrant splicing of the PTPRD gene mimics microdeletions identified at this locus in neuroblastomas.Nair P et al
85248291995The LAR/PTP delta/PTP sigma subfamily of transmembrane protein-tyrosine-phosphatases: multiple human LAR, PTP delta, and PTP sigma isoforms are expressed in a tissue-specific manner and associate with the LAR-interacting protein LIP.1.Pulido R et al
174209882007Allelic imbalances and microdeletions affecting the PTPRD gene in cutaneous squamous cell carcinomas detected using single nucleotide polymorphism microarray analysis.Purdie KJ et al
161140342005Identification of chromosome arm 9p as the most frequent target of homozygous deletions in lung cancer.Sato M et al
186608102008PTPRD (protein tyrosine phosphatase receptor type delta) is associated with restless legs syndrome.Schormair B et al
184145092008The polymorphisms of protein-tyrosine phosphatase receptor-type delta gene and its association with pediatric asthma in the Taiwanese population.Shyur SD et al
169599742006The consensus coding sequences of human breast and colorectal cancers.Sjöblom T et al
165851932006High-resolution analysis of chromosomal breakpoints and genomic instability identifies PTPRD as a candidate tumor suppressor gene in neuroblastoma.Stallings RL et al
173635832007Genome-wide loss of heterozygosity and copy number analysis in melanoma using high-density single-nucleotide polymorphism arrays.Stark M et al
167382282006Mammalian motoneuron axon targeting requires receptor protein tyrosine phosphatases sigma and delta.Uetani N et al
108562232000Impaired learning with enhanced hippocampal long-term potentiation in PTPdelta-deficient mice.Uetani N et al
94720991998The selective reduction in PTPdelta expression in hepatomas.Urushibara N et al
97624701998Protein phosphatase 1 delta is associated with focal adhesions.Villa-Moruzzi E et al
100801921999Neuronal defects and posterior pituitary hypoplasia in mice lacking the receptor tyrosine phosphatase PTPsigma.Wallace MJ et al
105883911999Receptor tyrosine phosphatase-delta is a homophilic, neurite-promoting cell adhesion molecular for CNS neurons.Wang J et al
179824422007Characterizing the cancer genome in lung adenocarcinoma.Weir BA et al
176377802007Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions.Winkelmann J et al
125708712003MIM-B, a putative metastasis suppressor protein, binds to actin and to protein tyrosine phosphatase delta.Woodings JA et al
159949282005Homozygous deletions and chromosome amplifications in human lung carcinomas revealed by single nucleotide polymorphism array analysis.Zhao X et al

Other Information

Locus ID:

NCBI: 5789
MIM: 601598
HGNC: 9668
Ensembl: ENSG00000153707


dbSNP: 5789
ClinVar: 5789
TCGA: ENSG00000153707


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Neuronal SystemREACTOMER-HSA-112316
SALM protein interactions at the synapsesREACTOMER-HSA-8849932
Protein-protein interactions at synapsesREACTOMER-HSA-6794362

Protein levels (Protein atlas)

Not detected


Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA443890Diabetes Mellitus, Type 2DiseaseClinicalAnnotationassociatedPD


Pubmed IDYearTitleCitations
201745582010A genome-wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese.137
185198262008Molecular genetics of successful smoking cessation: convergent genome-wide association study results.130
194780612009The tyrosine phosphatase PTPRD is a tumor suppressor that is frequently inactivated and mutated in glioblastoma and other human cancers.108
194780612009The tyrosine phosphatase PTPRD is a tumor suppressor that is frequently inactivated and mutated in glioblastoma and other human cancers.108
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
192400612009Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling.75
186608102008PTPRD (protein tyrosine phosphatase receptor type delta) is associated with restless legs syndrome.71
186608102008PTPRD (protein tyrosine phosphatase receptor type delta) is associated with restless legs syndrome.71
201394222010Trans-synaptic adhesions between netrin-G ligand-3 (NGL-3) and receptor tyrosine phosphatases LAR, protein-tyrosine phosphatase delta (PTPdelta), and PTPsigma via specific domains regulate excitatory synapse formation.65
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62


Laavanya Parthasarathi ; Raymond L Stallings

PTPRD (protein tyrosine phosphatase, receptor type, D)

Atlas Genet Cytogenet Oncol Haematol. 2009-01-01

Online version: