PTPRN: Protein Tyrosine Phosphatase Receptor Type N
A key autoantigen in type 1 diabetes and regulator of insulin secretion
Gene Information Card
| Symbol | PTPRN |
|---|---|
| Full Name | Protein Tyrosine Phosphatase Receptor Type N |
| Gene Type | Protein coding |
| Chromosomal Location | 2q35 |
| NCBI Gene ID | 5798 ncbi.nlm.nih.gov/gene/5798 |
| Ensembl ID | ENSG00000054356 |
| UniProt ID | Q16849 |
| OMIM ID | 601773 |
| HGNC ID | 9676 |
| Aliases | IA-2, ICA512, R-PTP-N |
Description
PTPRN encodes a member of the protein tyrosine phosphatase (PTP) family, specifically a receptor-type PTP. The protein is a transmembrane autoantigen in insulin-dependent diabetes mellitus (type 1 diabetes). It is localized to secretory vesicles in neuroendocrine cells, including pancreatic beta cells, and is involved in insulin granule exocytosis and neurotransmitter release. PTPRN undergoes proteolytic processing and its intracellular domain can translocate to the nucleus to regulate gene expression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Type 1 Diabetes Mellitus | Autoantibodies against PTPRN (IA-2) are present in the majority of patients; the protein is a major autoantigen targeted by the immune system, leading to beta-cell destruction. | ClinVar, OMIM |
| Autoimmune Polyendocrine Syndrome Type 1 | PTPRN is one of the autoantigens recognized in APS-1, associated with chronic mucocutaneous candidiasis and multiple endocrine deficiencies. | OMIM |
| Insulinoma | PTPRN expression is altered in insulin-secreting tumors; its role in tumorigenesis is under investigation. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | 33.2 | High |
| Brain | 12.5 | Medium |
| Pituitary Gland | 8.9 | Medium |
| Adrenal Gland | 6.3 | Low |
| Testis | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| INS-1 (rat beta cell) | 45.0 | High expression; used in insulin secretion studies |
| MIN6 (mouse beta cell) | 38.5 | High expression; model for type 1 diabetes |
| HeLa | 1.2 | Very low expression |
| HEK293 | 0.8 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2020C>T (p.Arg674Trp) | Missense | 0.01% | Reported in type 1 diabetes; may alter autoantibody binding |
| c.2485G>A (p.Gly829Ser) | Missense | 0.005% | Found in a patient with autoimmune polyendocrine syndrome; functional impact unknown |
| c.1234delC | Frameshift | <0.001% | Predicted loss of function; rare in population databases |
Mutation functional classification
Loss of Function (LOF)
Frameshift or nonsense mutations that truncate the protein, impairing its role in insulin granule exocytosis.
Gain of Function (GOF)
Not well characterized; no clear gain-of-function mutations reported in PTPRN.
Dominant Negative (DN)
Missense mutations in the PTP domain may interfere with dimerization or substrate binding, potentially acting in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Insulin secretion (Reactome: R-HSA-422356)
• Protein tyrosine phosphatase signaling (KEGG: hsa04630)
Protein Summary
PTPRN (IA-2) is a 979-amino-acid transmembrane protein with a large extracellular domain, a single transmembrane region, and an intracellular protein tyrosine phosphatase (PTP) domain. The PTP domain is catalytically inactive due to substitution of critical residues, but it functions as a substrate-trapping domain. The protein is cleaved by furin-like proteases, generating a 65 kDa extracellular fragment and a 40 kDa intracellular fragment. The intracellular fragment can translocate to the nucleus and regulate transcription of genes involved in beta-cell function. PTPRN is essential for normal insulin granule exocytosis and glucose homeostasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PTPRN Knockout HEK293 Cell Line | EDJ-KQ5602 | Human | 5798 | Details Get a Quote |
| PTPRN2 Knockout HEK293 Cell Line | EDJ-KQ5606 | Human | 5799 | Details Get a Quote |
| PTPRN2 Knockout HCT 116 Cell Line | EDJ-KQ28890 | Human | 5799 | Details Get a Quote |
| PTPRN Knockout HeLa Cell Line | EDJ-KQ54275 | Human | 5798 | Details Get a Quote |
| PTPRN2 Knockout HeLa Cell Line | EDJ-KQ54276 | Human | 5799 | Details Get a Quote |
| PTPRN Knockout A-549 Cell Line | EDJ-KQ62767 | Human | 5798 | Details Get a Quote |
| PTPRN2 Knockout A-549 Cell Line | EDJ-KQ62768 | Human | 5799 | Details Get a Quote |
| PTPRN Knockout HCT 116 Cell Line | EDJ-KQ71235 | Human | 5798 | Details Get a Quote |
