PTPN2
protein tyrosine phosphatase non-receptor type 2, the group of Protein tyrosine phosphatases non-receptor type
Basic information
Region (hg38): 18:12785478-12929643
Previous symbols: [ "PTPT" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PTPN2 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | |||||
| missense | 12 | 14 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 12 | 2 | 2 |
Variants in PTPN2
This is a list of pathogenic ClinVar variants found in the PTPN2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 18-12794301-A-C | not specified | Uncertain significance (Jun 04, 2024) | ||
| 18-12794316-C-A | not specified | Uncertain significance (Apr 23, 2024) | ||
| 18-12801978-G-A | Likely benign (May 01, 2022) | |||
| 18-12801998-G-T | not specified | Uncertain significance (Jun 22, 2023) | ||
| 18-12814242-T-C | not specified | Uncertain significance (Jul 20, 2022) | ||
| 18-12814339-T-C | not specified | Uncertain significance (Apr 07, 2023) | ||
| 18-12814349-T-C | not specified | Uncertain significance (Dec 03, 2021) | ||
| 18-12817161-C-T | Benign (Feb 26, 2018) | |||
| 18-12817164-G-T | not specified | Uncertain significance (Jun 02, 2023) | ||
| 18-12817325-G-C | not specified | Uncertain significance (Mar 05, 2024) | ||
| 18-12817349-G-T | Benign (Jun 18, 2018) | |||
| 18-12825833-G-C | not specified | Uncertain significance (Sep 16, 2021) | ||
| 18-12825902-G-T | not specified | Uncertain significance (Feb 07, 2023) | ||
| 18-12825909-T-A | not specified | Uncertain significance (Dec 15, 2022) | ||
| 18-12830986-G-C | not specified | Uncertain significance (Nov 17, 2022) | ||
| 18-12831024-T-C | Likely benign (Jul 11, 2018) | |||
| 18-12859244-T-C | not specified | Uncertain significance (Mar 06, 2023) | ||
| 18-12884083-G-A | not specified | Uncertain significance (May 04, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PTPN2 | protein_coding | protein_coding | ENST00000309660 | 9 | 144166 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.000470 | 125696 | 0 | 3 | 125699 | 0.0000119 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.38 | 163 | 221 | 0.739 | 0.0000110 | 2728 |
| Missense in Polyphen | 34 | 72.242 | 0.47064 | 917 | ||
| Synonymous | 0.628 | 66 | 72.8 | 0.906 | 0.00000340 | 747 |
| Loss of Function | 4.59 | 1 | 26.4 | 0.0378 | 0.00000167 | 280 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000266 | 0.0000264 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Non-receptor type tyrosine-specific phosphatase that dephosphorylates receptor protein tyrosine kinases including INSR, EGFR, CSF1R, PDGFR. Also dephosphorylates non-receptor protein tyrosine kinases like JAK1, JAK2, JAK3, Src family kinases, STAT1, STAT3 and STAT6 either in the nucleus or the cytoplasm. Negatively regulates numerous signaling pathways and biological processes like hematopoiesis, inflammatory response, cell proliferation and differentiation, and glucose homeostasis. Plays a multifaceted and important role in the development of the immune system. Functions in T-cell receptor signaling through dephosphorylation of FYN and LCK to control T-cells differentiation and activation. Dephosphorylates CSF1R, negatively regulating its downstream signaling and macrophage differentiation. Negatively regulates cytokine (IL2/interleukin-2 and interferon)-mediated signaling through dephosphorylation of the cytoplasmic kinases JAK1, JAK3 and their substrate STAT1, that propagate signaling downstream of the cytokine receptors. Also regulates the IL6/interleukin-6 and IL4/interleukin-4 cytokine signaling through dephosphorylation of STAT3 and STAT6 respectively. In addition to the immune system, it is involved in anchorage-dependent, negative regulation of EGF- stimulated cell growth. Activated by the integrin ITGA1/ITGB1, it dephosphorylates EGFR and negatively regulates EGF signaling. Dephosphorylates PDGFRB and negatively regulates platelet-derived growth factor receptor-beta signaling pathway and therefore cell proliferation. Negatively regulates tumor necrosis factor-mediated signaling downstream via MAPK through SRC dephosphorylation. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of the hepatocyte growth factor receptor MET. Plays also an important role in glucose homeostasis. For instance, negatively regulates the insulin receptor signaling pathway through the dephosphorylation of INSR and control gluconeogenesis and liver glucose production through negative regulation of the IL6 signaling pathways. May also bind DNA. {ECO:0000269|PubMed:10734133, ECO:0000269|PubMed:11909529, ECO:0000269|PubMed:12138178, ECO:0000269|PubMed:12612081, ECO:0000269|PubMed:14966296, ECO:0000269|PubMed:15592458, ECO:0000269|PubMed:18819921, ECO:0000269|PubMed:22080863, ECO:0000269|PubMed:9488479}.;
- Pathway
- Jak-STAT signaling pathway - Homo sapiens (human);IGF-Ncore;JAK-STAT-Ncore;The human immune response to tuberculosis;Signal Transduction;Cytokine Signaling in Immune system;Regulation of IFNG signaling;Immune System;Signaling events mediated by TCPTP;Interferon gamma signaling;IFN-gamma pathway;Negative regulation of MET activity;Signaling by MET;Signaling by Receptor Tyrosine Kinases;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);Interferon Signaling;PDGFR-beta signaling pathway;Signaling events mediated by VEGFR1 and VEGFR2
(Consensus)
Intolerance Scores
- loftool
- 0.0804
- rvis_EVS
- 0.75
- rvis_percentile_EVS
- 86.57
Haploinsufficiency Scores
- pHI
- 0.947
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.415
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.871
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ptpn2
- Phenotype
- endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; vision/eye phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; immune system phenotype;
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;negative regulation of cell population proliferation;insulin receptor signaling pathway;negative regulation of tumor necrosis factor-mediated signaling pathway;negative regulation of lipid storage;B cell differentiation;T cell differentiation;erythrocyte differentiation;peptidyl-tyrosine dephosphorylation;negative regulation of epidermal growth factor receptor signaling pathway;negative regulation of tyrosine phosphorylation of STAT protein;glucose homeostasis;negative regulation of macrophage differentiation;positive regulation of gluconeogenesis;negative regulation of insulin receptor signaling pathway;negative regulation of inflammatory response;negative regulation of T cell receptor signaling pathway;negative regulation of chemotaxis;regulation of interferon-gamma-mediated signaling pathway;negative regulation of interferon-gamma-mediated signaling pathway;negative regulation of type I interferon-mediated signaling pathway;negative regulation of protein tyrosine kinase activity;negative regulation of interleukin-6-mediated signaling pathway;negative regulation of ERK1 and ERK2 cascade;cellular response to cytokine stimulus;regulation of hepatocyte growth factor receptor signaling pathway;negative regulation of interleukin-2-mediated signaling pathway;negative regulation of interleukin-4-mediated signaling pathway;negative regulation of macrophage colony-stimulating factor signaling pathway;negative regulation of positive thymic T cell selection;positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway;positive regulation of PERK-mediated unfolded protein response;negative regulation of platelet-derived growth factor receptor-beta signaling pathway
- Cellular component
- nucleoplasm;endoplasmic reticulum;endoplasmic reticulum-Golgi intermediate compartment;cytosol;plasma membrane
- Molecular function
- protein tyrosine phosphatase activity;non-membrane spanning protein tyrosine phosphatase activity;integrin binding;protein binding;protein kinase binding;syntaxin binding;receptor tyrosine kinase binding;STAT family protein binding