PTPN6
protein tyrosine phosphatase non-receptor type 6, the group of Protein tyrosine phosphatases non-receptor type|SH2 domain containing
Basic information
Region (hg38): 12:6946467-6961316
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 PTPN6 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 | 6 | |||||
| missense | 19 | 21 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| splice region | 1 | 1 | 1 | 3 | ||
| non coding | 3 | |||||
| Total | 0 | 0 | 20 | 2 | 9 |
Variants in PTPN6
This is a list of pathogenic ClinVar variants found in the PTPN6 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 12-6951528-C-A | Likely benign (Dec 31, 2018) | |||
| 12-6951602-C-T | Uncertain significance (Mar 30, 2021) | |||
| 12-6951603-G-A | Conflicting classifications of pathogenicity (Mar 30, 2021) | |||
| 12-6951726-C-T | Benign (Dec 31, 2019) | |||
| 12-6951727-G-A | not specified | Uncertain significance (Jan 10, 2022) | ||
| 12-6952116-C-T | not specified | Uncertain significance (Mar 24, 2023) | ||
| 12-6954843-C-T | not specified | Uncertain significance (Feb 23, 2023) | ||
| 12-6954948-G-A | not specified | Uncertain significance (Feb 13, 2024) | ||
| 12-6955157-C-T | not specified | Uncertain significance (Oct 03, 2022) | ||
| 12-6955181-A-T | not specified | Uncertain significance (Jul 12, 2023) | ||
| 12-6955201-C-G | not specified | Uncertain significance (Mar 20, 2023) | ||
| 12-6955247-G-A | not specified | Uncertain significance (Jul 11, 2023) | ||
| 12-6955483-G-A | not specified | Uncertain significance (Sep 07, 2022) | ||
| 12-6956138-CCAGTTGACCA-C | Neurodevelopmental abnormality | Uncertain significance (Apr 03, 2020) | ||
| 12-6956446-G-A | not specified | Likely benign (Jan 29, 2024) | ||
| 12-6956472-T-T | Benign (Dec 31, 2019) | |||
| 12-6956576-G-GC | Benign (Dec 26, 2018) | |||
| 12-6957662-C-T | Benign (Dec 31, 2019) | |||
| 12-6957678-G-A | not specified | Uncertain significance (Aug 09, 2021) | ||
| 12-6957745-A-C | not specified | Uncertain significance (Apr 11, 2023) | ||
| 12-6957776-G-A | Benign (Dec 31, 2019) | |||
| 12-6957787-T-G | Autism spectrum disorder | Uncertain significance (Apr 13, 2022) | ||
| 12-6957911-C-T | Benign (Nov 16, 2018) | |||
| 12-6957924-C-A | not specified | Uncertain significance (Mar 07, 2024) | ||
| 12-6958043-C-A | not specified | Uncertain significance (May 25, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PTPN6 | protein_coding | protein_coding | ENST00000456013 | 15 | 14849 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.0000140 | 124871 | 0 | 2 | 124873 | 0.00000801 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.87 | 216 | 371 | 0.582 | 0.0000255 | 4059 |
| Missense in Polyphen | 40 | 112.94 | 0.35417 | 1159 | ||
| Synonymous | 0.390 | 150 | 156 | 0.960 | 0.0000116 | 1220 |
| Loss of Function | 5.39 | 1 | 35.8 | 0.0279 | 0.00000206 | 381 |
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 | 0.0000464 | 0.0000464 |
| European (Non-Finnish) | 0.00000888 | 0.00000882 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Modulates signaling by tyrosine phosphorylated cell surface receptors such as KIT and the EGF receptor/EGFR. The SH2 regions may interact with other cellular components to modulate its own phosphatase activity against interacting substrates. Together with MTUS1, induces UBE2V2 expression upon angiotensin II stimulation. Plays a key role in hematopoiesis. {ECO:0000269|PubMed:11266449}.;
- Pathway
- T cell receptor signaling pathway - Homo sapiens (human);B cell receptor signaling pathway - Homo sapiens (human);Adherens junction - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);Natural killer cell mediated cytotoxicity - Homo sapiens (human);Leishmaniasis - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);JAK-STAT-Ncore;Regulation of toll-like receptor signaling pathway;Prolactin Signaling Pathway;B Cell Receptor Signaling Pathway;T-Cell Receptor and Co-stimulatory Signaling;JAK-STAT;IL-3 Signaling Pathway;Kit receptor signaling pathway;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;IL-4 Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;Microglia Pathogen Phagocytosis Pathway;Interferon type I signaling pathways;Antigen activates B Cell Receptor (BCR) leading to generation of second messengers;Neutrophil degranulation;Signal Transduction;Signaling by Interleukins;Growth hormone receptor signaling;il-2 receptor beta chain in t cell activation;ras-independent pathway in nk cell-mediated cytotoxicity;Prolactin;Cytokine Signaling in Immune system;PD-1 signaling;Costimulation by the CD28 family;Signaling by the B Cell Receptor (BCR);Regulation of IFNG signaling;il 3 signaling pathway;TCR;Innate Immune System;Immune System;Interleukin receptor SHC signaling;Interleukin-2 family signaling;Adaptive Immune System;CD22 mediated BCR regulation;BCR;GPVI-mediated activation cascade;epo signaling pathway;Platelet activation, signaling and aggregation;Regulation of KIT signaling;IL-4 signaling;EGFR1;growth hormone signaling pathway;PECAM1 interactions;CXCR4-mediated signaling events;Cell surface interactions at the vascular wall;Hemostasis;BCR signaling pathway;JAK STAT pathway and regulation;IL2;Posttranslational regulation of adherens junction stability and dissassembly;IL3;Interferon gamma signaling;IL4;EPO signaling pathway;Signaling by SCF-KIT;Regulation of IFNA signaling;Interferon alpha/beta signaling;Signaling by Receptor Tyrosine Kinases;Signal regulatory protein family interactions;Platelet sensitization by LDL;Platelet homeostasis;Cell-Cell communication;Interferon Signaling;TCR signaling in naïve CD8+ T cells;Signaling events mediated by Stem cell factor receptor (c-Kit);IL4-mediated signaling events;Signaling events mediated by VEGFR1 and VEGFR2;TCR signaling in naïve CD4+ T cells;Interleukin-3, 5 and GM-CSF signaling
(Consensus)
Recessive Scores
- pRec
- 0.543
Intolerance Scores
- loftool
- 0.127
- rvis_EVS
- -0.62
- rvis_percentile_EVS
- 17.31
Haploinsufficiency Scores
- pHI
- 0.774
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.543
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ptpn6
- Phenotype
- respiratory system phenotype; pigmentation 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); reproductive system phenotype; hematopoietic system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; digestive/alimentary phenotype; skeleton phenotype; cellular phenotype; homeostasis/metabolism phenotype; immune system phenotype; endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype;
Zebrafish Information Network
- Gene name
- ptpn6
- Affected structure
- leukocyte
- Phenotype tag
- abnormal
- Phenotype quality
- accumulation
Gene ontology
- Biological process
- hematopoietic progenitor cell differentiation;negative regulation of humoral immune response mediated by circulating immunoglobulin;protein dephosphorylation;apoptotic process;G protein-coupled receptor signaling pathway;cell population proliferation;positive regulation of cell population proliferation;negative regulation of cell population proliferation;positive regulation of phosphatidylinositol 3-kinase signaling;peptidyl-tyrosine phosphorylation;cytokine-mediated signaling pathway;cell differentiation;platelet activation;platelet formation;T cell costimulation;negative regulation of interleukin-6 production;negative regulation of tumor necrosis factor production;abortive mitotic cell cycle;positive regulation of cell adhesion mediated by integrin;peptidyl-tyrosine dephosphorylation;intracellular signal transduction;megakaryocyte development;negative regulation of T cell proliferation;natural killer cell mediated cytotoxicity;neutrophil degranulation;negative regulation of MAP kinase activity;regulation of B cell differentiation;negative regulation of peptidyl-tyrosine phosphorylation;B cell receptor signaling pathway;negative regulation of B cell receptor signaling pathway;negative regulation of T cell receptor signaling pathway;leukocyte migration;regulation of release of sequestered calcium ion into cytosol;regulation of type I interferon-mediated signaling pathway;regulation of ERK1 and ERK2 cascade;platelet aggregation;cellular response to cytokine stimulus;regulation of G1/S transition of mitotic cell cycle
- Cellular component
- extracellular region;nucleus;nucleoplasm;nucleolus;cytoplasm;cytosol;cell-cell junction;membrane;protein-containing complex;specific granule lumen;alpha-beta T cell receptor complex;extracellular exosome;tertiary granule lumen
- Molecular function
- phosphotyrosine residue binding;protein tyrosine phosphatase activity;transmembrane receptor protein tyrosine phosphatase activity;protein binding;SH3 domain binding;protein kinase binding;SH2 domain binding;cell adhesion molecule binding;phosphorylation-dependent protein binding