PTPN22
protein tyrosine phosphatase non-receptor type 22, the group of Protein tyrosine phosphatases non-receptor type
Basic information
Region (hg38): 1:113813811-113871753
Previous symbols: [ "PTPN8" ]
Links
Phenotypes
GenCC
Source:
- type 1 diabetes mellitus 1 (Limited), mode of inheritance: AR
- rheumatoid arthritis (Limited), mode of inheritance: Unknown
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 PTPN22 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 | 9 | |||||
| missense | 30 | 35 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| splice region | 2 | 2 | 4 | |||
| non coding | 1 | |||||
| Total | 0 | 0 | 31 | 10 | 5 |
Variants in PTPN22
This is a list of pathogenic ClinVar variants found in the PTPN22 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 1-113814951-G-A | not specified | Uncertain significance (Jan 26, 2023) | ||
| 1-113819566-A-G | Likely benign (Nov 01, 2023) | |||
| 1-113825151-T-C | not specified | Uncertain significance (Apr 15, 2024) | ||
| 1-113825156-C-T | not specified | Uncertain significance (Dec 03, 2021) | ||
| 1-113829592-C-G | not specified • PTPN22-related disorder | Conflicting classifications of pathogenicity (Aug 01, 2024) | ||
| 1-113829641-G-A | Uncertain significance (Aug 16, 2022) | |||
| 1-113829671-C-G | Uncertain significance (Aug 09, 2021) | |||
| 1-113829710-TA-T | Benign (Oct 30, 2019) | |||
| 1-113829710-TAA-T | Benign (Jun 28, 2017) | |||
| 1-113830002-G-C | not specified | Uncertain significance (Dec 14, 2021) | ||
| 1-113830002-G-T | not specified | Uncertain significance (Jul 19, 2022) | ||
| 1-113830008-G-C | Benign (Dec 31, 2019) | |||
| 1-113830026-A-G | not specified | Uncertain significance (Jun 17, 2024) | ||
| 1-113833137-C-G | not specified | Uncertain significance (Jul 19, 2023) | ||
| 1-113834340-A-G | not specified | Likely benign (Feb 23, 2023) | ||
| 1-113834363-A-T | Benign (Dec 31, 2019) | |||
| 1-113834908-A-G | Rheumatoid arthritis | Uncertain significance (-) | ||
| 1-113834946-A-A | Addison disease, susceptibility to • Diabetes mellitus, insulin-dependent, susceptibility to • Rheumatoid arthritis • Systemic lupus erythematosus, susceptibility to • Hashimoto thyroiditis, susceptibility to • chronic fatigue syndrome with infection-triggered onset | Benign (Oct 17, 2018) | ||
| 1-113834964-G-C | Uncertain significance (Feb 01, 2024) | |||
| 1-113837699-C-T | Likely benign (-) | |||
| 1-113837761-A-G | not specified | Uncertain significance (Aug 04, 2023) | ||
| 1-113837773-T-C | PTPN22-related disorder | Likely benign (May 18, 2018) | ||
| 1-113837817-T-C | not specified | Uncertain significance (Apr 17, 2023) | ||
| 1-113837852-C-T | Likely benign (Apr 03, 2018) | |||
| 1-113837871-C-T | not specified | Uncertain significance (Dec 14, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PTPN22 | protein_coding | protein_coding | ENST00000359785 | 21 | 57949 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 3.49e-21 | 0.0307 | 125359 | 3 | 385 | 125747 | 0.00154 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.869 | 356 | 405 | 0.878 | 0.0000191 | 5308 |
| Missense in Polyphen | 93 | 130.09 | 0.71489 | 1710 | ||
| Synonymous | -0.622 | 145 | 136 | 1.07 | 0.00000604 | 1483 |
| Loss of Function | 1.07 | 36 | 43.7 | 0.825 | 0.00000199 | 587 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00214 | 0.00213 |
| Ashkenazi Jewish | 0.000108 | 0.0000992 |
| East Asian | 0.000833 | 0.000816 |
| Finnish | 0.00400 | 0.00393 |
| European (Non-Finnish) | 0.000468 | 0.000448 |
| Middle Eastern | 0.000833 | 0.000816 |
| South Asian | 0.00601 | 0.00586 |
| Other | 0.00155 | 0.00147 |
dbNSFP
Source:
- Function
- FUNCTION: Acts as negative regulator of T-cell receptor (TCR) signaling by direct dephosphorylation of the Src family kinases LCK and FYN, ITAMs of the TCRz/CD3 complex, as well as ZAP70, VAV, VCP and other key signaling molecules (PubMed:16461343, PubMed:18056643). Associates with and probably dephosphorylates CBL. Dephosphorylates LCK at its activating 'Tyr-394' residue (PubMed:21719704). Dephosphorylates ZAP70 at its activating 'Tyr- 493' residue (PubMed:16461343). Dephosphorylates the immune system activator SKAP2 (PubMed:21719704). Positively regulates toll-like receptor (TLR)-induced type 1 interferon production (PubMed:23871208). Promotes host antiviral responses mediated by type 1 interferon (By similarity). Regulates NOD2-induced pro- inflammatory cytokine secretion and autophagy (PubMed:23991106). {ECO:0000250|UniProtKB:P29352, ECO:0000269|PubMed:16461343, ECO:0000269|PubMed:18056643, ECO:0000269|PubMed:19167335, ECO:0000269|PubMed:21719704, ECO:0000269|PubMed:23871208, ECO:0000269|PubMed:23991106}.;
- Disease
- DISEASE: Systemic lupus erythematosus (SLE) [MIM:152700]: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. {ECO:0000269|PubMed:15273934}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Diabetes mellitus, insulin-dependent (IDDM) [MIM:222100]: A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:15004560}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Rheumatoid arthritis (RA) [MIM:180300]: An inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. {ECO:0000269|PubMed:15208781}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Vitiligo (VTLG) [MIM:193200]: A pigmentary disorder of the skin and mucous membranes. It is characterized by circumscribed depigmented macules and patches, commonly on extensor aspects of extremities, on the face or neck and in skin folds. Vitiligo is a progressive disorder in which some or all of the melanocytes in the affected skin are selectively destroyed. It is a multifactorial disorder with a complex etiology probably including autoimmune mechanisms, and is associated with an elevated risk of other autoimmune diseases. {ECO:0000269|PubMed:16015369}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
- Pathway
- Phosphorylation of CD3 and TCR zeta chains;Translocation of ZAP-70 to Immunological synapse;TCR signaling;TCR;Immune System;Adaptive Immune System
(Consensus)
Recessive Scores
- pRec
- 0.355
Intolerance Scores
- loftool
- 0.607
- rvis_EVS
- 0.27
- rvis_percentile_EVS
- 70.64
Haploinsufficiency Scores
- pHI
- 0.158
- hipred
- N
- hipred_score
- 0.273
- ghis
- 0.469
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.322
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ptpn22
- Phenotype
- growth/size/body region phenotype; endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype; renal/urinary system phenotype; respiratory system phenotype; liver/biliary 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; digestive/alimentary phenotype; immune system phenotype;
Gene ontology
- Biological process
- protein dephosphorylation;autophagy;negative regulation of autophagy;positive regulation of gene expression;negative regulation of gene expression;T cell differentiation;lipopolysaccharide-mediated signaling pathway;positive regulation of type I interferon production;response to lipopolysaccharide;negative regulation of tumor necrosis factor production;regulation of natural killer cell proliferation;positive regulation of toll-like receptor 3 signaling pathway;positive regulation of toll-like receptor 4 signaling pathway;peptidyl-tyrosine dephosphorylation;phosphoanandamide dephosphorylation;negative regulation of JUN kinase activity;regulation of innate immune response;T cell receptor signaling pathway;regulation of B cell receptor signaling pathway;negative regulation of T cell receptor signaling pathway;negative regulation of T cell activation;positive regulation of ERK1 and ERK2 cascade;negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway;cellular response to muramyl dipeptide;negative regulation of interleukin-6 secretion;regulation of NIK/NF-kappaB signaling;positive regulation of protein K63-linked ubiquitination;positive regulation of interferon-gamma secretion;negative regulation of p38MAPK cascade;negative regulation of interleukin-8 secretion
- Cellular component
- nucleus;cytoplasm;cytosol;cytoplasmic side of plasma membrane;perinuclear region of cytoplasm
- Molecular function
- protein tyrosine phosphatase activity;protein binding;phosphatase activity;SH3 domain binding;kinase binding;ubiquitin protein ligase binding