PTPN22

protein tyrosine phosphatase non-receptor type 22, the group of Protein tyrosine phosphatases non-receptor type

Basic information

Region (hg38): 1:113813810-113871753

Previous symbols: [ "PTPN8" ]

Links

ENSG00000134242 ∙ NCBI:26191 ∙ OMIM:600716 ∙ HGNC:9652 ∙ Uniprot:Q9Y2R2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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 ClinVar and linked to the PTPN22 gene.

• Inborn genetic diseases (24 variants)
• not provided (20 variants)
• Rheumatoid arthritis (2 variants)
• Diabetes mellitus, insulin-dependent, susceptibility to (1 variants)
• not specified (1 variants)
• chronic fatigue syndrome with infection-triggered onset (1 variants)
• Hashimoto thyroiditis, susceptibility to (1 variants)
• Systemic lupus erythematosus, susceptibility to (1 variants)
• Addison disease, susceptibility to (1 variants)

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				6	2	8
missense			25	3	2	30
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region				1	2	3
non coding					1	1
Total	0	0	26	9	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)
1-113825156-C-T		not specified	Uncertain significance (Dec 03, 2021)
1-113829592-C-G		not specified	Conflicting classifications of pathogenicity (Mar 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)
1-113833137-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		Diabetes mellitus, insulin-dependent, susceptibility to • Rheumatoid arthritis • Systemic lupus erythematosus, susceptibility to • Hashimoto thyroiditis, susceptibility to • Addison disease, 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	Benign/Likely benign (Nov 14, 2019)
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)
1-113837886-G-C		PTPN22-related disorder	Benign (Dec 31, 2019)
1-113837969-A-G			Likely benign (Aug 16, 2018)

GnomAD

Source: gnomAD

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: dbNSFP

• 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