PTPN22 (Q9Y2R2) variants and mutations
PTPN22 (also known as Q9Y2R2) is a human protein-coding gene encoding a tyrosine-protein phosphatase non-receptor type 22 protein. It tunes antigen-receptor signaling thresholds in T and B cells and helps maintain immune tolerance. The common R620W variant is a major non-HLA genetic risk factor for several autoimmune diseases, including type 1 diabetes and rheumatoid arthritis. This analysis covers 9 PTPN22 variants and mutations. Of these, 44% have computational variant effect predictions. Disease context includes rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes mellitus. Example PTPN22 variants include S35A, S201F, and R263Q.
Variant analysis overview
- Gene: PTPN22
- Protein: Q9Y2R2
- UniProt accession: Q9Y2R2
- Organism: Homo sapiens
- Variants analyzed: 9
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 4 unspecified-consequence records; 5 substitution
- Prediction scores: 4 variants have prediction scores (44% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, hypothyroidism, autoimmune disease, vitiligo, thyroid gland disorder, Hashimoto thyroiditis, Crohn disease, diabetes mellitus, autoimmune thyroid disease, Graves disease.
Protein structure and variant hotspots
- Protein features: 1 domains; 2 binding sites; 5 post-translational modification sites.
- Structural context: 3 variants have structural context.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable PTPN22 variants
Examples include S35A, S201F, R263Q, R266W, S302L, S362C, P535X, R620W. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- S35A (p.Ser35Ala), rs960090191, []
- S201F (p.Ser201Phe), rs7416347, UniProt VAR 072629, REVEL 0.67, CADD 32.00, Benign
- R263Q (p.Arg263Gln), rs33996649, UniProt VAR 072630, REVEL 0.20, CADD 14.40, Benign, PTPN22-related disorder
- R266W (p.Arg266Trp), rs72650670, UniProt VAR 072631, REVEL 0.92, CADD 29.00, Uncertain significance, not provided
- S302L (p.Ser302Leu), rs778423592, []
- S362C (p.Ser362Cys), rs779556517, []
- P535X, rs920720791, []
- R620W (p.Arg620Trp), rs2476601, UniProt VAR 022605, AlphaMissense 0.02, MetaLR 0.00, Benign, probable protective factor against Crohn disease
Public PTPN22 analysis runs
- PTPN22 analysis run — PTPN22 (9 variants) — completed 2026-08-19