UniProtKB/Swiss-Prot Q9Y2R2: Variant p.Arg620Trp

Tyrosine-protein phosphatase non-receptor type 22
Gene: PTPN22
Chromosomal location: 1p13.2
Variant information

Variant position:  620
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Arginine (R) to Tryptophan (W) at position 620 (R620W, p.Arg620Trp).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from large size and basic (R) to large size and aromatic (W)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Involvement in 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.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Involvement in 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.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Involvement in 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.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Involvement in 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.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In IDDM, RA, SLE and VTLG; also found in patients with Graves disease, Hashimoto thyroiditis and Addison disease; associated with reduced risk of Crohn disease but not of ulcerative colitis; affects CSK kinase binding; alters B cell receptor signaling and memory B cell proliferation.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  620
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  807
The length of the canonical sequence.

Location on the sequence:   SAVLATAPRIDDEIPPPLPV  R TPESFIVVEEAGEFSPNVPK
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         SAVLATAPRIDDEIPPPLPVRTPESFIVVEEAGEFSPNVPK

Mouse                         TAVEAPSRRTDDEIPPPLPERTPESFIVVEEAGEPSPRVTE

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 1 – 807 Tyrosine-protein phosphatase non-receptor type 22
Modified residue 635 – 635 Phosphoserine
Alternative sequence 204 – 807 Missing. In isoform 5.


Literature citations

Identification of a variant form of tyrosine phosphatase LYP.
Wang S.; Dong H.; Han J.; Ho W.T.; Fu X.; Zhao Z.J.;
BMC Mol. Biol. 11:78-78(2010)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4); VARIANT TRP-620;

Human protein tyrosine phosphatase (70zpep) homolog.
Liu T.; Zhang J.; Fu G.; Zhang Q.; Ye M.; Zhou J.; Wu J.; Shen Y.; Yu M.; Chen S.; Mao M.; Chen Z.;
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANT TRP-620;

The DNA sequence and biological annotation of human chromosome 1.
Gregory S.G.; Barlow K.F.; McLay K.E.; Kaul R.; Swarbreck D.; Dunham A.; Scott C.E.; Howe K.L.; Woodfine K.; Spencer C.C.A.; Jones M.C.; Gillson C.; Searle S.; Zhou Y.; Kokocinski F.; McDonald L.; Evans R.; Phillips K.; Atkinson A.; Cooper R.; Jones C.; Hall R.E.; Andrews T.D.; Lloyd C.; Ainscough R.; Almeida J.P.; Ambrose K.D.; Anderson F.; Andrew R.W.; Ashwell R.I.S.; Aubin K.; Babbage A.K.; Bagguley C.L.; Bailey J.; Beasley H.; Bethel G.; Bird C.P.; Bray-Allen S.; Brown J.Y.; Brown A.J.; Buckley D.; Burton J.; Bye J.; Carder C.; Chapman J.C.; Clark S.Y.; Clarke G.; Clee C.; Cobley V.; Collier R.E.; Corby N.; Coville G.J.; Davies J.; Deadman R.; Dunn M.; Earthrowl M.; Ellington A.G.; Errington H.; Frankish A.; Frankland J.; French L.; Garner P.; Garnett J.; Gay L.; Ghori M.R.J.; Gibson R.; Gilby L.M.; Gillett W.; Glithero R.J.; Grafham D.V.; Griffiths C.; Griffiths-Jones S.; Grocock R.; Hammond S.; Harrison E.S.I.; Hart E.; Haugen E.; Heath P.D.; Holmes S.; Holt K.; Howden P.J.; Hunt A.R.; Hunt S.E.; Hunter G.; Isherwood J.; James R.; Johnson C.; Johnson D.; Joy A.; Kay M.; Kershaw J.K.; Kibukawa M.; Kimberley A.M.; King A.; Knights A.J.; Lad H.; Laird G.; Lawlor S.; Leongamornlert D.A.; Lloyd D.M.; Loveland J.; Lovell J.; Lush M.J.; Lyne R.; Martin S.; Mashreghi-Mohammadi M.; Matthews L.; Matthews N.S.W.; McLaren S.; Milne S.; Mistry S.; Moore M.J.F.; Nickerson T.; O'Dell C.N.; Oliver K.; Palmeiri A.; Palmer S.A.; Parker A.; Patel D.; Pearce A.V.; Peck A.I.; Pelan S.; Phelps K.; Phillimore B.J.; Plumb R.; Rajan J.; Raymond C.; Rouse G.; Saenphimmachak C.; Sehra H.K.; Sheridan E.; Shownkeen R.; Sims S.; Skuce C.D.; Smith M.; Steward C.; Subramanian S.; Sycamore N.; Tracey A.; Tromans A.; Van Helmond Z.; Wall M.; Wallis J.M.; White S.; Whitehead S.L.; Wilkinson J.E.; Willey D.L.; Williams H.; Wilming L.; Wray P.W.; Wu Z.; Coulson A.; Vaudin M.; Sulston J.E.; Durbin R.M.; Hubbard T.; Wooster R.; Dunham I.; Carter N.P.; McVean G.; Ross M.T.; Harrow J.; Olson M.V.; Beck S.; Rogers J.; Bentley D.R.;
Nature 441:315-321(2006)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]; VARIANT TRP-620;

Submission
Mural R.J.; Istrail S.; Sutton G.G.; Florea L.; Halpern A.L.; Mobarry C.M.; Lippert R.; Walenz B.; Shatkay H.; Dew I.; Miller J.R.; Flanigan M.J.; Edwards N.J.; Bolanos R.; Fasulo D.; Halldorsson B.V.; Hannenhalli S.; Turner R.; Yooseph S.; Lu F.; Nusskern D.R.; Shue B.C.; Zheng X.H.; Zhong F.; Delcher A.L.; Huson D.H.; Kravitz S.A.; Mouchard L.; Reinert K.; Remington K.A.; Clark A.G.; Waterman M.S.; Eichler E.E.; Adams M.D.; Hunkapiller M.W.; Myers E.W.; Venter J.C.;
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]; VARIANT TRP-620;

A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis.
Begovich A.B.; Carlton V.E.; Honigberg L.A.; Schrodi S.J.; Chokkalingam A.P.; Alexander H.C.; Ardlie K.G.; Huang Q.; Smith A.M.; Spoerke J.M.; Conn M.T.; Chang M.; Chang S.Y.; Saiki R.K.; Catanese J.J.; Leong D.U.; Garcia V.E.; McAllister L.B.; Jeffery D.A.; Lee A.T.; Batliwalla F.; Remmers E.; Criswell L.A.; Seldin M.F.; Kastner D.L.; Amos C.I.; Sninsky J.J.; Gregersen P.K.;
Am. J. Hum. Genet. 75:330-337(2004)
Cited for: VARIANT RA TRP-620; INTERACTION WITH CSK; TISSUE SPECIFICITY;

Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE.
Kyogoku C.; Langefeld C.D.; Ortmann W.A.; Lee A.; Selby S.; Carlton V.E.H.; Chang M.; Ramos P.; Baechler E.C.; Batliwalla F.M.; Novitzke J.; Williams A.H.; Gillett C.; Rodine P.; Graham R.R.; Ardlie K.G.; Gaffney P.M.; Moser K.L.; Petri M.; Begovich A.B.; Gregersen P.K.; Behrens T.W.;
Am. J. Hum. Genet. 75:504-507(2004)
Cited for: VARIANT SLE TRP-620;

A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes.
Bottini N.; Musumeci L.; Alonso A.; Rahmouni S.; Nika K.; Rostamkhani M.; MacMurray J.; Meloni G.F.; Lucarelli P.; Pellecchia M.; Eisenbarth G.S.; Comings D.; Mustelin T.;
Nat. Genet. 36:337-338(2004)
Cited for: VARIANT IDDM TRP-620; CHARACTERIZATION OF VARIANT IDDM TRP-620;

The codon 620 tryptophan allele of the lymphoid tyrosine phosphatase (LYP) gene is a major determinant of Graves' disease.
Velaga M.R.; Wilson V.; Jennings C.E.; Owen C.J.; Herington S.; Donaldson P.T.; Ball S.G.; James R.A.; Quinton R.; Perros P.; Pearce S.H.;
J. Clin. Endocrinol. Metab. 89:5862-5865(2004)
Cited for: INVOLVEMENT IN GRAVES DISEASE; INVOLVEMENT IN ADDISON DISEASE; VARIANT TRP-620;

Analysis of families in the multiple autoimmune disease genetics consortium (MADGC) collection: the PTPN22 620W allele associates with multiple autoimmune phenotypes.
Criswell L.A.; Pfeiffer K.A.; Lum R.F.; Gonzales B.; Novitzke J.; Kern M.; Moser K.L.; Begovich A.B.; Carlton V.E.; Li W.; Lee A.T.; Ortmann W.; Behrens T.W.; Gregersen P.K.;
Am. J. Hum. Genet. 76:561-571(2005)
Cited for: INVOLVEMENT IN HASHIMOTO THYROIDITIS; VARIANT TRP-620;

A single-nucleotide polymorphism in the gene encoding lymphoid protein tyrosine phosphatase (PTPN22) confers susceptibility to generalised vitiligo.
Canton I.; Akhtar S.; Gavalas N.G.; Gawkrodger D.J.; Blomhoff A.; Watson P.F.; Weetman A.P.; Kemp E.H.;
Genes Immun. 6:584-587(2005)
Cited for: VARIANT VTLG TRP-620;

Cutting edge: the PTPN22 allelic variant associated with autoimmunity impairs B cell signaling.
Arechiga A.F.; Habib T.; He Y.; Zhang X.; Zhang Z.Y.; Funk A.; Buckner J.H.;
J. Immunol. 182:3343-3347(2009)
Cited for: VARIANT TRP-620; CHARACTERIZATION OF VARIANT TRP-620;

Differential association of two PTPN22 coding variants with Crohn's disease and ulcerative colitis.
Diaz-Gallo L.M.; Espino-Paisan L.; Fransen K.; Gomez-Garcia M.; van Sommeren S.; Cardena C.; Rodrigo L.; Mendoza J.L.; Taxonera C.; Nieto A.; Alcain G.; Cueto I.; Lopez-Nevot M.A.; Bottini N.; Barclay M.L.; Crusius J.B.; van Bodegraven A.A.; Wijmenga C.; Ponsioen C.Y.; Gearry R.B.; Roberts R.L.; Weersma R.K.; Urcelay E.; Merriman T.R.; Alizadeh B.Z.; Martin J.;
Inflamm. Bowel Dis. 17:2287-2294(2011)
Cited for: VARIANTS GLN-263 AND TRP-620; CHARACTERIZATION OF VARIANTS GLN-263 AND TRP-620;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.