UniProtKB/Swiss-Prot Q9Y2R2: Variant p.Arg620Trp

Tyrosine-protein phosphatase non-receptor type 22
Gene: PTPN22
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Variant information Variant position:

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

LB/B The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

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
Variant description:

Risk factor for T1D; risk factor for RA; risk factor for SLE; risk factor for VTLG; probable protective factor against Crohn disease; also found in patients with Graves disease, Hashimoto thyroiditis and Addison disease; 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.

Variant rs2476601 [ dbSNP | Ensembl ]

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.

Type	Positions	Description
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 TRP-620; INVOLVEMENT IN RA; 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 TRP-620; INVOLVEMENT IN SLE; 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 TRP-620; INVOLVEMENT IN T1D; CHARACTERIZATION OF VARIANT 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: 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: 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 TRP-620; INVOLVEMENT IN VTLG; 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.