UniProtKB/Swiss-Prot P16410: Variant p.Thr17Ala

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 17 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 Threonine (T) to Alanine (A) at position 17 (T17A, p.Thr17Ala). 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 medium size and polar (T) to small size and hydrophobic (A) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: 0 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
Polymorphism: Genetic variations in CTLA4 are associated with susceptibility to several autoimmune disorders (PubMed:18595775, PubMed:12724780, PubMed:10189842, PubMed:10924276, PubMed:15138458, PubMed:15657618, PubMed:15688186, PubMed:25329329, PubMed:25213377). They influence responsiveness to hepatitis B virus (HBV) infection [MIM:610424] (PubMed:15452244). Additional information on the polymorphism described.
Variant description: Increased risk for Graves disease, insulin-dependent diabetes mellitus, thyroid-associated orbitopathy, systemic lupus erythematosus and susceptibility to HBV infection. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs231775 [ dbSNP | Ensembl ]

Sequence information

Variant position: 17 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 223 The length of the canonical sequence.
Location on the sequence: MACLGFQRHKAQLNLA T RTWPCTLLFFLLFIPVFCKA 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.
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
Signal peptide	1 – 35

Literature citations

CTLA-4 and CD28 activated lymphocyte molecules are closely related in both mouse and human as to sequence, message expression, gene structure, and chromosomal location.
Harper K.; Balzano C.; Rouvier E.; Mattei M.-G.; Luciani M.-F.; Golstein P.;
J. Immunol. 147:1037-1044(1991)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1); TISSUE SPECIFICITY; ALTERNATIVE SPLICING; VARIANT ALA-17; Identification of CTLA-4 isoforms produced by alternative splicing and their association with myasthenia gravis.
Gu M.; Kakoulidou M.; Giscombe R.; Pirskanen R.; Lefvert A.K.; Klareskog L.; Wang X.;
Clin. Immunol. 128:374-381(2008)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4); VARIANT ALA-17; ALTERNATIVE SPLICING; POLYMORPHISM; Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups.
Marron M.P.; Raffel L.J.; Garchon H.-J.; Jacob C.O.; Serrano-Rios M.; Martinez Larrad M.T.; Teng W.-P.; Park Y.; Zhang Z.-X.; Goldstein D.R.; Tao Y.-W.; Beaurain G.; Bach J.-F.; Huang H.-S.; Luo D.-F.; Zeidler A.; Rotter J.I.; Yang M.C.K.; Modilevsky T.; Maclaren N.K.; She J.-X.;
Hum. Mol. Genet. 6:1275-1282(1997)
Cited for: VARIANT ALA-17; INVOLVEMENT IN T1D12; Cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphism confers susceptibility to thyroid associated orbitopathy.
Vaidya B.; Imrie H.; Perros P.; Dickinson J.; McCarthy M.I.; Kendall-Taylor P.; Pearce S.H.S.;
Lancet 354:743-744(1999)
Cited for: VARIANT ALA-17; INVOLVEMENT IN THYROID ASSOCIATED ORBITOPATHY; Complex association analysis of Graves disease using a set of polymorphic markers.
Chistyakov D.A.; Savost'anov K.V.; Turakulov R.I.; Petunina N.A.; Trukhina L.V.; Kudinova A.V.; Balabolkin M.I.; Nosikov V.V.;
Mol. Genet. Metab. 70:214-218(2000)
Cited for: POLYMORPHISM; VARIANT ALA-17; INVOLVEMENT IN GRAVES DISEASE; Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene.
Deng Z.; Morse J.H.; Slager S.L.; Cuervo N.; Moore K.J.; Venetos G.; Kalachikov S.; Cayanis E.; Fischer S.G.; Barst R.J.; Hodge S.E.; Knowles J.A.;
Am. J. Hum. Genet. 67:737-744(2000)
Cited for: VARIANT ALA-17; Cytotoxic T-lymphocyte antigen 4 gene and recovery from hepatitis B virus infection.
Thio C.L.; Mosbruger T.L.; Kaslow R.A.; Karp C.L.; Strathdee S.A.; Vlahov D.; O'Brien S.J.; Astemborski J.; Thomas D.L.;
J. Virol. 78:11258-11262(2004)
Cited for: POLYMORPHISM; INVOLVEMENT IN SUSCEPTIBILITY TO HBV INFECTION; VARIANT ALA-17;