UniProtKB/SwissProt variant VAR

Variant information

Variant position:

59

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 implicated in disease according to literature reports.
Polymorphism: Variants not reported to be implicated in disease.
Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:

From Cysteine (C) to Serine (S) at position 59 (C59S, p.Cys59Ser).

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 (C) to small size and polar (S)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-1

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:

Familial hibernian fever (FHF) [MIM:142680]: A hereditary periodic fever syndrome characterized by recurrent fever, abdominal pain, localized tender skin lesions and myalgia. Reactive amyloidosis is the main complication and occurs in 25% of cases. {ECO:0000269|PubMed:10199409, ECO:0000269|PubMed:10902757, ECO:0000269|PubMed:11443543, ECO:0000269|PubMed:13130484, ECO:0000269|PubMed:14610673}. Note=The disease is caused by mutations 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 FHF.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs104895223 [ dbSNP | Ensembl ]

Sequence information

Variant position:

59

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

Protein sequence length:

455

The length of the canonical sequence.

Location on the sequence:

KRDSVCPQGKYIHPQNNSIC C TKCHKGTYLYNDCPGPGQDT

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                         KRDSVCPQGKYIHPQNNSICCTKCHKGTYLYNDCPGPGQDT

Mouse                         KRDSLCPQGKYVHSKNNSICCTKCHKGTYLVSDCPSPGRDT

Rat                           KRDNLCPQGKYAHPKNNSICCTKCHKGTYLVSDCPSPGQET

Pig                           KRESLCPQGKYSHPQNRSICCTKCHKGTYLHNDCLGPGLDT

Bovine                        KRESPCPQGKYNHPQNSTICCTKCHKGTYLYNDCPGPGRDT

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	30 – 455	Tumor necrosis factor receptor superfamily member 1A, membrane form
Chain	41 – 201	Tumor necrosis factor-binding protein 1
Topological domain	30 – 211	Extracellular
Repeat	43 – 82	TNFR-Cys 1
Glycosylation	54 – 54	N-linked (GlcNAc...) asparagine
Disulfide bond	59 – 72
Alternative sequence	1 – 232	Missing. In isoform 3.
Alternative sequence	1 – 108	Missing. In isoform 2.
Beta strand	58 – 60

Literature citations

A novel missense mutation (C30S) in the gene encoding tumor necrosis factor receptor 1 linked to autosomal-dominant recurrent fever with localized myositis in a French family.
Dode C.; Papo T.; Fieschi C.; Pecheux C.; Dion E.; Picard F.; Godeau P.; Bienvenu J.; Piette J.-C.; Delpech M.; Grateau G.;
Arthritis Rheum. 43:1535-1542(2000)
Cited for: VARIANT FHF SER-59;

The tumor-necrosis-factor receptor-associated periodic syndrome: new mutations in TNFRSF1A, ancestral origins, genotype-phenotype studies, and evidence for further genetic heterogeneity of periodic fevers.
Aksentijevich I.; Galon J.; Soares M.; Mansfield E.; Hull K.; Oh H.-H.; Goldbach-Mansky R.; Dean J.; Athreya B.; Reginato A.J.; Henrickson M.; Pons-Estel B.; O'Shea J.J.; Kastner D.L.;
Am. J. Hum. Genet. 69:301-314(2001)
Cited for: VARIANTS FHF GLN-51; SER-59; GLY-62; LEU-75; GLY-115 AND GLN-121;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P19438: Variant p.Cys59Ser