UniProtKB/SwissProt variant VAR

Variant information

Variant position:

385

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

Type of variant:

LP/P [Disclaimer]

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 Methionine (M) at position 385 (T385M, p.Thr385Met).

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 medium size and hydrophobic (M)

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

Variant description:

In IMD31C; gain of function; increases phosphorylation in response to IFNG, IFNA and IL27 due to a loss of dephosphorylation.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs587777630 [ dbSNP | Ensembl ]

Sequence information

Variant position:

385

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

Protein sequence length:

750

The length of the canonical sequence.

Location on the sequence:

DKDVNERNTVKGFRKFNILG T HTKVMNMEESTNGSLAAEFR

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                         DKDVN----ERNTVKGFRKFNILGTHTKVMN-MEESTNGSLAAEFR

Mouse                         DKDVN----EKNTVKGFRKFNILGTHTKVMN-MEESTNGSL

Pig                           DKDVS----ERNTVKGFRKFNILGTHTKVMN-MEESTNGSL

Caenorhabditis elegans        EDEAKQLSVDYDAHKEIRNNKTVGTISNDFEKLTMNERGHL

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	2 – 750	Signal transducer and activator of transcription 1-alpha/beta
Modified residue	366 – 366	N6-methyllysine
Mutagenesis	366 – 366	K -> A. No effect on IFN-alpha-induced STAT1 phosphorylation and nuclear translocation.

Literature citations

New and recurrent gain-of-function STAT1 mutations in patients with chronic mucocutaneous candidiasis from Eastern and Central Europe.
Soltesz B.; Toth B.; Shabashova N.; Bondarenko A.; Okada S.; Cypowyj S.; Abhyankar A.; Csorba G.; Tasko S.; Sarkadi A.K.; Mehes L.; Rozsival P.; Neumann D.; Chernyshova L.; Tulassay Z.; Puel A.; Casanova J.L.; Sediva A.; Litzman J.; Marodi L.;
J. Med. Genet. 50:567-578(2013)
Cited for: VARIANTS IMD31C GLY-165; LYS-179; GLN-274; TRP-274; ARG-285 AND MET-385; CHARACTERIZATION OF VARIANTS IMD31C LYS-179; GLN-274; TRP-274; ARG-285 AND MET-385; CHARACTERIZATION OF VARIANT IMD31B CYS-701;

Two novel gain-of-function mutations of STAT1 responsible for chronic mucocutaneous candidiasis disease: impaired production of IL-17A and IL-22, and the presence of anti-IL-17F autoantibody.
Yamazaki Y.; Yamada M.; Kawai T.; Morio T.; Onodera M.; Ueki M.; Watanabe N.; Takada H.; Takezaki S.; Chida N.; Kobayashi I.; Ariga T.;
J. Immunol. 193:4880-4887(2014)
Cited for: VARIANTS IMD31C GLU-278 AND ASP-384; CHARACTERIZATION OF VARIANTS IMD31C GLU-278; ASP-384 AND MET-385;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P42224: Variant p.Thr385Met