UniProtKB/Swiss-Prot O00206: Variant p.Asp299Gly

Toll-like receptor 4
Gene: TLR4
Feedback?

Variant information Variant position:

299 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 Aspartate (D) to Glycine (G) at position 299 (D299G, p.Asp299Gly). 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 acidic (D) to glycine (G) 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
Polymorphism:

Allele TLR4*B (Gly-299, Ile-399) is associated with a blunted response to inhaled LPS. Additional information on the polymorphism described.
Variant description:

In allele TLR4*B; reduced LPS-response; associated with an increased risk for age-related macular degeneration in Caucasian carriers. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs4986790 [ dbSNP | Ensembl ]

Sequence information Variant position:

299 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

839 The length of the canonical sequence.
Location on the sequence:

GLCNLTIEEFRLAYLDYYLD D IIDLFNCLTNVSSFSLVSVT 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                         GLCNLTIEEFRLAYLDYY-LDDIIDLFNCLTNVSSFSLVSVT

Gorilla                       GLCNLTIEEFRLAYLDYY-LDDIIDLFNCLTNVSSFSLVSV

Mouse                         GLCDVTIDEFRLTYTNDF-SDDIVK-FHCLANVSAMSLAGV

Rat                           GLCNVSIDEFRLTYINHF-SDDIYN-LNCLANISAMSFTGV

Pig                           ELCNLTLEQFRIAHFGEF-PDDVSDLFNCLANASVISLLSL

Bovine                        GLCNLTIEQFRIAYLDKF-SGDDTDLFNCLANVSVISLLSI

Cat                           GLCNLIIEKFRIAYFDKF-SEDAIDSFNCLANVSTISLVHL

Horse                         GLHNLTIEEFRLAYIDNYSSKDSIDLLNCLADISKISLVSL

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	24 – 839	Toll-like receptor 4
Topological domain	24 – 631	Extracellular
Glycosylation	282 – 282	N-linked (GlcNAc...) asparagine
Glycosylation	309 – 309	N-linked (GlcNAc...) asparagine
Disulfide bond	281 – 306

Literature citations
Phylogenetic variation and polymorphism at the Toll-like receptor 4 locus (TLR4).
Smirnova I.; Poltorak A.; Chan E.K.L.; McBride C.; Beutler B.;
Genome Biol. 1:RESEARCH002.1-RESEARCH002.10(2000)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; FUNCTION; VARIANTS GLY-299 AND ILE-399; CHARACTERIZATION OF VARIANTS GLY-299 AND ILE-399; POLYMORPHISM; TLR4 mutations are associated with endotoxin hyporesponsiveness in humans.
Arbour N.C.; Lorenz E.; Schutte B.C.; Zabner J.; Kline J.N.; Jones M.; Frees K.; Watt J.L.; Schwartz D.A.;
Nat. Genet. 25:187-191(2000)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS GLY-299 AND ILE-399; The heterogeneous allelic repertoire of human Toll-Like receptor (TLR) genes.
Georgel P.; Macquin C.; Bahram S.;
PLoS ONE 4:E7803-E7803(2009)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS GLY-299 AND ILE-399; Excess of rare amino acid polymorphisms in the Toll-like receptor 4 in humans.
Smirnova I.; Hamblin M.T.; McBride C.; Beutler B.; Di Rienzo A.;
Genetics 158:1657-1664(2001)
Cited for: VARIANTS ARG-188; SER-246; GLY-299; SER-329; ILE-399; LEU-443; LYS-474; HIS-510; ARG-694; HIS-763 AND HIS-834; Toll-like receptor 4 variant D299G is associated with susceptibility to age-related macular degeneration.
Zareparsi S.; Buraczynska M.; Branham K.E.H.; Shah S.; Eng D.; Li M.; Pawar H.; Yashar B.M.; Moroi S.E.; Lichter P.R.; Petty H.R.; Richards J.E.; Abecasis G.R.; Elner V.M.; Swaroop A.;
Hum. Mol. Genet. 14:1449-1455(2005)
Cited for: VARIANT GLY-299; ASSOCIATION WITH ARMD SUSCEPTIBILITY;

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.