UniProtKB/Swiss-Prot P58753: Variant p.Ser180Leu

Toll/interleukin-1 receptor domain-containing adapter protein
Gene: TIRAP
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Variant information Variant position:

180 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 Serine (S) to Leucine (L) at position 180 (S180L, p.Ser180Leu). 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 small size and polar (S) to medium size and hydrophobic (L) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-2 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 TIRAP have been proposed to influence susceptibility or resistance to invasive pneumococcal disease, malaria [MIM:611162], and tuberculosis [MIM:607948]. It may define the bacteremia susceptibility locus 1 (BACTS1) [MIM:614382] (PubMed:17322885, PubMed:19602285). Indeed it has been reported that heterozygous carriage of p.Ser180Leu in populations from the U.K., Vietnam, and several African countries may confer protection against invasive pneumococcal disease, bacteremia, malaria, and tuberculosis (PubMed:17322885). However, analyzes of Russian, Ghanaian and Indonesian populations fail to replicate the association between p.Ser180Leu and susceptibility to tuberculosis formerly observed in West African and Algerian populations (PubMed:17322885, PubMed:18305471). Additional information on the polymorphism described.
Variant description:

The functional impact of this variant is unclear; it has been reported both to affect interaction with TLR2, hence attenuating TLR2 signal transduction and to have no effect on NF-kappa-B activation and TNF production. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs8177374 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

QMLQALTEAPGAEGCTIPLL S GLSRAAYPPELRFMYYVDGR 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                         QMLQALTEAPGAEGCTIPLLSGLSRAAYPPELRFMYYVDGR

Mouse                         QMLQALTEAPASEGCTIPLLSGLSRAAYPPELRFMYYVDGR

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 – 221	Toll/interleukin-1 receptor domain-containing adapter protein
Domain	84 – 213	TIR

Literature citations
Submission
SeattleSNPs variation discovery resource;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS PRO-9; TRP-13; ASN-96 AND LEU-180; A TIR domain variant of MyD88 adapter-like (Mal)/TIRAP results in loss of MyD88 binding and reduced TLR2/TLR4 signaling.
Nagpal K.; Plantinga T.S.; Wong J.; Monks B.G.; Gay N.J.; Netea M.G.; Fitzgerald K.A.; Golenbock D.T.;
J. Biol. Chem. 284:25742-25748(2009)
Cited for: FUNCTION; INTERACTION WITH MYD88; VARIANT ASN-96; CHARACTERIZATION OF VARIANTS PRO-9; TRP-13; ASN-96; LEU-180 AND ILE-197; A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis.
Khor C.C.; Chapman S.J.; Vannberg F.O.; Dunne A.; Murphy C.; Ling E.Y.; Frodsham A.J.; Walley A.J.; Kyrieleis O.; Khan A.; Aucan C.; Segal S.; Moore C.E.; Knox K.; Campbell S.J.; Lienhardt C.; Scott A.; Aaby P.; Sow O.Y.; Grignani R.T.; Sillah J.; Sirugo G.; Peshu N.; Williams T.N.; Maitland K.; Davies R.J.O.; Kwiatkowski D.P.; Day N.P.; Yala D.; Crook D.W.; Marsh K.; Berkley J.A.; O'Neill L.A.J.; Hill A.V.S.;
Nat. Genet. 39:523-528(2007)
Cited for: VARIANT LEU-180; POLYMORPHISM; INTERACTION WITH MYD88 AND TLR2; HOMODIMERIZATION; Analysis of association of the TIRAP (MAL) S180L variant and tuberculosis in three populations.
Nejentsev S.; Thye T.; Szeszko J.S.; Stevens H.; Balabanova Y.; Chinbuah A.M.; Hibberd M.; van de Vosse E.; Alisjahbana B.; van Crevel R.; Ottenhoff T.H.; Png E.; Drobniewski F.; Todd J.A.; Seielstad M.; Horstmann R.D.;
Nat. Genet. 40:261-262(2008)
Cited for: VARIANT LEU-180; POLYMORPHISM; Low frequency of the TIRAP S180L polymorphism in Africa, and its potential role in malaria, sepsis, and leprosy.
Hamann L.; Kumpf O.; Schuring R.P.; Alpsoy E.; Bedu-Addo G.; Bienzle U.; Oskam L.; Mockenhaupt F.P.; Schumann R.R.;
BMC Med. Genet. 10:65-65(2009)
Cited for: VARIANT LEU-180; POLYMORPHISM;

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.