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UniProtKB/Swiss-Prot Q99836: Variant p.Met178Ile

Myeloid differentiation primary response protein MyD88
Gene: MYD88
Variant information

Variant position:  178
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Unclassified
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 Methionine (M) to Isoleucine (I) at position 178 (M178I, p.Met178Ile).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
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:  Found in hematological malignancies; somatic mutation; unknown pathological significance; no effect on NF-kappaB complex activation.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  178
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  296
The length of the canonical sequence.

Location on the sequence:   PERFDAFICYCPSDIQFVQE  M IRQLEQTNYRLKLCVSDRDV
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                         PERFDAFICYCPSDIQFVQEMIRQLEQTNYRLKLCVSDRDV

Gorilla                       PERFDAFICYCPSDIQFVQEMIRQLEQTNYRLKLCVSDRDV

Rhesus macaque                PERFDAFICYCPSDIQFVQEMIRQLEQTNYRLKLCVSDRDV

Chimpanzee                    PERFDAFICYCPSDIQFVQEMIRQLEQTNYRLKLCVSDRDV

Mouse                         PELFDAFICYCPNDIEFVQEMIRQLEQTDYRLKLCVSDRDV

Rat                           PELFDAFICYCPSDIEFVQEMIRQLEQTDYRLKLCVSDRDV

Pig                           PEHFDAFICYCPSDIQFVQEMIRQLEQTNYRLKLCVSDRDV

Bovine                        PECFDAFICYCPSDIEFVHEMIRQLEQTNYRLKLCVSDRDV

Sheep                         PEYFDAFICYCPSDIEFVHEMIRQLEQTNYRLKLCVSDRDV

Chicken                       TEMFDAFICYCQKDLQFVQEMIRELEQTEFKLKLCVFDRDV

Xenopus tropicalis            PETFDAFICYCAQDISFVQEMISRLEQTDYKLKLCVFDRDV

Zebrafish                     PETFDAFICYCQSDIQFVHEMIKQLEHTEYNLKLCVFDRDV

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.

TypePositionsDescription
Chain 1 – 296 Myeloid differentiation primary response protein MyD88
Domain 159 – 296 TIR
Alternative sequence 156 – 296 HMPERFDAFICYCPSDIQFVQEMIRQLEQTNYRLKLCVSDRDVLPGTCVWSIASELIEKRCRRMVVVVSDDYLQSKECDFQTKFALSLSPGAHQKRLIPIKYKAMKKEFPSILRFITVCDYTNPCTKSWFWTRLAKALSLP -> AAGWWWLSLMITCRARNVTSRPNLHSASLQVPIRSD. In isoform 3 and isoform 4.
Mutagenesis 196 – 196 R -> A. Reduced interaction with TIRAP, and strongly reduced activity. Strongly reduced interaction with TIRAP; when associated with A-288.
Mutagenesis 197 – 197 D -> A. Slightly reduced activity.
Helix 172 – 183


Literature citations

Two human MYD88 variants, S34Y and R98C, interfere with MyD88-IRAK4-myddosome assembly.
George J.; Motshwene P.G.; Wang H.; Kubarenko A.V.; Rautanen A.; Mills T.C.; Hill A.V.; Gay N.J.; Weber A.N.;
J. Biol. Chem. 286:1341-1353(2011)
Cited for: INTERACTION WITH IRAK4; CHARACTERIZATION OF VARIANTS TYR-34; CYS-98 AND ILE-178;

Functional assessment of the mutational effects of human IRAK4 and MyD88 genes.
Yamamoto T.; Tsutsumi N.; Tochio H.; Ohnishi H.; Kubota K.; Kato Z.; Shirakawa M.; Kondo N.;
Mol. Immunol. 58:66-76(2014)
Cited for: FUNCTION; INTERACTION WITH IRAK4; CHARACTERIZATION OF VARIANTS TYR-34; CYS-98 AND ILE-178; CHARACTERIZATION OF VARIANTS MYD88D GLU-52 DEL; PRO-93 AND CYS-196;

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.