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UniProtKB/Swiss-Prot O14920: Variant p.Val203Ile

Inhibitor of nuclear factor kappa-B kinase subunit beta
Gene: IKBKB
Variant information

Variant position:  203
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 Valine (V) to Isoleucine (I) at position 203 (V203I, p.Val203Ile).
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:  3
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:  Immunodeficiency 15A (IMD15A) [MIM:618204]: An autosomal dominant primary immunodeficiency disorder characterized by lymphopenia, inflammation and immune activation of both CD4+ and CD8+ T cells. Patients suffer from recurrent respiratory tract infections, oral candidiasis, and otitis media. {ECO:0000269|PubMed:30337470}. 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 IMD15A; gain-of-function mutation resulting in increased activation of NF-kappa-B signaling pathway.
Any additional useful information about the variant.



Sequence information

Variant position:  203
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  756
The length of the canonical sequence.

Location on the sequence:   VGTLQYLAPELLEQQKYTVT  V DYWSFGTLAFECITGFRPFL
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                         VGTLQYLAPELLEQQKYTVTVDYWSFGTLAFECITGFRPFL

Mouse                         VGTLQYLAPELLEQQKYTVTVDYWSFGTLAFECITGFRPFL

Rat                           VGTLQYLAPELLEQQKYTVTVDYWSFGTLAFECITGFRPFL

Bovine                        VGTLQYLAPELLEQQKYTVTVDYWSFGTLAFECITGFRPFL

Drosophila                    VGTRHYYAPEVVENGFYNSTVDLWSFGVIAYELVTGELPFI

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 – 756 Inhibitor of nuclear factor kappa-B kinase subunit beta
Domain 15 – 300 Protein kinase
Modified residue 191 – 191 Hydroxyproline
Mutagenesis 191 – 191 P -> A. Loss of hypoxic inducibility.
Helix 202 – 217


Literature citations

Gain-of-function IKBKB mutation causes human combined immune deficiency.
Cardinez C.; Miraghazadeh B.; Tanita K.; da Silva E.; Hoshino A.; Okada S.; Chand R.; Asano T.; Tsumura M.; Yoshida K.; Ohnishi H.; Kato Z.; Yamazaki M.; Okuno Y.; Miyano S.; Kojima S.; Ogawa S.; Andrews T.D.; Field M.A.; Burgio G.; Morio T.; Vinuesa C.G.; Kanegane H.; Cook M.C.;
J. Exp. Med. 215:2715-2724(2018)
Cited for: FUNCTION; INVOLVEMENT IN IMD15A; VARIANT IMD15A ILE-203; CHARACTERIZATION OF VARIANT IMD15A ILE-203; MUTAGENESIS OF LYS-171 AND 272-ARG--SER-756;

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.