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UniProtKB/Swiss-Prot P24394: Variant p.Ile75Val

Interleukin-4 receptor subunit alpha
Gene: IL4R
Chromosomal location: 16p11.2-p12.1
Variant information

Variant position:  75
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Polymorphism
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 Isoleucine (I) to Valine (V) at position 75 (I75V, p.Ile75Val).
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

Polymorphism:  Allelic variants in IL4RA are associated with a susceptibility to atopy, an immunological condition that can lead to clinical symptoms such as allergic rhinitis, sinusitis, asthma and eczema.Allelic variants in IL4RA are associated with cedar pollen sensitization. Individuals develop Japanese cedar pollinosis with increased exposure to cedar pollen. Japanese cedar pollinosis is a type I allergic disease with ocular and nasal symptoms that develop paroxysmally on contact with Japanese cedar pollen. These symptoms, which occur seasonally each year, are typical features of allergic rhinitis, such as sneezing, excessive nasal secretion, nasal congestion, and conjunctival itching. -
Additional information on the polymorphism described.

Variant description:  Associated with atopic asthma and cedar pollen sensitization.
Any additional useful information about the variant.

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

Sequence information

Variant position:  75
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  825
The length of the canonical sequence.

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.






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.

Chain 26 – 825 Interleukin-4 receptor subunit alpha
Topological domain 26 – 232 Extracellular
Site 64 – 64 Minor IL4 binding determinant
Site 66 – 66 Minor IL4 binding determinant
Site 92 – 92 Minor IL4 binding determinant
Site 94 – 94 Minor IL4 binding determinant
Disulfide bond 74 – 86
Mutagenesis 64 – 64 L -> A. 100-fold reduction in IL4 binding.
Mutagenesis 66 – 66 F -> A. 45-fold reduction in IL4 binding.
Mutagenesis 67 – 67 L -> A. No effect on IL4 binding.
Mutagenesis 68 – 68 L -> A. No effect on IL4 binding.
Mutagenesis 91 – 91 D -> A. Little effect on IL4 binding.
Mutagenesis 92 – 92 D -> A. 50-fold reduction in IL4 binding.
Mutagenesis 93 – 93 V -> A. Little effect on IL4 binding.
Mutagenesis 94 – 94 V -> A. 35-fold reduction in IL4 binding.
Mutagenesis 95 – 95 S -> A. No effect on IL4 binding.

Literature citations

SeattleSNPs variation discovery resource;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS VAL-75; ALA-400; ARG-431; LEU-436; PRO-503; ARG-576; ILE-579; SER-675 AND ALA-752;

Common polymorphisms in the coding part of the IL4-receptor gene.
Deichmann K.; Bardutzky J.; Forster J.; Heinzmann A.; Kuehr J.;
Biochem. Biophys. Res. Commun. 231:696-697(1997)
Cited for: VARIANTS VAL-75; ALA-400; ARG-431; LEU-436 AND PRO-786;

Ile50Val variant of IL4R alpha upregulates IgE synthesis and associates with atopic asthma.
Mitsuyasu H.; Izuhara K.; Mao X.-Q.; Gao P.S.; Arinobu Y.; Enomoto T.; Kawai M.; Sasaki S.; Dake Y.; Hamasaki N.; Shirakawa T.; Hopkin J.M.;
Nat. Genet. 19:119-120(1998)
Cited for: VARIANT VAL-75;

No association between atopy/asthma and the Ile50Val polymorphism of IL-4 receptor.
Noguchi E.; Shibasaki M.; Arinami T.; Takeda K.; Yokouchi Y.; Kobayashi K.; Imoto N.; Nakahara S.; Matsui A.; Hamaguchi H.;
Am. J. Respir. Crit. Care Med. 160:342-345(1999)
Cited for: VARIANT VAL-75;

High contribution contrast between the genes of eosinophil peroxidase and IL-4 receptor alpha-chain in Japanese cedar pollinosis.
Nakamura H.; Miyagawa K.; Ogino K.; Endo T.; Imai T.; Ozasa K.; Motohashi Y.; Matsuzaki I.; Sasahara S.; Hatta K.; Eboshida A.;
J. Allergy Clin. Immunol. 112:1127-1131(2003)

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.