UniProtKB/Swiss-Prot P24394: Variant p.Gln576Arg

Interleukin-4 receptor subunit alpha
Gene: IL4R
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Variant information Variant position:

576 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 Glutamine (Q) to Arginine (R) at position 576 (Q576R, p.Gln576Arg). 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 polar (Q) to large size and basic (R) 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:

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:

Probable risk factor for atopic dermatitis; lowered total IgE concentration; no effect on IL4-induced signal transduction. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs1801275 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

RNVLQHGAAAAPVSAPTSGY Q EFVHAVEQGGTQASAVVGLG 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                         RNVLQHGAAAAPVSAP-TSGYQEFVHAVEQGGTQASAVVGLG

Mouse                         MSVLQHGAAAGSTPAP-AGGYQEFVQAVKQGAAQDPGVPGV

Rat                           MSVLQHGTA-GSTPAP-TSGYQEFVQAVKQGASQDAGVPGV

Pig                           QSVLQRRAAPAPASGPSSSGYREFVHAVEQG-TQDRRAAGS

Horse                         QSVLQQGAAPAPASAP-TGGYREFAQVVKQGG----GAAGS

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	26 – 825	Interleukin-4 receptor subunit alpha
Topological domain	257 – 825	Cytoplasmic
Region	558 – 657	Required for IL4-induced gene expression
Modified residue	575 – 575	Phosphotyrosine
Alternative sequence	228 – 825	Missing. In isoform 2.
Mutagenesis	575 – 575	Y -> F. Loss of CD23 gene induction; when associated with F-603 and F-631.

Literature citations
Submission
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; Identification of a novel single-nucleotide polymorphism (Val554Ile) and definition of eight common alleles for human IL4RA exon 11.
Lozano F.; Places L.; Vila J.-M.; Padilla O.; Arman M.; Gimferrer I.; Suarez B.; Lopez de la Iglesia A.; Miserachs N.; Vives J.;
Tissue Antigens 57:216-220(2001)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 301-825 (ISOFORM 1); VARIANTS ALA-400; ARG-431; LEU-436; PRO-503; ARG-576 AND ILE-579; The association of atopy with a gain-of-function mutation in the alpha subunit of the interleukin-4 receptor.
Hershey G.K.K.; Friedrich M.F.; Esswein L.A.; Thomas M.L.; Chatila T.A.;
N. Engl. J. Med. 337:1720-1725(1997)
Cited for: VARIANT ARG-576; The polymorphisms S503P and Q576R in the interleukin-4 receptor alpha gene are associated with atopy and influence the signal transduction.
Kruse S.; Japha T.; Tedner M.; Sparholt S.H.; Forster J.; Kuehr J.; Deichmann K.A.;
Immunology 96:365-371(1999)
Cited for: VARIANTS PRO-503 AND ARG-576; Effects of an allergy-associated mutation in the human IL-4R alpha (Q576R) on human IL-4-induced signal transduction.
Wang H.Y.; Shelburne C.P.; Zamorano J.; Kelly A.E.; Ryan J.J.; Keegan A.D.;
J. Immunol. 162:4385-4389(1999)
Cited for: CHARACTERIZATION OF VARIANT ARG-576; MUTAGENESIS OF TYR-575; Interleukin 4 receptor alpha chain polymorphism Gln551Arg is associated with adult atopic dermatitis in Japan.
Oiso N.; Fukai K.; Ishii M.;
Br. J. Dermatol. 142:1003-1006(2000)
Cited for: VARIANT ARG-576;

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.