UniProtKB/SwissProt variant VAR

Variant information

Variant position:

279

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

Type of variant:

LP/P [Disclaimer]

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 Isoleucine (I) to Asparagine (N) at position 279 (I279N, p.Ile279Asn).

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 hydrophobic (I) to medium size and polar (N)

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

Variant description:

In HIES5; decreased STAT1 and STAT3 phosphorylation.

Any additional useful information about the variant.

Sequence information

Variant position:

279

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

Protein sequence length:

468

The length of the canonical sequence.

Location on the sequence:

AERSKTFTTWMVKDLQHHCV I HDAWSGLRHVVQLRAQEEFG

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                         AERSKTFTTWMVKDLQHHCVIHDAWSGLRHVVQLRAQEEFG

Mouse                         PVWSKEFTVLLLPVAQYQCVIHDALRGVKHVVQVRGKEELD

Rat                           PVWSKXFTVWPLQVAQHQCVIHDALRGVKHVVQVRGKEEFD

Pig                           AERSKTFTTWMVKELQHHCIIHDAWSGMRHVVQLRAQEEFG

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	20 – 468	Interleukin-6 receptor subunit alpha
Chain	20 – 355	Soluble interleukin-6 receptor subunit alpha
Topological domain	20 – 365	Extracellular
Domain	218 – 316	Fibronectin type-III 2
Mutagenesis	277 – 277	C -> D. 30% increase of ligand-binding and 100% increase in IL6 signaling.
Mutagenesis	278 – 278	V -> N. 50% Decrease of ligand-binding and 50% increase in IL6 signaling.
Mutagenesis	279 – 279	I -> D. Complete loss of ligand-binding.
Mutagenesis	280 – 280	H -> I. No change of ligand-binding and no IL6 signaling.
Mutagenesis	281 – 281	D -> G. 70% decrease of ligand-binding and no IL6 signaling.
Mutagenesis	285 – 285	G -> D. 80% decrease of ligand-binding and no IL6 signaling.
Mutagenesis	291 – 291	Q -> K. Complete loss of ligand-binding.
Mutagenesis	293 – 293	R -> G. Complete loss of ligand-binding.
Beta strand	275 – 281

Literature citations

Loss of the interleukin-6 receptor causes immunodeficiency, atopy, and abnormal inflammatory responses.
Spencer S.; Koestel Bal S.; Egner W.; Lango Allen H.; Raza S.I.; Ma C.A.; Guerel M.; Zhang Y.; Sun G.; Sabroe R.A.; Greene D.; Rae W.; Shahin T.; Kania K.; Ardy R.C.; Thian M.; Staples E.; Pecchia-Bekkum A.; Worrall W.P.M.; Stephens J.; Brown M.; Tuna S.; York M.; Shackley F.; Kerrin D.; Sargur R.; Condliffe A.; Tipu H.N.; Kuehn H.S.; Rosenzweig S.D.; Turro E.; Tavare S.; Thrasher A.J.; Jodrell D.I.; Smith K.G.C.; Boztug K.; Milner J.D.; Thaventhiran J.E.D.;
J. Exp. Med. 216:1986-1998(2019)
Cited for: INVOLVEMENT IN HIES5; VARIANTS HIES5 ASN-279 AND PRO-280; CHARACTERIZATION OF VARIANTS HIES5 ASN-279 AND PRO-280; FUNCTION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P08887: Variant p.Ile279Asn