UniProtKB/SwissProt variant VAR

Variant information

Variant position:

210

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 Tyrosine (Y) to Cysteine (C) at position 210 (Y210C, p.Tyr210Cys).

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 large size and aromatic (Y) to medium size and polar (C)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-2

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, common variable, 13 (CVID13) [MIM:616873]: A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. CVID13 is an autosomal dominant disease associated with a striking decrease in B-cell numbers. {ECO:0000269|PubMed:21548011, ECO:0000269|PubMed:26981933}. 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 CVID13; decreases binding to pericentromeric heterochromatin DNA; has diffuse nuclear localization.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs869312883 [ dbSNP | Ensembl ]

Sequence information

Variant position:

210

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

Protein sequence length:

519

The length of the canonical sequence.

Location on the sequence:

GHLRTHSVGKPHKCGYCGRS Y KQRSSLEEHKERCHNYLESM

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                         GHLRTHSVGKPHKCGYCGRSYKQRSSLEEHKERCHNYLESM

Mouse                         GHLRTHSVGKPHKCGYCGRSYKQRSSLEEHKERCHNYLESM

Chicken                       GHLRTHSVGKPHKCGYCGRSYKQRSSLEEHKERCHNYLQTM

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	1 – 519	DNA-binding protein Ikaros
Zinc finger	201 – 224	C2H2-type 4
Modified residue	196 – 196	Phosphoserine
Alternative sequence	54 – 283	Missing. In isoform Ik6.
Alternative sequence	141 – 283	Missing. In isoform Ik5.
Alternative sequence	197 – 283	Missing. In isoform Ik3 and isoform Ik4.
Alternative sequence	197 – 238	Missing. In isoform Ik7 and isoform Ikx.
Mutagenesis	191 – 191	H -> R. Abolishes binding to DNA and has diffuse nuclear localization.

Literature citations

Congenital pancytopenia and absence of B lymphocytes in a neonate with a mutation in the Ikaros gene.
Goldman F.D.; Gurel Z.; Al-Zubeidi D.; Fried A.J.; Icardi M.; Song C.; Dovat S.;
Pediatr. Blood Cancer 58:591-597(2012)
Cited for: INVOLVEMENT IN CVID13; VARIANT CVID13 CYS-210; CHARACTERIZATION OF VARIANT CVID13 CYS-210; SUBCELLULAR LOCATION;

Loss of B Cells in Patients with Heterozygous Mutations in IKAROS.
Kuehn H.S.; Boisson B.; Cunningham-Rundles C.; Reichenbach J.; Stray-Pedersen A.; Gelfand E.W.; Maffucci P.; Pierce K.R.; Abbott J.K.; Voelkerding K.V.; South S.T.; Augustine N.H.; Bush J.S.; Dolen W.K.; Wray B.B.; Itan Y.; Cobat A.; Sorte H.S.; Ganesan S.; Prader S.; Martins T.B.; Lawrence M.G.; Orange J.S.; Calvo K.R.; Niemela J.E.; Casanova J.L.; Fleisher T.A.; Hill H.R.; Kumanovics A.; Conley M.E.; Rosenzweig S.D.;
N. Engl. J. Med. 374:1032-1043(2016)
Cited for: VARIANTS CVID13 GLN-162; LEU-162; ARG-167 AND GLN-184; CHARACTERIZATION OF VARIANTS CVID13 GLN-162; LEU-162; ARG-167; GLN-184 AND CYS-210; MUTAGENESIS OF ASN-159 AND HIS-191;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q13422: Variant p.Tyr210Cys