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UniProtKB/Swiss-Prot Q13422: Variant p.Tyr210Cys

DNA-binding protein Ikaros
Gene: IKZF1
Chromosomal location: 7p11.1-p13
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.



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.

TypePositionsDescription
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;

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.