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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q96QS3: Variant p.Pro353Leu

Homeobox protein ARX
Gene: ARX
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Variant information Variant position: help 353 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Proline (P) to Leucine (L) at position 353 (P353L, p.Pro353Leu). 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: help 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: help -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: help In DEE1; corpus callosum hypoplasia and simplified gyral pattern observed in one patient; reduces sequence-specific DNA-binding; slightly reduces transcriptional repression of LMO1. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 353 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 562 The length of the canonical sequence.
Location on the sequence: help TTFTSYQLEELERAFQKTHY P DVFTREELAMRLDLTEARVQ 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         TTFTSYQLEELERAFQKTHYPDVFTREELAMRLDLTEARVQ

Mouse                         TTFTSYQLEELERAFQKTHYPDVFTREELAMRLDLTEARVQ

Rat                           TTFTSYQLEELERAFQKTHYPDVFTREELAMRLDLTEARVQ

Zebrafish                     TTFTSYQLEELERAFQKTHYPDVFTREELAMRLDLTEARVQ
Sequence annotation in neighborhood: help 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 – 562 Homeobox protein ARX
DNA binding 328 – 387 Homeobox
Mutagenesis 358 – 358 R -> S. Abolishes sequence-specific DNA-binding; reduces transcriptional repression of LMO1 and SHOX2. Abolishes transcriptional activation of KDM5C.



Literature citations
Mutations in the human ortholog of aristaless cause X-linked mental retardation and epilepsy.
Stroemme P.; Mangelsdorf M.E.; Shaw M.A.; Lower K.M.; Lewis S.M.E.; Bruyere H.; Luetcherath V.; Gedeon A.K.; Wallace R.H.; Scheffer I.E.; Turner G.; Partington M.; Frints S.G.M.; Fryns J.-P.; Sutherland G.R.; Mulley J.C.; Gecz J.;
Nat. Genet. 30:441-445(2002)
Cited for: FUNCTION; VARIANTS DEE1 ALA-ALA-ALA-ALA-ALA-ALA-ALA-115 INS; ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-155 INS AND LEU-353; VARIANT PRTS ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-155 INS; TISSUE SPECIFICITY; ARX homeodomain mutations abolish DNA binding and lead to a loss of transcriptional repression.
Shoubridge C.; Tan M.H.; Seiboth G.; Gecz J.;
Hum. Mol. Genet. 21:1639-1647(2012)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANT ACCAG ASN-333; CHARACTERIZATION OF VARIANT DEE1 LEU-353; CHARACTERIZATION OF VARIANTS LISX2 PRO-332; GLN-343 AND ARG-353; MUTAGENESIS OF ARG-358 AND ARG-379; Diagnostic targeted resequencing in 349 patients with drug-resistant pediatric epilepsies identifies causative mutations in 30 different genes.
Parrini E.; Marini C.; Mei D.; Galuppi A.; Cellini E.; Pucatti D.; Chiti L.; Rutigliano D.; Bianchini C.; Virdo S.; De Vita D.; Bigoni S.; Barba C.; Mari F.; Montomoli M.; Pisano T.; Rosati A.; Guerrini R.;
Hum. Mutat. 38:216-225(2017)
Cited for: VARIANT DEE1 LEU-353;
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.