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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O95343: Variant p.Val250Ala

Homeobox protein SIX3
Gene: SIX3
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Variant information Variant position: help 250 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 Valine (V) to Alanine (A) at position 250 (V250A, p.Val250Ala). 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 Change from medium size and hydrophobic (V) to small size and hydrophobic (A) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 0 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 HPE2; Significantly decreased its ability to activate NR4A3. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 250 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 332 The length of the canonical sequence.
Location on the sequence: help YPNPSKKRELAQATGLTPTQ V GNWFKNRRQRDRAAAAKNRL 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                         YPNPSKKRELAQATGLTPTQVGNWFKNRRQRDRAAAAKNRL

Mouse                         YPNPSKKRELAQATGLTPTQVGNWFKNRRQRDRAAAAKNRL

Chicken                       YPNPSKKRELAQATGLTPTQVGNWFKNRRQRDRAAAAKNRL
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 – 332 Homeobox protein SIX3
DNA binding 206 – 265 Homeobox
Region 232 – 251 Disordered



Literature citations
Functional characterization of SIX3 homeodomain mutations in holoprosencephaly: interaction with the nuclear receptor NR4A3/NOR1.
Laflamme C.; Filion C.; Labelle Y.;
Hum. Mutat. 24:502-508(2004)
Cited for: CHARACTERIZATION OF VARIANTS HPE2 ALA-250 AND PRO-257; Mutations in the homeodomain of the human SIX3 gene cause holoprosencephaly.
Wallis D.E.; Roessler E.; Hehr U.; Nanni L.; Wiltshire T.; Richieri-Costa A.; Gillessen-Kaesbach G.; Zackai E.H.; Rommens J.; Muenke M.;
Nat. Genet. 22:196-198(1999)
Cited for: VARIANTS HPE2 VAL-226; ALA-250 AND PRO-257;
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.