UniProtKB/Swiss-Prot Q15475: Variant p.Tyr129Cys

Homeobox protein SIX1
Gene: SIX1
Chromosomal location: 14q22.3-q23
Variant information

Variant position:  129
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Tyrosine (Y) to Cysteine (C) at position 129 (Y129C, p.Tyr129Cys).
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

Variant description:  In BOS3; crucial for interaction with EYA1, DNA binding and transcription factor activity.
Any additional useful information about the variant.



Sequence information

Variant position:  129
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  284
The length of the canonical sequence.

Location on the sequence:   YRVRRKFPLPRTIWDGEETS  Y CFKEKSRGVLREWYAHNPYP
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                         YRVRRKFPLPRTIWDGEETSYCFKEKSRGVLREWYAHNPYP

Gorilla                       YRVRRKFPLPRTIWDGEETSYCFKEKSRGVLREWYAHNPYP

Mouse                         YRVRRKFPLPRTIWDGEETSYCFKEKSRGVLREWYAHNPYP

Xenopus laevis                YRVRRKFPLPRTIWDGEETSYCFKEKSRGVLREWYAHNPYP

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 – 284 Homeobox protein SIX1
DNA binding 124 – 183 Homeobox


Literature citations

SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexes.
Ruf R.G.; Xu P.-X.; Silvius D.; Otto E.A.; Beekmann F.; Muerb U.T.; Kumar S.; Neuhaus T.J.; Kemper M.J.; Raymond R.M. Jr.; Brophy P.D.; Berkman J.; Gattas M.; Hyland V.; Ruf E.-M.; Schwartz C.; Chang E.H.; Smith R.J.H.; Stratakis C.A.; Weil D.; Petit C.; Hildebrandt F.;
Proc. Natl. Acad. Sci. U.S.A. 101:8090-8095(2004)
Cited for: VARIANTS BOS3 TRP-110 AND CYS-129; VARIANT DFNA23 GLU-133 DEL; CHARACTERIZATION OF VARIANTS BOS3 TRP-110 AND CYS-129; CHARACTERIZATION OF VARIANT DFNA23 GLU-133 DEL; FUNCTION; INTERACTION WITH EYA1;

SIX1 mutation screening in 247 branchio-oto-renal syndrome families: a recurrent missense mutation associated with BOR.
Kochhar A.; Orten D.J.; Sorensen J.L.; Fischer S.M.; Cremers C.W.; Kimberling W.J.; Smith R.J.;
Hum. Mutat. 29:565-565(2008)
Cited for: VARIANTS BOS3 GLU-17; PRO-73; GLY-106; GLN-110; TRP-110; CYS-112 AND CYS-129;

Mutation screening of the EYA1, SIX1, and SIX5 genes in a large cohort of patients harboring branchio-oto-renal syndrome calls into question the pathogenic role of SIX5 mutations.
Krug P.; Moriniere V.; Marlin S.; Koubi V.; Gabriel H.D.; Colin E.; Bonneau D.; Salomon R.; Antignac C.; Heidet L.;
Hum. Mutat. 32:183-190(2011)
Cited for: VARIANT BOS3 CYS-129; VARIANT BOR LEU-249;

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.