UniProtKB/Swiss-Prot Q05066: Variant p.Val60Leu

Sex-determining region Y protein
Gene: SRY
Chromosomal location: Yp11.3
Variant information

Variant position:  60
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 Valine (V) to Leucine (L) at position 60 (V60L, p.Val60Leu).
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:  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:  1
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:  46,XY sex reversal 1 (SRXY1) [MIM:400044]: A condition characterized by male-to-female sex reversal in the presence of a normal 46,XY karyotype. Patients manifest rapid and early degeneration of their gonads, which are present in the adult as 'streak gonads', consisting mainly of fibrous tissue and variable amounts of ovarian stroma. As a result these patients do not develop secondary sexual characteristics at puberty. The external genitalia in these subjects are completely female, and Muellerian structures are normal. 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 SRXY1.
Any additional useful information about the variant.



Sequence information

Variant position:  60
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  204
The length of the canonical sequence.

Location on the sequence:   CNSKYQCETGENSKGNVQDR  V KRPMNAFIVWSRDQRRKMAL
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                         CNSKYQCETGENSKGNVQDRVKRPMNAFIVWSRDQRRKMAL

Gorilla                       CNSKYQCETGENSKGSVQDRVKRPMNAFIVWSRDQRRKMAL

Rhesus macaque                CSSKYQCEAGENSKGSVQDKVKRPMNAFIVWSRDQKRKMAL

Chimpanzee                    YNSKYQRETGENSKDSVQDRVKRPMNAFFVWSRDQRRKMAL

Mouse                         ----------------MEGHVKRPMNAFMVWSRGERHKLAQ

Pig                           HSSNDGRETRGSGRESGQDRVKRPMNAFIVWSRDQRRKVAL

Bovine                        HSANDQCERGEHVRESSQDHVKRPMNAFIVWSRERRRKVAL

Goat                          HSANDQCERGENVTESSQDHVKRPMNAFIVWSRERRRKVAL

Sheep                         HSANDQRERGENVRESSQNHVKRPMNAFIVWSRERRRKVAL

Cat                           PTSNYRCETRGKGRDRGQDRVKRPMNAFMVWSRDQRRKVAL

Dog                           STSNYRCESGGNGRDSGRNRVRRPMNAFLVWSRDQRRKMAL

Horse                         PGSHFRSETRGNGRENGQDRVKRPMNAFMVWSRDHRRKVAL

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 – 204 Sex-determining region Y protein
DNA binding 60 – 128 HMG box
Region 59 – 136 Sufficient for interaction with KPNB1
Mutagenesis 62 – 62 R -> G. Strongly reduces nuclear localization. Strongly reduces nuclear localization; when associated with W-133. Reduces interaction with KPNB1. Abolishes DNA-binding.
Mutagenesis 64 – 64 M -> I. Abolishes nuclear localization.
Mutagenesis 75 – 75 R -> N. Strongly reduces nuclear localization. Abolishes DNA-binding. Does not reduce interaction with KPNB1 and CAML.
Mutagenesis 76 – 76 R -> P. Reduces nuclear localization. Reduces DNA-binding. Does not reduce interaction with KPNB1 and CAML.


Literature citations

Genetic evidence equating SRY and the testis-determining factor.
Berta P.; Hawkins J.R.; Sinclair A.H.; Taylor A.; Griffiths B.L.; Goodfellow P.N.; Fellous M.;
Nature 348:448-450(1990)
Cited for: VARIANTS SRXY1 LEU-60 AND ILE-64;

Familial case with sequence variant in the testis-determining region associated with two sex phenotypes.
Vilain E.; McElreavey K.; Jaubert F.; Raymond J.-P.; Richaud F.; Fellous M.;
Am. J. Hum. Genet. 50:1008-1011(1992)
Cited for: VARIANT SRXY1 LEU-60;

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.