UniProtKB/Swiss-Prot P58012: Variant p.Ser58Leu

Forkhead box protein L2
Gene: FOXL2
Chromosomal location: 3q23
Variant information

Variant position:  58
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 Serine (S) to Leucine (L) at position 58 (S58L, p.Ser58Leu).
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 small size and polar (S) to medium size and hydrophobic (L)
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 BPES; sporadic; nuclear and cytoplasmic aggregation; impaired transactivation activity.
Any additional useful information about the variant.



Sequence information

Variant position:  58
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  376
The length of the canonical sequence.

Location on the sequence:   GGGGGGTAPEKPDPAQKPPY  S YVALIAMAIRESAEKRLTLS
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                         GGGGGGTAPEKPDPAQKPPYSYVALIAMAIRESAEKRLTLS

Mouse                         GG----TTPEKPDPAQKPPYSYVALIAMAIRESAEKRLTLS

Pig                           GGGGASTAPEKPDPAQKPPYSYVALIAMAIRESAEKRLTLS

Bovine                        GGGGTGTAPEKPDPAQKPPYSYVALIAMAIRESAEKRLTLS

Rabbit                        GGGGGGSAAEKPDPAQKPPYSYVALIAMAIRESAEKRLTLS

Goat                          GGGGAGAAPEKPDPAQKPPYSYVALIAMAIRESAEKRLTLS

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 – 376 Forkhead box protein L2
DNA binding 54 – 148 Fork-head


Literature citations

Missense mutations in the forkhead domain of FOXL2 lead to subcellular mislocalization, protein aggregation and impaired transactivation.
Beysen D.; Moumne L.; Veitia R.; Peters H.; Leroy B.P.; De Paepe A.; De Baere E.;
Hum. Mol. Genet. 17:2030-2038(2008)
Cited for: CHARACTERIZATION OF VARIANTS BPES LEU-58; VAL-66; LYS-69; THR-80; ASN-84; SER-90; GLY-98; ARG-101; THR-102; CYS-103; ARG-104; PHE-106; PRO-106; LYS-109 AND PHE-217;

Identification of 34 novel and 56 known FOXL2 mutations in patients with blepharophimosis syndrome.
Beysen D.; De Jaegere S.; Amor D.; Bouchard P.; Christin-Maitre S.; Fellous M.; Touraine P.; Grix A.W.; Hennekam R.; Meire F.; Oyen N.; Wilson L.C.; Barel D.; Clayton-Smith J.; de Ravel T.; Decock C.; Delbeke P.; Ensenauer R.; Ebinger F.; Gillessen-Kaesbach G.; Hendriks Y.; Kimonis V.; Laframboise R.; Laissue P.; Leppig K.; Leroy B.P.; Miller D.T.; Mowat D.; Neumann L.; Plomp A.; Van Regemorter N.; Wieczorek D.; Veitia R.A.; De Paepe A.; De Baere E.;
Hum. Mutat. 29:E205-E219(2008)
Cited for: VARIANTS BPES LEU-58; VAL-65; VAL-66; LYS-69; THR-80; ASN-84; SER-90; GLY-98; ARG-101; THR-102; CYS-103 AND PRO-106;

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.