UniProtKB/Swiss-Prot P58012: Variant p.Ser217Phe

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

Variant position:  217
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 Phenylalanine (F) at position 217 (S217F, p.Ser217Phe).
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 large size and aromatic (F)
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; diffuse nuclear localization; increased transactivation activity.
Any additional useful information about the variant.



Sequence information

Variant position:  217
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:   SGFLNNSWPLPQPPSPMPYA  S CQMAAAAAAAAAAAAAAGPG
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                         SGFLNNSWPLPQPPSPMPYASCQMAAAAAAAAAAAAAAGPG

Mouse                         SGFLNNSWPLPQPPSPMPYASCQMAAAAAAAAAAAAAAGPG

Pig                           SGFLNNSWPLPQPPSPMPYASCQMAAAAAAAAAAAAAAGPG

Bovine                        SGFLNNSWPLPQPPSPMPYASCQMAAAAAAAAAAAAAAGPG

Rabbit                        SGFLNNSWPLPQPPSPMPYASCQMAAAAAAAAAAAAAAGPG

Goat                          SGFLNNSWPLPQPPSPMPYASCQMAAAAAAAAAAAAAAGPG

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


Literature citations

Spectrum of FOXL2 gene mutations in blepharophimosis-ptosis-epicanthus inversus (BPES) families demonstrates a genotype --phenotype correlation.
De Baere E.; Dixon M.J.; Small K.W.; Jabs E.W.; Leroy B.P.; Devriendt K.; Gillerot Y.; Mortier G.; Meire F.; Van Maldergem L.; Courtens W.; Hjalgrim H.; Huang S.; Liebaers I.; Van Regemorter N.; Touraine P.; Praphanphoj V.; Verloes A.; Udar N.; Yellore V.; Chalukya M.; Yelchits S.; De Paepe A.; Kuttenn F.; Fellous M.; Veitia R.; Messiaen L.;
Hum. Mol. Genet. 10:1591-1600(2001)
Cited for: VARIANTS BPES ILE-85 DEL AND PHE-217;

FOXL2 and BPES: mutational hotspots, phenotypic variability, and revision of the genotype-phenotype correlation.
De Baere E.; Beysen D.; Oley C.; Lorenz B.; Cocquet J.; De Sutter P.; Devriendt K.; Dixon M.J.; Fellous M.; Fryns J.-P.; Garza A.; Jonsrud C.; Koivisto P.A.; Krause A.; Leroy B.P.; Meire F.; Plomp A.; Van Maldergem L.; De Paepe A.; Veitia R.; Messiaen L.;
Am. J. Hum. Genet. 72:478-487(2003)
Cited for: VARIANTS BPES PHE-106; LYS-109 AND PHE-217;

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;

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.