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UniProtKB/Swiss-Prot Q12948: Variant p.Ser131Leu

Forkhead box protein C1
Gene: FOXC1
Variant information

Variant position:  131
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 implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Serine (S) to Leucine (L) at position 131 (S131L, p.Ser131Leu).
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 RIEG3 and ASGD3; with glaucoma; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  131
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  553
The length of the canonical sequence.

Location on the sequence:   RFPFYRDNKQGWQNSIRHNL  S LNECFVKVPRDDKKPGKGSY
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                         RFPFYRDNKQGWQNSIRHNLSLNECFVKVPRDDKKPGKGSY

Mouse                         RFPFYRDNKQGWQNSIRHNLSLNECFVKVPRDDKKPGKGSY

Xenopus tropicalis            RFPFYRDNKQGWQNSIRHNLSLNECFVKVPRDDKKPGKGSY

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 – 553 Forkhead box protein C1
DNA binding 77 – 168 Fork-head
Mutagenesis 126 – 126 I -> A. Decreased nuclear localization. Decreased DNA-binding activity. Decreased transcriptional activity.
Mutagenesis 126 – 126 I -> E. Decreased nuclear localization. Decreased DNA-binding activity. Decreased transcriptional activity.
Mutagenesis 126 – 126 I -> K. Decreased nuclear localization. Decreased DNA-binding activity. Decreased transcriptional activity.
Mutagenesis 127 – 127 R -> A. Decreased nuclear localization. Decreased DNA-binding activity. Decreased transcriptional activity.
Mutagenesis 127 – 127 R -> E. Decreased nuclear localization. Decreased DNA-binding activity. Decreased transcriptional activity.
Mutagenesis 127 – 127 R -> K. Decreased nuclear localization. Decreased DNA-binding activity. Decreased transcriptional activity.


Literature citations

The forkhead transcription factor gene FKHL7 is responsible for glaucoma phenotypes which map to 6p25.
Nishimura D.Y.; Swiderski R.E.; Alward W.L.M.; Searby C.C.; Patil S.R.; Bennet S.R.; Kanis A.B.; Gastier J.M.; Stone E.M.; Sheffield V.C.;
Nat. Genet. 19:140-147(1998)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS ASGD3 SER-112; MET-126 AND LEU-131; INVOLVEMENT IN ASGD3;

A spectrum of FOXC1 mutations suggests gene dosage as a mechanism for developmental defects of the anterior chamber of the eye.
Nishimura D.Y.; Searby C.C.; Alward W.L.; Walton D.; Craig J.E.; Mackey D.A.; Kawase K.; Kanis A.B.; Patil S.R.; Stone E.M.; Sheffield V.C.;
Am. J. Hum. Genet. 68:364-372(2001)
Cited for: VARIANTS RIEG3 LEU-79 AND LEU-131;

Analyses of the effects that disease-causing missense mutations have and function of the winged-helix protein FOXC1.
Saleem R.A.; Banerjee-Basu S.; Berry F.B.; Baxevanis A.D.; Walter M.A.;
Am. J. Hum. Genet. 68:627-641(2001)
Cited for: VARIANTS RIEG3 THR-82; MET-87; SER-112; MET-126 AND LEU-131; CHARACTERIZATION OF VARIANTS RIEG3 THR-82; MET-87; SER-112; MET-126 AND LEU-131;

Structural and functional analyses of disease-causing missense mutations in the forkhead domain of FOXC1.
Saleem R.A.; Banerjee-Basu S.; Berry F.B.; Baxevanis A.D.; Walter M.A.;
Hum. Mol. Genet. 12:2993-3005(2003)
Cited for: CHARACTERIZATION OF VARIANTS RIEG3 LEU-79; THR-79; THR-82; SER-91; THR-91; SER-112; MET-126; HIS-127 AND LEU-131; FUNCTION; DNA-BENDING;

Functional interactions between FOXC1 and PITX2 underlie the sensitivity to FOXC1 gene dose in Axenfeld-Rieger syndrome and anterior segment dysgenesis.
Berry F.B.; Lines M.A.; Oas J.M.; Footz T.; Underhill D.A.; Gage P.J.; Walter M.A.;
Hum. Mol. Genet. 15:905-919(2006)
Cited for: CHARACTERIZATION OF VARIANTS RIEG3 HIS-127 AND LEU-131; FUNCTION; INTERACTION WITH PITX2; SUBCELLULAR LOCATION;

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.