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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q12948: Variant p.Ile126Met

Forkhead box protein C1
Gene: FOXC1
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Variant information Variant position: help 126 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance
Residue change: help From Isoleucine (I) to Methionine (M) at position 126 (I126M, p.Ile126Met). 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: help 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: help 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
Variant description: help In ASGD3 and RIEG3; 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: help Links to websites of interest for the variant.


Sequence information Variant position: help 126 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 553 The length of the canonical sequence.
Location on the sequence: help QFIMDRFPFYRDNKQGWQNS I RHNLSLNECFVKVPRDDKKP 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         QFIMDRFPFYRDNKQGWQNSIRHNLSLNECFVKVPRDDKKP

Mouse                         QFIMDRFPFYRDNKQGWQNSIRHNLSLNECFVKVPRDDKKP

Xenopus tropicalis            QFIMERFPFYRDNKQGWQNSIRHNLSLNECFVKVPRDDKKP
Sequence annotation in neighborhood: help 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; 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;
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.