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UniProtKB/Swiss-Prot P26367: Variant p.Phe258Ser

Paired box protein Pax-6
Gene: PAX6
Chromosomal location: 11p13
Variant information

Variant position:  258
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 Phenylalanine (F) to Serine (S) at position 258 (F258S, p.Phe258Ser).
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 large size and aromatic (F) to small size and polar (S)
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

Involvement in disease:  Coloboma of optic nerve (COLON) [MIM:120430]: An ocular defect that is due to malclosure of the fetal intraocular fissure affecting the optic nerve head. In some affected individuals, it appears as enlargement of the physiologic cup with severely affected eyes showing huge cavities at the site of the disk. {ECO:0000269|PubMed:12721955}. 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.

Involvement in disease:  Coloboma, ocular, autosomal dominant (COAD) [MIM:120200]: A set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). The clinical presentation is variable. Some individuals may present with minimal defects in the anterior iris leaf without other ocular defects. More complex malformations create a combination of iris, uveoretinal and/or optic nerve defects without or with microphthalmia or even anophthalmia. {ECO:0000269|PubMed:12721955}. 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 COAD and COLON; significant impairment of transcriptional activation ability.
Any additional useful information about the variant.

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



Sequence information

Variant position:  258
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  422
The length of the canonical sequence.

Location on the sequence:   FARERLAAKIDLPEARIQVW  F SNRRAKWRREEKLRNQRRQA
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                         FARERLAAKIDLPEARIQVWFSNRRAKWRREEKLRNQRR--------------------------------------------------------------------QA

Mouse                         FARERLAAKIDLPEARIQVWFSNRRAKWRREEKLRNQRR--

Rat                           FARERLAAKIDLPEARIQVWFSNRRAKWRREEKLRNQRR--

Bovine                        FARERLAAKIDLPEARIQVWFSNRRAKWRREEKLRNQRR--

Xenopus laevis                FARERLAAKIDLPEARIQVWFSNRRAKWRREEKLRNQRR--

Zebrafish                     FARERLAAKIDLPEARIQVWFSNRRAKWRREEKLRNQRR--

Drosophila                    FARERLAGKIGLPEARIQVWFSNRRAKWRREEKLRNQRRTP

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 – 422 Paired box protein Pax-6
DNA binding 210 – 269 Homeobox
Helix 251 – 275


Literature citations

Mutations of the PAX6 gene detected in patients with a variety of optic-nerve malformations.
Azuma N.; Yamaguchi Y.; Handa H.; Tadokoro K.; Asaka A.; Kawase E.; Yamada M.;
Am. J. Hum. Genet. 72:1565-1570(2003)
Cited for: INVOLVEMENT IN OPTIC-NERVE MALFORMATIONS; VARIANT MORNING GLORY DISK ANOMALY SER-68; VARIANT COLON SER-258; VARIANT COAD SER-258; VARIANT ASGD5 PRO-363; VARIANTS BONH ILE-292; ARG-378; VAL-381 AND ALA-391;

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.