Home  |  Contact

UniProtKB/Swiss-Prot Q99697: Variant p.Arg136Cys

Pituitary homeobox 2
Gene: PITX2
Chromosomal location: 4q25-q27
Variant information

Variant position:  136
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 Arginine (R) to Cysteine (C) at position 136 (R136C, p.Arg136Cys).
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 basic (R) to medium size and polar (C)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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:  Axenfeld-Rieger syndrome 1 (RIEG1) [MIM:180500]: An autosomal dominant disorder of morphogenesis that results in abnormal development of the anterior segment of the eye, and results in blindness from glaucoma in approximately 50% of affected individuals. Additional features include aniridia, maxillary hypoplasia, hypodontia, anal stenosis, redundant periumbilical skin. {ECO:0000269|PubMed:10937553, ECO:0000269|PubMed:11487566, ECO:0000269|PubMed:12381896, ECO:0000269|PubMed:16936096, ECO:0000269|PubMed:8944018}. 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 RIEG1.
Any additional useful information about the variant.



Sequence information

Variant position:  136
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  317
The length of the canonical sequence.

Location on the sequence:   EEIAVWTNLTEARVRVWFKN  R RAKWRKRERNQQAELCKNGF
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                         EEIAVWTNLTEARVRVWFKNRRAKWRKRERNQQAELCKNGF

Mouse                         EEIAVWTNLTEARVRVWFKNRRAKWRKRERNQQAELCKNGF

Rat                           EEIAVWTNLTEARVRVWFKNRRAKWRKRERNQQAELCKNGF

Chicken                       EEIAVWTNLTEARVRVWFKNRRAKWRKRERNQQAELCKNGF

Xenopus laevis                EEIAVWTNLTEARVRVWFKNRRAKWRKRERNQQAELCKNGF

Zebrafish                     EEIAVWTNLTEARVRVWFKNRRAKWRKRERNQQAELCKNGF

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 – 317 Pituitary homeobox 2
DNA binding 85 – 144 Homeobox
Helix 126 – 141


Literature citations

Phenotypic variability and asymmetry of Rieger syndrome associated with PITX2 mutations.
Perveen R.; Lloyd I.C.; Clayton-Smith J.; Churchill A.; van Heyningen V.; Hanson I.; Taylor D.; McKeown C.; Super M.; Kerr B.; Winter R.; Black G.C.M.;
Invest. Ophthalmol. Vis. Sci. 41:2456-2460(2000)
Cited for: VARIANTS RIEG1 GLU-134 AND CYS-136;

Four novel mutations in the PITX2 gene in patients with Axenfeld-Rieger syndrome.
Phillips J.C.;
Ophthalmic Res. 34:324-326(2002)
Cited for: VARIANTS RIEG1 LEU-110; CYS-136; VAL-151 AND THR-154;

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.