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UniProtKB/Swiss-Prot Q99697: Variant p.Arg108His

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

Variant position:  108
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 Histidine (H) at position 108 (R108H, p.Arg108His).
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 (H)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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:  Ring dermoid of cornea (RDC) [MIM:180550]: An ocular disorder characterized by bilateral annular limbal dermoids (growths with a skin-like structure) with corneal and conjunctival extension. {ECO:0000269|PubMed:15591271, ECO:0000269|PubMed:22224469}. 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 RDC; results in 25% loss of transactivation activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  108
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:   QRTHFTSQQLQELEATFQRN  R YPDMSTREEIAVWTNLTEAR
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                         QRTHFTSQQLQELEATFQRNRYPDMSTREEIAVWTNLTEAR

Mouse                         QRTHFTSQQLQELEATFQRNRYPDMSTREEIAVWTNLTEAR

Rat                           QRTHFTSQQLQELEATFQRNRYPDMSTREEIAVWTNLTEAR

Chicken                       QRTHFTSQQLQELEATFQRNRYPDMSTREEIAVWTNLTEAR

Xenopus laevis                QRTHFTSQQLQELEATFQRNRYPDMSTREEIAVWTNLTEAR

Zebrafish                     QRTHFTSQQLQELEATFQRNRYPDMSTREEIAVWTNLTEAR

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
Modified residue 90 – 90 Phosphothreonine; by PKB/AKT2


Literature citations

Structural and biophysical insights into the ligand-free Pitx2 homeodomain and a ring dermoid of the cornea inducing homeodomain mutant.
Doerdelmann T.; Kojetin D.J.; Baird-Titus J.M.; Solt L.A.; Burris T.P.; Rance M.;
Biochemistry 51:665-676(2012)
Cited for: STRUCTURE BY NMR OF 85-144 OF WILD-TYPE AND MUTANT HIS-108 IN COMPLEX WITH DNA; VARIANT RDC HIS-108;

Mutation in PITX2 is associated with ring dermoid of the cornea.
Xia K.; Wu L.; Liu X.; Xi X.; Liang D.; Zheng D.; Cai F.; Pan Q.; Long Z.; Dai H.; Hu Z.; Tang B.; Zhang Z.; Xia J.;
J. Med. Genet. 41:E129-E129(2004)
Cited for: VARIANT RDC HIS-108;

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.