UniProtKB/Swiss-Prot Q9Y2S0: Variant p.Thr50Ile

DNA-directed RNA polymerases I and III subunit RPAC2
Gene: POLR1D
Chromosomal location: 13q12.2
Variant information

Variant position:  50
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Threonine (T) to Isoleucine (I) at position 50 (T50I, p.Thr50Ile).
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 medium size and polar (T) to medium size and hydrophobic (I)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -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:  In TCS2.
Any additional useful information about the variant.



Sequence information

Variant position:  50
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  133
The length of the canonical sequence.

Location on the sequence:   VQAAGTDRHCVTFVLHEEDH  T LGNSLRYMIMKNPEVEFCGY
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                         VQAAGT---------------------DRHCVTFVLHEEDHTLGNSLRYMIMKNPEVEFCGY

Mouse                         VQAAGT---------------------DRQCVTFVLHEEDH

Bovine                        VQAAGT---------------------DRHCVTFVLHEEDH

Xenopus laevis                VQAQGN---------------------EESCVTFVLHEEDH

Zebrafish                     VRTDGA---------------------DEGCVTFVLNEEDH

Caenorhabditis elegans        PQVDDEEDLNVPSKKKMEILDPKSFEQDPSNLTLIMYEEDH

Drosophila                    AELAGDE------------------KNGEGSRTFVFTNEGH

Baker's yeast                 VDMTGDEEQEEEPDREKIKLLTQATSEDGTSASFQIVEEDH

Fission yeast                 IILPGH-------------------SADLTSVTFQIQKEDH

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 – 133 DNA-directed RNA polymerases I and III subunit RPAC2
Alternative sequence 11 – 133 ISGLKTSMAEGERKTALEMVQAAGTDRHCVTFVLHEEDHTLGNSLRYMIMKNPEVEFCGYTTTHPSESKINLRIQTRGTLPAVEPFQRGLNELMNVCQHVLDKFEASIKDYKDQKASRNESTF -> AIEELLKEAKRGKTRAETMGPMGWMKCPLASTNKRFLINTIKNTLPSHKEQDHEQKEGDKEPAKSQAQKEENPKKHRSHPYKHSFRARGSASYSPPRKRSSQDKYEKRSNRR. In isoform 2.


Literature citations

Mutations in genes encoding subunits of RNA polymerases I and III cause Treacher Collins syndrome.
Dauwerse J.G.; Dixon J.; Seland S.; Ruivenkamp C.A.; van Haeringen A.; Hoefsloot L.H.; Peters D.J.; Boers A.C.; Daumer-Haas C.; Maiwald R.; Zweier C.; Kerr B.; Cobo A.M.; Toral J.F.; Hoogeboom A.J.; Lohmann D.R.; Hehr U.; Dixon M.J.; Breuning M.H.; Wieczorek D.;
Nat. Genet. 43:20-22(2011)
Cited for: VARIANTS TCS2 LYS-47; ILE-50; ARG-51; GLU-52; CYS-56; SER-82 AND SER-99;

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.