UniProtKB/Swiss-Prot O14802: Variant p.Ser636Tyr

DNA-directed RNA polymerase III subunit RPC1
Gene: POLR3A
Chromosomal location: 10q22-q23
Variant information

Variant position:  636
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 Serine (S) to Tyrosine (Y) at position 636 (S636Y, p.Ser636Tyr).
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 small size and polar (S) to large size and aromatic (Y)
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

Variant description:  In HLD7.
Any additional useful information about the variant.



Sequence information

Variant position:  636
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1390
The length of the canonical sequence.

Location on the sequence:   NLRTKGKQYCGKGEDLCAND  S YVTIQNSELMSGSMDKGTLG
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                         NLRTKGKQYCGKG-----EDLCANDSYVTIQNSELMSGSMDKGTLG

Bovine                        NLRTKGKQYCGRG-----EDLCVNDSYVTIQNSELMSGSMD

Chicken                       NLRTKGKQYCGKG-----EDLCYNDSYVTIQNSELMSGSMD

Slime mold                    NFETRSRTYSKN------LYMCPKDGYVYFRNSELMCGSID

Baker's yeast                 NLDAKNKVFVPPKSKSLPNEMSQNDGFVIIRGSQILSGVMD

Fission yeast                 NLDAKTRSFSRIKSKT--PEMCPKDGYLMIRNSEIIAGVVD

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 – 1390 DNA-directed RNA polymerase III subunit RPC1


Literature citations

Mutations of POLR3A encoding a catalytic subunit of RNA polymerase Pol III cause a recessive hypomyelinating leukodystrophy.
Bernard G.; Chouery E.; Putorti M.L.; Tetreault M.; Takanohashi A.; Carosso G.; Clement I.; Boespflug-Tanguy O.; Rodriguez D.; Delague V.; Abou Ghoch J.; Jalkh N.; Dorboz I.; Fribourg S.; Teichmann M.; Megarbane A.; Schiffmann R.; Vanderver A.; Brais B.;
Am. J. Hum. Genet. 89:415-423(2011)
Cited for: VARIANTS HLD7 ASN-372; LEU-558; TYR-636; GLU-672; TYR-724; ILE-775; VAL-852 AND THR-1247 INS; TISSUE SPECIFICITY;

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.