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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O95602: Variant p.Glu593Gln

DNA-directed RNA polymerase I subunit RPA1
Gene: POLR1A
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Variant information Variant position: help 593 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance
Residue change: help From Glutamate (E) to Glutamine (Q) at position 593 (E593Q, p.Glu593Gln). 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: help Change from medium size and acidic (E) to medium size and polar (Q) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 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: help In AFDCIN; likely pathogenic; results in decreased rRNA transcription in transfected cells. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 593 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 1720 The length of the canonical sequence.
Location on the sequence: help KVLRLHYANCKAYNADFDGD E MNAHFPQSELGRAEAYVLAC 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         KVLRLHYANCKAYNADFDGDEMNAHFPQSELGRAEAYVLAC

Mouse                         KVLRLHYANCKAYNADFDGDEMNAHFPQSELGRAEAYVLAC

Rat                           KVLRLHYANCKAYNADFDGDEMNAHFPQSELGRAEAYVLAC

Drosophila                    KTFRLHYSNCKAYNADFDGDEMNAHYPQSEVARAEAYNLVN

Slime mold                    KTLRMHYSNCSTYNADFDGDEMNIHFPQSLLASAEIREICA

Baker's yeast                 KTLRLHYANTGAYNADFDGDEMNMHFPQNENARAEALNLAN

Fission yeast                 KTIRMHYANCNSYNADFDGDEMNMHFPQSTNARSEAQFIAN
Sequence annotation in neighborhood: help 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 – 1720 DNA-directed RNA polymerase I subunit RPA1
Binding site 588 – 588
Binding site 588 – 588
Binding site 590 – 590
Binding site 590 – 590
Binding site 592 – 592
Binding site 592 – 592
Beta strand 593 – 597



Literature citations
Acrofacial dysostosis, Cincinnati type, a mandibulofacial dysostosis syndrome with limb anomalies, is caused by POLR1A dysfunction.
Weaver K.N.; Watt K.E.; Hufnagel R.B.; Navajas Acedo J.; Linscott L.L.; Sund K.L.; Bender P.L.; Koenig R.; Lourenco C.M.; Hehr U.; Hopkin R.J.; Lohmann D.R.; Trainor P.A.; Wieczorek D.; Saal H.M.;
Am. J. Hum. Genet. 96:765-774(2015)
Cited for: VARIANTS AFDCIN GLN-593 AND PHE-1299; INVOLVEMENT IN AFDCIN; POLR1A variants underlie phenotypic heterogeneity in craniofacial, neural, and cardiac anomalies.
Smallwood K.; Watt K.E.N.; Ide S.; Baltrunaite K.; Brunswick C.; Inskeep K.; Capannari C.; Adam M.P.; Begtrup A.; Bertola D.R.; Demmer L.; Demo E.; Devinsky O.; Gallagher E.R.; Guillen Sacoto M.J.; Jech R.; Keren B.; Kussmann J.; Ladda R.; Lansdon L.A.; Lunke S.; Mardy A.; McWalters K.; Person R.; Raiti L.; Saitoh N.; Saunders C.J.; Schnur R.; Skorvanek M.; Sell S.L.; Slavotinek A.; Sullivan B.R.; Stark Z.; Symonds J.D.; Wenger T.; Weber S.; Whalen S.; White S.M.; Winkelmann J.; Zech M.; Zeidler S.; Maeshima K.; Stottmann R.W.; Trainor P.A.; Weaver K.N.;
Am. J. Hum. Genet. 110:809-825(2023)
Cited for: VARIANTS AFDCIN VAL-59; HIS-393; LYS-481; ILE-496; ILE-1241; 1284-GLN--ARG-1720 DEL; GLU-1330 DEL; PHE-1562; MET-1631 AND LEU-1638; INVOLVEMENT IN AFDCIN; CHARACTERIZATION OF VARIANTS AFDCIN VAL-59; HIS-393; GLN-593; GLU-1330 DEL AND PHE-1562;
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.