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UniProtKB/Swiss-Prot Q99814: Variant p.Pro534Leu

Endothelial PAS domain-containing protein 1
Gene: EPAS1
Variant information

Variant position:  534
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 Proline (P) to Leucine (L) at position 534 (P534L, p.Pro534Leu).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
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:  Erythrocytosis, familial, 4 (ECYT4) [MIM:611783]: An autosomal dominant disorder characterized by elevated serum hemoglobin and hematocrit, and normal platelet and leukocyte counts. {ECO:0000269|PubMed:18184961, ECO:0000269|PubMed:18378852, ECO:0000269|PubMed:19208626, ECO:0000269|PubMed:22367913}. 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 ECYT4; impairs interaction with EGLN1 and VHL.
Any additional useful information about the variant.



Sequence information

Variant position:  534
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  870
The length of the canonical sequence.

Location on the sequence:   QCSTQTDFNELDLETLAPYI  P MDGEDFQLSPICPEERLLAE
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                         QCSTQTDFNELDLETLAPYIPMDGEDFQLSPICPEERLLAE

Mouse                         PGSTQTDFSELDLETLAPYIPMDGEDFQLSPICPEEPLMPE

Rat                           QCSTQTDFNELDLETLAPYIPMDGEDFQLSPICPEEPLVPE

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 – 870 Endothelial PAS domain-containing protein 1
Region 496 – 542 NTAD
Modified residue 531 – 531 4-hydroxyproline


Literature citations

Erythrocytosis-associated HIF-2alpha mutations demonstrate a critical role for residues C-terminal to the hydroxylacceptor proline.
Furlow P.W.; Percy M.J.; Sutherland S.; Bierl C.; McMullin M.F.; Master S.R.; Lappin T.R.; Lee F.S.;
J. Biol. Chem. 284:9050-9058(2009)
Cited for: INTERACTION WITH EGLN1 AND VHL; VARIANT ECYT4 LEU-534; CHARACTERIZATION OF VARIANTS ECYT4 LEU-534; VAL-535 AND ARG-537;

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.