UniProtKB/Swiss-Prot Q99814: Variant p.Gly537Trp

Endothelial PAS domain-containing protein 1
Gene: EPAS1
Chromosomal location: 2p16-p21
Variant information

Variant position:  537
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 Glycine (G) to Tryptophan (W) at position 537 (G537W, p.Gly537Trp).
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 glycine (G) to large size and aromatic (W)
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

Involvement in disease:  Erythrocytosis, familial, 4 (ECYT4) [MIM:611783]: An autosomal dominant disorder characterized by increased serum red blood cell mass, elevated serum hemoglobin and hematocrit, and normal platelet and leukocyte counts. 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; gain of function; affects hydroxylation.
Any additional useful information about the variant.



Sequence information

Variant position:  537
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:   TQTDFNELDLETLAPYIPMD  G EDFQLSPICPEERLLAENPQ
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                         TQTDFNELDLETLAPYIPMDGEDFQLSPICPEERLLAENPQ

Mouse                         TQTDFSELDLETLAPYIPMDGEDFQLSPICPEEPLMPESPQ

Rat                           TQTDFNELDLETLAPYIPMDGEDFQLSPICPEEPLVPESPQ

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

A gain-of-function mutation in the HIF2A gene in familial erythrocytosis.
Percy M.J.; Furlow P.W.; Lucas G.S.; Li X.; Lappin T.R.; McMullin M.F.; Lee F.S.;
N. Engl. J. Med. 358:162-168(2008)
Cited for: VARIANT ECYT4 TRP-537; IDENTIFICATION BY MASS SPECTROMETRY; CHARACTERIZATION OF VARIANT ECYT4 TRP-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.