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UniProtKB/Swiss-Prot P49447: Variant p.Gly88Arg

Cytochrome b561
Gene: CYB561
Variant information

Variant position:  88
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 Glycine (G) to Arginine (R) at position 88 (G88R, p.Gly88Arg).
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 basic (R)
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:  Orthostatic hypotension 2 (ORTHYP2) [MIM:618182]: An autosomal recessive disorder characterized by severe orthostatic hypotension apparent from infancy or early childhood, low plasma and urinary levels of norepinephrine and epinephrine, and episodic hypoglycemia. Some patients may also have renal dysfunction and reduced life expectancy. Orthostatic hypotension, also known as postural hypotension, is a finding defined as a 20-mm Hg decrease in systolic pressure or a 10-mm Hg decrease in diastolic pressure occurring 3 minutes after a person has risen from supine to standing. Symptoms include dizziness, blurred vision, and sometimes syncope. {ECO:0000269|PubMed:29343526}. 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 ORTHYP2.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  88
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  251
The length of the canonical sequence.

Location on the sequence:   ALLVYRVFRNEAKRTTKVLH  G LLHIFALVIALVGLVAVFDY
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                         ALLVYRVFRNEAKRTTKVLHGLLHIFALVIALVGLVAVFDY

Mouse                         ALLVYRVFRREAKRTTKILHGLLHVFAFIIALVGLVAVFDY

Pig                           ALLVYRVFRNEAKRTTKILHGLLHVLAFVIALVGLVAVFDY

Bovine                        ALLVYRVFRNEAKRTTKVLHGLLHVFAFVIALVGLVAVFEH

Sheep                         ALLVYRVFRNEAKRTTKVLHGLLHVFAFVIALVGLVAVFEH

Xenopus laevis                ALLVYRVFRHETKRSTKILHGVLHIMALVISLVGVIAVFQY

Caenorhabditis elegans        ALLVYRVFRNERKKFSKTLHVILHSCVLVFMLMALKAVFDY

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 – 251 Cytochrome b561
Transmembrane 86 – 106 Helical
Domain 19 – 220 Cytochrome b561
Metal binding 87 – 87 Iron (heme axial ligand)
Metal binding 91 – 91 Iron (heme axial ligand)


Literature citations

Mutations in CYB561 causing a novel orthostatic hypotension syndrome.
van den Berg M.P.; Almomani R.; Biaggioni I.; van Faassen M.; van der Harst P.; Sillje H.H.W.; Mateo Leach I.; Hemmelder M.H.; Navis G.; Luijckx G.J.; de Brouwer A.P.M.; Venselaar H.; Verbeek M.M.; van der Zwaag P.A.; Jongbloed J.D.H.; van Tintelen J.P.; Wevers R.A.; Kema I.P.;
Circ. Res. 122:846-854(2018)
Cited for: INVOLVEMENT IN ORTHYP2; VARIANTS ORTHYP2 44-TRP--GLN-251 DEL AND ARG-88; 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.