UniProtKB/Swiss-Prot Q8NFG4: Variant p.Lys508Arg

Folliculin
Gene: FLCN
Chromosomal location: 17p11.2
Variant information

Variant position:  508
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 Lysine (K) to Arginine (R) at position 508 (K508R, p.Lys508Arg).
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 large size and basic.
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 BHD; does not impair protein stability, growth suppression activity or intracellular localization of folliculin.
Any additional useful information about the variant.



Sequence information

Variant position:  508
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  579
The length of the canonical sequence.

Location on the sequence:   AALTNQNLSVDVVDQCLVCL  K EEWMNKVKVLFKFTKVDSRP
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                         AALTNQNLSVDVVDQCLVCLKEEWMNKVKVLFKFTKVDSRP

Mouse                         AALTNQNLSVDVVDQCLICLKEEWMNKVKVLFKFTKVDSRP

Rat                           AALTNQNLSVDVVDQCLVCLKEEWMNKVKVLFKFTKVDSRP

Bovine                        AALTNQNLSVDVVDQCLVCLKEEWMNKVKVLFKFTKVDSRP

Xenopus tropicalis            AALSNENLSMDVVDQCLICLKEEWMNKVKVLFKFTKVDSRP

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 – 579 Folliculin
Alternative sequence 198 – 579 Missing. In isoform 3.
Alternative sequence 343 – 579 Missing. In isoform 2.
Helix 497 – 521


Literature citations

BHD mutations, clinical and molecular genetic investigations of Birt-Hogg-Dube syndrome: a new series of 50 families and a review of published reports.
Toro J.R.; Wei M.H.; Glenn G.M.; Weinreich M.; Toure O.; Vocke C.; Turner M.; Choyke P.; Merino M.J.; Pinto P.A.; Steinberg S.M.; Schmidt L.S.; Linehan W.M.;
J. Med. Genet. 45:321-331(2008)
Cited for: VARIANT BHD ARG-508;

Birt Hogg-Dube syndrome-associated FLCN mutations disrupt protein stability.
Nahorski M.S.; Reiman A.; Lim D.H.; Nookala R.K.; Seabra L.; Lu X.; Fenton J.; Boora U.; Nordenskjold M.; Latif F.; Hurst L.D.; Maher E.R.;
Hum. Mutat. 32:921-929(2011)
Cited for: VARIANT CYS-362; CHARACTERIZATION OF VARIANTS PHE-157 DEL; CYS-239; CYS-362 AND ARG-508;

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.