UniProtKB/Swiss-Prot Q8NFG4: Variant p.Lys508Arg

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 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 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

Involvement in disease:  Birt-Hogg-Dube syndrome (BHD) [MIM:135150]: A rare autosomal dominant genodermatosis characterized by hair follicle hamartomas (fibrofolliculomas), kidney tumors, and spontaneous pneumothorax. Fibrofolliculomas are part of the triad of Birt-Hogg-Dube syndrome skin lesions that also includes trichodiscomas and acrochordons. Onset of this dermatologic condition is invariably in adulthood. Birt-Hogg-Dube syndrome is associated with a variety of histologic types of renal tumors, including chromophobe renal cell carcinoma (RCC), benign renal oncocytoma, clear-cell RCC and papillary type I RCC. Multiple lipomas, angiolipomas, and parathyroid adenomas are also seen in Birt-Hogg-Dube syndrome patients. {ECO:0000269|PubMed:12204536, ECO:0000269|PubMed:15852235, ECO:0000269|PubMed:18234728, ECO:0000269|PubMed:19785621}. 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 BHD; does not impair protein stability, growth suppression activity or intracellular localization of folliculin.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for 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.

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.






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.

Chain 1 – 579 Folliculin
Domain 493 – 558 dDENN FLCN/SMCR8-type
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)

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.