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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P35637: Variant p.Arg521His

RNA-binding protein FUS
Gene: FUS
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Variant information Variant position: help 521 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance
Residue change: help From Arginine (R) to Histidine (H) at position 521 (R521H, p.Arg521His). 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: help Change from large size and basic (R) to medium size and polar (H) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 0 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: help In ALS6; results in aberrant trafficking and cytoplasmic retention of the protein. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 521 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 526 The length of the canonical sequence.
Location on the sequence: help GDRGGFGPGKMDSRGEHRQD R RERPY 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         GDRGGFGPGKMDSRGEHRQDRRERPY

Mouse                         GDRGGFGPGKMDSRGEHRQDRRERPY

Bovine                        GDRGGFGPGKMDSRGEHRQDRRERPY
Sequence annotation in neighborhood: help 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 – 526 RNA-binding protein FUS
Region 444 – 526 Disordered
Compositional bias 509 – 526 Basic and acidic residues
Modified residue 503 – 503 Asymmetric dimethylarginine; alternate
Modified residue 503 – 503 Omega-N-methylarginine; alternate
Helix 514 – 521



Literature citations
Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis.
Kwiatkowski T.J. Jr.; Bosco D.A.; Leclerc A.L.; Tamrazian E.; Vanderburg C.R.; Russ C.; Davis A.; Gilchrist J.; Kasarskis E.J.; Munsat T.; Valdmanis P.; Rouleau G.A.; Hosler B.A.; Cortelli P.; de Jong P.J.; Yoshinaga Y.; Haines J.L.; Pericak-Vance M.A.; Yan J.; Ticozzi N.; Siddique T.; McKenna-Yasek D.; Sapp P.C.; Horvitz H.R.; Landers J.E.; Brown R.H. Jr.;
Science 323:1205-1208(2009)
Cited for: VARIANTS ALS6 CYS-244; SER-514; CYS-515; LYS-518; CYS-521; GLY-521; HIS-521; GLY-522; SER-524; THR-524 AND LEU-525; VARIANT GLN-517; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANT ALS6 GLY-521; CHARACTERIZATION OF VARIANT GLN-517; Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6.
Vance C.; Rogelj B.; Hortobagyi T.; De Vos K.J.; Nishimura A.L.; Sreedharan J.; Hu X.; Smith B.; Ruddy D.; Wright P.; Ganesalingam J.; Williams K.L.; Tripathi V.; Al-Saraj S.; Al-Chalabi A.; Leigh P.N.; Blair I.P.; Nicholson G.; de Belleroche J.; Gallo J.M.; Miller C.C.; Shaw C.E.;
Science 323:1208-1211(2009)
Cited for: VARIANTS ALS6 GLY-514; CYS-521 AND HIS-521; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS ALS6 CYS-521 AND HIS-521; Genetic contribution of FUS to frontotemporal lobar degeneration.
Van Langenhove T.; van der Zee J.; Sleegers K.; Engelborghs S.; Vandenberghe R.; Gijselinck I.; Van den Broeck M.; Mattheijssens M.; Peeters K.; De Deyn P.P.; Cruts M.; Van Broeckhoven C.;
Neurology 74:366-371(2010)
Cited for: VARIANT ALS6 HIS-521; VARIANT VAL-254; Screening of SOD1, FUS and TARDBP genes in patients with amyotrophic lateral sclerosis in central-southern China.
Hou L.; Jiao B.; Xiao T.; Zhou L.; Zhou Z.; Du J.; Yan X.; Wang J.; Tang B.; Shen L.;
Sci. Rep. 6:32478-32478(2016)
Cited for: VARIANTS ALS6 HIS-521 AND TYR-526 EXT;
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.