UniProtKB/Swiss-Prot P35637: Variant p.Arg521Cys

RNA-binding protein FUS
Gene: FUS
Chromosomal location: 16p11.2
Variant information

Variant position:  521
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 Arginine (R) to Cysteine (C) at position 521 (R521C, p.Arg521Cys).
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 large size and basic (R) to medium size and polar (C)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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:  Amyotrophic lateral sclerosis 6 (ALS6) [MIM:608030]: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. 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 ALS6; results in aberrant trafficking and cytoplasmic retention of the protein.
Any additional useful information about the variant.



Sequence information

Variant position:  521
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  526
The length of the canonical sequence.

Location on the sequence:   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: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         GDRGGFGPGKMDSRGEHRQDRRERPY

Mouse                         GDRGGFGPGKMDSRGEHRQDRRERPY

Bovine                        GDRGGFGPGKMDSRGEHRQDRRERPY

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 – 526 RNA-binding protein FUS
Compositional bias 371 – 526 Arg/Gly-rich
Modified residue 503 – 503 Asymmetric dimethylarginine
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;

Mutations of FUS gene in sporadic amyotrophic lateral sclerosis.
Corrado L.; Del Bo R.; Castellotti B.; Ratti A.; Cereda C.; Penco S.; Soraru G.; Carlomagno Y.; Ghezzi S.; Pensato V.; Colombrita C.; Gagliardi S.; Cozzi L.; Orsetti V.; Mancuso M.; Siciliano G.; Mazzini L.; Comi G.P.; Gellera C.; Ceroni M.; D'Alfonso S.; Silani V.;
J. Med. Genet. 47:190-194(2010)
Cited for: VARIANTS ALS6 SER-191; CYS-216; VAL-225; CYS-230; CYS-234; ASP-507 AND CYS-521;

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.