UniProtKB/Swiss-Prot P35637: Variant p.Arg216Cys

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

Variant position:  216
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 216 (R216C, p.Arg216Cys).
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:  Tremor, hereditary essential 4 (ETM4) [MIM:614782]: A common movement disorder mainly characterized by postural tremor of the arms. Head, legs, trunk, voice, jaw, and facial muscles also may be involved. The condition can be aggravated by emotions, hunger, fatigue and temperature extremes, and may cause a functional disability or even incapacitation. Inheritance is autosomal dominant. 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.

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 and ETM4.
Any additional useful information about the variant.



Sequence information

Variant position:  216
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:   NQDQSGGGGSGGYGQQDRGG  R GRGGSGGGGGGGGGGYNRSS
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                         NQDQSGGGGSG-GYGQQDRGGRGRGGSGGGGGGGGGGYNRSS

Mouse                         NQDQSGGGGGGYGGGQQDRGGRGRGG--------GGGYNRS

Bovine                        NQDQSG----GYGGGQQDRGGRGRGG--------GGGYNRS

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 166 – 267 Gly-rich
Modified residue 221 – 221 Phosphoserine


Literature citations

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;

Exome sequencing identifies fus mutations as a cause of essential tremor.
Merner N.D.; Girard S.L.; Catoire H.; Bourassa C.V.; Belzil V.V.; Riviere J.B.; Hince P.; Levert A.; Dionne-Laporte A.; Spiegelman D.; Noreau A.; Diab S.; Szuto A.; Fournier H.; Raelson J.; Belouchi M.; Panisset M.; Cossette P.; Dupre N.; Bernard G.; Chouinard S.; Dion P.A.; Rouleau G.A.;
Am. J. Hum. Genet. 91:313-319(2012)
Cited for: VARIANTS ETM4 CYS-216 AND LEU-431;

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.