UniProtKB/Swiss-Prot P60709: Variant p.Arg183Trp

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 183 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LP/P [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.] 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: From Arginine (R) to Tryptophan (W) at position 183 (R183W, p.Arg183Trp). 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 large size and aromatic (W) 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
Variant description: In DDS1; likely pathogenic; results in reduced actin polymerization rate and increased depolymerization; results in higher ATP hydrolysis compared to the wild type; does not affect thermal stability; modifies cell response to latrunculin A. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs104894003 [ dbSNP | Ensembl ]

Sequence information

Variant position: 183 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 375 The length of the canonical sequence.
Location on the sequence: VPIYEGYALPHAILRLDLAG R DLTDYLMKILTERGYSFTTT 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.
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.

Type	Positions	Description
Chain	1 – 375	Actin, cytoplasmic 1
Chain	2 – 375	Actin, cytoplasmic 1, N-terminally processed
Helix	182 – 193

Literature citations

A mutation of beta -actin that alters depolymerization dynamics is associated with autosomal dominant developmental malformations, deafness, and dystonia.
Procaccio V.; Salazar G.; Ono S.; Styers M.L.; Gearing M.; Davila A.; Jimenez R.; Juncos J.; Gutekunst C.-A.; Meroni G.; Fontanella B.; Sontag E.; Sontag J.-M.; Faundez V.; Wainer B.H.;
Am. J. Hum. Genet. 78:947-960(2006)
Cited for: VARIANT DDS1 TRP-183; CHARACTERIZATION OF VARIANT DDS1 TRP-183; Molecular mechanisms of disease-related human beta-actin mutations p.R183W and p.E364K.
Hundt N.; Preller M.; Swolski O.; Ang A.M.; Mannherz H.G.; Manstein D.J.; Mueller M.;
FEBS J. 281:5279-5291(2014)
Cited for: CHARACTERIZATION OF VARIANT DDS1 TRP-183; CHARACTERIZATION OF VARIANT THC8 LYS-364; CATALYTIC ACTIVITY; FUNCTION; INTERACTION WITH PFN1; Pathogenic Variant in ACTB, p.Arg183Trp, Causes Juvenile-Onset Dystonia, Hearing Loss, and Developmental Delay without Midline Malformation.
Conboy E.; Vairo F.; Waggoner D.; Ober C.; Das S.; Dhamija R.; Klee E.W.; Pichurin P.;
Case Rep. Genet. 2017:9184265-9184265(2017)
Cited for: VARIANT DDS1 TRP-183; Dystonia-deafness syndrome caused by ACTB p.Arg183Trp heterozygosity shows striatal dopaminergic dysfunction and response to pallidal stimulation.
Skogseid I.M.; Roesby O.; Konglund A.; Connelly J.P.; Nedregaard B.; Jablonski G.E.; Kvernmo N.; Stray-Pedersen A.; Glover J.C.;
J. Neurodev. Disord. 10:17-17(2018)
Cited for: VARIANT DDS1 TRP-183; Dystonia-Deafness Syndrome: ACTB Pathogenic Variant in an Argentinean Family.
Zavala L.; Ziegler G.; Moron D.G.; Garretto N.;
Mov. Disord. Clin. Pract. 9:122-124(2022)
Cited for: VARIANT DDS1 TRP-183;