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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P55072: Variant p.Leu198Trp

Transitional endoplasmic reticulum ATPase
Gene: VCP
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Variant information Variant position: help 198 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 Leucine (L) to Tryptophan (W) at position 198 (L198W, p.Leu198Trp). 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 medium size and hydrophobic (L) to large size and aromatic (W) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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
Variant description: help In IBMPFD1; increased ATPase activity; impaired autophagic function. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 198 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 806 The length of the canonical sequence.
Location on the sequence: help PDTVIHCEGEPIKREDEEES L NEVGYDDIGGCRKQLAQIKE 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                         PDTVIHCEGEPIKREDEEESLNEVGYDDIGGCRKQLAQIKE

Mouse                         PDTVIHCEGEPIKREDEEESLNEVGYDDIGGCRKQLAQIKE

Rat                           PDTVIHCEGEPIKREDEEESLNEVGYDDIGGCRKQLAQIKE

Pig                           PDTVIHCEGEPIKREDEEESLNEVGYDDIGGCRKQLAQIKE

Bovine                        PDTVIHCEGEPIKREDEEESLNEVGYDDIGGCRKQLAQIKE

Xenopus laevis                PDTVIHCEGEPIKREDEEESLNEVGYDDIGGCRKQLAQIKE

Xenopus tropicalis            PDTVIHCEGEPIKREDEEESLNEVGYDDIGGCRKQLAQIKE

Zebrafish                     PDTVIHCEGEPIKREDEEESLNEVGYDDIGGVRKQLAQIKE

Drosophila                    PETVIFCDGDPIKREEEEESLNAVGYDDIGGCRKQLAQIKE
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 2 – 806 Transitional endoplasmic reticulum ATPase
Mutagenesis 179 – 179 D -> R. No effect on binding to DERL1.
Mutagenesis 183 – 183 H -> W. Severely reduced binding to DERL1.
Beta strand 198 – 200



Literature citations
Novel VCP mutations in inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia.
Watts G.D.; Thomasova D.; Ramdeen S.K.; Fulchiero E.C.; Mehta S.G.; Drachman D.A.; Weihl C.C.; Jamrozik Z.; Kwiecinski H.; Kaminska A.; Kimonis V.E.;
Clin. Genet. 72:420-426(2007)
Cited for: VARIANTS IBMPFD1 TRP-198 AND HIS-387; Two Australian families with inclusion-body myopathy, Paget's disease of bone and frontotemporal dementia: novel clinical and genetic findings.
Kumar K.R.; Needham M.; Mina K.; Davis M.; Brewer J.; Staples C.; Ng K.; Sue C.M.; Mastaglia F.L.;
Neuromuscul. Disord. 20:330-334(2010)
Cited for: VARIANTS IBMPFD1 LEU-155 AND TRP-198; Rare Manifestation of a c.290 C>T, p.Gly97Glu VCP Mutation.
Jerath N.U.; Crockett C.D.; Moore S.A.; Shy M.E.; Weihl C.C.; Chou T.F.; Grider T.; Gonzalez M.A.; Zuchner S.; Swenson A.;
Case Rep. Genet. 2015:239167-239167(2015)
Cited for: VARIANT CMT2Y GLU-97; CHARACTERIZATION OF VARIANT CMT2Y GLU-97; CHARACTERIZATION OF VARIANTS IBMPFD1 HIS-155; TRP-198 AND GLU-232; VCP/p97 cooperates with YOD1, UBXD1 and PLAA to drive clearance of ruptured lysosomes by autophagy.
Papadopoulos C.; Kirchner P.; Bug M.; Grum D.; Koerver L.; Schulze N.; Poehler R.; Dressler A.; Fengler S.; Arhzaouy K.; Lux V.; Ehrmann M.; Weihl C.C.; Meyer H.;
EMBO J. 36:135-150(2017)
Cited for: FUNCTION; INTERACTION WITH PLAA; UBXN6 AND YOD1; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS IBMPFD1 HIS-155; TRP-198 AND GLU-232; MUTAGENESIS OF GLU-578;
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.