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UniProtKB/Swiss-Prot P55072: Variant p.Leu198Trp

Transitional endoplasmic reticulum ATPase
Gene: VCP
Variant information

Variant position:  198
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 implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  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:  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:  -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:  In IBMPFD1; increased ATPase activity; impaired autophagic function.
Any additional useful information about the variant.



Sequence information

Variant position:  198
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  806
The length of the canonical sequence.

Location on the sequence:   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: 
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:  
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
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.