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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O95292: Variant p.Pro56Ser

Vesicle-associated membrane protein-associated protein B/C
Gene: VAPB
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Variant information Variant position: help 56 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 Proline (P) to Serine (S) at position 56 (P56S, p.Pro56Ser). 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 (P) to small size and polar (S) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -1 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 ALS8 and SMAPAD; it forms insoluble cytosolic aggregates; cannot activate the UPR pathway; affects interaction with RMDN3; affects cellular calcium homeostasis; induces mislocalization to the non-ER compartments; enhances homodimerization. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 56 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 243 The length of the canonical sequence.
Location on the sequence: help TDRNVCFKVKTTAPRRYCVR P NSGIIDAGASINVSVMLQPF 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                         TDRNVCFKVKTTAPRRYCVRPNSGIIDAGASINVSVMLQPF

Mouse                         TDRNVCFKVKTTVPRRYCVRPNSGVIDAGASLNVSVMLQPF

Rat                           TDRNVCFKVKTTAPRRYCVRPNSGVIDAGASLNVSVMLQPF

Pig                           TDRNVCFKVKTTAPRRYCVRPNSGIIDAGASINVSVMLQPF

Bovine                        TDRNVCFKVKTTAPRRYCVRPNSGIIDAGASINVSVMLQPF
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 – 243 Vesicle-associated membrane protein-associated protein B/C
Topological domain 2 – 222 Cytoplasmic
Domain 7 – 124 MSP
Site 43 – 43 Involved in binding the phosphorylated serine of the phospho-FFAT motif
Mutagenesis 43 – 43 K -> L. Does not affect interaction with the conventional FFAT motif of OSBPL1A. Impairs the interactions of the MSP domain with the phosphorylated FFAT motif of STARD3.
Beta strand 52 – 61



Literature citations
Characterization of amyotrophic lateral sclerosis-linked P56S mutation of vesicle-associated membrane protein-associated protein B (VAPB/ALS8).
Kanekura K.; Nishimoto I.; Aiso S.; Matsuoka M.;
J. Biol. Chem. 281:30223-30233(2006)
Cited for: FUNCTION IN ENDOPLASMIC RETICULUM UNFOLDED PROTEIN RESPONSE; CHARACTERIZATION OF VARIANT ALS8 SER-56; Characterization of the properties of a novel mutation in VAPB in familial amyotrophic lateral sclerosis.
Chen H.J.; Anagnostou G.; Chai A.; Withers J.; Morris A.; Adhikaree J.; Pennetta G.; de Belleroche J.S.;
J. Biol. Chem. 285:40266-40281(2010)
Cited for: FUNCTION IN ENDOPLASMIC RETICULUM UNFOLDED PROTEIN RESPONSE; VARIANT ALS8 ILE-46; CHARACTERIZATION OF VARIANTS ALS8 ILE-46 AND SER-56; SUBUNIT; INTERACTION WITH VAPA; VAMP1 AND VAMP2; VAPB interacts with the mitochondrial protein PTPIP51 to regulate calcium homeostasis.
De Vos K.J.; Morotz G.M.; Stoica R.; Tudor E.L.; Lau K.F.; Ackerley S.; Warley A.; Shaw C.E.; Miller C.C.;
Hum. Mol. Genet. 21:1299-1311(2012)
Cited for: FUNCTION IN CELLULAR CALCIUM HOMEOSTASIS REGULATION; SUBCELLULAR LOCATION; INTERACTION WITH RMDN3; CHARACTERIZATION OF VARIANT ALS8 SER-56; A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis.
Nishimura A.L.; Mitne-Neto M.; Silva H.C.; Richieri-Costa A.; Middleton S.; Cascio D.; Kok F.; Oliveira J.R.; Gillingwater T.; Webb J.; Skehel P.; Zatz M.;
Am. J. Hum. Genet. 75:822-831(2004)
Cited for: VARIANT ALS8 SER-56; VARIANT SMAPAD SER-56;
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.