VariO protein type annotation examples

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Examples of annotation of protein type variation using the Variation Ontology VariO.

Examples are discussed in Vihinen, M., in press. Types and effects of protein variations

The root terms for these examples are (hovering over the terms will show you the definition of the term):

VariO:0002 variation affecting protein

VariO:0012 protein variation type

VariO:0325 protein variation classification

VariO:0014 amino acid deletion

VariO:0017 amphigoric amino acid deletion

VariO:0015 protein truncation

NP_001121371.1:p.Arg718*
A variation in the CLCN5 gene coding for the ClC-5 chloride:proton transporter causing Dent's disease. A C-terminal truncation lacking 28 residues from the carboxy terminus with enhanced protease susceptibility of both the cytosolic C-terminal and the membrane domain, with direct evidence of misfolding.
PUBMED

VariO:0016 sequence retaining amino acid deletion

NP_000052.1:p.Gln260_Glu280del
In X-linked agammaglobulinemia (XLA) patients, coding exon 8 in the BTK gene was skipped, causing in-frame splicing of exon 7 to exon 9, and deletion of 63 nucleotides. The resulting shortened mRNA translated into a truncated protein with a 21 amino acid deletion (residues 260-280) within the SH3 domain and the loop joining SH3 and SH2 of the BTK protein.
PUBMED

VariO:0022 amino acid indel

NP_000052.1:p.Gln151Alafs*43
A variation in the BTK gene coding for Bruton tyrosine kinase causing X-linked agammaglobulinemia. A single base insertion to the BTK gene region encoding the pleckstrin homology (PH) domain changes the protein sequence at the deletion/insertion site at position 151.
PUBMED

VariO:0023 amphigoric amino acid indel

NP_000052.1:p.Gln151Alafs*43
A variation in the BTK gene coding for Bruton tyrosine kinase. A single base insertion to the BTK gene region encoding the pleckstrin homology (PH) domain changes the protein sequence from the deletion/insertion site at position 151 and creates a new premature stop codon which ends the protein at position 43 (counting from the insertion/deletion position).
PUBMED

VariO:0029 sequence retaining amino acid indel

NP_000479.1:p.Glu241_Lys242delinsValLysValLysValAsnThrArgThrSer
An eight-amino acid sequence retaining amino acid indel in SERPINC1 is a complex variant that consists of a two-amino acid deletion, a seven-residue inserted repeat and a three-amino acid insertion. It causes type II antithrombin deficiency due to missing serine protease inhibitory activity.
PUBMED

VariO:0018 amino acid insertion

NP_000052.1:p.Ser604_Glu605insAspSer
A variation in the BTK gene coding for Bruton tyrosine kinase. Duplication of 6 nucleotides causes insertion of two amino acids between positions 604-605.
PUBMED

VariO:0020 sequence retaining amino acid insertion

VariO:0021 amino acid substitution

NP_000052.1:p.Arg525Gln
A variation in the BTK gene coding for Bruton tyrosine kinase substituting one amino acid (R525) by another one (Q).
PUBMED

VariO:0240 missing protein

NP_000368.1:p.Glu31Lys; NP_000368.1:p.Arg41*
Variations in the WAS gene coding for the Wiskott-Aldrich Syndrome Protein (WASP) cause the Wiskott-Aldrich syndrome, an X-linked recessive immune deficiency disorder. Because of a premature stop codon (NP_000368.1:p.Arg41*) no protein is produced.
PUBMED

VariO:0323 protein variation origin

VariO:0013 protein variation of genetic origin

NP_000052.1:p.Arg525Gln
Genetic origin of a variation in the BTK gene coding for Bruton tyrosine kinase.
PUBMED

VariO:0024 variation emerging at protein level

BTK (auto)phosphorylation at Tyr551.
PUBMED

VariO:0246 artificial protein variation

NEMO is a scaffolding protein that, together with the catalytic subunits IKKα and IKKβ, plays an essential role in the formation of the IKK complex and in the activation of the canonical NF-κβ pathway. A homodimeric coiled-coil adapter sequence stabilizes the minimal IKK=-binding domeain NEMO(44-111). The engineered constructs incorporating the ccoiled coil at the N-terminus, C-terminus, or both ends fo NEMO(44-111) present high thermal stability and cooperative melting and, most important, restore IKKβ binding affinity.
PUBMED