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Seventeen years after the sequencing of the human genome, the human proteome is still under revision. We have carried out an in-depth investigation on the genes classified as coding by one or more sets of manual curators and not coding by others. Data from large-scale genetic variation analyses suggests that most are not under protein-like purifying selection and so are unlikely to code for functional proteins. A further genes annotated as coding in all three reference sets have characteristics that are typical of non-coding genes or pseudogenes.

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