Why is a gene is missing from TreeFam, even if the protein is present in the proteome used to build TreeFam?

This can have two reasons, a biological and a technical.

The biological reason are orphan genes (1). Orphan genes might arise from duplication and rearrangement processes followed by fast divergence. E.g. a gene was duplicated in the human lineage and one ifs copies evolved by acquiring mutations. It has become too dissimilar to be assigned to any TreeFam family and has no homologs in other species.

A technical explanation is that to build a family at least three genes are required. The gene you are looking for might be a result of a very recent duplication and forms a group with one other gene only.

  1. Tautz D, Domazet-Lošo T (2011) The evolutionary origin of orphan genes. NATURE REVIEWS| GENETICS 12: 692–702. doi:10.1038/nrg3053.