Q (sonnet-5.5): <conversation_so_far>
<user>
I'm importing a study into my own cBioPortal instance and the validator says some genes are not known to cBioPortal. What does that mean?
</user>

<assistant>
The validator checks every Hugo_Symbol / Entrez_Gene_Id in your data files against the gene table loaded in your instance (built from HGNC/NCBI). "Gene not known" means the symbol or ID isn't in that table — usually an outdated symbol, an alias, or a typo.
</assistant>
</conversation_so_far>

Continue this conversation: reply to the user's new message.

<user>
what if the genes, like AC002511.1 or LOC100506271, just aren't in HGNC or NCBI at all?
</user>

═ answer (success)
Then cBioPortal can't load them as they stand. This is general importer knowledge, not something I looked up in the database, so check it against the docs for your version.

**Why it happens**
- **`AC002511.1`** is a clone-based name from Ensembl/GENCODE, typically for lncRNAs or unannotated transcripts. NCBI and HGNC don't assign these names, so they never appear in the gene table.
- **`LOC100506271`** is an NCBI placeholder for a computationally predicted gene with no official symbol. These are often withdrawn or replaced in later NCBI releases, so the gene table your instance was built from may not include them.

**What the importer does**
- Genes are matched to the gene table by Entrez ID or symbol. If neither matches, the importer can't attach the row to a gene, so it skips the row and logs a warning. The rest of the study still loads.
- Check whether your validator output lists these as warnings or as errors. That determines whether the import is blocked.

**Your options**
1. **Drop them.** This is usually fine for lncRNA and clone-based names, which have no clinical or functional annotation in cBioPortal anyway. Filter them out of the mutation, expression and CNA files before import. Then the validator output stays clean and you know exactly what was excluded.
2. **Map them to a known gene.** Look up the `LOC` ID on NCBI Gene, including its history. If it was merged or renamed, use the current Entrez ID and symbol. For Ensembl-style names, map through an Ensembl-to-HGNC/Entrez table such as BioMart. If there is no mapping, it isn't recoverable this way.
3. **Update your gene table.** If the genes exist in a newer NCBI release than your instance uses, reloading the gene reference data (the importer's gene-info step) may resolve them. The exact procedure depends on your version, so check the cBioPortal docs on updating gene definitions.
4. **Add them as custom genes.** This is possible in principle, but genes with no Entrez ID are awkward. It is rarely worth it for a few non-coding features, and I'm not confident of the exact procedure. Check the docs or ask on the cBioPortal community forums before trying it.

For a handful of unrecognized clone or `LOC` names, option 1 is the usual choice. If the list is long, it's worth checking whether the file was annotated against a different genome build or annotation release than your instance.

If you paste the validator lines for these genes, I can help work out whether they're warnings or blockers.