# 1. Gene Aliases

Curators will manually extract data from “Aliases for xx Gene” section of the GeneCards database, i.e., https://www.genecards.org/cgi-bin/carddisp.pl?gene=HAVCR1.

# 2. Association with Toxicity and/or Disease at a Transcriptional Level

Curators will manual exact data from publications. Note that only include publications related to transcriptional level associations. In vitro models can be used as second tier evidence as long as the cells used are primary cells from rat. We do not regard mutagenicity as an adverse effect unless the study is focusing on model of action or association mechanisms. Studies that show the gene of interest association with disease or toxicity using IHC or ELISA (or other protein assays) should not be included here (Purely on mRNA).

# 3. Summary of Protein Family and Structure

Curators will need to provide basic information about the protein, including the AA length, protein domains, and extract information on how domains are related to the protein function. Curators can find relate information under “GeneName INFORMATION” section and “PROTEIN FUNCTION” section of HPA (i.e, https://www.proteinatlas.org/ENSG00000113249-HAVCR1), “Proteins for Gene” section of Genecards (i.e., https://www.genecards.org/cgi-bin/carddisp.pl?gene=HAVCR1) and “Function” section from Uniprot by the protein, i.e.,: https://www.uniprot.org/uniprotkb/Q96D42/entry). Relationship of the protein domains with the protein functions could also be extracted based on publications.

# 6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

## Pathways:

BZ: Curators can find related info in the Genecards database-> “Pathways & Interactions for Gene” section. When there are too many pathways, use “Reactome” pathways only.

# 9. Mechanistic Information

(Why Does Expression Change with Toxicity and/or Disease?) – Curator will manually extract info for this section based on publications (mainly from review papers). This section should be written in a narrative style. If necessary, results from several publications should be summarized.

# 10. Upstream Regulators

BZ: We will do manual curation of this section for now, but we can consider automate this in the future. Curators will “Search” the gene name under SCREEN Registry v3 (https://screen.encodeproject.org/, SCREEN is a web interface for searching and visualizing the Registry of candidate cis-Regulatory Elements (cCREs) derived from ENCODE data) -> Search Human (and then search Mouse)->search for relevant tissue under “Biosamples”, pick a biosample that is derived from tissue of interest-> select “Table View” and select one of the “accession” ->select “TF and His-mod Intersection” to find TFs that bind this cCRE (add “factor”s that have the most # of experiments that support TF binding.

# 12. Role of Gene in Other Tissues

BZ: Curators will extract data for this section based on relevant publications.