/ensembl_database

name: ensembl-database
description: >
  Query the Ensembl database to resolve gene, transcript, and protein IDs,
  fetch genomic or protein sequences, retrieve gene structures (exons), and
  get variant consequence and effect predictions (VEP). Use this skill as a
  primary ID translator, genomic sequence database and variant effect prediction
  tool.

Ensembl Database: ID Mapping and Genomic Features

Prerequisites

1. **`uv`**: Read the `uv` skill and follow its Setup instructions to ensure `uv` is installed and on PATH. 2. **User Notification**: If .licenses/ensembl_database_LICENSE.txt does not already exist in the workspace root directory then (1) prominently notify the user to check the terms at https://useast.ensembl.org/index.html and https://github.com/Ensembl/ensembl-rest/wiki, then (2) create the file recording the notification text and timestamp.

Overview

The Ensembl database is a resource for genome annotation. This skill allows you to interact with the Ensembl REST API to resolve ambiguous symbols, cross-reference IDs (RefSeq, HGNC, UniProt, ENSG), fetch raw sequences, and retrieve detailed transcript structures.

**Key Concepts:**

• **ENSG (Gene):** Stable identifier for a human gene. Other species will have

different three-letter species codes.

• **ENST (Transcript):** Stable identifier for a transcript (splicing

isoform).

• **ENSP (Protein):** Stable identifier for a translated protein.
• **MANE Select:** The consensus primary transcript agreed upon by Ensembl and

NCBI.

• **Canonical:** Ensembl's representative transcript (used if MANE is not

available or non-human).

Core Rules

• **Use the Wrapper**: ALWAYS execute the provided helper scripts to query the

database rather than accessing the database directly. The scripts automatically enforce the required rate limit gracefully.

• **Default Species:** If the species is absent or ambiguous in the prompt,

default to `"human"`. You MUST explicitly flag this default to the user to ensure they are aware.

• **Primary Transcripts:** When listing transcripts for a gene, only return

the MANE Select transcript (for human) or the Canonical transcript (for others) unless the user explicitly asks for all alternative isoforms. You MUST flag to the user when multiple transcripts are available and you are defaulting to the primary one.

• **Assembly Handling:** The default assembly is GRCh38. For GRCh37 requests,

you MUST use the `--assembly GRCh37` flag. You MUST explicitly flag to the user when a non-default assembly is being used.

• **Output Location:** The script writes full JSON/FASTA output to temporary

files in `/tmp` by default, or to a user-specified file using the `--output` flag. It also prints a concise summary to stdout.

• **Notification**: If this skill is used, ensure this is mentioned in the

output.

Available Commands

**1. Resolve Gene ID** — Resolve a symbol, alias, or RefSeq ID to ENSG ID(s). Automatically falls back to resolving synonyms if primary symbol is not found.

uv run scripts/ensembl_api.py resolve-gene TP53 --species human --output tp53.json
uv run scripts/ensembl_api.py resolve-gene PCL2 --output pcl2.json # Falls back to synonym resolution

**2. Map ID to External Database** — Cross-reference an Ensembl ID to UniProt, HGNC, RefSeq, etc.

uv run scripts/ensembl_api.py map-id ENSG00000141510 --external-db UniProt --output uniprot_map.json
uv run scripts/ensembl_api.py map-id ENST00000269305 --external-db RefSeq_mRNA --output refseq_map.json

**3. Get Genomic Sequence** — Fetch raw DNA for a coordinate window. Supports GRCh37 via `--assembly GRCh37`.

uv run scripts/ensembl_api.py get-sequence 17:7661779-7687550 --species human --output seq.txt
uv run scripts/ensembl_api.py get-sequence chr9:21971100-21971200 --assembly GRCh37 --output seq_grch37.txt

**4. Gene Summary** — High-level metadata: symbol, biotype, description, chromosomal location.

uv run scripts/ensembl_api.py gene-summary ENSG00000141510 --output gene_summary.json

**5. List Transcripts** — All transcripts for a gene, with optional `--only-mane` or `--only-canonical` filters. Output includes Transcript Support Level (TSL).

uv run scripts/ensembl_api.py transcripts ENSG00000141510 --only-mane --output transcripts_mane.json
uv run scripts/ensembl_api.py transcripts ENSG00000141510 --only-canonical --output transcripts_canonical.json
uv run scripts/ensembl_api.py transcripts ENSG00000141510 --output transcripts_all.json

**5b. Canonical TSS** — Get the single coordinate of the Transcription Start Site (TSS) for the canonical transcript of a gene.

> [!NOTE] Unlike the standard `transcripts` command, `canonical-tss` accepts > both symbols (e.g., `TP53`) and Ensembl IDs, and automatically resolves them. > It also does the math for strand orientation (TSS is `Start` for `+` strand > and `End` for `-` strand), outputting the single integer coordinate directly.

uv run scripts/ensembl_api.py canonical-tss TP53 --output tp53_tss.json
uv run scripts/ensembl_api.py canonical-tss ENSG00000141510 --output tss.json

**6. Transcript Structure** — Exon coordinates, CDS boundaries, and computed 5'/3' UTR regions for a transcript.

uv run scripts/ensembl_api.py transcript-structure ENST00000269305 --output structure.json

**7. Protein Info** — ENSP ID and sequence length for a transcript.

uv run scripts/ensembl_api.py protein-info ENST00000269305 --output protein_info.json

**8. Protein Sequence** — Amino acid FASTA for a transcript (ENST) or protein (ENSP) ID.

uv run scripts/ensembl_api.py protein-sequence ENST00000269305 --output protein.fasta
uv run scripts/ensembl_api.py protein-sequence ENSP00000269305 --output protein_ensp.fasta

**9. Variant Consequence (VEP)** — Predict molecular consequences for a genomic v