ensembl-mcp-server

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  <h1>@cyanheads/ensembl-mcp-server</h1>
  <p><b>Look up genes, fetch sequences, predict variant consequences, find orthologs, and retrieve cross-database xrefs from Ensembl REST via MCP. STDIO or Streamable HTTP.</b>
  <div>7 Tools • 4 Resources • 1 Prompt</div>
  </p>
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**Public Hosted Server:** [https://ensembl.caseyjhand.com/mcp](https://ensembl.caseyjhand.com/mcp)

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---

## Overview

Gene, sequence, and variant data for vertebrates and other model organisms from the Ensembl REST API. Look up genes, fetch sequences, predict variant consequences, find orthologs, and cross-reference external databases.

### Tools

| Tool | Description |
|:-----|:------------|
| `ensembl_list_species` | List species supported by Ensembl with display name, common name, assembly, taxon ID, and division |
| `ensembl_lookup_gene` | Resolve a gene by symbol (synonyms and former symbols included) + species or by stable ID to its Ensembl ID, genomic location, biotype, and transcript list |
| `ensembl_get_sequence` | Fetch the DNA, cDNA, CDS, or protein sequence for a gene, transcript, protein, or genomic region |
| `ensembl_query_region` | Find genomic features (genes, transcripts, variants, regulatory elements, exons) overlapping a chromosomal region |
| `ensembl_predict_variant` | Predict functional consequences of a sequence variant using the Ensembl Variant Effect Predictor (VEP) |
| `ensembl_get_homology` | Find orthologs and/or paralogs of a gene across species with percent identity and taxonomy level |
| `ensembl_get_xrefs` | Retrieve cross-database references for a gene — HGNC, UniProt, EntrezGene, OMIM, RefSeq, Reactome, and others |

### Resources

| Resource | Description |
|:---|:---|
| `ensembl://gene/{id}` | Gene record by stable ID (`ENSG…`) — location, biotype, description, and transcript list |
| `ensembl://transcript/{id}` | Transcript record by stable ID (`ENST…`) — parent gene, location, biotype, canonical flag, and length |
| `ensembl://species` | Supported Ensembl species for the endpoint default division (vertebrates on the default endpoint) |
| `ensembl://species/{division}` | Supported species in one division (`EnsemblVertebrates`, `EnsemblPlants`, `EnsemblFungi`, `EnsemblMetazoa`, `EnsemblProtists`) |

The species resources return the first 50 species by internal name; the `ensembl_list_species` tool pages through the rest and filters by name.

### Prompts

| Prompt | Description |
|:---|:---|
| `ensembl_gene_dossier` | Structured workflow for assembling a complete gene profile: symbol → ID + location → sequence → variants → orthologs → xrefs |

## Capability reference

Ensembl's stable-ID endpoints answer a versioned ID (`ENSG00000139618.19`) as not found, so every tool and resource that takes an Ensembl stable ID drops a trailing `.N` from an `ENS…` ID before the request and returns the current version. HGVS input to `ensembl_predict_variant` (`ENST00000380152.8:c.2T>A`) keeps its version, and IDs from other sources (`AT3G52430.1`) are forwarded unchanged.

### `ensembl_list_species` <sub>tool</sub>

- Optional `division` (`EnsemblVertebrates`, `EnsemblPlants`, `EnsemblFungi`, `EnsemblMetazoa`, `EnsemblProtists`; omitted, the endpoint default — vertebrates, ~356 species on GRCh38) and `nameContains`, a substring match against name, display name, and common name
- Returns the internal name every other tool expects (`homo_sapiens`), plus display name, common name, taxon ID, assembly, and division
- Sorted by internal name and paged by `offset` (default `0`) and `max_results` (default `50`, `0` uncapped); `totalCount` reports every match, and `nextOffset` is where the next page starts when more follow

---

### `ensembl_lookup_gene` <sub>tool</sub>

- Exactly one of `symbol` (+ `species`, default `homo_sapiens`), `id`, `ids`, or `symbols` (up to 1,000 submitted items; first 20 distinct trimmed queries processed); `expand_transcripts` (default `false`) adds the transcript list with biotype and canonical flag
- `canonicalTranscript` identifies the canonical transcript without expansion; transcript-ID lookups also return `parentGeneId`. Expanded transcripts include `maneSelect` RefSeq accessions when available (BRCA2: `ENST00000380152.8`, `NM_000059.4`)
- A symbol that is not a current gene name falls back to synonyms and former symbols (`HER2` → `ERBB2`), reported as `matchedAlias`; a name shared by several genes (`MDR1`) returns `ambiguous` with candidates to retry by `id`
- A single lookup returns `gene` (or `ambiguous`); a `batch` returns ordered `succeeded` items carrying the submitted `query`, `failed` items with `query`, `reason` (`not_found`, `ambiguous` with `candidates`, or `unavailable`), `error`, and `recovery`, and `omitted` queries past the processing cap. Omitted queries are never requested or reported as failed; resubmit them separately. Errors: `not_found`, `invalid_species`, `no_input`, `conflicting_input`

---

### `ensembl_get_sequence` <sub>tool</sub>

- A stable ID (`ENSG…`/`ENST…`/`ENSP…`) or a region (`species:chr:start-end`, or `chr:start-end` with `species`; at most 10,000,000 bases); `type` is `genomic` (default), `cdna`, `cds`, or `protein` — `cdna` and `cds` from a transcript ID only, `protein` from a transcript or protein ID; `expand_5prime`/`expand_3prime` add flanking bases
- Regions take a `:1`/`:-1` strand suffix (`1:1000000-1000020:-1` returns the reverse complement); the mitochondrion is `MT` in vertebrates (`mitochondrion_genome` in Drosophila, `MtDNA` in C. elegans), and `M`/`chrM` are rejected as `invalid_region` where they would not resolve to it
- Returns a window set by `offset` (default `0`) and `max_length` (default `10000`, `0` uncapped); `length` is the full sequence length, and `truncated`/`nextOffset` say where to resume
- Errors: `not_found`, `type_mismatch` (also a protein ID asked for `genomic`/`cdna`/`cds`, or a non-coding transcript asked for `protein`/`cds`), `invalid_species`, `missing_species`, `invalid_region` (also an id with a colon that is not a valid region)

---

### `ensembl_query_region` <sub>tool</sub>

- `region` as `species:chr:start-end`, or `chr:start-end` with `species` (at most 5,000,000 bases; reversed coordinates are rejected; mitochondrion naming as in `ensembl_get_sequence`); `feature` defaults to `["gene"]` and also accepts `transcript`, `variation`, `regulatory`, `exon`; optional case-sensitive `biotype` filter (`protein_coding`, `lncRNA`). An empty filtered result suggests removing the filter without inferring the locus is intergenic
- `max_results` caps the list (default `100`, `0` uncapped) while `totalCount` reports the true count; `assemblyName` names the coordinates' assembly, and exon rows carry `parentId` and `rank`. Errors: `invalid_region`, `invalid_species`, `missing_species`

---

### `ensembl_predict_variant` <sub>tool</sub>

- `variant` as HGVS (transcript-relative or genomic), region+allele (`chr:start:end:strand/allele`), or a dbSNP rsID
- Returns the most severe consequence, per-transcript impact (HIGH/MODERATE/LOW/MODIFIER), and colocated known variants with clinical significance. Errors: `invalid_notation`, `not_found`, `invalid_species`
- Requests HGVS, canonical and MANE annotations on every input route. Consequences retain `variantAllele`, optional `canonical`/`maneSelect`, HGVS and available SIFT/PolyPhen prediction-score pairs; records retain `alleleString`
- Colocated `clinicalSignificance` is aggregate, not a classification of the submitted allele. `clinicalSignificanceByAllele` preserves explicit per-allele terms and `clinicalSignificanceReferenceAllele` identifies their reference allele; absent annotations remain omitted
- `max_transcript_consequences` and `max_pubmed_ids_per_variant` (default `10` each, `0` uncapped; `include_all_colocated_pubmed` lifts the PubMed cap) bound the result, while `transcriptConsequencesTotal` and `pubmedTotal` report the full counts

---

### `ensembl_get_homology` <sub>tool</sub>

- Exactly one of `symbol` (+ `spe