@cyanheads/ensembl-mcp-server
Look up genes, fetch sequences, predict variant consequences, find orthologs, and retrieve cross-database xrefs from Ensembl REST via MCP. STDIO or Streamable HTTP.
7 Tools • 4 Resources • 1 Prompt
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**Public Hosted Server:** [https://ensembl.caseyjhand.com/mcp](https://ensembl.caseyjhand.com/mcp)
---
## 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` tool
- 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` tool
- 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` tool
- 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` tool
- `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` tool
- `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` tool
- Exactly one of `symbol` (+ `species`, default `homo_sapiens`) or `id`; `type` is `orthologues` (default), `paralogues`, or `all`; optional `target_species` filter
- A `target_species` outside the comparison Ensembl runs for the source species (a fly gene to `homo_sapiens`) is answered from Ensembl's pan-taxonomic comparison when it holds both species, with a notice saying so
- `max_results` caps the list (default `25`, `0` uncapped) while `totalCount` reports the true count. Errors: `not_found`, `invalid_species` (unknown `species` or `target_species`), `target_not_compared` (a target outside the source species' comparison that the pan-taxonomic comparison cannot answer), `no_input`, `conflicting_input`
- Each row retains optional `targetProteinId` for `ensembl_get_sequence` with `type:"protein"`. Optional `targetSymbol` comes from a lookup of the returned rows' distinct gene IDs, in chunks of at most 1,000, with one five-second budget bounded by the call's remaining deadline and no retries. Missing names or failed lookups retain every primary homolog with a notice; cancellation still aborts
---
### `ensembl_get_xrefs` tool
- `id` (`ENSG…`/`ENST…`/`ENSP…`) required; optional `dbname` filter (e.g. `HGNC`, `Uniprot_gn`, `Uniprot/SWISSPROT` for the reviewed UniProt accession on the translation, `EntrezGene`, `MIM_GENE`, `RefSeq_mRNA`, `Reactome_gene` for gene pathways, `Reactome` for translation pathways, `GO`)
- Default `all_levels:false` queries the requested object's level. Set `all_levels:true` to include a gene's transcript and translation references, independently of `dbname`; for example, gene-level `RefSeq_mRNA` may need this or a transcript ID. Empty lists remain successful with `totalCount:0`. Errors: `not_found`
- Each reference carries how Ensembl assigned it (`infoType`: `DIRECT`, `DEPENDENT`, `PROJECTION`, …; `infoText`: its source, such as `UniProt` or the ortholog a projection came from) and its evidence codes (`linkageTypes`, GO evidence such as `IDA` or `IEA`) when supplied, so `GO` and `Projected GO` rows, and experimental and electronic annotations, stay distinct on both surfaces
---
### `ensembl://gene/{id}` resource
- `id` is a gene stable ID (`ENSG…`); a version suffix is optional and dropped
- Returns location, biotype, description, and transcript list. Errors: `not_found`
---
### `ensembl://transcript/{id}` resource
- `id` is a transcript stable ID (`ENST…`); a version suffix is optional and dropped
- Returns parent gene, location, biotype, canonical flag, and length. Errors: `not_found`
---
### `ensembl://species` resource
- No parameters — covers the endpoint default division (vertebrates, ~356 species on the default GRCh38 endpoint)
- Returns the first 50 species by internal name with `totalCount`, `shown`, and `truncated`; a truncated body's `notice` points to `ensembl_list_species` (`offset`, `max_results`) for the rest
- For a named division, read `ensembl://species/{division}` instead
---
### `ensembl://species/{division}` resource
- `division` required: `EnsemblVertebrates`, `EnsemblPlants`, `EnsemblFungi`, `EnsemblMetazoa`, or `EnsemblProtists`
- Returns that division's first 50 species by internal name — internal name, display name, assembly, taxon ID, and division — with `totalCount`, `shown`, and `truncated`; a truncated body's `notice` points to `ensembl_list_species` (`division`, `offset`, `max_results`) for the rest
---
### `ensembl_gene_dossier` prompt
- Arguments: `gene_symbol` required; `species` optional (default `homo_sapiens`)
- Sequences a 7-step workflow: resolve the gene → fetch the protein sequence → find variants in the locus → predict variant consequences → find model-organism orthologs → get external database IDs → synthesize the dossier
## Features
Built on [`@cyanheads/mcp-ts-core`](https://github.com/cyanheads/mcp-ts-core): stdio and Streamable HTTP transports, pluggable auth (`none` / `jwt` / `oauth`), swappable storage (`in-memory`, `filesystem`, `Supabase`, `Cloudflare KV/R2/D1`), structured logging with optional OpenTelemetry tracing.
Ensembl-specific:
- Keyless REST API — no API key required; Ensembl REST is fully public at 55,000 req/hr
- Retries 429 responses (honoring `Retry-After`) and transient 5xx errors
- Upstream calls time out at 180 s per attempt and 240 s per call, so a stalled Ensembl fails instead of hanging
- Batch lookups use `POST /lookup/id` and `POST /lookup/symbol/{species}` to avoid N+1 round trips
- GRCh37 legacy support via `ENSEMBL_BASE_URL` — point the entire server at `https://grch37.rest.ensembl.org` for clinical workflows on the older assembly
- All coordinate-bearing responses echo the assembly name so agents never see a bare genomic position without assembly context
Agent-friendly output:
- `ensembl_get_sequence` returns bounded windows (10,000 characters by default) with the full length and a `nextOffset` to continue
- `ensembl_list_species` is the discovery step for internal species names, 50 per page with a `nextOffset`
- Xref IDs from `ensembl_get_xrefs` are described as inputs for protein, disease, pathway, and structure servers; the `ensembl_gene_dossier` prompt chains 6 of the 7 tools
## Getting started
Connect to the hosted instance, no install:
```sh
claude mcp add --transport http ensembl-mcp-server https://ensembl.caseyjhand.com/mcp
```
Or run it locally:
```sh
claude mcp add ensembl-mcp-server -- npx -y @cyanheads/ensembl-mcp-server
```
For other clients, add this to the MCP config file:
```json
{
"mcpServers": {
"ensembl-mcp-server": {
"command": "npx",
"args": ["-y", "@cyanheads/ensembl-mcp-server"]
}
}
}
```
Ensembl REST is public, so no API key is needed. Set `ENSEMBL_BASE_URL` to `https://grch37.rest.ensembl.org` to query the GRCh37 assembly instead of GRCh38. For Docker or a source build, see [Running the server](#running-the-server).
## Configuration
All configuration is validated at startup via Zod schemas in `src/config/server-config.ts`.
| Variable | Description | Default |
|:---------|:------------|:--------|
| `ENSEMBL_BASE_URL` | Ensembl REST API base URL. Override for GRCh37 (`https://grch37.rest.ensembl.org`) or a local mirror. | `https://rest.ensembl.org` |
| `MCP_TRANSPORT_TYPE` | Transport: `stdio` or `http` | `stdio` |
| `MCP_HTTP_PORT` | HTTP server port | `3010` |
| `MCP_HTTP_ENDPOINT_PATH` | HTTP endpoint path | `/mcp` |
| `MCP_SESSION_MODE` | HTTP session mode: `auto`, `stateful`, or `stateless` | `stateless` |
| `MCP_AUTH_MODE` | Authentication: `none`, `jwt`, or `oauth` | `none` |
| `MCP_LOG_LEVEL` | Log level (`debug`, `info`, `warning`, `error`, etc.) | `info` |
| `LOGS_DIR` | Directory for log files (Node.js only) | `/logs` |
| `LOG_TOOL_FAILURE_PAYLOADS` | Log each failed tool call's arguments and result, redacted by key name and capped at `LOG_TOOL_FAILURE_PAYLOAD_MAX_BYTES` (default `16384`). A secret inside a free-form value is not redacted. | `false` |
| `OTEL_ENABLED` | Enable OpenTelemetry | `false` |
See [`.env.example`](./.env.example) for the full list of optional overrides.
## Running the server
### Local development
Requires [Bun v1.4.0](https://bun.sh/) or higher (or Node.js v24+).
- **Clone and install:**
```sh
git clone https://github.com/cyanheads/ensembl-mcp-server.git
cd ensembl-mcp-server && bun install
cp .env.example .env # optional: set ENSEMBL_BASE_URL for GRCh37 or a mirror
```
- **Build and run:**
```sh
# One-time build
bun run rebuild
# Run the built server
bun run start:stdio
# or
bun run start:http
```
- **Run checks and tests:**
```sh
bun run devcheck # Lint, format, typecheck, security
bun run test # Vitest test suite
bun run lint:mcp # Validate MCP definitions against spec
```
### Docker
```sh
docker run --rm -p 3010:3010 ghcr.io/cyanheads/ensembl-mcp-server:latest
```
The image defaults to HTTP transport, stateless session mode, and logs to `/var/log/ensembl-mcp-server`. To run it over stdio from an MCP client, use `"command": "docker"` with `"args": ["run", "-i", "--rm", "-e", "MCP_TRANSPORT_TYPE=stdio", "ghcr.io/cyanheads/ensembl-mcp-server:latest"]`. To build locally, `docker build -t ensembl-mcp-server .`; OpenTelemetry peer dependencies are installed by default — build with `--build-arg OTEL_ENABLED=false` to omit them.
## Project structure
| Directory | Purpose |
|:----------|:--------|
| `src/index.ts` | `createApp()` entry point — registers tools/resources/prompts and inits services |
| `src/config` | Server-specific environment variable parsing and validation with Zod |
| `src/mcp-server/tools` | Tool definitions (`*.tool.ts`) — 7 tools |
| `src/mcp-server/resources` | Resource definitions (`*.resource.ts`) — gene, transcript, species |
| `src/mcp-server/prompts` | Prompt definitions (`*.prompt.ts`) — gene dossier workflow |
| `src/services/ensembl` | Ensembl REST API client — HTTP, rate-limit handling, retry, error normalization |
| `tests/` | Unit and integration tests mirroring `src/` |
## Development guide
See [`CLAUDE.md`](./CLAUDE.md) for development guidelines and architectural rules. The short version:
- Handlers throw, framework catches — no `try/catch` in tool logic
- Use `ctx.log` for request-scoped logging, `ctx.state` for tenant-scoped storage
- Register new tools and resources in the `createApp()` arrays in `src/index.ts`
- Wrap external API calls: validate raw → normalize to domain type → return output schema; never fabricate missing fields
## Contributing
Issues are welcome. Run checks and tests before submitting:
```sh
bun run devcheck
bun run test
```
## License
Apache-2.0 — see [LICENSE](LICENSE) for details.