io.github.cyanheads/ensembl-mcp-server

Official

by cyanheads · TypeScript

Look up genes, fetch sequences, predict variant consequences, find orthologs and xrefs via Ensembl.

Look up genes, fetch sequences, predict variant consequences via Ensembl.

Topics

ai-agentsai-toolsbioinformaticscyanheadsensemblgenesgenomicsmcpmcp-servermodel-context-protocoltypescript

README.md15 KBView on GitHub

<div align="center"> <h1>@cyanheads/ensembl-mcp-server</h1> <p><b>Look up genes, fetch sequences, predict variant consequences, find orthologs and cross-database xrefs via Ensembl REST via MCP. STDIO or Streamable HTTP.</b> <div>7 Tools • 4 Resources • 1 Prompt</div> </p> </div> <div align="center">

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Public Hosted Server: https://ensembl.caseyjhand.com/mcp

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Tools

Seven tools covering the core Ensembl REST API surface — species discovery, gene/transcript lookup, sequence retrieval, genomic region overlap, variant consequence prediction, cross-species homology, and external database cross-references:

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 + 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

`ensembl_list_species`

Discovery tool for the Ensembl species catalog.

Filter by division: vertebrates, plants, fungi, metazoa, or protists
Optional name filter (nameContains) for local substring matching
Returns display name, common name, assembly, taxon ID, and Ensembl division for each species
Required first step — species names like homo_sapiens are opaque to non-biologists and are the input format every other tool expects

`ensembl_lookup_gene`

Single entry point for resolving gene identity.

Symbol + species lookup (BRCA2 + homo_sapiens) or direct stable ID lookup (ENSG00000139618)
Batch lookup of up to 20 IDs or symbols in one call via POST endpoints
Optional transcript expansion — returns full transcript list with biotype and canonical flag
Returns Ensembl stable ID, genomic location (chr:start-end:strand), biotype, description, and transcript list
Errors: not_found (symbol or ID not in Ensembl), invalid_species (call ensembl_list_species to discover valid names)

`ensembl_get_sequence`

Fetch any sequence type for any Ensembl feature.

Molecule types: genomic (default, includes introns), cdna (spliced), cds (coding only), protein
Accepts stable IDs or species:chr:start-end region format for genomic region mode
Optional flanking sequence (expand_5prime, expand_3prime) in base pairs
Returns sequence with stable ID, molecule type, and character count — large sequences (e.g. BRCA2 at 85,183 bp genomic) returned in full with explicit length so callers can budget context usage

`ensembl_query_region`

Find all genomic features overlapping a chromosomal window.

Region format: chr:start-end (e.g. 13:32315086-32400268) — no chr prefix for vertebrates
Feature types: gene (default), transcript, variation, regulatory, exon
Optional biotype filter
Defaults to gene only to prevent context overload — a large locus can contain 44,000+ variants when all feature types are selected

`ensembl_predict_variant`

Predict variant consequences via the Ensembl VEP.

Accepts HGVS notation (transcript-relative: ENST00000380152.8:c.2T>A) or genomic region+allele format (13:32316462:32316462:1/A)
Returns most severe consequence term, affected transcripts and genes, impact level (HIGH/MODERATE/LOW/MODIFIER)
Includes colocated known variants with clinical significance (ClinVar, dbSNP)
Errors: invalid_notation (check format), not_found (location outside any known transcript)

`ensembl_get_homology`

Cross-species homolog lookup.

Returns orthologs (default) or paralogs, or both
Optional target_species filter to narrow to specific organisms
Each homolog carries stable ID, species, relationship type (ortholog_one2one, ortholog_one2many, etc.), perc_id, perc_pos, and taxonomy level

`ensembl_get_xrefs`

Full cross-database reference set for any Ensembl feature.

Returns all external IDs by default: HGNC, UniProt, EntrezGene, OMIM, RefSeq, Reactome, and more (56 xrefs for BRCA2)
Optional dbname filter (e.g. HGNC, Uniprot_gn, EntrezGene, MIM_GENE) to narrow output
Uses the xrefs/id endpoint (not xrefs/symbol) — returns the full cross-reference set
IDs returned here chain directly to protein, literature, disease, and pathway resources in other MCP servers

Resources and prompts

Type	Name	Description
Resource	`ensembl://gene/{id}`	Gene record by stable ID (`ENSG…`) — location, biotype, description, and transcript list
Resource	`ensembl://transcript/{id}`	Transcript record by stable ID (`ENST…`) — parent gene, location, biotype, canonical flag, and length
Resource	`ensembl://species`	Supported Ensembl species for the endpoint default division (vertebrates on the default endpoint) with name, display name, assembly, taxon ID, and division
Resource	`ensembl://species/{division}`	Supported species in one division (`EnsemblVertebrates`, `EnsemblPlants`, `EnsemblFungi`, `EnsemblMetazoa`, `EnsemblProtists`)
Prompt	`ensembl_gene_dossier`	Structured workflow for assembling a complete gene profile: symbol → ID + location → sequence → variants → orthologs → xrefs

All resource data is also reachable via tools. ensembl://species returns the endpoint default division (vertebrates) and ensembl://species/{division} returns a named division; ensembl_list_species is the tool equivalent, filtering by division and name.

Features

Built on @cyanheads/mcp-ts-core:

Declarative tool, resource, and prompt definitions — single file per primitive, framework handles registration and validation
Unified error handling — handlers throw, framework catches, classifies, and formats
Pluggable auth: none, jwt, oauth
Swappable storage backends: in-memory, filesystem, Supabase, Cloudflare KV/R2/D1
Structured logging with optional OpenTelemetry tracing
STDIO and Streamable HTTP transports

Ensembl-specific:

Keyless REST API — no API key required; Ensembl REST is fully public at 55,000 req/hr
Rate-limit-aware service layer: tracks x-ratelimit-remaining, retries 429 with Retry-After, and retries transient 5xx
Batch POST endpoints used throughout — POST /lookup/id (up to 50 IDs) and POST /lookup/symbol/{species} reduce N+1 round trips in multi-gene workflows
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:

Sequence character count stated on every ensembl_get_sequence response so callers can budget context before consuming large genomic sequences
ensembl_list_species is explicitly the discovery step — tool descriptions call out the opaque internal-name format and direct agents to it before using species-dependent tools
Cross-tool chaining made explicit: xref IDs from ensembl_get_xrefs are described as inputs for protein and literature servers; the ensembl_gene_dossier prompt sequences the full 7-tool research workflow

Getting started

Public Hosted Instance

A public instance is available at https://ensembl.caseyjhand.com/mcp — no installation required. Point any MCP client at it via Streamable HTTP:

json

{
  "mcpServers": {
    "ensembl-mcp-server": {
      "type": "streamable-http",
      "url": "https://ensembl.caseyjhand.com/mcp"
    }
  }
}

Self-Hosted / Local

Add the following to your MCP client configuration file.

json

{
  "mcpServers": {
    "ensembl-mcp-server": {
      "type": "stdio",
      "command": "bunx",
      "args": ["@cyanheads/ensembl-mcp-server@latest"],
      "env": {
        "MCP_TRANSPORT_TYPE": "stdio",
        "MCP_LOG_LEVEL": "info"
      }
    }
  }
}

Or with npx (no Bun required):

json

{
  "mcpServers": {
    "ensembl-mcp-server": {
      "type": "stdio",
      "command": "npx",
      "args": ["-y", "@cyanheads/ensembl-mcp-server@latest"],
      "env": {
        "MCP_TRANSPORT_TYPE": "stdio",
        "MCP_LOG_LEVEL": "info"
      }
    }
  }
}

Or with Docker:

json

{
  "mcpServers": {
    "ensembl-mcp-server": {
      "type": "stdio",
      "command": "docker",
      "args": [
        "run", "-i", "--rm",
        "-e", "MCP_TRANSPORT_TYPE=stdio",
        "ghcr.io/cyanheads/ensembl-mcp-server:latest"
      ]
    }
  }
}

For Streamable HTTP, set the transport and start the server:

MCP_TRANSPORT_TYPE=http MCP_HTTP_PORT=3010 bun run start:http
# Server listens at http://localhost:3010/mcp

Prerequisites

Bun v1.3.11 or higher (or Node.js v24+).
No API key required — Ensembl REST is fully public.

Installation

Clone the repository:

git clone https://github.com/cyanheads/ensembl-mcp-server.git

Navigate into the directory:

cd ensembl-mcp-server

Install dependencies:

bun install

Configure environment:

cp .env.example .env
# edit .env if you need to override ENSEMBL_BASE_URL (e.g. for GRCh37)

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_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)	`<project-root>/logs`
`OTEL_ENABLED`	Enable OpenTelemetry	`false`

See .env.example for the full list of optional overrides.

Running the server

Local development

Build and run:

# One-time build
bun run rebuild

# Run the built server
bun run start:stdio
# or
bun run start:http

Run checks and tests:

bun run devcheck   # Lint, format, typecheck, security
bun run test       # Vitest test suite
bun run lint:mcp   # Validate MCP definitions against spec

Docker

docker build -t ensembl-mcp-server .
docker run --rm -p 3010:3010 ensembl-mcp-server

The Dockerfile defaults to HTTP transport, stateless session mode, and logs to /var/log/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 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 and pull requests are welcome. Run checks and tests before submitting:

bun run devcheck
bun run test

License

Apache-2.0 — see LICENSE for details.

Install

Configuration

Environment variables

ENSEMBL_BASE_URLdefault https://rest.ensembl.org

Ensembl REST API base URL. Override to use GRCh37 endpoint or a local mirror.

MCP_LOG_LEVELdefault info

Sets the minimum log level for output (e.g., 'debug', 'info', 'warn').

MCP_HTTP_HOSTdefault 127.0.0.1

The hostname for the HTTP server.

MCP_HTTP_PORTdefault 3010

The port to run the HTTP server on.

MCP_HTTP_ENDPOINT_PATHdefault /mcp

The endpoint path for the MCP server.

MCP_AUTH_MODEdefault none

Authentication mode to use: 'none', 'jwt', or 'oauth'.

claude_desktop_config.json

{
  "mcpServers": {
    "ensembl-mcp-server": {
      "command": "npx",
      "args": [
        "-y",
        "@cyanheads/ensembl-mcp-server@0.4.0",
        "run",
        "start:stdio"
      ],
      "env": {
        "ENSEMBL_BASE_URL": "https://rest.ensembl.org",
        "MCP_LOG_LEVEL": "info"
      }
    }
  }
}