CausalSentinel

Protein Dossier — AGRP (Agouti-related protein)

MR feasibility tier: A — Published pQTL-MR estimates exist for this protein (retrieved below - not computed here).

1. Published MR estimates (retrieved, not computed)

Outcome	beta	se	p	method	nSNP	cis/trans	coloc
Height	-0.0536	0.00901	2.75e-09	Wald ratio	1	cis	NA
Non-cancer illness code self-reported: hypothyroidism or myxoedema	0.157	0.0273	8.84e-09	Wald ratio	1	cis	NA
Heel bone mineral density (BMD) T-score automated	0.0426	0.00931	4.65e-06	Wald ratio	1	cis	NA
Multiple sclerosis	-0.196	0.052	1.59e-04	Wald ratio	1	cis	NA
Sodium in urine	-0.0246	0.00705	4.82e-04	Wald ratio	1	cis	NA
Diagnoses - main ICD10: K60 Fissure and fistula of anal and rectal regions	0.275	0.0812	7.23e-04	Wald ratio	1	cis	NA
Subjective well being	0.0329	0.00974	7.38e-04	Wald ratio	1	cis	NA
Bipolar disorder	0.212	0.067	0.00152	Wald ratio	1	cis	NA
Forced vital capacity (FVC)	-0.018	0.00589	0.00225	Wald ratio	1	cis	NA
Urate	-0.0451	0.0158	0.00443	Wald ratio	1	cis	NA
Ferritin	-0.0773	0.0278	0.00535	Wald ratio	1	cis	NA
Anorexia nervosa	-0.377	0.137	0.00608	Wald ratio	1	cis	NA
…and 106 more outcomes (see JSON)

2. pQTL instrument availability (Tier-B probe)

Dataset	Trait	Author	Year
prot-c-2813_11_2	ART	Suhre K	2019

3. GWAS Catalog results — traits with signal at this locus

No GWAS Catalog associations mapped to this gene.

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 298 total). Associations are loci, not causal claims. The causal-status column is a four-state triage per pair: established (curated) = a curated clinical assertion exists (ClinGen/G2P/GEL/Orphanet/ClinVar — any validity level, MR adds little); exploratory rare-variant signal = ExWAS burden evidence without curation — a candidate NEW gene-disease relationship; common-variant locus = GWAS signal, classic pQTL-MR territory; multi-layer = burden+GWAS together, an allelic-series candidate (the strongest causal setup). Burden estimand is carrier-vs-noncarrier, not per-SD MR.

Disease	genetic assoc.	burden (ExWAS)	causal status	MR status
Obesity	0.195	—	established (curated)	MR: beta=0.00996, p=0.164 (cis)
Abnormality of the skeletal system	0.66	—	common-variant locus	no MR -> candidate analysis
androgenetic alopecia	0.329	—	common-variant locus	no MR -> candidate analysis
poisoning	0.289	—	common-variant locus	no MR -> candidate analysis
hypothyroidism	0.252	—	common-variant locus	MR: beta=0.157, p=8.84e-09 (cis)
smoking behavior	0.208	—	common-variant locus	no MR -> candidate analysis
dermatophytosis	0.113	—	common-variant locus	no MR -> candidate analysis

Of the 7 rows above, 5 have no MR estimate in this resource. Across all retrieved diseases for this gene: 0 exploratory rare-variant signal(s), 0 multi-layer (allelic-series candidate) pair(s). Final triage still belongs to a statistical geneticist.

5. Downstream annotation (druggability & safety preview)

Layer	Result
ChEMBL druggability	not available — no ChEMBL target (undrugged)
gnomAD constraint	pLI=0.023, LOEUF=1.06 — LoF-tolerant
GWAS Catalog	60 unique SNPs / 120 rows
ClinVar	58 records; 5 pathogenic in sample of 30
PharmGKB/ClinPGx	no annotations

Caveats declared by the tools

• phenome — Top 30 of 298 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.
• chembl — No ChEMBL target for ‘AGRP’.
• clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 58 ClinVar records for this gene; it is a sample, not a rate.
• pharmgkb — No PharmGKB/ClinPGx clinical annotations (gene may not be a pharmacogene).
• gwas_traits — No GWAS Catalog associations mapped to this gene.

Sources

• uniprot: https://www.uniprot.org/uniprotkb/O00253 — UniProt release 2026_02 (10-June-2026)
• mr_outcomes: https://epigraphdb.org/pqtl/ — EpiGraphDB pQTL MR (Zheng et al., Nat Genet 2020) — pre-computed two-sample MR; retrieved, not computed by this agent; EpiGraphDB build 1.0, pQTL dataset v3.0
• phenome: https://platform.opentargets.org/target/ENSG00000159723/associations — Open Targets data release 26.06
• gnomad: https://gnomad.broadinstitute.org/gene/AGRP — gnomAD constraint via GraphQL API (reference genome GRCh38)
• gwas: https://www.ebi.ac.uk/gwas/genes/AGRP — GWAS Catalog REST (live; release not exposed by this endpoint)
• clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=AGRP%5Bgene%5D — ClinVar build Build260809-1055.1

Provenance

• Generated: 2026-08-14T00:58:14 · Tier: A
• Fully mechanical: every cell above is rendered from tool return values. No language model wrote any part of this dossier.
• MR estimates, where present, are retrieved from published work (EpiGraphDB pQTL, Zheng et al. Nat Genet 2020); nothing is computed here.
• Tool errors this run: none

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