CausalSentinel

Protein Dossier — MANF (Mesencephalic astrocyte-derived neurotrophic factor)

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	-0.0563	0.0107	1.62e-07	Wald ratio	1	cis	NA
Body mass index (BMI)	0.0372	0.00864	1.64e-05	Wald ratio	1	cis	NA
Fracture resulting from simple fall	-0.0854	0.0248	5.81e-04	Wald ratio	1	cis	NA
Parkinson’s disease	-0.529	0.154	5.83e-04	Wald ratio	1	cis	NA
Hip osteoarthritis	-0.313	0.0979	0.00141	Wald ratio	1	cis	NA
Non-cancer illness code self-reported: hayfever or allergic rhinitis	0.0947	0.0324	0.00342	Wald ratio	1	cis	NA
Age at menarche	-0.0614	0.0211	0.0036	Wald ratio	1	cis	NA
Diagnoses - main ICD10: D12 Benign neoplasm of colon rectum anus and anal canal	0.148	0.0632	0.0189	Wald ratio	1	cis	NA
Diagnoses - main ICD10: Z09 Follow-up examination after treatment for conditions other than malignant neoplasms	0.143	0.0612	0.0192	Wald ratio	1	cis	NA
Diagnoses - main ICD10: R04 Haemorrhage from respiratory passages	0.223	0.0971	0.0214	Wald ratio	1	cis	NA
Invasive mucinous ovarian cancer	0.337	0.149	0.0237	Wald ratio	1	cis	NA
Diagnoses - main ICD10: G56 Mononeuropathies of upper limb	-0.176	0.0789	0.026	Wald ratio	1	cis	NA
…and 111 more outcomes (see JSON)

2. pQTL instrument availability (Tier-B probe)

No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).

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 460 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
diabetes, deafness, developmental delay, and short stature syndrome	0.733	—	established (curated)	no MR -> candidate analysis
Abnormality of the skeletal system	0.73	—	common-variant locus	no MR -> candidate analysis
Cerebro-costo-mandibular syndrome	0.486	—	established (curated)	no MR -> candidate analysis
smoking behavior	0.285	—	common-variant locus	no MR -> candidate analysis
obesity disorder	0.196	—	common-variant locus	no MR -> candidate analysis
major depressive disorder	0.181	—	common-variant locus	MR: beta=0.0731, p=0.349 (cis)
Alzheimer disease	0.079	—	common-variant locus	no MR -> candidate analysis
asthma	0.185	—	common-variant locus	MR: beta=0.0305, p=0.195 (cis)
dysthymic disorder	0.181	—	common-variant locus	no MR -> candidate analysis
stroke disorder	0.042	—	common-variant locus	no MR -> candidate analysis
liver disorder	0.154	—	common-variant locus	no MR -> candidate analysis
multinodular goiter	0.154	—	common-variant locus	no MR -> candidate analysis

Of the 12 rows above, 10 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=0.1, LOEUF=0.822 — LoF-tolerant
GWAS Catalog	107 unique SNPs / 252 rows
ClinVar	50 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx	no annotations

Caveats declared by the tools

• phenome — Top 30 of 460 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 ‘MANF’.
• clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 50 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/P55145 — 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/ENSG00000145050/associations — Open Targets data release 26.06
• gnomad: https://gnomad.broadinstitute.org/gene/MANF — gnomAD constraint via GraphQL API (reference genome GRCh38)
• gwas: https://www.ebi.ac.uk/gwas/genes/MANF — GWAS Catalog REST (live; release not exposed by this endpoint)
• clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=MANF%5Bgene%5D — ClinVar build Build260809-1055.1

Provenance

• Generated: 2026-08-14T03:42:38 · 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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