CausalSentinel

Protein Dossier — OLFM1 (Noelin)

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
Non-cancer illness code self-reported: hiatus hernia	0.254	0.0818	0.0019	Wald ratio	1	cis	NA
Eye problems or disorders: Cataract	0.186	0.0725	0.0103	Wald ratio	1	cis	NA
Lumbar spine bone mineral density	0.147	0.0586	0.0124	Wald ratio	1	cis	NA
Neuroticism	0.0518	0.0207	0.0124	Wald ratio	1	cis	NA
Non-cancer illness code self-reported: muscle or soft tissue injuries	0.34	0.137	0.013	Wald ratio	1	cis	NA
Non-cancer illness code self-reported: arthritis (nos)	0.331	0.135	0.014	Wald ratio	1	cis	NA
Body mass index (BMI)	0.0391	0.0159	0.0142	Wald ratio	1	cis	NA
Non-cancer illness code self-reported: chronic obstructive airways disease or copd	0.442	0.183	0.0156	Wald ratio	1	cis	NA
Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis)	-0.106	0.0446	0.0171	Wald ratio	1	cis	NA
Non-cancer illness code self-reported: emphysema or chronic bronchitis	0.254	0.109	0.0194	Wald ratio	1	cis	NA
Non-cancer illness code self-reported: bladder problem (not cancer)	0.344	0.153	0.0243	Wald ratio	1	cis	NA
Diagnoses - main ICD10: K44 Diaphragmatic hernia	0.229	0.103	0.0259	Wald ratio	1	cis	NA
…and 64 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

162 association rows across 85 traits (123 genome-wide significant rows). Associations are loci, not causal claims; the mapped gene at a locus is not necessarily the effector gene.

Trait	best p	lead SNP	n assoc	study	MR status
FCN2 protein levels	9e-173	rs3012792	24	GCST90469204	no MR -> candidate analysis
Semaphorin-4A levels	3e-161	rs11103604	2	GCST90249488	no MR -> candidate analysis
Ficolin-1 levels (FCN1.3613.62.5)	2e-106	rs11103602	2	GCST90241184	no MR -> candidate analysis
Serum levels of protein FCN1	3e-98	rs7873100	2	GCST90088459	no MR -> candidate analysis
FCN1 protein levels	2e-75	rs148959363	17	GCST90469203	no MR -> candidate analysis
Blood protein levels	4e-66	rs11103604	2	GCST006585	no MR -> candidate analysis
Ficolin-1 levels	1e-64	rs11103604	6	GCST90161856	no MR -> candidate analysis
Kidney-associated antigen 1 levels	3e-43	rs1038193	1	GCST90248152	no MR -> candidate analysis
Smoking initiation	1e-29	rs10858334	5	GCST90243985	no MR -> candidate analysis
Circulating TNFRSF10C levels	1e-26	rs10858304	1	GCST90859942	no MR -> candidate analysis
Neutrophil count	1e-24	rs1038193	3	GCST90002351	no MR -> candidate analysis
White blood cell count	5e-22	rs1038193	5	GCST90002374	no MR -> candidate analysis
…and 73 more traits (see JSON)

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

Top diseases by Open Targets association (of 283 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
Abnormality of the skeletal system	0.724	—	common-variant locus	no MR -> candidate analysis
smoking initiation	0.7	—	common-variant locus	no MR -> candidate analysis
obesity disorder	0.666	—	common-variant locus	no MR -> candidate analysis
mathematical ability	0.645	—	common-variant locus	no MR -> candidate analysis
attention deficit-hyperactivity disorder	0.518	—	common-variant locus	no MR -> candidate analysis
substance abuse	0.518	—	common-variant locus	no MR -> candidate analysis
smoking behavior	0.51	—	common-variant locus	no MR -> candidate analysis
post-traumatic stress disorder	0.485	—	common-variant locus	no MR -> candidate analysis
overnutrition	0.45	—	common-variant locus	no MR -> candidate analysis
Blindness	0.4	—	common-variant locus	no MR -> candidate analysis
temporomandibular joint disorder	0.324	—	common-variant locus	no MR -> candidate analysis
cholelithiasis	0.245	—	common-variant locus	MR: beta=-0.13, p=0.313 (cis)
gangrene	0.241	—	common-variant locus	no MR -> candidate analysis
idiopathic pulmonary fibrosis	0.219	—	common-variant locus	no MR -> candidate analysis
poisoning	0.189	—	common-variant locus	no MR -> candidate analysis

Of the 15 rows above, 14 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=1, LOEUF=0.316 — LoF-INTOLERANT
GWAS Catalog	132 unique SNPs / 210 rows
ClinVar	97 records; 6 pathogenic in sample of 30
PharmGKB/ClinPGx	no annotations

Caveats declared by the tools

• phenome — Top 30 of 283 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 ‘OLFM1’.
• clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 97 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 — Top 20 of 85 traits by best p-value, aggregated from 162 association rows. These are GWAS ASSOCIATIONS (loci), not causal claims; mapped genes at a locus are not necessarily the effector gene.

Sources

• uniprot: https://www.uniprot.org/uniprotkb/Q99784 — 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/ENSG00000130558/associations — Open Targets data release 26.06
• gnomad: https://gnomad.broadinstitute.org/gene/OLFM1 — gnomAD constraint via GraphQL API (reference genome GRCh38)
• gwas: https://www.ebi.ac.uk/gwas/genes/OLFM1 — GWAS Catalog REST (live; release not exposed by this endpoint)
• clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=OLFM1%5Bgene%5D — ClinVar build Build260809-1055.1
• gwas_traits: https://www.ebi.ac.uk/gwas/genes/OLFM1 — GWAS Catalog search API (live; release not exposed)

Provenance

• Generated: 2026-08-14T04:09:05 · 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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