CausalSentinel

Protein Dossier — CD14 (Monocyte differentiation antigen CD14)

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
Systolic blood pressure automated reading	-0.0216	0.00738	0.00335	Inverse variance weighted	2	trans	NA
Systolic blood pressure automated reading	-0.0216	0.00738	0.00335	Inverse variance weighted	2	cis	NA
IgA nephropathy	-0.585	0.235	0.0126	Inverse variance weighted	2	trans	NA
IgA nephropathy	-0.585	0.235	0.0126	Inverse variance weighted	2	cis	NA
Diagnoses - main ICD10: R07 Pain in throat and chest	-0.132	0.0568	0.0201	Inverse variance weighted	2	trans	NA
Diagnoses - main ICD10: R07 Pain in throat and chest	-0.132	0.0568	0.0201	Inverse variance weighted	2	cis	NA
Diagnoses - main ICD10: R11 Nausea and vomiting	0.212	0.0938	0.0238	Inverse variance weighted	2	trans	NA
Diagnoses - main ICD10: R11 Nausea and vomiting	0.212	0.0938	0.0238	Inverse variance weighted	2	cis	NA
Lumbar spine bone mineral density	-0.0586	0.0264	0.0265	Inverse variance weighted	2	trans	NA
Lumbar spine bone mineral density	-0.0586	0.0264	0.0265	Inverse variance weighted	2	cis	NA
Parkinson’s disease	-0.518	0.234	0.0272	Wald ratio	1	trans	NA
Diagnoses - main ICD10: K29 Gastritis and duodenitis	0.0933	0.0426	0.0285	Inverse variance weighted	2	trans	NA
…and 193 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

45 association rows across 27 traits (43 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
Soluble CD14 levels	7e-124	rs75652866	3	GCST90093300	no MR -> candidate analysis
Monocyte differentiation antigen CD14 levels	2e-73	rs5744441	3	GCST90246929	no MR -> candidate analysis
CD14 protein levels	3e-68	rs190828983	4	GCST90468598	no MR -> candidate analysis
Height	2e-63	rs2569193	2	GCST90245848	MR: beta=-0.0593, p=0.11 (trans)
Monocyte differentiation antigen CD14, soluble levels	2e-52	rs5744454	3	GCST90249440	no MR -> candidate analysis
Cerebrospinal fluid protein CD14 levels	2e-46	rs2569193	1	GCST90944962	no MR -> candidate analysis
CPXM1/HBEGF protein level ratio	1e-27	rs778582	1	GCST90314219	no MR -> candidate analysis
Serum levels of protein CD14	6e-20	rs60745418	1	GCST90090416	no MR -> candidate analysis
HLA class II histocompatibility antigen, DR beta 3 chain lev	3e-16	rs778583	1	GCST90426852	no MR -> candidate analysis
Monocyte differentiation antigen CD14, soluble level in Chro	1e-15	rs75652866	1	GCST90234613	no MR -> candidate analysis
Monocyte differentiation antigen CD14 level in Chronic kidne	4e-14	rs5744451	1	GCST90239125	no MR -> candidate analysis
Body shape phenotype PC2	5e-14	rs2569178	1	GCST90832990	no MR -> candidate analysis
…and 15 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 1347 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
gout	0.249	—	common-variant locus	no MR -> candidate analysis
Back pain	0.223	—	common-variant locus	no MR -> candidate analysis

Of the 2 rows above, 2 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	2 known modulators (Monocyte differentiation antigen CD14)
gnomAD constraint	pLI=0.0085, LOEUF=3.72 — LoF-tolerant
GWAS Catalog	72 unique SNPs / 144 rows
ClinVar	74 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx	1 clinical annotations across 1 drugs

Caveats declared by the tools

• phenome — Top 30 of 1347 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.
• chembl — ChEMBL target matched by text search on ‘CD14’ and resolved to ‘Monocyte differentiation antigen CD14’ — confirm this is the intended target.
• clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 74 ClinVar records for this gene; it is a sample, not a rate.
• gwas_traits — Top 20 of 27 traits by best p-value, aggregated from 45 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/P08571 — 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/ENSG00000170458/associations — Open Targets data release 26.06
• chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL2384897/ — ChEMBL_37 (released 2026-05-01)
• gnomad: https://gnomad.broadinstitute.org/gene/CD14 — gnomAD constraint via GraphQL API (reference genome GRCh38)
• gwas: https://www.ebi.ac.uk/gwas/genes/CD14 — GWAS Catalog REST (live; release not exposed by this endpoint)
• clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=CD14%5Bgene%5D — ClinVar build Build260809-1055.1
• pharmgkb: https://www.pharmgkb.org/search?query=CD14 — ClinPGx clinicalAnnotation via https://api.clinpgx.org/v1/data
• gwas_traits: https://www.ebi.ac.uk/gwas/genes/CD14 — GWAS Catalog search API (live; release not exposed)

Provenance

• Generated: 2026-08-14T01:40:25 · 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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