Protein Dossier — CD274 (Programmed cell death 1 ligand 1)
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: hypothyroidism or myxoedema |
0.144 |
0.0342 |
2.47e-05 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: K43 Ventral hernia |
0.259 |
0.104 |
0.013 |
Wald ratio |
1 |
cis |
NA |
| Intracranial volume |
1.59e+04 |
6.92e+03 |
0.022 |
Wald ratio |
1 |
cis |
NA |
| 2hr glucose |
0.155 |
0.0677 |
0.0223 |
Wald ratio |
1 |
cis |
NA |
| Cardioembolic stroke |
-0.256 |
0.113 |
0.0235 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: I84 Haemorrhoids |
0.115 |
0.0511 |
0.0245 |
Wald ratio |
1 |
cis |
NA |
| Primary sclerosing cholangitis |
-0.236 |
0.11 |
0.0312 |
Wald ratio |
1 |
cis |
NA |
| High grade serous ovarian cancer |
0.123 |
0.0575 |
0.032 |
Wald ratio |
1 |
cis |
NA |
| Hearing difficulty or problems: Yes |
0.0316 |
0.0149 |
0.0334 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: depression |
-0.0844 |
0.0399 |
0.0345 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: bladder problem (not cancer) |
0.203 |
0.0962 |
0.0352 |
Wald ratio |
1 |
cis |
NA |
| Neuroticism |
0.0258 |
0.0129 |
0.0455 |
Wald ratio |
1 |
cis |
NA |
| …and 90 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-5060_62_3 |
B7-H1 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
60 association rows across 22 traits (55 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 |
| Circulating CD274 levels (id: OID00799_OID20966) |
4e-501 |
rs7041009 |
8 |
GCST90860130 |
no MR -> candidate analysis |
| CD274/EFNA4 protein level ratio |
4e-500 |
rs822340 |
1 |
GCST90313768 |
no MR -> candidate analysis |
| Circulating CD274 levels (id: OID00518_OID20966) |
8e-470 |
rs7041009 |
8 |
GCST90859874 |
no MR -> candidate analysis |
| PDCD1LG2 protein levels |
9e-237 |
rs76778936 |
12 |
GCST90470180 |
no MR -> candidate analysis |
| CD274 protein levels |
3e-135 |
rs7875928 |
7 |
GCST90468613 |
no MR -> candidate analysis |
| Programmed cell death 1 ligand 1 levels |
2e-100 |
rs7048841 |
7 |
GCST90426218 |
no MR -> candidate analysis |
| Cerebrospinal fluid protein CD274 levels |
2e-67 |
rs7048841 |
1 |
GCST90943153 |
no MR -> candidate analysis |
| Serum levels of protein CD274 |
1e-56 |
rs1411262 |
1 |
GCST90088892 |
no MR -> candidate analysis |
| Blood protein levels |
2e-29 |
rs1411262 |
1 |
GCST006585 |
no MR -> candidate analysis |
| Circulating PDCD1LG2 levels (id: OID00831_OID21273) |
2e-25 |
rs117829177 |
1 |
GCST90860159 |
no MR -> candidate analysis |
| Circulating PDCD1LG2 levels (id: OID00458_OID21273) |
3e-24 |
rs117829177 |
1 |
GCST90859819 |
no MR -> candidate analysis |
| Serum levels of protein PDCD1LG2 |
1e-21 |
rs10975153 |
1 |
GCST90088180 |
no MR -> candidate analysis |
| …and 10 more traits (see JSON) |
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|
|
|
4. Phenome map — where this gene is a genetic locus, vs. where MR exists
Top diseases by Open Targets association (of 1982 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 |
| neoplasm |
0.195 |
— |
established (curated) |
MR: beta=0.0949, p=0.167 (cis) |
| hypothyroidism |
0.659 |
— |
common-variant locus |
MR: beta=0.144, p=2.47e-05 (cis) |
Of the 2 rows above, 0 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 |
13 known modulators (Programmed cell death 1 ligand 1) |
| gnomAD constraint |
pLI=0.99, LOEUF=0.48 — LoF-INTOLERANT |
| GWAS Catalog |
96 unique SNPs / 192 rows |
| ClinVar |
196 records; 14 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 1982 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 ‘CD274’ and resolved to ‘Programmed cell death 1 ligand 1’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 196 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 22 traits by best p-value, aggregated from 60 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/Q9NZQ7 — 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 v3.0phenome: https://platform.opentargets.org/target/ENSG00000120217/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL3580522/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/CD274 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/CD274 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=CD274%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/CD274 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T01:41:22 · 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