Protein Dossier — CCL21 (C-C motif chemokine 21)
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 |
| Total cholesterol |
0.0646 |
0.013 |
6.98e-07 |
Wald ratio |
1 |
trans |
NA |
| LDL cholesterol |
0.0646 |
0.0133 |
1.30e-06 |
Wald ratio |
1 |
trans |
NA |
| Age at menopause |
-0.181 |
0.0494 |
2.46e-04 |
Wald ratio |
1 |
trans |
NA |
| Height |
0.028 |
0.00774 |
2.98e-04 |
Wald ratio |
1 |
trans |
NA |
| Non-cancer illness code self-reported: high cholesterol |
0.0548 |
0.016 |
6.46e-04 |
Wald ratio |
1 |
trans |
NA |
| HOMA-IR |
0.028 |
0.00988 |
0.00461 |
Wald ratio |
1 |
trans |
NA |
| Lung adenocarcinoma |
-0.222 |
0.0789 |
0.00493 |
Wald ratio |
1 |
trans |
NA |
| Iron |
-0.0697 |
0.0254 |
0.00602 |
Wald ratio |
1 |
trans |
NA |
| Triglycerides |
0.0319 |
0.012 |
0.00787 |
Wald ratio |
1 |
trans |
NA |
| HOMA-B |
0.0214 |
0.00807 |
0.00798 |
Wald ratio |
1 |
trans |
NA |
| Serum creatinine (eGFRcrea) |
0.0056 |
0.00214 |
0.00891 |
Wald ratio |
1 |
trans |
NA |
| Paget’s disease |
-0.375 |
0.145 |
0.00995 |
Wald ratio |
1 |
trans |
NA |
| …and 109 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-2516_57_3 |
6Ckine |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
34 association rows across 23 traits (31 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 |
| CCL27 protein levels |
1e-67 |
rs10814133 |
1 |
GCST90468579 |
no MR -> candidate analysis |
| CCL21 protein levels |
2e-55 |
rs10814138 |
1 |
GCST90468573 |
no MR -> candidate analysis |
| Circulating CCL21 levels |
2e-54 |
rs10814138 |
1 |
GCST90860611 |
no MR -> candidate analysis |
| Circulating CCL19 levels (id: OID00513_OID21030) |
1e-50 |
rs10972202 |
1 |
GCST90859869 |
no MR -> candidate analysis |
| Circulating CCL19 levels (id: OID00794_OID21030) |
1e-29 |
rs10972202 |
1 |
GCST90860126 |
no MR -> candidate analysis |
| CCL19 protein levels |
2e-29 |
rs11574915 |
1 |
GCST90468571 |
no MR -> candidate analysis |
| COVID-19 hospitalization or rheumatoid arthritis (MTAG) |
3e-19 |
rs10972201 |
1 |
GCST90255368 |
no MR -> candidate analysis |
| C-C motif chemokine 19 levels |
8e-18 |
rs11574915 |
1 |
GCST90274765 |
no MR -> candidate analysis |
| Rheumatoid arthritis (rheumatoid factor and/or anti-cyclic c |
6e-16 |
rs2812378 |
2 |
GCST90132225 |
no MR -> candidate analysis |
| Rheumatoid arthritis |
2e-15 |
rs11574914 |
10 |
GCST002318 |
no MR -> candidate analysis |
| Height |
3e-13 |
rs10124246 |
1 |
GCST90245844 |
MR: beta=0.028, p=2.98e-04 (trans) |
| Lymphocyte count |
1e-12 |
rs11574914 |
1 |
GCST90002320 |
no MR -> candidate analysis |
| …and 11 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 926 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 |
| rheumatoid arthritis |
0.809 |
— |
common-variant locus |
no MR -> candidate analysis |
| autoimmune disease |
0.54 |
— |
common-variant locus |
no MR -> candidate analysis |
| ulcerative colitis |
0.541 |
— |
common-variant locus |
MR: beta=-0.0239, p=0.47 (trans) |
| Crohn disease |
0.541 |
— |
common-variant locus |
no MR -> candidate analysis |
| psoriasis |
0.541 |
— |
common-variant locus |
no MR -> candidate analysis |
| ankylosing spondylitis |
0.541 |
— |
common-variant locus |
no MR -> candidate analysis |
| sclerosing cholangitis |
0.541 |
— |
common-variant locus |
no MR -> candidate analysis |
| COVID-19 |
0.304 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 8 rows above, 7 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=0.00066, LOEUF=1.18 — LoF-tolerant |
| GWAS Catalog |
59 unique SNPs / 118 rows |
| ClinVar |
103 records; 8 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 926 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 ‘CCL21’.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 103 ClinVar records for this gene; it is a sample, not a rate.gwas_traits — Top 20 of 23 traits by best p-value, aggregated from 34 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/O00585 — 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/ENSG00000137077/associations — Open Targets data release 26.06gnomad: https://gnomad.broadinstitute.org/gene/CCL21 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/CCL21 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=CCL21%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/CCL21 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T01:34:25 · 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: pharmgkb