Protein Dossier — CRLF1 (Cytokine receptor-like factor 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 |
| Potassium in urine |
0.0382 |
0.0105 |
2.87e-04 |
Wald ratio |
1 |
cis |
NA |
| Age at menarche |
0.0699 |
0.0248 |
0.0048 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hypertension |
-0.0521 |
0.0186 |
0.00517 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: R10 Abdominal and pelvic pain |
-0.157 |
0.0588 |
0.0077 |
Wald ratio |
1 |
cis |
NA |
| Hirschsprung’s disease |
-1.22 |
0.473 |
0.00981 |
Wald ratio |
1 |
cis |
NA |
| Cancer code self-reported: small intestine or small bowel cancer |
0.651 |
0.28 |
0.0199 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hayfever or allergic rhinitis |
-0.106 |
0.0475 |
0.0253 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: N20 Calculus of kidney and ureter |
0.222 |
0.1 |
0.0263 |
Wald ratio |
1 |
cis |
NA |
| HDL cholesterol |
0.0469 |
0.0213 |
0.028 |
Wald ratio |
1 |
cis |
NA |
| Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
-0.0629 |
0.029 |
0.0301 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: J33 Nasal polyp |
0.253 |
0.119 |
0.0332 |
Wald ratio |
1 |
cis |
NA |
| ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
-0.0734 |
0.035 |
0.0357 |
Wald ratio |
1 |
cis |
NA |
| …and 104 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-2607_54_2 |
CLF-1/CLC Complex |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
14 association rows across 12 traits (13 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 |
| Serum levels of protein CRLF1 |
1e-34 |
rs2238647 |
1 |
GCST90087917 |
no MR -> candidate analysis |
| COMP protein levels |
1e-23 |
rs72995446 |
1 |
GCST90468827 |
no MR -> candidate analysis |
| Blood protein levels |
1e-22 |
rs2238647 |
1 |
GCST006585 |
no MR -> candidate analysis |
| Mouth ulcers |
1e-20 |
rs144474740 |
1 |
GCST007839 |
no MR -> candidate analysis |
| Smoking initiation |
8e-11 |
rs4808821 |
1 |
GCST90243968 |
no MR -> candidate analysis |
| Spine osteoarthritis |
1e-9 |
rs117943325 |
1 |
GCST90566801 |
no MR -> candidate analysis |
| Neutrophil-to-lymphocyte ratio |
2e-9 |
rs4808822 |
2 |
GCST90866310 |
no MR -> candidate analysis |
| Post-traumatic stress disorder symptom severity (total) |
3e-9 |
rs2314662 |
2 |
GCST90271779 |
no MR -> candidate analysis |
| Post-traumatic stress disorder symptom severity (avoidance) |
3e-9 |
rs2314662 |
1 |
GCST90271780 |
no MR -> candidate analysis |
| ICD10 K22.1: Ulcer of esophagus |
2e-8 |
rs79286782 |
1 |
GCST90432131 |
no MR -> candidate analysis |
| Total fatty acid levels |
3e-8 |
rs117943325 |
1 |
GCST90502711 |
no MR -> candidate analysis |
| Height |
3e-7 |
rs4808822 |
1 |
GCST90245848 |
MR: beta=0.0154, p=0.234 (cis) |
4. Phenome map — where this gene is a genetic locus, vs. where MR exists
Top diseases by Open Targets association (of 141 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 |
| Cold-induced sweating syndrome 1 |
0.948 |
— |
established (curated) |
no MR -> candidate analysis |
| cold-induced sweating syndrome |
0.717 |
— |
established (curated) |
no MR -> candidate analysis |
| Crisponi syndrome |
0.608 |
— |
established (curated) |
no MR -> candidate analysis |
| spinal stenosis |
0.693 |
— |
common-variant locus |
no MR -> candidate analysis |
| hereditary disease |
0.682 |
— |
established (curated) |
no MR -> candidate analysis |
| dentures |
0.478 |
— |
common-variant locus |
no MR -> candidate analysis |
| cone-rod dystrophy 12 |
0.438 |
— |
established (curated) |
no MR -> candidate analysis |
| esophageal disorder |
0.425 |
— |
common-variant locus |
no MR -> candidate analysis |
| diaphragmatic hernia |
0.363 |
— |
common-variant locus |
MR: beta=-0.135, p=0.161 (cis) |
| cholelithiasis |
0.242 |
— |
common-variant locus |
MR: beta=0.073, p=0.279 (cis) |
| Barrett esophagus |
0.1 |
— |
common-variant locus |
no MR -> candidate analysis |
| gastroesophageal reflux disease |
0.082 |
— |
common-variant locus |
no MR -> candidate analysis |
| Hiatus hernia |
0.07 |
— |
common-variant locus |
MR: beta=-0.155, p=0.0524 (cis) |
| Hernia |
0.07 |
— |
common-variant locus |
MR: beta=-0.155, p=0.0524 (cis) |
| osteoarthritis, spine |
0.052 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 15 rows above, 11 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=1.3e-09, LOEUF=0.972 — LoF-tolerant |
| GWAS Catalog |
108 unique SNPs / 210 rows |
| ClinVar |
256 records; 3 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 141 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 ‘CRLF1’.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 256 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 12 of 12 traits by best p-value, aggregated from 14 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/O75462 — 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/ENSG00000006016/associations — Open Targets data release 26.06gnomad: https://gnomad.broadinstitute.org/gene/CRLF1 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/CRLF1 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=CRLF1%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/CRLF1 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T02:03:58 · 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