Protein Dossier — CHL1 (Neural cell adhesion molecule L1-like protein)
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 |
| Heel bone mineral density (BMD) T-score automated |
-0.0458 |
0.0154 |
0.00299 |
Wald ratio |
1 |
cis |
NA |
| Cancer code self-reported: basal cell carcinoma |
0.274 |
0.0957 |
0.00426 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: osteoarthritis |
0.1 |
0.0361 |
0.0055 |
Wald ratio |
1 |
cis |
NA |
| Knee osteoarthritis |
-0.37 |
0.136 |
0.00668 |
Wald ratio |
1 |
cis |
NA |
| Nucleus accumbens volume |
13.5 |
5.22 |
0.00949 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hiatus hernia |
0.163 |
0.0669 |
0.0151 |
Wald ratio |
1 |
cis |
NA |
| Mean cell haemoglobin concentration |
0.0403 |
0.0168 |
0.0164 |
Wald ratio |
1 |
cis |
NA |
| Putamen volume |
65.6 |
29 |
0.0236 |
Wald ratio |
1 |
cis |
NA |
| Years of schooling |
0.0432 |
0.0192 |
0.0244 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: joint disorder |
0.291 |
0.133 |
0.0286 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: M17 Gonarthrosis [arthrosis of knee] |
0.16 |
0.0736 |
0.0293 |
Wald ratio |
1 |
cis |
NA |
| Coronary heart disease |
0.097 |
0.045 |
0.031 |
Wald ratio |
1 |
cis |
NA |
| …and 90 more outcomes (see JSON) |
|
|
|
|
|
|
|
2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3601_54_3 |
CHL1 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
96 association rows across 56 traits (66 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 CHL1 levels |
3e-501 |
rs7618545 |
8 |
GCST90860420 |
no MR -> candidate analysis |
| CHL1 protein levels |
3e-241 |
rs116421102 |
23 |
GCST90468745 |
no MR -> candidate analysis |
| Neural cell adhesion molecule L1-like protein levels |
2e-111 |
rs13077895 |
5 |
GCST90248617 |
no MR -> candidate analysis |
| CNTN4 protein levels |
9e-56 |
rs12491457 |
1 |
GCST90468806 |
no MR -> candidate analysis |
| Circulating CNTN4 levels |
2e-54 |
rs12491457 |
1 |
GCST90860657 |
no MR -> candidate analysis |
| Adolescent idiopathic scoliosis |
5e-37 |
rs11129708 |
2 |
GCST006287 |
no MR -> candidate analysis |
| Serum levels of protein CHL1 |
1e-22 |
rs13077895 |
2 |
GCST90090409 |
no MR -> candidate analysis |
| Contactin-6 level in Chronic kidney disease with hypertensio |
3e-22 |
rs115676652 |
1 |
GCST90235474 |
no MR -> candidate analysis |
| Neural cell adhesion molecule L1-like protein levels (CHL1.3 |
3e-16 |
rs1015456 |
1 |
GCST90242057 |
no MR -> candidate analysis |
| GLIPR1 protein levels |
2e-15 |
rs144689375 |
1 |
GCST90469357 |
no MR -> candidate analysis |
| Contactin-4 levels |
2e-14 |
rs12491457 |
1 |
GCST90247124 |
no MR -> candidate analysis |
| Hair color |
8e-14 |
rs4685448 |
1 |
GCST007082 |
no MR -> candidate analysis |
| …and 44 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 558 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 |
| alcohol drinking |
0.68 |
— |
common-variant locus |
no MR -> candidate analysis |
| mathematical ability |
0.67 |
— |
common-variant locus |
no MR -> candidate analysis |
| digestive system disorder |
0.559 |
— |
common-variant locus |
no MR -> candidate analysis |
| idiopathic generalized epilepsy |
0.544 |
— |
common-variant locus |
no MR -> candidate analysis |
| risk-taking behaviour |
0.529 |
— |
common-variant locus |
no MR -> candidate analysis |
| cervical carcinoma |
0.523 |
— |
common-variant locus |
no MR -> candidate analysis |
| disease of peritoneum |
0.516 |
— |
common-variant locus |
no MR -> candidate analysis |
| Abnormality of the gastrointestinal tract |
0.516 |
— |
common-variant locus |
no MR -> candidate analysis |
| Paralytic ileus |
0.501 |
— |
common-variant locus |
no MR -> candidate analysis |
| adolescent idiopathic scoliosis |
0.493 |
— |
common-variant locus |
no MR -> candidate analysis |
| Respiratory insufficiency |
0.49 |
— |
common-variant locus |
no MR -> candidate analysis |
| pericarditis |
0.489 |
— |
common-variant locus |
MR: beta=0.5, p=0.38 (cis) |
| urolithiasis |
0.485 |
— |
common-variant locus |
no MR -> candidate analysis |
| Apnea |
0.485 |
— |
common-variant locus |
no MR -> candidate analysis |
| response to xenobiotic stimulus |
0.473 |
— |
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 |
0 known modulators (CHL-1) |
| gnomAD constraint |
pLI=2e-21, LOEUF=0.802 — LoF-tolerant |
| GWAS Catalog |
69 unique SNPs / 134 rows |
| ClinVar |
498 records; 1 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 558 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 ‘CHL1’ and resolved to ‘CHL-1’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 498 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 56 traits by best p-value, aggregated from 96 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/O00533 — 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/ENSG00000134121/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL1075422/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/CHL1 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/CHL1 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=CHL1%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/CHL1 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T01:50:54 · 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