CausalSentinel

Protein Dossier — CNTNAP2 (Contactin-associated protein-like 2)

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: depression 0.0885 0.0232 1.37e-04 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypothyroidism or myxoedema 0.0873 0.025 4.93e-04 Wald ratio 1 cis NA
Non-cancer illness code self-reported: ankylosing spondylitis 0.266 0.0899 0.00309 Wald ratio 1 cis NA
2hr glucose 0.127 0.0485 0.00882 Wald ratio 1 cis NA
Non-cancer illness code self-reported: osteoarthritis -0.057 0.0218 0.00884 Wald ratio 1 cis NA
Non-cancer illness code self-reported: pneumothorax 0.482 0.194 0.0131 Wald ratio 1 cis NA
Non-cancer illness code self-reported: gastro-oesophageal reflux (gord) or gastric reflux 0.0675 0.0277 0.0148 Wald ratio 1 cis NA
Years of schooling 0.0208 0.00923 0.0244 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypertension 0.0218 0.0103 0.0338 Wald ratio 1 cis NA
Large vessel disease 0.186 0.0905 0.0395 Wald ratio 1 cis NA
Eye problems or disorders: Cataract 0.0623 0.0316 0.0485 Wald ratio 1 cis NA
Cancer code self-reported: basal cell carcinoma -0.147 0.0748 0.0496 Wald ratio 1 cis NA
…and 86 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

276 association rows across 161 traits (115 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
CNTNAP2/DPP6 protein level ratio 5e-1518 rs10952625 1 GCST90314168 no MR -> candidate analysis
Circulating CNTNAP2 levels 2e-1464 rs6969500 7 GCST90860176 no MR -> candidate analysis
CD200/CNTNAP2 protein level ratio 1e-1409 rs10952625 1 GCST90313747 no MR -> candidate analysis
CNTNAP2/DPP10 protein level ratio 2e-1350 rs10952625 1 GCST90314167 no MR -> candidate analysis
Contactin-associated protein-like 2 levels 1e-393 rs6969311 3 GCST90247081 no MR -> candidate analysis
Serum levels of protein CNTNAP2 2e-222 rs6979892 2 GCST90089595 no MR -> candidate analysis
CNTNAP2 protein levels 2e-165 rs2462603 20 GCST90468808 no MR -> candidate analysis
Bone mineral density mean 5e-110 rs141299713 5 GCST90321120 no MR -> candidate analysis
Contactin-associated protein-like 2 levels (CNTNAP2.6965.19. 1e-60 rs10274393 1 GCST90240789 no MR -> candidate analysis
Height 3e-15 rs12535047 3 GCST90245848 no MR -> candidate analysis
Blood protein levels 5e-15 rs6943324 1 GCST006585 no MR -> candidate analysis
Self-reported math ability (MTAG) 1e-14 rs34438057 1 GCST006569 no MR -> candidate analysis
…and 149 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 934 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
cortical dysplasia-focal epilepsy syndrome 0.944 established (curated) no MR -> candidate analysis
Cortical dysplasia - focal epilepsy syndrome 0.608 established (curated) no MR -> candidate analysis
Pitt-Hopkins-like syndrome 0.559 established (curated) no MR -> candidate analysis
hereditary disease 0.881 established (curated) no MR -> candidate analysis
Rolandic epilepsy 0.816 established (curated) no MR -> candidate analysis
self-limited epilepsy with centrotemporal spikes 0.816 established (curated) no MR -> candidate analysis
alcohol drinking 0.696 common-variant locus no MR -> candidate analysis
mathematical ability 0.667 common-variant locus no MR -> candidate analysis
dislocation 0.621 common-variant locus no MR -> candidate analysis
stroke disorder 0.611 common-variant locus no MR -> candidate analysis
Alzheimer disease 0.603 common-variant locus no MR -> candidate analysis
ulcerative colitis 0.606 common-variant locus no MR -> candidate analysis
urolithiasis 0.546 common-variant locus no MR -> candidate analysis
Intellectual disability 0.527 established (curated) no MR -> candidate analysis
peripheral vascular disease 0.52 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 15 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-19, LOEUF=0.747 — LoF-tolerant
GWAS Catalog 180 unique SNPs / 487 rows
ClinVar 2159 records; 6 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance