CausalSentinel

Protein Dossier — DNER (Delta and Notch-like epidermal growth factor-related receptor)

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
Birth weight 0.0648 0.0265 0.0146 Wald ratio 1 cis NA
Diagnoses - main ICD10: M16 Coxarthrosis [arthrosis of hip] 0.256 0.108 0.0175 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hyperthyroidism or thyrotoxicosis 0.307 0.145 0.0343 Wald ratio 1 cis NA
Fractured bone site(s): Other bones 0.132 0.0633 0.0377 Wald ratio 1 cis NA
Diagnoses - main ICD10: I84 Haemorrhoids 0.182 0.0894 0.0414 Wald ratio 1 cis NA
Non-cancer illness code self-reported: iron deficiency anaemia 0.34 0.167 0.0415 Wald ratio 1 cis NA
Caudate volume 74.2 37.1 0.0457 Wald ratio 1 cis NA
Hearing difficulty or problems: Yes 0.0501 0.0272 0.0652 Wald ratio 1 cis NA
Non-cancer illness code self-reported: uterine fibroids 0.199 0.111 0.0727 Wald ratio 1 cis NA
Diagnoses - main ICD10: Z09 Follow-up examination after treatment for conditions other than malignant neoplasms 0.195 0.112 0.0825 Wald ratio 1 cis NA
Rheumatoid arthritis -0.252 0.147 0.0864 Wald ratio 1 cis NA
Diagnoses - main ICD10: C50 Malignant neoplasm of breast 0.184 0.109 0.0909 Wald ratio 1 cis NA
…and 55 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

121 association rows across 93 traits (65 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 DNER levels 5e-491 rs62193248 7 GCST90860417 no MR -> candidate analysis
DNER protein levels 1e-159 rs35565740 6 GCST90469019 no MR -> candidate analysis
Delta and Notch-like epidermal growth factor-related recepto 1e-67 rs62193248 5 GCST90274785 no MR -> candidate analysis
Lung function (FEV1/FVC) 4e-26 rs1862106 3 GCST90244094 no MR -> candidate analysis
Height 2e-23 rs6761377 1 GCST90245848 no MR -> candidate analysis
Creatinine levels 1e-18 rs62190394 1 GCST90662902 no MR -> candidate analysis
Arm fat percentage left (UKB data field 23123) 1e-17 rs62190394 1 GCST90468157 no MR -> candidate analysis
Body mass index 7e-17 rs62190394 8 GCST007039 no MR -> candidate analysis
Predicted visceral adipose tissue 2e-16 rs62190394 1 GCST008744 no MR -> candidate analysis
FEV1 FVC ratio Z score (UKB data field 20258) 1e-15 rs207667 1 GCST90468165 no MR -> candidate analysis
Serum levels of protein DNER 2e-14 rs34661502 1 GCST90090814 no MR -> candidate analysis
Whole body fat mass (UKB data field 23100) 3e-14 rs62190394 2 GCST90428121 no MR -> candidate analysis
…and 81 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 1635 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
breast carcinoma 0.496 common-variant locus no MR -> candidate analysis
knee fracture 0.512 common-variant locus no MR -> candidate analysis
tongue cancer 0.482 common-variant locus no MR -> candidate analysis
respiratory tract infectious disorder 0.482 common-variant locus no MR -> candidate analysis
cardiomyopathy 0.461 common-variant locus no MR -> candidate analysis
Abnormality of the skeletal system 0.441 common-variant locus no MR -> candidate analysis
Her2-receptor negative breast cancer 0.434 common-variant locus no MR -> candidate analysis
response to antineoplastic agent 0.434 common-variant locus no MR -> candidate analysis
progesterone-receptor positive breast cancer 0.434 common-variant locus no MR -> candidate analysis
estrogen-receptor positive breast cancer 0.434 common-variant locus no MR -> candidate analysis
Abnormal pupillary function 0.414 common-variant locus no MR -> candidate analysis
tooth disorder 0.362 common-variant locus no MR -> candidate analysis
Hirsutism 0.247 common-variant locus no MR -> candidate analysis

Of the 13 rows above, 13 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 (Delta and Notch-like epidermal growth factor-related receptor)
gnomAD constraint pLI=0.11, LOEUF=0.565 — LoF-tolerant
GWAS Catalog 104 unique SNPs / 210 rows
ClinVar 186 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance