CausalSentinel

Protein Dossier — PDLIM4 (PDZ and LIM domain protein 4)

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
Height 0.0414 0.00754 4.01e-08 Wald ratio 1 cis NA
Weight 0.018 0.00545 9.29e-04 Wald ratio 1 cis NA
Urate 0.0444 0.0138 0.00126 Wald ratio 1 cis NA
Rheumatoid arthritis -0.0862 0.0285 0.00249 Wald ratio 1 cis NA
Non-cancer illness code self-reported: emphysema or chronic bronchitis 0.119 0.0475 0.0121 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypothyroidism or myxoedema -0.0738 0.0296 0.0126 Wald ratio 1 cis NA
Neuroticism -0.0207 0.00888 0.0196 Wald ratio 1 cis NA
Diagnoses - main ICD10: R04 Haemorrhage from respiratory passages -0.243 0.111 0.0284 Wald ratio 1 cis NA
Eczema 0.0967 0.0459 0.0353 Wald ratio 1 cis NA
Fractured bone site(s): Other bones 0.0529 0.0255 0.038 Wald ratio 1 cis NA
Non-cancer illness code self-reported: osteoarthritis -0.044 0.0216 0.0417 Wald ratio 1 cis NA
Diagnoses - main ICD10: G47 Sleep disorders -0.197 0.0991 0.0472 Wald ratio 1 cis NA
…and 83 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

35 association rows across 29 traits (32 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
PDZ and LIM domain protein 4 levels 2e-104 rs4877 1 GCST90248933 no MR -> candidate analysis
Height 7e-85 rs7735891 3 GCST90435412 MR: beta=0.0414, p=4.01e-08 (cis)
Appendicular lean mass 1e-42 rs7735891 1 GCST90000025 no MR -> candidate analysis
Physical function (baseline) 6e-42 rs10479000 1 GCST90565837 no MR -> candidate analysis
Lymphocyte count 6e-33 rs10076701 2 GCST90002316 no MR -> candidate analysis
lymphocyte (absolute count, mean, inv-norm transformed) 4e-21 rs55633655 1 GCST90475426 no MR -> candidate analysis
N,N,N-trimethyl-5-aminovalerate levels 7e-21 rs10479001 1 GCST90200147 no MR -> candidate analysis
lymphocyte (absolute count, maximum, inv-norm transformed) 1e-20 rs55633655 2 GCST90475423 no MR -> candidate analysis
Mosquito bite size 3e-20 rs55722650 1 GCST004863 no MR -> candidate analysis
Lymphocyte count (UKB data field 30120) 1e-19 rs10076701 1 GCST90468082 no MR -> candidate analysis
Height (baseline) 2e-19 rs162882 2 GCST90565843 no MR -> candidate analysis
Urate levels (UKB data field 30880) 2e-16 rs7736102 1 GCST90468107 no MR -> candidate analysis
…and 17 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 151 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
dermatitis 0.572 common-variant locus no MR -> candidate analysis
inflammatory bowel disease 0.349 common-variant locus no MR -> candidate analysis
gout 0.35 common-variant locus no MR -> candidate analysis
Eczematoid dermatitis 0.284 common-variant locus no MR -> candidate analysis
hypertensive disorder 0.254 common-variant locus no MR -> candidate analysis
Nasal polyposis 0.21 common-variant locus no MR -> candidate analysis
allergic rhinitis 0.16 common-variant locus MR: beta=-0.0271, p=0.298 (cis)
skin aging 0.154 common-variant locus no MR -> candidate analysis
rosacea 0.153 common-variant locus no MR -> candidate analysis
prurigo nodularis 0.15 common-variant locus no MR -> candidate analysis
brain aneurysm 0.134 common-variant locus no MR -> candidate analysis
chalazion 0.111 common-variant locus no MR -> candidate analysis
asthma 0.068 common-variant locus no MR -> candidate analysis
breast cancer 0.075 common-variant locus MR: beta=-0.0269, p=0.348 (cis)
acne 0.074 common-variant locus no MR -> candidate analysis

Of the 15 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 not available — no ChEMBL target (undrugged)
gnomAD constraint pLI=0.00023, LOEUF=0.89 — LoF-tolerant
GWAS Catalog 146 unique SNPs / 368 rows
ClinVar 67 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance