CausalSentinel

Protein Dossier — KIAA1549L (UPF0606 protein KIAA1549L)

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
Diagnoses - main ICD10: K57 Diverticular disease of intestine 0.115 0.0349 9.97e-04 Wald ratio 1 cis NA
Sodium in urine -0.0158 0.00547 0.00384 Wald ratio 1 cis NA
Eye problems or disorders: Glaucoma -0.15 0.054 0.00539 Wald ratio 1 cis NA
Myocardial infarction -0.0644 0.0237 0.00652 Wald ratio 1 cis NA
Diagnoses - main ICD10: N40 Hyperplasia of prostate 0.131 0.0509 0.00973 Wald ratio 1 cis NA
Microalbuminuria 0.114 0.0478 0.0173 Wald ratio 1 cis NA
Fasting glucose -0.0173 0.00752 0.0213 Wald ratio 1 cis NA
Years of schooling -0.0205 0.00911 0.0244 Wald ratio 1 cis NA
Coronary heart disease -0.0424 0.0214 0.0478 Wald ratio 1 cis NA
Non-cancer illness code self-reported: osteoporosis -0.0974 0.0493 0.0482 Wald ratio 1 cis NA
Non-cancer illness code self-reported: gout -0.101 0.0517 0.0502 Wald ratio 1 cis NA
Diagnoses - main ICD10: G56 Mononeuropathies of upper limb -0.0908 0.0464 0.0504 Wald ratio 1 cis NA
…and 96 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

34 association rows across 30 traits (20 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
UPF0606 protein KIAA1549L levels 8e-361 rs2753408 3 GCST90250103 no MR -> candidate analysis
Serum levels of protein KIAA1549L 2e-176 rs2753408 2 GCST90086567 no MR -> candidate analysis
Blood protein levels 7e-68 rs12792396 1 GCST006585 no MR -> candidate analysis
CD59 protein levels 2e-35 rs831609 1 GCST90468639 no MR -> candidate analysis
Open-angle glaucoma (PheCode 365.1) 2e-13 rs34828249 1 GCST90480067 no MR -> candidate analysis
Glaucoma 3e-13 rs34828249 1 GCST90480069 MR: beta=-0.15, p=0.00539 (cis)
Pulse pressure 6e-13 rs755901261 2 GCST90000065 no MR -> candidate analysis
UPF0606 protein KIAA1549L level in Chronic kidney disease wi 4e-12 rs2753408 1 GCST90233085 no MR -> candidate analysis
Arthropathy associated with other disorders (PheCode 713) 3e-11 rs550171641 1 GCST90480499 no MR -> candidate analysis
Gut microbial network clusters (Salmon (at 1 year) x Househo 2e-10 rs77101501 1 GCST90569455 no MR -> candidate analysis
Vertical cup-disc ratio 2e-9 rs3898926 1 GCST90129627 no MR -> candidate analysis
Vertical cup-disc ratio (multi-trait analysis) 2e-9 rs2753411 1 GCST009724 no MR -> candidate analysis
…and 18 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 60 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
glaucoma 0.654 common-variant locus MR: beta=-0.15, p=0.00539 (cis)
open-angle glaucoma 0.654 common-variant locus no MR -> candidate analysis
brain cancer 0.443 common-variant locus no MR -> candidate analysis
aortic disorder 0.424 common-variant locus no MR -> candidate analysis
hyperaldosteronism 0.424 common-variant locus no MR -> candidate analysis
adrenal gland hyperfunction 0.424 common-variant locus no MR -> candidate analysis
blood coagulation disease 0.4 common-variant locus no MR -> candidate analysis
tonsillitis 0.394 common-variant locus no MR -> candidate analysis
vitiligo 0.345 common-variant locus no MR -> candidate analysis
arthropathy 0.331 common-variant locus no MR -> candidate analysis
drug-induced dyskinesia 0.3 common-variant locus no MR -> candidate analysis
cataract 0.3 common-variant locus MR: beta=-0.021, p=0.497 (cis)
gastritis 0.294 common-variant locus no MR -> candidate analysis
bone fracture 0.282 common-variant locus no MR -> candidate analysis

Of the 14 rows above, 12 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=4.5e-13, LOEUF=0.654 — LoF-tolerant
GWAS Catalog 47 unique SNPs / 94 rows
ClinVar 320 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance