CausalSentinel

Protein Dossier — CLN5 (Bis(monoacylglycero)phosphate synthase CLN5)

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
Total cholesterol 0.114 0.04 0.00437 Wald ratio 1 cis NA
Diagnoses - main ICD10: R11 Nausea and vomiting 0.506 0.189 0.00747 Wald ratio 1 cis NA
Myocardial infarction 0.173 0.0738 0.0188 Wald ratio 1 cis NA
Non-cancer illness code self-reported: mania or bipolar disorder or manic depression 0.504 0.239 0.0352 Wald ratio 1 cis NA
Diastolic blood pressure automated reading 0.0402 0.0193 0.0376 Wald ratio 1 cis NA
Fracture resulting from simple fall -0.114 0.0554 0.0389 Wald ratio 1 cis NA
Coronary heart disease 0.127 0.0654 0.0516 Wald ratio 1 cis NA
Heel bone mineral density (BMD) T-score automated 0.0469 0.0243 0.0542 Wald ratio 1 cis NA
Glioma 0.639 0.341 0.0614 Wald ratio 1 cis NA
LDL cholesterol 0.0746 0.0406 0.0661 Wald ratio 1 cis NA
Neo-neuroticism 1.34 0.74 0.0693 Wald ratio 1 cis NA
Major depressive disorder 0.296 0.166 0.0754 Wald ratio 1 cis NA
…and 77 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

10 association rows across 9 traits (9 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
Ceroid-lipofuscinosis neuronal protein 5 levels 2e-63 rs1773045 1 GCST90247065 no MR -> candidate analysis
Ceroid-lipofuscinosis neuronal protein 5:Lumenal domain leve 3e-40 rs700363 1 GCST90427516 no MR -> candidate analysis
Morning person 5e-36 rs9573980 2 GCST007565 no MR -> candidate analysis
Chronotype 5e-36 rs9573980 1 GCST007576 no MR -> candidate analysis
Morningness 1e-28 rs9565309 1 GCST007983 no MR -> candidate analysis
Ease of getting up in the morning 5e-11 rs7332608 1 GCST007986 no MR -> candidate analysis
Blood protein levels 1e-10 rs7996555 1 GCST006585 no MR -> candidate analysis
Morning vs. evening chronotype 4e-8 rs9565309 1 GCST003429 no MR -> candidate analysis
5alpha-pregnan-3beta,20alpha-diol monosulfate (2) levels in 6e-6 rs1579 1 GCST90133850 no MR -> candidate analysis

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 511 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
CLN5 disease 0.951 established (curated) no MR -> candidate analysis
neuronal ceroid lipofuscinosis 5 0.943 established (curated) no MR -> candidate analysis
neuronal ceroid lipofuscinosis 0.944 established (curated) no MR -> candidate analysis
intellectual disability, short stature, facial anomalies, and joint dislocations 0.792 established (curated) no MR -> candidate analysis
hereditary disease 0.773 established (curated) no MR -> candidate analysis
juvenile neuronal ceroid lipofuscinosis 5 0.608 established (curated) no MR -> candidate analysis
late infantile neuronal ceroid lipofuscinosis 5 0.608 established (curated) no MR -> candidate analysis
adult neuronal ceroid lipofuscinosis 5 0.608 established (curated) no MR -> candidate analysis
Retinal dystrophy 0.559 established (curated) no MR -> candidate analysis
Abnormality of metabolism/homeostasis 0.559 established (curated) no MR -> candidate analysis
pontocerebellar hypoplasia type 2D 0.438 established (curated) no MR -> candidate analysis
Hirsutism 0.081 common-variant locus no MR -> candidate analysis
alcohol drinking 0.061 common-variant locus no MR -> candidate analysis
urolithiasis 0.061 common-variant locus no MR -> candidate analysis
celiac disease 0.058 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=2e-11, LOEUF=1.23 — LoF-tolerant
GWAS Catalog 19 unique SNPs / 38 rows
ClinVar 866 records; 16 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance