CausalSentinel

Protein Dossier — HSD17B14 (L-fucose dehydrogenase)

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: S76 Injury of muscle and tendon at hip and thigh level 1.15 0.287 5.96e-05 Wald ratio 1 cis NA
Non-cancer illness code self-reported: gastro-oesophageal reflux (gord) or gastric reflux 0.202 0.0686 0.00322 Wald ratio 1 cis NA
Sodium in urine 0.0502 0.0171 0.00323 Wald ratio 1 cis NA
Forearm bone mineral density 0.278 0.108 0.01 Wald ratio 1 cis NA
Cough on most days -0.286 0.12 0.0176 Wald ratio 1 cis NA
Lumbar spine bone mineral density 0.137 0.0622 0.0279 Wald ratio 1 cis NA
Femoral neck bone mineral density 0.114 0.0538 0.0342 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hayfever or allergic rhinitis 0.129 0.0629 0.04 Wald ratio 1 cis NA
Non-cancer illness code self-reported: asthma 0.0879 0.0446 0.0486 Wald ratio 1 cis NA
Alcohol intake frequency 0.0496 0.0256 0.0528 Wald ratio 1 cis NA
Diagnoses - main ICD10: K20 Oesophagitis 0.265 0.137 0.0532 Wald ratio 1 cis NA
Caudate volume -82.3 43.4 0.0579 Wald ratio 1 cis NA
…and 67 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

41 association rows across 32 traits (39 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
MUC2 protein levels 6e-106 rs116922356 1 GCST90469965 no MR -> candidate analysis
HSD17B14 protein levels 2e-102 rs141119542 5 GCST90469483 no MR -> candidate analysis
ALPI protein levels 9e-92 rs116922356 1 GCST90468285 no MR -> candidate analysis
PRSS27 protein levels 2e-80 rs116922356 1 GCST90470342 no MR -> candidate analysis
Isoleucine levels 5e-80 rs10685064 4 GCST90501133 no MR -> candidate analysis
FAM3D protein levels 3e-58 rs473464 1 GCST90469188 no MR -> candidate analysis
KLK1 protein levels 7e-48 rs140351309 1 GCST90469702 no MR -> candidate analysis
CDH17 protein levels 2e-47 rs4459651 1 GCST90468669 no MR -> candidate analysis
Metabolite levels (fucose) 3e-45 rs35299026 2 GCST90300006 no MR -> candidate analysis
BPIFA2 protein levels 4e-39 rs632115 1 GCST90468461 no MR -> candidate analysis
Metabolite levels (ribose) 1e-30 rs35299026 1 GCST90300217 no MR -> candidate analysis
SERPINI2 protein levels 3e-26 rs632115 1 GCST90470603 no MR -> candidate analysis
…and 20 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 135 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
myopia 0.182 established (curated) no MR -> candidate analysis
pathological myopia 0.182 established (curated) no MR -> candidate analysis
head and neck cancer 0.125 common-variant locus no MR -> candidate analysis
placental abruption 0.086 common-variant locus no MR -> candidate analysis
cholelithiasis 0.085 common-variant locus MR: beta=-0.183, p=0.218 (cis)

Of the 5 rows above, 4 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 (17-beta-hydroxysteroid dehydrogenase 14)
gnomAD constraint pLI=1.8e-11, LOEUF=1.33 — LoF-tolerant
GWAS Catalog 183 unique SNPs / 472 rows
ClinVar 67 records; 1 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance