CausalSentinel

Protein Dossier — ASPH (Aspartyl/asparaginyl beta-hydroxylase)

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: M23 Internal derangement of knee 0.186 0.0672 0.00578 Wald ratio 1 cis NA
Forced vital capacity (FVC) 0.0255 0.00982 0.00948 Wald ratio 1 cis NA
Diagnoses - main ICD10: R55 Syncope and collapse 0.235 0.102 0.021 Wald ratio 1 cis NA
Diagnoses - main ICD10: S76 Injury of muscle and tendon at hip and thigh level 0.715 0.312 0.0219 Wald ratio 1 cis NA
Bipolar disorder 0.241 0.113 0.0326 Wald ratio 1 cis NA
Creatinine (enzymatic) in urine 0.0238 0.0115 0.0384 Wald ratio 1 cis NA
Potassium in urine 0.0251 0.0122 0.0391 Wald ratio 1 cis NA
Forced expiratory volume in 1-second (FEV1) 0.0205 0.0104 0.0474 Wald ratio 1 cis NA
Fractured bone site(s): Wrist -0.206 0.106 0.053 Wald ratio 1 cis NA
Age at menarche -0.0536 0.0282 0.057 Wald ratio 1 cis NA
Alcohol intake frequency 0.0333 0.0177 0.0596 Wald ratio 1 cis NA
Heel bone mineral density (BMD) T-score automated -0.0282 0.0155 0.0678 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

16 association rows across 13 traits (8 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
Serum levels of protein ASPH 5e-24 rs115581627 2 GCST90089611 no MR -> candidate analysis
Aspartyl/asparaginyl beta-hydroxylase levels (ASPH.6998.106. 4e-17 rs112760834 1 GCST90240346 no MR -> candidate analysis
Aspartyl/asparaginyl beta-hydroxylase level in Chronic kidne 3e-13 rs61731238 1 GCST90238436 no MR -> candidate analysis
Triglyceride levels x long total sleep time interaction (1df 3e-13 rs147261056 1 GCST90837574 no MR -> candidate analysis
Height 1e-8 rs7812327 1 GCST90245848 no MR -> candidate analysis
Dental caries 1e-8 rs185994551 1 GCST90837178 no MR -> candidate analysis
Resting heart rate 2e-8 rs142916219 1 GCST004213 no MR -> candidate analysis
Bone mineral density variability 5e-8 rs72657080 2 GCST90321121 no MR -> candidate analysis
Complement factor H-related protein 3 levels 3e-7 rs139396667 1 GCST90026531 no MR -> candidate analysis
BRCA1/2-negative high-risk breast cancer 8e-7 rs2350923 1 GCST006719 no MR -> candidate analysis
Breast area percent density 1e-6 rs181314234 2 GCST90293092 no MR -> candidate analysis
Intestinal gastric cancer in H. pylori positive individuals 3e-6 rs6471966 1 GCST90432161 no MR -> candidate analysis
…and 1 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 842 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
facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome 0.829 established (curated) no MR -> candidate analysis
Abnormality of the skeletal system 0.738 common-variant locus no MR -> candidate analysis
malignant hyperthermia of anesthesia 0.684 established (curated) no MR -> candidate analysis
exercise-induced malignant hyperthermia 0.684 established (curated) no MR -> candidate analysis
alcohol drinking 0.625 common-variant locus no MR -> candidate analysis
COVID-19 0.579 common-variant locus no MR -> candidate analysis
inherited retinal dystrophy 0.531 common-variant locus no MR -> candidate analysis
Sjogren syndrome 0.51 common-variant locus no MR -> candidate analysis
injury 0.505 common-variant locus MR: beta=0.715, p=0.0219 (cis)
upper extremity fracture 0.485 common-variant locus no MR -> candidate analysis
Hypernatremia 0.485 common-variant locus no MR -> candidate analysis
acidosis disorder 0.479 common-variant locus no MR -> candidate analysis
chronic laryngitis 0.479 common-variant locus no MR -> candidate analysis
splenic disorder 0.461 common-variant locus no MR -> candidate analysis
frozen shoulder 0.419 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 14 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 (Aspartyl/asparaginyl beta-hydroxylase)
gnomAD constraint pLI=9.5e-29, LOEUF=0.998 — LoF-tolerant
GWAS Catalog 37 unique SNPs / 67 rows
ClinVar 346 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx 1 clinical annotations across 1 drugs

Caveats declared by the tools

Sources

Provenance