CausalSentinel

Protein Dossier — HDHD2 (Haloacid dehalogenase-like hydrolase domain-containing protein 2)

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
Sodium in urine 0.0176 0.00732 0.0164 Wald ratio 1 cis NA
Diagnoses - main ICD10: R11 Nausea and vomiting 0.227 0.0954 0.0173 Wald ratio 1 cis NA
Weight 0.0144 0.00657 0.028 Wald ratio 1 cis NA
Creatinine (enzymatic) in urine 0.0154 0.00712 0.0311 Wald ratio 1 cis NA
Cough on most days 0.0753 0.0353 0.0332 Wald ratio 1 cis NA
Diagnoses - main ICD10: R14 Flatulence and related conditions 0.441 0.21 0.0357 Wald ratio 1 cis NA
Rheumatoid arthritis 0.0964 0.0476 0.043 Wald ratio 1 cis NA
Non-cancer illness code self-reported: pulmonary embolism (with or without) dvt 0.144 0.0719 0.0456 Wald ratio 1 cis NA
Non-cancer illness code self-reported: diverticular disease or diverticulitis 0.124 0.0624 0.0464 Wald ratio 1 cis NA
Diagnoses - main ICD10: Z09 Follow-up examination after treatment for conditions other than malignant neoplasms 0.108 0.0545 0.0468 Wald ratio 1 cis NA
Bulimia nervosa 0.0442 0.0228 0.0527 Wald ratio 1 cis NA
Non-cancer illness code self-reported: deep venous thrombosis (dvt) 0.092 0.0482 0.0564 Wald ratio 1 cis NA
…and 61 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

14 association rows across 10 traits (7 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 HDHD2 5e-133 rs78720782 1 GCST90087461 no MR -> candidate analysis
Height 1e-30 rs3809966 2 GCST90245848 no MR -> candidate analysis
GLIPR1 protein levels 1e-12 rs188778473 1 GCST90469357 no MR -> candidate analysis
Bioavailable testosterone levels 1e-11 rs561968051 1 GCST90012104 no MR -> candidate analysis
Haloacid dehalogenase-like hydrolase domain-containing prote 3e-11 rs118090589 1 GCST90422159 no MR -> candidate analysis
P-selectin glycoprotein ligand 1 levels 4e-11 rs143459388 1 GCST90012046 no MR -> candidate analysis
Femur bone mineral density x serum urate levels interaction 2e-9 rs140964667 1 GCST012490 no MR -> candidate analysis
Vaginal microbiome relative abundance (c_Gammaproteobacteria 2e-6 rs115747623 3 GCST90026665 no MR -> candidate analysis
Sitting height ratio 4e-6 rs16958432 2 GCST002843 no MR -> candidate analysis
Response to paliperidone in schizophrenia (Multivariate) 7e-6 rs76297747 1 GCST004043 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 35 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
Abnormality of the skeletal system 0.065 common-variant locus no MR -> candidate analysis
Abnormal urine sodium concentration 0.062 common-variant locus no MR -> candidate analysis
alcohol drinking 0.053 common-variant locus no MR -> candidate analysis
ankylosing spondylitis 0.039 common-variant locus no MR -> candidate analysis
urolithiasis 0.033 common-variant locus no MR -> candidate analysis
stomach disorder 0.031 common-variant locus no MR -> candidate analysis

Of the 6 rows above, 6 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=6.8e-10, LOEUF=1.45 — LoF-tolerant
GWAS Catalog 48 unique SNPs / 96 rows
ClinVar 95 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance