MR feasibility tier: A — Published pQTL-MR estimates exist for this protein (retrieved below - not computed here).
| Outcome | beta | se | p | method | nSNP | cis/trans | coloc |
|---|---|---|---|---|---|---|---|
| Diastolic blood pressure automated reading | 0.0127 | 0.00397 | 0.00141 | Wald ratio | 1 | cis | NA |
| Pulse rate | 0.0215 | 0.00685 | 0.00168 | Wald ratio | 1 | cis | NA |
| Diagnoses - main ICD10: M16 Coxarthrosis [arthrosis of hip] | 0.0871 | 0.0296 | 0.00325 | Wald ratio | 1 | cis | NA |
| Systolic blood pressure automated reading | 0.011 | 0.00397 | 0.00538 | Wald ratio | 1 | cis | NA |
| Non-cancer illness code self-reported: hypothyroidism or myxoedema | -0.0505 | 0.0181 | 0.00538 | Wald ratio | 1 | cis | NA |
| Rheumatoid arthritis | -0.0622 | 0.0233 | 0.00772 | Wald ratio | 1 | cis | NA |
| Diagnoses - main ICD10: I83 Varicose veins of lower extremities | 0.0663 | 0.0253 | 0.00894 | Wald ratio | 1 | cis | NA |
| HOMA-IR | -0.0157 | 0.00634 | 0.0133 | Wald ratio | 1 | cis | NA |
| Non-cancer illness code self-reported: high cholesterol | 0.0229 | 0.0102 | 0.0255 | Wald ratio | 1 | cis | NA |
| Diagnoses - main ICD10: K35 Acute appendicitis | -0.14 | 0.0643 | 0.0296 | Wald ratio | 1 | cis | NA |
| HDL cholesterol | 0.0158 | 0.00761 | 0.0372 | Wald ratio | 1 | cis | NA |
| Serum cystatin C (eGFRcys) | 0.00586 | 0.00285 | 0.0398 | Wald ratio | 1 | cis | NA |
| …and 105 more outcomes (see JSON) |
No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).
31 association rows across 22 traits (27 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 HIBCH | 2e-258 | rs291444 | 1 | GCST90086956 | no MR -> candidate analysis |
| Methylmalonate (mma) levels | 9e-168 | rs291459 | 1 | GCST90140220 | no MR -> candidate analysis |
| Blood protein levels | 3e-152 | rs291447 | 1 | GCST006585 | no MR -> candidate analysis |
| 3-hydroxyisobutyryl-CoA hydrolase, mitochondrial levels | 1e-137 | rs291466 | 2 | GCST90421688 | no MR -> candidate analysis |
| Cerebrospinal fluid methylmalonate (MMA) levels | 2e-87 | rs291429 | 1 | GCST90318243 | no MR -> candidate analysis |
| INPP1 protein levels | 2e-77 | rs141472596 | 1 | GCST90469616 | no MR -> candidate analysis |
| Plasma methylmalonate (MMA) levels in chronic kidney disease | 6e-58 | rs291466 | 1 | GCST90265503 | no MR -> candidate analysis |
| Bone mineral density mean | 6e-49 | rs112946311 | 2 | GCST90321120 | no MR -> candidate analysis |
| Urine methylmalonate (MMA) levels in chronic kidney disease | 9e-43 | rs291468 | 1 | GCST90265504 | no MR -> candidate analysis |
| Protein quantitative trait loci (liver) | 5e-37 | rs1361284625 | 6 | GCST011427 | no MR -> candidate analysis |
| 3-hydroxyisobutyryl-CoA hydrolase, mitochondrial level in Ch | 1e-26 | rs291430 | 1 | GCST90233434 | no MR -> candidate analysis |
| Urinary metabolites | 2e-20 | rs13006833 | 1 | GCST003119 | no MR -> candidate analysis |
| …and 10 more traits (see JSON) |
Top diseases by Open Targets association (of 131 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 |
|---|---|---|---|---|
| 3-hydroxyisobutyryl-CoA hydrolase deficiency | 0.864 | — | established (curated) | no MR -> candidate analysis |
| Neurodegeneration due to 3-hydroxyisobutyryl-CoA hydrolase deficiency | 0.608 | — | established (curated) | no MR -> candidate analysis |
| hereditary disease | 0.783 | — | established (curated) | no MR -> candidate analysis |
| liver disorder | 0.557 | — | common-variant locus | no MR -> candidate analysis |
| cervical carcinoma | 0.419 | — | common-variant locus | no MR -> candidate analysis |
| placental retention | 0.404 | — | common-variant locus | no MR -> candidate analysis |
| mitochondrial disease | 0.195 | — | established (curated) | no MR -> candidate analysis |
| hypothyroidism | 0.089 | — | common-variant locus | MR: beta=-0.0505, p=0.00538 (cis) |
| bronchial disorder | 0.061 | — | common-variant locus | no MR -> candidate analysis |
| upper extremity fracture | 0.052 | — | common-variant locus | no MR -> candidate analysis |
| hypertensive disorder | 0.05 | — | common-variant locus | no MR -> candidate analysis |
| juvenile idiopathic arthritis | 0.046 | — | common-variant locus | no MR -> candidate analysis |
| thyroid gland disorder | 0.046 | — | common-variant locus | no MR -> candidate analysis |
| systemic lupus erythematosus | 0.043 | — | common-variant locus | MR: beta=-0.122, p=0.1 (cis) |
| atopic eczema | 0.042 | — | common-variant locus | no MR -> candidate analysis |
Of the 15 rows above, 13 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.
| Layer | Result |
|---|---|
| ChEMBL druggability | 0 known modulators (3-hydroxyisobutyryl-CoA hydrolase, mitochondrial) |
| gnomAD constraint | pLI=3.7e-15, LOEUF=1.09 — LoF-tolerant |
| GWAS Catalog | 64 unique SNPs / 126 rows |
| ClinVar | 324 records; 3 pathogenic in sample of 30 |
| PharmGKB/ClinPGx | no annotations |
phenome — Top 30 of 131 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.chembl — ChEMBL target matched by text search on ‘HIBCH’ and resolved to ‘3-hydroxyisobutyryl-CoA hydrolase, mitochondrial’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 324 ClinVar records for this gene; it is a sample, not a rate.pharmgkb — No PharmGKB/ClinPGx clinical annotations (gene may not be a pharmacogene).gwas_traits — Top 20 of 22 traits by best p-value, aggregated from 31 association rows. These are GWAS ASSOCIATIONS (loci), not causal claims; mapped genes at a locus are not necessarily the effector gene.uniprot: https://www.uniprot.org/uniprotkb/Q6NVY1 — UniProt release 2026_02 (10-June-2026)mr_outcomes: https://epigraphdb.org/pqtl/ — EpiGraphDB pQTL MR (Zheng et al., Nat Genet 2020) — pre-computed two-sample MR; retrieved, not computed by this agent; EpiGraphDB build 1.0, pQTL dataset v3.0phenome: https://platform.opentargets.org/target/ENSG00000198130/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL3817723/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/HIBCH — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/HIBCH — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=HIBCH%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/HIBCH — GWAS Catalog search API (live; release not exposed)