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 | -0.0223 | 0.00464 | 1.62e-06 | Wald ratio | 1 | cis | NA |
| Serum creatinine (eGFRcrea) | 0.00715 | 0.00164 | 1.37e-05 | Wald ratio | 1 | cis | NA |
| Non-cancer illness code self-reported: hypertension | -0.0324 | 0.00799 | 4.87e-05 | Wald ratio | 1 | cis | NA |
| Body mass index (BMI) | -0.0152 | 0.00453 | 8.10e-04 | Wald ratio | 1 | cis | NA |
| Non-cancer illness code self-reported: asthma | -0.04 | 0.0132 | 0.00247 | Wald ratio | 1 | cis | NA |
| Non-cancer illness code self-reported: hayfever or allergic rhinitis | -0.0599 | 0.0198 | 0.00249 | Wald ratio | 1 | cis | NA |
| Subjective well being | 0.0161 | 0.00536 | 0.0027 | Wald ratio | 1 | cis | NA |
| Fasting glucose | -0.0168 | 0.00572 | 0.00331 | Wald ratio | 1 | cis | NA |
| Schizophrenia | 0.0529 | 0.0198 | 0.00767 | Wald ratio | 1 | cis | NA |
| Primary sclerosing cholangitis | 0.147 | 0.0554 | 0.00778 | Wald ratio | 1 | cis | NA |
| Non-cancer illness code self-reported: hypopituitarism | 0.437 | 0.164 | 0.00781 | Wald ratio | 1 | cis | NA |
| Serum cystatin C (eGFRcys) | 0.00893 | 0.0034 | 0.0085 | Wald ratio | 1 | cis | NA |
| …and 112 more outcomes (see JSON) |
No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).
105 association rows across 76 traits (95 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 |
|---|---|---|---|---|---|
| Beta-mannosidase levels | 2e-291 | rs223492 | 2 | GCST90246709 | no MR -> candidate analysis |
| Beta-mannosidase levels (MANBA.6382.17.3) | 8e-113 | rs227370 | 1 | GCST90240437 | no MR -> candidate analysis |
| Lymphocyte count | 1e-84 | rs5026470 | 6 | GCST90002316 | no MR -> candidate analysis |
| Blood protein levels | 3e-69 | rs223489 | 1 | GCST006585 | no MR -> candidate analysis |
| Lymphocyte count (UKB data field 30120) | 2e-59 | rs1077358 | 1 | GCST90468082 | no MR -> candidate analysis |
| Lymphocyte percentage (UKB data field 30180) | 1e-55 | rs200731261 | 1 | GCST90468083 | no MR -> candidate analysis |
| Lymphocyte-to-monocyte ratio | 3e-41 | rs5026473 | 1 | GCST90056181 | no MR -> candidate analysis |
| Neutrophill percentage (UKB data field 30200) | 6e-35 | rs200731261 | 1 | GCST90468093 | no MR -> candidate analysis |
| Neutrophil-to-lymphocyte ratio | 1e-34 | rs11724614 | 9 | GCST90056182 | no MR -> candidate analysis |
| Neutrophil percentage of white cells | 8e-34 | rs11726195 | 1 | GCST90002399 | no MR -> candidate analysis |
| Primary biliary cholangitis | 2e-32 | rs6533022 | 6 | GCST90061442 | no MR -> candidate analysis |
| Platelet-to-lymphocyte ratio | 2e-31 | rs5026473 | 1 | GCST90056184 | no MR -> candidate analysis |
| …and 64 more traits (see JSON) |
Top diseases by Open Targets association (of 391 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 |
|---|---|---|---|---|
| beta-mannosidosis | 0.902 | — | established (curated) | no MR -> candidate analysis |
| primary biliary cholangitis | 0.809 | — | common-variant locus | no MR -> candidate analysis |
| Hypercholesterolemia | 0.527 | — | common-variant locus | MR: beta=0.0139, p=0.251 (cis) |
| ventricular septal defect | 0.516 | — | common-variant locus | no MR -> candidate analysis |
| obesity disorder | 0.513 | — | common-variant locus | no MR -> candidate analysis |
| biliary liver cirrhosis | 0.48 | — | common-variant locus | no MR -> candidate analysis |
| systemic lupus erythematosus | 0.48 | — | common-variant locus | MR: beta=0.059, p=0.492 (cis) |
| allergic disease | 0.478 | — | common-variant locus | no MR -> candidate analysis |
| Hearing impairment | 0.474 | — | established (curated) | no MR -> candidate analysis |
| skin disorder | 0.469 | — | common-variant locus | no MR -> candidate analysis |
| Abnormal mastoid morphology | 0.464 | — | common-variant locus | no MR -> candidate analysis |
| middle ear disorder | 0.464 | — | common-variant locus | no MR -> candidate analysis |
| diabetes mellitus | 0.443 | — | common-variant locus | no MR -> candidate analysis |
| cataract | 0.422 | — | common-variant locus | MR: beta=-0.0983, p=0.0859 (cis) |
| diabetic neuropathy | 0.422 | — | common-variant locus | no MR -> candidate analysis |
Of the 15 rows above, 12 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 (Beta-mannosidase) |
| gnomAD constraint | pLI=3.7e-21, LOEUF=0.897 — LoF-tolerant |
| GWAS Catalog | 113 unique SNPs / 257 rows |
| ClinVar | 909 records; 10 pathogenic in sample of 30 |
| PharmGKB/ClinPGx | no annotations |
phenome — Top 30 of 391 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 ‘MANBA’ and resolved to ‘Beta-mannosidase’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 909 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 76 traits by best p-value, aggregated from 105 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/O00462 — 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/ENSG00000109323/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL3903/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/MANBA — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/MANBA — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=MANBA%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/MANBA — GWAS Catalog search API (live; release not exposed)