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 |
| Height |
0.113 |
0.0177 |
1.97e-10 |
Wald ratio |
1 |
cis |
6.8e-06 |
| Heel bone mineral density (BMD) T-score automated |
0.115 |
0.0189 |
1.26e-09 |
Wald ratio |
1 |
cis |
0.21 |
| Forced vital capacity (FVC) |
0.0625 |
0.012 |
1.80e-07 |
Wald ratio |
1 |
cis |
0.0463 |
| Weight |
0.0664 |
0.0129 |
2.54e-07 |
Wald ratio |
1 |
cis |
0.603 |
| Forced expiratory volume in 1-second (FEV1) |
0.0461 |
0.0126 |
2.58e-04 |
Wald ratio |
1 |
cis |
NA |
| Birth weight |
0.0725 |
0.0215 |
7.38e-04 |
Wald ratio |
1 |
cis |
NA |
| Creatinine (enzymatic) in urine |
0.0447 |
0.014 |
0.00136 |
Wald ratio |
1 |
cis |
NA |
| Birth length |
0.164 |
0.0612 |
0.00727 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: K80 Cholelithiasis |
0.22 |
0.0822 |
0.00743 |
Wald ratio |
1 |
cis |
NA |
| Femoral neck bone mineral density |
0.122 |
0.0457 |
0.00747 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: M16 Coxarthrosis [arthrosis of hip] |
0.252 |
0.0954 |
0.00813 |
Wald ratio |
1 |
cis |
NA |
| Potassium in urine |
0.037 |
0.0148 |
0.0125 |
Wald ratio |
1 |
cis |
NA |
| …and 112 more outcomes (see JSON) |
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|
2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-2962_50_2 |
PTHrP |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
290 association rows across 130 traits (249 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 |
| MANSC4 protein levels |
4e-215 |
rs12425609 |
11 |
GCST90469848 |
no MR -> candidate analysis |
| Height |
4e-176 |
rs10843078 |
35 |
GCST90245848 |
MR: beta=0.113, p=1.97e-10 (cis) |
| Breast cancer |
6e-72 |
rs7297051 |
16 |
GCST90090980 |
no MR -> candidate analysis |
| Type 2 diabetes |
1e-69 |
rs10842991 |
22 |
GCST90492734 |
MR: beta=0.202, p=0.199 (cis) |
| Osteoarthritis (with total hip replacement) |
5e-57 |
rs10843013 |
2 |
GCST90566802 |
no MR -> candidate analysis |
| Standing height (UKB data field 50) |
4e-49 |
rs180958337 |
4 |
GCST90468178 |
no MR -> candidate analysis |
| Whole brain restricted isotropic diffusion (multivariate ana |
2e-44 |
rs10843091 |
1 |
GCST90131904 |
no MR -> candidate analysis |
| Osteoarthritis (hip) |
1e-41 |
rs10843013 |
4 |
GCST90566798 |
MR: beta=0.313, p=0.0271 (cis) |
| Unsupervised deep imaging phenotypes (UDIP-FA) |
3e-31 |
rs2054474 |
6 |
GCST90860937 |
no MR -> candidate analysis |
| Whole brain free water diffusion (multivariate analysis) |
7e-31 |
rs10843091 |
1 |
GCST90131906 |
no MR -> candidate analysis |
| Vertex-wise cortical surface area |
1e-30 |
rs10843104 |
2 |
GCST90095130 |
no MR -> candidate analysis |
| Fasting blood glucose |
2e-30 |
rs10771370 |
2 |
GCST90662896 |
no MR -> candidate analysis |
| …and 118 more traits (see JSON) |
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4. Phenome map — where this gene is a genetic locus, vs. where MR exists
Top diseases by Open Targets association (of 2581 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 |
| brachydactyly type E |
0.81 |
— |
established (curated) |
no MR -> candidate analysis |
| Abnormality of the skeletal system |
0.775 |
— |
common-variant locus |
no MR -> candidate analysis |
| breast carcinoma |
0.667 |
— |
common-variant locus |
no MR -> candidate analysis |
| breast neoplasm |
0.63 |
— |
common-variant locus |
MR: beta=0.161, p=0.101 (cis) |
| breast cancer |
0.602 |
— |
common-variant locus |
no MR -> candidate analysis |
| androgenetic alopecia |
0.636 |
— |
common-variant locus |
no MR -> candidate analysis |
| cancer |
0.525 |
— |
common-variant locus |
MR: beta=1.01, p=0.0335 (cis) |
| open-angle glaucoma |
0.555 |
— |
common-variant locus |
no MR -> candidate analysis |
| hereditary disease |
0.553 |
— |
established (curated) |
no MR -> candidate analysis |
| breast disorder |
0.537 |
— |
common-variant locus |
no MR -> candidate analysis |
| Abnormality of the breast |
0.52 |
— |
common-variant locus |
no MR -> candidate analysis |
| alopecia |
0.511 |
— |
common-variant locus |
no MR -> candidate analysis |
| estrogen-receptor negative breast cancer |
0.5 |
— |
common-variant locus |
no MR -> candidate analysis |
| Breast hypertrophy |
0.472 |
— |
common-variant locus |
no MR -> candidate analysis |
| spinal stenosis |
0.473 |
— |
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.
5. Downstream annotation (druggability & safety preview)
| Layer |
Result |
| ChEMBL druggability |
1 known modulators (Parathyroid hormone-related protein) |
| gnomAD constraint |
pLI=0.92, LOEUF=0.564 — LoF-INTOLERANT |
| GWAS Catalog |
149 unique SNPs / 354 rows |
| ClinVar |
167 records; 6 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 2581 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 ‘PTHLH’ and resolved to ‘Parathyroid hormone-related protein’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 167 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 130 traits by best p-value, aggregated from 290 association rows. These are GWAS ASSOCIATIONS (loci), not causal claims; mapped genes at a locus are not necessarily the effector gene.
Sources
uniprot: https://www.uniprot.org/uniprotkb/P12272 — 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/ENSG00000087494/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL3712869/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/PTHLH — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/PTHLH — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=PTHLH%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/PTHLH — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T04:41:36 · Tier: A
- Fully mechanical: every cell above is rendered from tool return values. No language model wrote any part of this dossier.
- MR estimates, where present, are retrieved from published work (EpiGraphDB pQTL, Zheng et al. Nat Genet 2020); nothing is computed here.
- Tool errors this run: none