Protein Dossier — SHBG (Sex hormone-binding globulin)
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 |
| Body fat |
0.106 |
0.0266 |
7.34e-05 |
Wald ratio |
1 |
cis |
NA |
| HDL cholesterol |
0.0893 |
0.0243 |
2.40e-04 |
Wald ratio |
1 |
cis |
NA |
| Hirschsprung’s disease |
2.19 |
0.606 |
2.97e-04 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: deep venous thrombosis (dvt) |
0.221 |
0.0646 |
6.33e-04 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hypertension |
0.0601 |
0.0182 |
9.35e-04 |
Wald ratio |
1 |
cis |
NA |
| Cardioembolic stroke |
-0.497 |
0.162 |
0.00212 |
Wald ratio |
1 |
cis |
NA |
| Alcohol intake frequency |
-0.0494 |
0.0167 |
0.00314 |
Wald ratio |
1 |
cis |
NA |
| Platelet count |
-6.61 |
2.25 |
0.00323 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: H25 Senile cataract |
0.265 |
0.1 |
0.00811 |
Wald ratio |
1 |
cis |
NA |
| Creatinine (enzymatic) in urine |
-0.027 |
0.0108 |
0.0125 |
Wald ratio |
1 |
cis |
NA |
| Birth length |
0.128 |
0.0523 |
0.0148 |
Wald ratio |
1 |
cis |
NA |
| Haemoglobin concentration |
0.0715 |
0.0294 |
0.0152 |
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-4929_55_1 |
SHBG |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
210 association rows across 88 traits (202 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 |
| Sex hormone-binding globulin levels |
2e-3373 |
rs6258 |
34 |
GCST90025958 |
no MR -> candidate analysis |
| Sex hormone-binding globulin levels adjusted for BMI |
2e-3229 |
rs858519 |
4 |
GCST90012110 |
no MR -> candidate analysis |
| Total testosterone levels |
1e-758 |
rs1799941 |
13 |
GCST90239819 |
no MR -> candidate analysis |
| Bioavailable testosterone levels |
8e-309 |
rs727428 |
8 |
GCST90012102 |
no MR -> candidate analysis |
| Testosterone levels (UKB data field 30850) |
2e-294 |
rs1799941 |
2 |
GCST90468103 |
no MR -> candidate analysis |
| Diamine acetyltransferase 2 levels |
3e-282 |
rs858522 |
3 |
GCST90247237 |
no MR -> candidate analysis |
| Free testosterone levels |
1e-233 |
rs727428 |
4 |
GCST90239826 |
no MR -> candidate analysis |
| Body fat percentage (adjusted for testosterone and SHBG) |
1e-224 |
rs1799941 |
15 |
GCST90432179 |
no MR -> candidate analysis |
| N6-acetyllysine levels |
9e-176 |
rs13894 |
6 |
GCST90245307 |
no MR -> candidate analysis |
| SAT2 protein levels |
1e-174 |
rs148093673 |
5 |
GCST90470529 |
no MR -> candidate analysis |
| Hypogonadism |
1e-136 |
rs1799941 |
4 |
GCST90570530 |
no MR -> candidate analysis |
| Blood protein levels |
1e-111 |
rs858519 |
5 |
GCST006585 |
no MR -> candidate analysis |
| …and 76 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 724 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 |
| testicular disorder |
0.726 |
— |
common-variant locus |
no MR -> candidate analysis |
| Abnormality of the skeletal system |
0.686 |
— |
common-variant locus |
no MR -> candidate analysis |
| type 2 diabetes mellitus |
0.633 |
— |
common-variant locus |
no MR -> candidate analysis |
| smoking cessation |
0.499 |
— |
common-variant locus |
no MR -> candidate analysis |
| hypogonadism |
0.435 |
— |
common-variant locus |
no MR -> candidate analysis |
| aging |
0.463 |
— |
common-variant locus |
no MR -> candidate analysis |
| osteoarthritis, hip |
0.385 |
— |
common-variant locus |
MR: beta=0.0925, p=0.474 (cis) |
| atrial fibrillation |
0.268 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 8 rows above, 7 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 (Sex hormone-binding globulin) |
| gnomAD constraint |
pLI=8.2e-12, LOEUF=1.16 — LoF-tolerant |
| GWAS Catalog |
225 unique SNPs / 584 rows |
| ClinVar |
127 records; 0 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 724 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 ‘SHBG’ and resolved to ‘Sex hormone-binding globulin’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 127 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 88 traits by best p-value, aggregated from 210 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/P04278 — 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/ENSG00000129214/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL3305/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/SHBG — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/SHBG — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=SHBG%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/SHBG — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T05:04:43 · 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