Protein Dossier — LEPR (Leptin receptor)
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 |
| Childhood intelligence |
-0.0359 |
0.0122 |
0.00328 |
Wald ratio |
1 |
cis |
NA |
| Body mass index (BMI) |
0.00658 |
0.00232 |
0.00462 |
Wald ratio |
1 |
cis |
NA |
| Chronic kidney disease |
-0.0386 |
0.0138 |
0.00528 |
Wald ratio |
1 |
cis |
NA |
| Autism |
-0.0707 |
0.0271 |
0.00903 |
Wald ratio |
1 |
cis |
NA |
| Eczema |
0.0422 |
0.0163 |
0.00966 |
Wald ratio |
1 |
cis |
NA |
| Birth weight |
-0.0088 |
0.00349 |
0.0117 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: G47 Sleep disorders |
0.0666 |
0.0283 |
0.0188 |
Wald ratio |
1 |
cis |
NA |
| Diastolic blood pressure automated reading |
0.00558 |
0.00238 |
0.019 |
Wald ratio |
1 |
cis |
NA |
| Sleep duration |
-0.00411 |
0.00181 |
0.0232 |
Wald ratio |
1 |
cis |
NA |
| Weight |
0.0046 |
0.00205 |
0.025 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: R10 Abdominal and pelvic pain |
0.0237 |
0.0109 |
0.0302 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: K60 Fissure and fistula of anal and rectal regions |
0.0669 |
0.0322 |
0.0375 |
Wald ratio |
1 |
cis |
NA |
| …and 86 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-5400_52_3 |
sLeptin R |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
481 association rows across 219 traits (464 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 |
| Leptin receptor levels |
1e-3146 |
rs10399687 |
26 |
GCST90248273 |
no MR -> candidate analysis |
| Leptin receptor levels (LEPR.5400.52.3) |
3e-861 |
rs3790438 |
3 |
GCST90241749 |
no MR -> candidate analysis |
| C-reactive protein levels |
2e-732 |
rs2154384 |
35 |
GCST009777 |
no MR -> candidate analysis |
| Leptin receptor, soluble levels |
2e-698 |
rs2376018 |
1 |
GCST90426339 |
no MR -> candidate analysis |
| Blood protein levels |
2e-654 |
rs6658330 |
1 |
GCST006585 |
no MR -> candidate analysis |
| C-reactive protein |
2e-560 |
rs12127241 |
5 |
GCST90018950 |
no MR -> candidate analysis |
| Circulating LEPR levels |
1e-311 |
rs2376018 |
3 |
GCST90860705 |
no MR -> candidate analysis |
| C-reactive protein levels (MTAG) |
2e-310 |
rs12030543 |
21 |
GCST90179146 |
no MR -> candidate analysis |
| IL6ST/LEPR protein level ratio |
2e-267 |
rs1805094 |
1 |
GCST90315165 |
no MR -> candidate analysis |
| LEPR protein levels |
3e-251 |
rs2376018 |
6 |
GCST90469756 |
no MR -> candidate analysis |
| C-reactive protein levels (UKB data field 30710) |
1e-187 |
rs6698653 |
8 |
GCST90468064 |
no MR -> candidate analysis |
| Protein quantitative trait loci |
4e-138 |
rs61781308 |
1 |
GCST010900 |
no MR -> candidate analysis |
| …and 207 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 2475 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 |
| obesity due to leptin receptor gene deficiency |
0.829 |
— |
established (curated) |
no MR -> candidate analysis |
| type 2 diabetes mellitus |
0.795 |
— |
common-variant locus |
no MR -> candidate analysis |
| obesity disorder |
0.552 |
— |
common-variant locus |
no MR -> candidate analysis |
| diabetes mellitus |
0.475 |
— |
common-variant locus |
no MR -> candidate analysis |
| Abnormality of the skeletal system |
0.672 |
— |
common-variant locus |
no MR -> candidate analysis |
| Obesity |
0.442 |
— |
established (curated) |
MR: beta=0.00658, p=0.00462 (cis) |
| metabolic dysfunction-associated steatohepatitis |
0.377 |
— |
common-variant locus |
no MR -> candidate analysis |
| morbid obesity |
0.545 |
— |
common-variant locus |
no MR -> candidate analysis |
| obesity due to congenital leptin deficiency |
0.438 |
— |
established (curated) |
no MR -> candidate analysis |
| smoking cessation |
0.46 |
— |
common-variant locus |
no MR -> candidate analysis |
| Barrett esophagus |
0.424 |
— |
common-variant locus |
no MR -> candidate analysis |
| eye disorder |
0.424 |
— |
common-variant locus |
no MR -> candidate analysis |
| ovarian dysfunction |
0.424 |
— |
common-variant locus |
no MR -> candidate analysis |
| hereditary disease |
0.318 |
— |
established (curated) |
no MR -> candidate analysis |
| monogenic diabetes |
0.302 |
— |
established (curated) |
no MR -> candidate analysis |
Of the 15 rows above, 14 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 |
2 known modulators (Leptin receptor) |
| gnomAD constraint |
pLI=5.3e-06, LOEUF=0.61 — LoF-tolerant |
| GWAS Catalog |
184 unique SNPs / 498 rows |
| ClinVar |
579 records; 5 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
5 clinical annotations across 4 drugs |
phenome — Top 30 of 2475 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 ‘LEPR’ and resolved to ‘Leptin receptor’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 579 ClinVar records for this gene; it is a sample, not a rate.gwas_traits — Top 20 of 219 traits by best p-value, aggregated from 481 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/P48357 — 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/ENSG00000116678/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL5913/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/LEPR — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/LEPR — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=LEPR%5Bgene%5D — ClinVar build Build260809-1055.1pharmgkb: https://www.pharmgkb.org/search?query=LEPR — ClinPGx clinicalAnnotation via https://api.clinpgx.org/v1/datagwas_traits: https://www.ebi.ac.uk/gwas/genes/LEPR — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T03:29:53 · 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