Protein Dossier — GRN (Progranulin)
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 |
| Serum cystatin C (eGFRcys) |
0.0217 |
0.00721 |
0.00268 |
Inverse variance weighted |
2 |
cis |
NA |
| Serum cystatin C (eGFRcys) |
0.0217 |
0.00721 |
0.00268 |
Inverse variance weighted |
2 |
trans |
NA |
| Parkinson’s disease |
-0.697 |
0.252 |
0.00571 |
Wald ratio |
1 |
trans |
NA |
| Age at menarche |
-0.058 |
0.0214 |
0.0066 |
Inverse variance weighted |
2 |
cis |
NA |
| Age at menarche |
-0.058 |
0.0214 |
0.0066 |
Inverse variance weighted |
2 |
trans |
NA |
| Lumbar spine bone mineral density |
-0.129 |
0.0517 |
0.0129 |
Wald ratio |
1 |
trans |
NA |
| Schizophrenia |
0.0865 |
0.0356 |
0.015 |
Inverse variance weighted |
2 |
cis |
NA |
| Schizophrenia |
0.0865 |
0.0356 |
0.015 |
Inverse variance weighted |
2 |
trans |
NA |
| Alzheimer’s disease |
-0.145 |
0.06 |
0.0158 |
Inverse variance weighted |
2 |
cis |
NA |
| Alzheimer’s disease |
-0.145 |
0.06 |
0.0158 |
Inverse variance weighted |
2 |
trans |
NA |
| Birth length |
0.0753 |
0.032 |
0.0185 |
Inverse variance weighted |
2 |
cis |
NA |
| Birth length |
0.0753 |
0.032 |
0.0185 |
Inverse variance weighted |
2 |
trans |
NA |
| …and 194 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-4992_49_1 |
GRN |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
32 association rows across 25 traits (28 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 |
| Circulating GRN levels |
8e-463 |
rs5848 |
1 |
GCST90859928 |
no MR -> candidate analysis |
| Circulating CEACAM8 levels |
6e-162 |
rs114641762 |
1 |
GCST90859796 |
no MR -> candidate analysis |
| CEACAM8 protein levels |
5e-125 |
rs114641762 |
1 |
GCST90468698 |
no MR -> candidate analysis |
| Granulins levels |
7e-60 |
rs5848 |
4 |
GCST90247801 |
no MR -> candidate analysis |
| Complement C1q tumor necrosis factor-related protein 1 level |
3e-59 |
rs5848 |
1 |
GCST90246766 |
no MR -> candidate analysis |
| SEMA3G protein levels |
2e-46 |
rs5848 |
1 |
GCST90470571 |
no MR -> candidate analysis |
| Cerebrospinal fluid protein GRN levels |
3e-44 |
rs5848 |
1 |
GCST90944774 |
no MR -> candidate analysis |
| LRRC37A2 protein levels |
5e-29 |
rs9895894 |
1 |
GCST90469802 |
no MR -> candidate analysis |
| Cerebrospinal fluid protein SEMA3G levels |
2e-27 |
rs5848 |
1 |
GCST90944562 |
no MR -> candidate analysis |
| Eosinophil side fluorescence |
1e-23 |
rs114641762 |
1 |
GCST90281231 |
no MR -> candidate analysis |
| Granulins levels (GRN.4992.49.1) |
8e-23 |
rs5848 |
1 |
GCST90241317 |
no MR -> candidate analysis |
| Eosinophil side scatter |
1e-22 |
rs114641762 |
1 |
GCST90281230 |
no MR -> candidate analysis |
| …and 13 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 1815 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 |
| neuronal ceroid lipofuscinosis 11 |
0.915 |
— |
established (curated) |
no MR -> candidate analysis |
| GRN-related frontotemporal lobar degeneration with Tdp43 inclusions |
0.848 |
— |
established (curated) |
no MR -> candidate analysis |
| CLN11 disease |
0.608 |
— |
established (curated) |
no MR -> candidate analysis |
| frontotemporal dementia |
0.887 |
— |
established (curated) |
no MR -> candidate analysis |
| Alzheimer disease |
0.713 |
— |
established (curated) |
no MR -> candidate analysis |
| dementia |
0.675 |
0.563 |
multi-layer: burden+GWAS (allelic-series candidate) |
no MR -> candidate analysis |
| hereditary disease |
0.801 |
— |
established (curated) |
no MR -> candidate analysis |
| amyotrophic lateral sclerosis |
0.608 |
— |
established (curated) |
MR: beta=-0.129, p=0.118 (cis) |
| primary progressive aphasia |
0.596 |
— |
established (curated) |
no MR -> candidate analysis |
| frontotemporal dementia and/or amyotrophic lateral sclerosis |
0.195 |
— |
established (curated) |
no MR -> candidate analysis |
| frontotemporal dementia with motor neuron disease |
0.608 |
— |
established (curated) |
no MR -> candidate analysis |
| neurodegenerative disease |
0.485 |
— |
common-variant locus |
no MR -> candidate analysis |
| Parkinson disease |
0.547 |
— |
established (curated) |
no MR -> candidate analysis |
| Cognitive impairment |
0.559 |
— |
established (curated) |
no MR -> candidate analysis |
| mental disorder |
0.558 |
0.558 |
exploratory rare-variant signal |
no MR -> candidate analysis |
Of the 15 rows above, 14 have no MR estimate in this resource. Across all retrieved diseases for this gene: 1 exploratory rare-variant signal(s), 1 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 (Sortilin/Progranulin) |
| gnomAD constraint |
pLI=0.015, LOEUF=0.61 — LoF-tolerant |
| GWAS Catalog |
66 unique SNPs / 132 rows |
| ClinVar |
844 records; 2 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 1815 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 ‘GRN’ and resolved to ‘Sortilin/Progranulin’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 844 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 25 traits by best p-value, aggregated from 32 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/P28799 — 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/ENSG00000030582/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL4680051/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/GRN — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/GRN — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=GRN%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/GRN — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T02:54:33 · 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