Protein Dossier — SIRT2 (NAD-dependent protein deacetylase sirtuin-2)
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 |
| Diagnoses - main ICD10: R11 Nausea and vomiting |
0.184 |
0.056 |
0.00101 |
Inverse variance weighted |
3 |
trans |
NA |
| Diagnoses - main ICD10: R11 Nausea and vomiting |
0.184 |
0.056 |
0.00101 |
Inverse variance weighted |
3 |
trans |
NA |
| Diagnoses - main ICD10: R11 Nausea and vomiting |
0.184 |
0.056 |
0.00101 |
Inverse variance weighted |
3 |
trans |
NA |
| Triglycerides |
-0.0247 |
0.00817 |
0.0025 |
Inverse variance weighted |
3 |
trans |
NA |
| Triglycerides |
-0.0247 |
0.00817 |
0.0025 |
Inverse variance weighted |
3 |
trans |
NA |
| Triglycerides |
-0.0247 |
0.00817 |
0.0025 |
Inverse variance weighted |
3 |
trans |
NA |
| Melanoma |
0.345 |
0.138 |
0.0127 |
Wald ratio |
1 |
trans |
NA |
| Diagnoses - main ICD10: N20 Calculus of kidney and ureter |
-0.168 |
0.0743 |
0.0239 |
Inverse variance weighted |
3 |
trans |
NA |
| Diagnoses - main ICD10: N20 Calculus of kidney and ureter |
-0.168 |
0.0743 |
0.0239 |
Inverse variance weighted |
3 |
trans |
NA |
| Diagnoses - main ICD10: N20 Calculus of kidney and ureter |
-0.168 |
0.0743 |
0.0239 |
Inverse variance weighted |
3 |
trans |
NA |
| Happiness |
-0.0114 |
0.00523 |
0.0286 |
Inverse variance weighted |
3 |
trans |
NA |
| Happiness |
-0.0114 |
0.00523 |
0.0286 |
Inverse variance weighted |
3 |
trans |
NA |
| …and 273 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-5030_52_1 |
SIRT2 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
3 association rows across 3 traits (3 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 SIRT2 levels |
1e-137 |
rs144373891 |
1 |
GCST90859891 |
no MR -> candidate analysis |
| SIRT2 protein levels |
5e-93 |
rs144373891 |
1 |
GCST90470642 |
no MR -> candidate analysis |
| SIR2-like protein 2 levels |
7e-34 |
rs144373891 |
1 |
GCST90012061 |
no MR -> candidate analysis |
4. Phenome map — where this gene is a genetic locus, vs. where MR exists
Top diseases by Open Targets association (of 518 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 |
| type 2 diabetes mellitus |
0.163 |
— |
common-variant locus |
no MR -> candidate analysis |
| diabetes mellitus |
0.163 |
— |
common-variant locus |
no MR -> candidate analysis |
| arthropathy |
0.165 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 3 rows above, 3 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 (NAD-dependent protein deacetylase sirtuin-2) |
| gnomAD constraint |
pLI=6.7e-10, LOEUF=0.908 — LoF-tolerant |
| GWAS Catalog |
47 unique SNPs / 94 rows |
| ClinVar |
101 records; 1 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
1 clinical annotations across 1 drugs |
phenome — Top 30 of 518 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 ‘SIRT2’ and resolved to ‘NAD-dependent protein deacetylase sirtuin-2’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 101 ClinVar records for this gene; it is a sample, not a rate.gwas_traits — Top 3 of 3 traits by best p-value, aggregated from 3 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/Q8IXJ6 — 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/ENSG00000068903/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL4462/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/SIRT2 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/SIRT2 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=SIRT2%5Bgene%5D — ClinVar build Build260809-1055.1pharmgkb: https://www.pharmgkb.org/search?query=SIRT2 — ClinPGx clinicalAnnotation via https://api.clinpgx.org/v1/datagwas_traits: https://www.ebi.ac.uk/gwas/genes/SIRT2 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T05:07:46 · 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