Protein Dossier — NAAA (N-acylethanolamine-hydrolyzing acid amidase)
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 |
| Rheumatoid arthritis |
-0.089 |
0.0309 |
0.00396 |
Wald ratio |
1 |
cis |
NA |
| Eczema |
-0.0963 |
0.0338 |
0.00435 |
Wald ratio |
1 |
cis |
NA |
| Hearing difficulty or problems: Yes |
-0.0244 |
0.00863 |
0.00474 |
Wald ratio |
1 |
cis |
NA |
| Thyroid cancer |
0.456 |
0.163 |
0.00507 |
Wald ratio |
1 |
cis |
NA |
| Endometrioid ovarian cancer |
0.148 |
0.0579 |
0.0105 |
Wald ratio |
1 |
cis |
NA |
| Alzheimer’s disease |
0.0797 |
0.0323 |
0.0136 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: migraine |
-0.0685 |
0.0302 |
0.0234 |
Wald ratio |
1 |
cis |
NA |
| Age at menopause |
-0.0729 |
0.0365 |
0.0455 |
Wald ratio |
1 |
cis |
NA |
| Fasting proinsulin |
0.0292 |
0.0146 |
0.0455 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: R04 Haemorrhage from respiratory passages |
0.119 |
0.0604 |
0.0488 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: K44 Diaphragmatic hernia |
0.0717 |
0.0364 |
0.0489 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: M23 Internal derangement of knee |
0.0601 |
0.0309 |
0.0517 |
Wald ratio |
1 |
cis |
NA |
| …and 98 more outcomes (see JSON) |
|
|
|
|
|
|
|
2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3173_49_2 |
ASAHL |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
42 association rows across 22 traits (40 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 NAAA levels |
2e-2150 |
rs112197434 |
3 |
GCST90859725 |
no MR -> candidate analysis |
| CTSF/NAAA protein level ratio |
6e-2078 |
rs4859572 |
1 |
GCST90314314 |
no MR -> candidate analysis |
| CREG1/NAAA protein level ratio |
3e-1897 |
rs4859572 |
1 |
GCST90314250 |
no MR -> candidate analysis |
| NAAA/SMPD1 protein level ratio |
2e-1786 |
rs4859572 |
1 |
GCST90315510 |
no MR -> candidate analysis |
| CTSZ/NAAA protein level ratio |
7e-1722 |
rs4859572 |
1 |
GCST90314320 |
no MR -> candidate analysis |
| N-acylethanolamine-hydrolyzing acid amidase levels |
1e-570 |
rs111981122 |
12 |
GCST90248592 |
no MR -> candidate analysis |
| Serum levels of protein NAAA |
1e-263 |
rs10518142 |
3 |
GCST90088245 |
no MR -> candidate analysis |
| CXCL10/CXCL9 protein level ratio |
1e-233 |
rs13118503 |
1 |
GCST90314331 |
no MR -> candidate analysis |
| Blood protein levels |
4e-159 |
rs58317633 |
2 |
GCST006585 |
no MR -> candidate analysis |
| N-acylethanolamine-hydrolyzing acid amidase levels (NAAA.317 |
4e-101 |
rs9996608 |
3 |
GCST90242013 |
no MR -> candidate analysis |
| NAAA protein levels |
4e-99 |
rs7664613 |
3 |
GCST90469991 |
no MR -> candidate analysis |
| N-acylethanolamine-hydrolyzing acid amidase level in Chronic |
4e-72 |
rs111427893 |
1 |
GCST90237251 |
no MR -> candidate analysis |
| …and 10 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 165 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 |
| Tietze syndrome |
0.41 |
— |
common-variant locus |
no MR -> candidate analysis |
| cellulitis |
0.41 |
— |
common-variant locus |
MR: beta=0.0877, p=0.0785 (cis) |
| abscess |
0.41 |
— |
common-variant locus |
no MR -> candidate analysis |
| familial hemolytic anemia |
0.295 |
— |
common-variant locus |
no MR -> candidate analysis |
| type 2 diabetes mellitus |
0.039 |
— |
common-variant locus |
no MR -> candidate analysis |
| device complication |
0.038 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 6 rows above, 5 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 (N-acylethanolamine-hydrolyzing acid amidase) |
| gnomAD constraint |
pLI=3.2e-12, LOEUF=1.14 — LoF-tolerant |
| GWAS Catalog |
93 unique SNPs / 186 rows |
| ClinVar |
110 records; 2 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 165 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 ‘NAAA’ and resolved to ‘N-acylethanolamine-hydrolyzing acid amidase’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 110 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 22 traits by best p-value, aggregated from 42 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/Q02083 — 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/ENSG00000138744/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL4349/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/NAAA — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/NAAA — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=NAAA%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/NAAA — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T03:54:05 · 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