CausalSentinel

Protein Dossier — NAALAD2 (N-acetylated-alpha-linked acidic dipeptidase 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
Celiac disease	0.417	0.085	8.97e-07	Wald ratio	1	trans	NA
Multiple sclerosis	-0.305	0.0696	1.18e-05	Wald ratio	1	trans	NA
Pulse rate	-0.0394	0.0118	8.66e-04	Inverse variance weighted	2	trans	NA
Pulse rate	-0.0394	0.0118	8.66e-04	Inverse variance weighted	2	trans	NA
Heel bone mineral density (BMD) T-score automated	0.0273	0.0086	0.00153	Inverse variance weighted	2	trans	NA
Heel bone mineral density (BMD) T-score automated	0.0273	0.0086	0.00153	Inverse variance weighted	2	trans	NA
Juvenile idiopathic arthritis	0.677	0.242	0.00516	Wald ratio	1	trans	NA
Transferrin	0.823	0.302	0.00647	Inverse variance weighted	2	trans	NA
Transferrin	0.823	0.302	0.00647	Inverse variance weighted	2	trans	NA
Non-cancer illness code self-reported: deep venous thrombosis (dvt)	-0.139	0.0544	0.0106	Inverse variance weighted	2	trans	NA
Non-cancer illness code self-reported: deep venous thrombosis (dvt)	-0.139	0.0544	0.0106	Inverse variance weighted	2	trans	NA
Rheumatoid arthritis	0.104	0.0447	0.0197	Inverse variance weighted	2	trans	NA
…and 205 more outcomes (see JSON)

2. pQTL instrument availability (Tier-B probe)

No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).

3. GWAS Catalog results — traits with signal at this locus

46 association rows across 24 traits (45 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
X-12748 levels	9e-249	rs1943379	1	GCST90245566	no MR -> candidate analysis
Beta-citrylglutamate levels	5e-167	rs489009	9	GCST90199911	no MR -> candidate analysis
Metabolite levels (beta-citrylglutamate)	2e-78	rs1943379	4	GCST90300292	no MR -> candidate analysis
Plasma beta-citrylglutamate levels in chronic kidney disease	3e-73	rs7108196	1	GCST90264850	no MR -> candidate analysis
Serum metabolite levels	2e-47	rs1943379	2	GCST012020	no MR -> candidate analysis
Urine beta-citrylglutamate levels in chronic kidney disease	2e-47	rs7108196	1	GCST90264851	no MR -> candidate analysis
Urinary metabolite levels in chronic kidney disease	3e-25	rs7108196	1	GCST009733	no MR -> candidate analysis
Height	3e-22	rs10501709	3	GCST90245848	no MR -> candidate analysis
White blood cell count (basophil)	2e-16	rs11018874	2	GCST005976	no MR -> candidate analysis
Urinary metabolite modules (eigenmetabolites) in chronic kid	2e-14	rs7108196	1	GCST009735	no MR -> candidate analysis
Hematological traits (multi-trait analysis)	5e-14	rs4366446	2	GCST90838663	no MR -> candidate analysis
Weight	2e-13	rs12803230	1	GCST90662910	MR: beta=-0.0137, p=0.194 (trans)
…and 12 more traits (see JSON)

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 76 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
actinic keratosis	0.525	—	common-variant locus	no MR -> candidate analysis
diabetes mellitus	0.072	—	common-variant locus	no MR -> candidate analysis
sleep apnea syndrome	0.072	—	common-variant locus	no MR -> candidate analysis
major depressive disorder	0.07	—	common-variant locus	MR: beta=0.083, p=0.18 (trans)
attention deficit-hyperactivity disorder	0.07	—	common-variant locus	no MR -> candidate analysis
substance abuse	0.07	—	common-variant locus	no MR -> candidate analysis
type 2 diabetes mellitus	0.069	—	common-variant locus	no MR -> candidate analysis
alcohol drinking	0.067	—	common-variant locus	no MR -> candidate analysis
obesity disorder	0.065	—	common-variant locus	no MR -> candidate analysis
mathematical ability	0.064	—	common-variant locus	no MR -> candidate analysis
squamous cell carcinoma	0.063	—	common-variant locus	no MR -> candidate analysis
vitiligo	0.063	—	common-variant locus	no MR -> candidate analysis
basal cell carcinoma	0.055	—	common-variant locus	no MR -> candidate analysis
intelligence	0.052	—	common-variant locus	no MR -> candidate analysis
Tietze syndrome	0.051	—	common-variant locus	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	0 known modulators (N-acetylated-alpha-linked acidic dipeptidase 2)
gnomAD constraint	pLI=1.8e-28, LOEUF=1.11 — LoF-tolerant
GWAS Catalog	40 unique SNPs / 80 rows
ClinVar	144 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx	no annotations

Caveats declared by the tools

• phenome — Top 30 of 76 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 ‘NAALAD2’ and resolved to ‘N-acetylated-alpha-linked acidic dipeptidase 2’ — confirm this is the intended target.
• clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 144 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 24 traits by best p-value, aggregated from 46 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/Q9Y3Q0 — 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 v3.0
• phenome: https://platform.opentargets.org/target/ENSG00000077616/associations — Open Targets data release 26.06
• chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL2609/ — ChEMBL_37 (released 2026-05-01)
• gnomad: https://gnomad.broadinstitute.org/gene/NAALAD2 — gnomAD constraint via GraphQL API (reference genome GRCh38)
• gwas: https://www.ebi.ac.uk/gwas/genes/NAALAD2 — GWAS Catalog REST (live; release not exposed by this endpoint)
• clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=NAALAD2%5Bgene%5D — ClinVar build Build260809-1055.1
• gwas_traits: https://www.ebi.ac.uk/gwas/genes/NAALAD2 — GWAS Catalog search API (live; release not exposed)

Provenance

• Generated: 2026-08-14T03:54:26 · 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

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