CausalSentinel

Protein Dossier — REG1A (Lithostathine-1-alpha)

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
Non-cancer illness code self-reported: pernicious anaemia	0.00121	0.000412	0.00326	Inverse variance weighted	2	cis	NA
Non-cancer illness code self-reported: pernicious anaemia	0.00121	0.000412	0.00326	Inverse variance weighted	2	trans	NA
Alcohol intake frequency	0.0252	0.0109	0.0213	Inverse variance weighted	2	cis	NA
Alcohol intake frequency	0.0252	0.0109	0.0213	Inverse variance weighted	2	trans	NA
Non-cancer illness code self-reported: vitiligo	0.000281	0.000126	0.0257	Inverse variance weighted	2	cis	NA
Non-cancer illness code self-reported: vitiligo	0.000281	0.000126	0.0257	Inverse variance weighted	2	trans	NA
Mean cell haemoglobin concentration	-0.0291	0.0132	0.0278	Wald ratio	1	cis	NA
Mean cell haemoglobin	-0.0808	0.0396	0.0415	Wald ratio	1	cis	NA
Internalizing problems	-0.174	0.0857	0.0427	Wald ratio	1	cis	NA
ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis)	-0.0692	0.0365	0.058	Inverse variance weighted	2	cis	NA
ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis)	-0.0692	0.0365	0.058	Inverse variance weighted	2	trans	NA
Diagnoses - main ICD10: N40 Hyperplasia of prostate	-0.00135	0.000716	0.0586	Inverse variance weighted	2	cis	NA
…and 153 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

25 association rows across 14 traits (21 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 REG1A levels	2e-379	rs11126696	2	GCST90860433	no MR -> candidate analysis
REG1A protein levels	2e-311	rs76841471	5	GCST90470447	no MR -> candidate analysis
REG1B protein levels	7e-207	rs76841471	3	GCST90470448	no MR -> candidate analysis
Lithostathine-1-alpha levels	2e-91	rs76841471	4	GCST90248306	no MR -> candidate analysis
Lithostathine-1-beta levels	2e-86	rs11126696	2	GCST90248307	no MR -> candidate analysis
REG3A protein levels	2e-37	rs12990484	1	GCST90470449	no MR -> candidate analysis
Serum levels of protein REG1A	3e-25	rs76841471	1	GCST90087370	no MR -> candidate analysis
Cerebrospinal fluid protein REG1A levels	3e-18	rs76841471	1	GCST90945040	no MR -> candidate analysis
Lithostathine-1-beta (analyte X16770.3) levels	1e-16	rs76841471	1	GCST90422860	no MR -> candidate analysis
Cerebrospinal fluid protein REG1B levels	2e-16	rs11126696	1	GCST90944880	no MR -> candidate analysis
Progression free survival in epithelial ovarian cancer treat	2e-6	rs2070707	1	GCST012474	no MR -> candidate analysis
Complement factor H-related protein 2 levels	4e-6	rs205549	1	GCST90026530	no MR -> candidate analysis
…and 2 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 404 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
focal segmental glomerulosclerosis	0.195	—	established (curated)	no MR -> candidate analysis
smoking initiation	0.144	—	common-variant locus	no MR -> candidate analysis
obesity disorder	0.121	—	common-variant locus	no MR -> candidate analysis
pyogenic granuloma	0.121	—	common-variant locus	no MR -> candidate analysis
substance abuse	0.105	—	common-variant locus	no MR -> candidate analysis
attention deficit-hyperactivity disorder	0.105	—	common-variant locus	no MR -> candidate analysis

Of the 6 rows above, 6 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	not available — no ChEMBL target (undrugged)
gnomAD constraint	pLI=2.1e-07, LOEUF=1.41 — LoF-tolerant
GWAS Catalog	55 unique SNPs / 110 rows
ClinVar	44 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx	no annotations

Caveats declared by the tools

• phenome — Top 30 of 404 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.
• chembl — No ChEMBL target for ‘REG1A’.
• clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 44 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 14 of 14 traits by best p-value, aggregated from 25 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/P05451 — 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/ENSG00000115386/associations — Open Targets data release 26.06
• gnomad: https://gnomad.broadinstitute.org/gene/REG1A — gnomAD constraint via GraphQL API (reference genome GRCh38)
• gwas: https://www.ebi.ac.uk/gwas/genes/REG1A — GWAS Catalog REST (live; release not exposed by this endpoint)
• clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=REG1A%5Bgene%5D — ClinVar build Build260809-1055.1
• gwas_traits: https://www.ebi.ac.uk/gwas/genes/REG1A — GWAS Catalog search API (live; release not exposed)

Provenance

• Generated: 2026-08-14T04:46:52 · 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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