CausalSentinel

Protein Dossier — ASIP (Agouti-signaling protein)

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
Weight -0.0316 0.00373 2.44e-17 Wald ratio 1 cis NA
Cancer code self-reported: basal cell carcinoma 0.209 0.0358 4.87e-09 Wald ratio 1 cis NA
Cancer code self-reported: malignant melanoma 0.202 0.0392 2.45e-07 Wald ratio 1 cis NA
Putamen volume -42.6 11.6 2.45e-04 Wald ratio 1 cis NA
Body mass index (BMI) -0.014 0.00422 8.94e-04 Wald ratio 1 cis NA
Pallidum volume -11.3 3.72 0.00238 Wald ratio 1 cis NA
Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.036 0.0122 0.00308 Wald ratio 1 cis NA
Sodium in urine 0.0117 0.00416 0.00474 Wald ratio 1 cis NA
Hearing difficulty or problems: Yes 0.0201 0.00715 0.00485 Wald ratio 1 cis NA
Amyotrophic lateral sclerosis -0.084 0.0344 0.0146 Wald ratio 1 cis NA
Diagnoses - main ICD10: N40 Hyperplasia of prostate 0.095 0.04 0.0176 Wald ratio 1 cis NA
Forced vital capacity (FVC) -0.008 0.00347 0.0209 Wald ratio 1 cis NA
…and 85 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

54 association rows across 51 traits (50 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
AHCY/FADD protein level ratio 4e-477 rs78639799 1 GCST90313209 no MR -> candidate analysis
Agouti-signaling protein levels 3e-428 rs565102642 1 GCST90246599 no MR -> candidate analysis
AHCY/KYAT1 protein level ratio 4e-401 rs78639799 1 GCST90313212 no MR -> candidate analysis
AHCY/HSPA1A protein level ratio 2e-395 rs78639799 1 GCST90313211 no MR -> candidate analysis
AHCY/SNAP23 protein level ratio 3e-345 rs78639799 1 GCST90313213 no MR -> candidate analysis
AHCY/FABP5 protein level ratio 2e-294 rs78639799 1 GCST90313208 no MR -> candidate analysis
Agouti-signaling protein levels (ASIP.5676.54.3) 1e-136 rs565102642 1 GCST90240218 no MR -> candidate analysis
soluble Endothelial protein C receptor levels 1e-62 rs17332951 1 GCST90424885 no MR -> candidate analysis
PROCR protein levels 1e-51 rs117964690 1 GCST90453400 no MR -> candidate analysis
Cutaneous melanoma (MTAG) 2e-38 rs4911412 1 GCST90103971 no MR -> candidate analysis
Burning and freckling 6e-37 rs1015362; rs4911414 1 GCST000196 no MR -> candidate analysis
Freckles 8e-29 rs1015362; rs4911414 1 GCST000197 no MR -> candidate analysis
…and 39 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 695 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
oculocutaneous albinism type 6 0.547 established (curated) no MR -> candidate analysis
hair color 0.592 common-variant locus no MR -> candidate analysis
obesity and hypopigmentation 0.547 established (curated) no MR -> candidate analysis
skin disorder 0.483 common-variant locus no MR -> candidate analysis
phototoxic dermatitis 0.425 common-variant locus no MR -> candidate analysis
systemic lupus erythematosus 0.395 common-variant locus no MR -> candidate analysis
neoplasm 0.36 common-variant locus MR: beta=0.0632, p=0.0414 (cis)
keloid 0.381 common-variant locus no MR -> candidate analysis
skin neoplasm 0.356 common-variant locus no MR -> candidate analysis
skin cancer 0.345 common-variant locus no MR -> candidate analysis
melanoma 0.321 common-variant locus MR: beta=0.202, p=2.45e-07 (cis)
cutaneous melanoma 0.336 common-variant locus no MR -> candidate analysis
seborrheic dermatitis 0.329 common-variant locus no MR -> candidate analysis
basal cell carcinoma 0.32 common-variant locus MR: beta=0.209, p=4.87e-09 (cis)
pathological myopia 0.265 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 12 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=7.4e-05, LOEUF=1.78 — LoF-tolerant
GWAS Catalog 69 unique SNPs / 132 rows
ClinVar 47 records; 7 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance