CausalSentinel

Protein Dossier — FAS (Fatty acid synthase)

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: ankylosing spondylitis 0.33 0.0984 7.93e-04 Wald ratio 1 cis NA
Diagnoses - main ICD10: K43 Ventral hernia -0.451 0.175 0.00995 Wald ratio 1 cis NA
Depressive symptoms -0.0248 0.011 0.0244 Wald ratio 1 cis NA
Height 0.0195 0.00881 0.0265 Wald ratio 1 cis NA
Serum creatinine (eGFRcrea) 0.00551 0.00253 0.0297 Wald ratio 1 cis NA
Inflammatory bowel disease -0.0669 0.0308 0.0298 Wald ratio 1 cis NA
Thyroid cancer -0.552 0.257 0.0319 Wald ratio 1 cis NA
Diagnoses - main ICD10: N40 Hyperplasia of prostate -0.188 0.0908 0.0385 Wald ratio 1 cis NA
Diagnoses - main ICD10: N92 Excessive frequent and irregular menstruation 0.0937 0.0455 0.0394 Wald ratio 1 cis NA
Crohn’s disease -0.0765 0.0372 0.0395 Wald ratio 1 cis NA
Serum cystatin C (eGFRcys) 0.0118 0.00578 0.0406 Wald ratio 1 cis NA
Neuroticism -0.022 0.011 0.0455 Wald ratio 1 cis NA
…and 93 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

121 association rows across 62 traits (106 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 FAS levels 8e-572 rs7911226 3 GCST90859960 no MR -> candidate analysis
Circulating FASLG levels (id: OID00694_OID20665) 8e-526 rs12775501 8 GCST90860038 no MR -> candidate analysis
Circulating FASLG levels (id: OID00792_OID20665) 1e-524 rs12775501 8 GCST90860124 no MR -> candidate analysis
Cerebrospinal fluid protein FAS levels 7e-241 rs6586166 1 GCST90944760 no MR -> candidate analysis
Tumor necrosis factor receptor superfamily member 6 levels 2e-185 rs982764 11 GCST90012035 no MR -> candidate analysis
Tumor necrosis factor receptor superfamily member 6 (analyte 2e-161 rs6586166 1 GCST90427702 no MR -> candidate analysis
Tumor necrosis factor receptor superfamily member 6 (analyte 6e-133 rs7069061 1 GCST90426338 no MR -> candidate analysis
Tumor necrosis factor receptor superfamily member 6 (analyte 6e-124 rs9658750 1 GCST90427817 no MR -> candidate analysis
Tumor necrosis factor receptor superfamily member 6 (analyte 1e-98 rs7072828 1 GCST90426610 no MR -> candidate analysis
FAS protein levels 4e-73 rs12761227 4 GCST90469192 no MR -> candidate analysis
FASLG protein levels 2e-61 rs28362318 7 GCST90469191 no MR -> candidate analysis
Tumor necrosis factor receptor superfamily member 6 levels ( 4e-43 rs7911226 4 GCST90243178 no MR -> candidate analysis
…and 50 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 3348 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
autoimmune lymphoproliferative syndrome type 1 0.94 established (curated) no MR -> candidate analysis
autoimmune lymphoproliferative syndrome 0.598 established (curated) no MR -> candidate analysis
lymphoid neoplasm 0.731 common-variant locus no MR -> candidate analysis
B-cell chronic lymphocytic leukemia 0.609 common-variant locus no MR -> candidate analysis
hypothyroidism 0.725 common-variant locus MR: beta=-0.0493, p=0.141 (cis)
hereditary disease 0.674 established (curated) no MR -> candidate analysis
lymphoid leukemia 0.607 common-variant locus no MR -> candidate analysis
immunodeficiency disease 0.559 established (curated) no MR -> candidate analysis

Of the 8 rows above, 7 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 (FAS-associated factor 1)
gnomAD constraint pLI=1, LOEUF=0.316 — LoF-INTOLERANT
GWAS Catalog 93 unique SNPs / 185 rows
ClinVar 558 records; 8 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance