CausalSentinel

Protein Dossier — FAM20A (Pseudokinase FAM20A)

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
Alzheimer’s disease 0.226 0.0772 0.00346 Wald ratio 1 cis NA
Lumbar spine bone mineral density 0.119 0.0412 0.00392 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypertrophic cardiomyopathy (hcm or hocm) 0.96 0.342 0.00503 Wald ratio 1 cis NA
Non-cancer illness code self-reported: vaginal prolapse or uterine prolapse 0.256 0.119 0.032 Wald ratio 1 cis NA
Diagnoses - main ICD10: K40 Inguinal hernia -0.171 0.0816 0.0358 Wald ratio 1 cis NA
Non-cancer illness code self-reported: kidney stone or ureter stone or bladder stone -0.4 0.197 0.0425 Wald ratio 1 cis NA
Non-cancer illness code self-reported: psoriasis 0.175 0.0891 0.0501 Wald ratio 1 cis NA
Caudate volume 44.2 23 0.0545 Wald ratio 1 cis NA
Pallidum volume 17.3 9 0.0547 Wald ratio 1 cis NA
Diagnoses - main ICD10: I83 Varicose veins of lower extremities 0.129 0.0689 0.0607 Wald ratio 1 cis NA
Diagnoses - main ICD10: K20 Oesophagitis -0.29 0.155 0.0618 Wald ratio 1 cis NA
Diagnoses - main ICD10: R10 Abdominal and pelvic pain -0.112 0.0605 0.0651 Wald ratio 1 cis NA
…and 62 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

23 association rows across 15 traits (15 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
Height 5e-30 rs2952317 6 GCST90245848 no MR -> candidate analysis
FAM20A protein levels 2e-29 rs72849705 2 GCST90469185 no MR -> candidate analysis
KLB protein levels 2e-23 rs193135916 1 GCST90469693 no MR -> candidate analysis
Pseudokinase FAM20A levels 4e-17 rs3214285 1 GCST90247538 no MR -> candidate analysis
Body shape phenotype PC2 3e-13 rs2907384 1 GCST90832990 no MR -> candidate analysis
Mosaic loss of chromosome X 9e-11 rs16973034 2 GCST90328148 no MR -> candidate analysis
Height (baseline) 3e-9 rs2907384 1 GCST90565843 no MR -> candidate analysis
Blood cell traits latent factor 17 (white cell) 2e-8 rs2952313 1 GCST90559259 no MR -> candidate analysis
Crohn’s disease (Tractor method with African ancestry) 5e-7 rs530538676 1 GCST90825984 no MR -> candidate analysis
Glioblastoma 3e-6 rs191695598 2 GCST90296481 no MR -> candidate analysis
Neonatal abstinence syndrome 3e-6 rs2952303 1 GCST90134524 no MR -> candidate analysis
3-hydroxy-1-methylpropylmercapturic acid levels in smokers 4e-6 rs12453524 1 GCST002957 no MR -> candidate analysis
…and 3 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 1428 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
amelogenesis imperfecta type 1G 0.891 established (curated) no MR -> candidate analysis
otosclerosis 0.543 common-variant locus no MR -> candidate analysis
Alzheimer disease 0.44 common-variant locus no MR -> candidate analysis
Chorioretinal scar 0.44 common-variant locus no MR -> candidate analysis
hearing loss, mixed conductive-sensorineural 0.343 common-variant locus no MR -> candidate analysis
cholelithiasis 0.324 common-variant locus no MR -> candidate analysis
hereditary disease 0.318 established (curated) no MR -> candidate analysis
Carney complex, type 1 0.243 established (curated) no MR -> candidate analysis
Acrodysostosis 1 with or without hormone resistance 0.195 established (curated) no MR -> candidate analysis
Hypercholesterolemia 0.204 common-variant locus MR: beta=0.0442, p=0.126 (cis)
familial atrial myxoma 0.195 established (curated) no MR -> candidate analysis
pigmented nodular adrenocortical disease, primary, 1 0.195 established (curated) no MR -> candidate analysis
metabolic disease 0.181 common-variant locus no MR -> candidate analysis
hyperlipidemia 0.181 common-variant locus no MR -> candidate analysis
Abnormality of the skeletal system 0.176 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 not available — no ChEMBL target (undrugged)
gnomAD constraint pLI=3.6e-12, LOEUF=1.04 — LoF-tolerant
GWAS Catalog 100 unique SNPs / 180 rows
ClinVar 390 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance