CausalSentinel

Protein Dossier — NHLRC3 (NHL repeat-containing protein 3)

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
Body mass index (BMI) 0.0193 0.00742 0.00934 Wald ratio 1 trans NA
Diagnoses - main ICD10: R04 Haemorrhage from respiratory passages 0.208 0.0844 0.0136 Wald ratio 1 trans NA
Lung cancer -0.128 0.0528 0.0152 Wald ratio 1 trans NA
Underlying (primary) cause of death: ICD10: E85.4 Organ-limited amyloidosis 1.36 0.606 0.0248 Wald ratio 1 trans NA
Diagnoses - main ICD10: J33 Nasal polyp 0.192 0.0898 0.0321 Wald ratio 1 trans NA
Diagnoses - main ICD10: K20 Oesophagitis 0.139 0.0655 0.0332 Wald ratio 1 trans NA
Non-cancer illness code self-reported: bone disorder 0.258 0.125 0.0386 Wald ratio 1 trans NA
Non-cancer illness code self-reported: kidney stone or ureter stone or bladder stone 0.149 0.0726 0.0396 Wald ratio 1 trans NA
Diagnoses - main ICD10: M17 Gonarthrosis [arthrosis of knee] 0.0969 0.0486 0.0464 Wald ratio 1 trans NA
Weight 0.0129 0.00655 0.0493 Wald ratio 1 trans NA
Non-cancer illness code self-reported: joint disorder -0.292 0.149 0.0501 Wald ratio 1 trans NA
Fractured bone site(s): Wrist -0.113 0.0595 0.0576 Wald ratio 1 trans NA
…and 68 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

7 association rows across 5 traits (5 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
NHLRC3 protein levels 5e-231 rs41286947 3 GCST90470046 no MR -> candidate analysis
Cerebrospinal fluid protein NHLRC3 levels 6e-17 rs149175958 1 GCST90944457 no MR -> candidate analysis
Height 7e-12 rs9576717 1 GCST90435412 no MR -> candidate analysis
Fibroblast growth factor basic levels 2e-6 rs183751764 1 GCST004459 no MR -> candidate analysis
Alzheimer’s disease (late onset) 4e-6 rs190094306 1 GCST007511 no MR -> candidate analysis

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

Top diseases by Open Targets association (of 65 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
musculoskeletal system disorder 0.45 common-variant locus no MR -> candidate analysis
adolescent idiopathic scoliosis 0.388 common-variant locus no MR -> candidate analysis
tooth disorder 0.31 common-variant locus no MR -> candidate analysis
polycystic ovary syndrome 0.31 common-variant locus no MR -> candidate analysis
gram-negative bacterial infections 0.125 common-variant locus no MR -> candidate analysis
bile duct disorder 0.121 common-variant locus no MR -> candidate analysis
preeclampsia 0.119 common-variant locus no MR -> candidate analysis
muscle cramp 0.119 common-variant locus no MR -> candidate analysis
Uterine leiomyoma 0.091 common-variant locus no MR -> candidate analysis
uterine corpus leiomyoma 0.079 common-variant locus no MR -> candidate analysis
Abnormal pupillary function 0.061 common-variant locus no MR -> candidate analysis
atrioventricular block 0.059 common-variant locus no MR -> candidate analysis
sialolithiasis 0.054 common-variant locus no MR -> candidate analysis
insomnia 0.054 common-variant locus no MR -> candidate analysis
Alkalosis 0.043 common-variant locus no MR -> candidate analysis

Of the 15 rows above, 15 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=2.4e-06, LOEUF=1.02 — LoF-tolerant
GWAS Catalog 44 unique SNPs / 87 rows
ClinVar 115 records; 2 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance