CausalSentinel

Protein Dossier — NDC80 (Kinetochore protein NDC80 homolog)

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
Diagnoses - main ICD10: M72 Fibroblastic disorders 0.378 0.125 0.00248 Wald ratio 1 trans NA
Eye problems or disorders: Glaucoma 0.246 0.0865 0.00443 Wald ratio 1 trans NA
Non-cancer illness code self-reported: retinal detachment 0.43 0.154 0.00512 Wald ratio 1 trans NA
Neuroticism 0.043 0.0172 0.0124 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hypertension 0.0522 0.0213 0.0142 Wald ratio 1 trans NA
Non-cancer illness code self-reported: depression 0.115 0.0485 0.0178 Wald ratio 1 trans NA
Sodium in urine 0.0297 0.013 0.0217 Wald ratio 1 trans NA
Diagnoses - main ICD10: R11 Nausea and vomiting 0.346 0.153 0.0234 Wald ratio 1 trans NA
Squamous cell lung cancer -0.308 0.137 0.0245 Wald ratio 1 trans NA
Non-cancer illness code self-reported: migraine 0.148 0.0659 0.0248 Wald ratio 1 trans NA
Intracranial volume -2.29e+04 1.03e+04 0.0256 Wald ratio 1 trans NA
Diagnoses - main ICD10: I80 Phlebitis and thrombophlebitis 0.318 0.144 0.0267 Wald ratio 1 trans NA
…and 78 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

4 association rows across 4 traits (0 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
Tinnitus 5e-7 rs145362852 1 GCST90267564 no MR -> candidate analysis
PR interval in Tripanosoma cruzi seropositivity 2e-6 rs182046301 1 GCST002279 no MR -> candidate analysis
Vaginal microbiome relative abundance (s_Aerococcus christen 4e-6 rs78805937 1 GCST90027005 no MR -> candidate analysis
Plasma neurofilament light levels 6e-6 rs764064487 1 GCST90837205 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 197 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
alcohol drinking 0.525 common-variant locus no MR -> candidate analysis
bronchial disorder 0.348 common-variant locus no MR -> candidate analysis
Abnormality of the skeletal system 0.346 common-variant locus no MR -> candidate analysis
Tietze syndrome 0.337 common-variant locus no MR -> candidate analysis
heart conduction disease 0.335 common-variant locus no MR -> candidate analysis
hemorrhage 0.335 common-variant locus no MR -> candidate analysis
gastric ulcer 0.335 common-variant locus no MR -> candidate analysis
ulcerative colitis 0.332 common-variant locus no MR -> candidate analysis
neuroendocrine neoplasm 0.332 common-variant locus no MR -> candidate analysis
nerve plexus disorder 0.332 common-variant locus no MR -> candidate analysis
pneumonitis 0.332 common-variant locus no MR -> candidate analysis
ovarian neoplasm 0.332 common-variant locus no MR -> candidate analysis
aortic disorder 0.332 common-variant locus no MR -> candidate analysis
chronic ulcer of skin 0.332 common-variant locus no MR -> candidate analysis
placental abruption 0.332 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 0 known modulators (Kinetochore protein NDC80 homolog)
gnomAD constraint pLI=2e-18, LOEUF=0.944 — LoF-tolerant
GWAS Catalog 22 unique SNPs / 44 rows
ClinVar 224 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance