CausalSentinel

Protein Dossier — CCNH (Cyclin-H)

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
Large vessel disease -0.666 0.168 7.19e-05 Wald ratio 1 cis NA
Weight -0.0385 0.011 4.83e-04 Wald ratio 1 cis NA
Height -0.0503 0.0147 6.07e-04 Wald ratio 1 cis NA
Diagnoses - main ICD10: K43 Ventral hernia 0.389 0.129 0.00263 Wald ratio 1 cis NA
Non-cancer illness code self-reported: hypothyroidism or myxoedema 0.132 0.0487 0.00658 Wald ratio 1 cis NA
Alcohol intake frequency -0.0486 0.0184 0.00847 Wald ratio 1 cis NA
Non-cancer illness code self-reported: depression -0.152 0.0602 0.0113 Wald ratio 1 cis NA
Diagnoses - main ICD10: H25 Senile cataract 0.268 0.11 0.0154 Wald ratio 1 cis NA
Childhood intelligence -0.153 0.065 0.0182 Wald ratio 1 cis NA
Body mass index (BMI) -0.0288 0.0125 0.021 Wald ratio 1 cis NA
Non-cancer illness code self-reported: arthritis (nos) 0.255 0.113 0.0244 Wald ratio 1 cis NA
Diagnoses - main ICD10: I30 Acute pericarditis 0.791 0.379 0.0369 Wald ratio 1 cis NA
…and 101 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

8 association rows across 7 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
Height 7e-32 rs4421140 1 GCST90245848 MR: beta=-0.0503, p=6.07e-04 (cis)
Cyclin-H levels (CCNH.9848.22.3) 1e-14 rs2230641 1 GCST90240828 no MR -> candidate analysis
Chronotype 4e-11 rs66507804 1 GCST007576 no MR -> candidate analysis
Morningness 1e-10 rs66507804 1 GCST007983 no MR -> candidate analysis
Macular thickness 4e-10 rs13157168 1 GCST006976 no MR -> candidate analysis
PHQ score x Polysocial risk score (PsRS) interaction 4e-6 rs75661393 1 GCST90451692 no MR -> candidate analysis
Oligodendroglioma 5e-6 rs146974076 2 GCST90296482 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 157 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
capillary malformation-arteriovenous malformation 1 0.933 established (curated) no MR -> candidate analysis
capillary malformation-arteriovenous malformation syndrome 0.917 established (curated) no MR -> candidate analysis
Capillary malformation - arteriovenous malformation 0.917 established (curated) no MR -> candidate analysis
Abnormality of the cardiovascular system 0.893 established (curated) no MR -> candidate analysis
angioosteohypertrophic syndrome 0.684 established (curated) no MR -> candidate analysis
hereditary disease 0.559 established (curated) no MR -> candidate analysis
capillary infantile hemangioma 0.559 established (curated) no MR -> candidate analysis
type 2 diabetes mellitus 0.546 common-variant locus no MR -> candidate analysis
Abnormality of the skeletal system 0.502 common-variant locus no MR -> candidate analysis
prostate carcinoma 0.44 common-variant locus no MR -> candidate analysis
health study participation 0.441 common-variant locus no MR -> candidate analysis
Wieacker-Wolff syndrome 0.438 established (curated) no MR -> candidate analysis
Intellectual disability-developmental delay-contractures syndrome 0.438 established (curated) no MR -> candidate analysis
smoking initiation 0.404 common-variant locus no MR -> candidate analysis
ulcerative colitis 0.388 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 (Cyclin-H)
gnomAD constraint pLI=1.8e-08, LOEUF=0.999 — LoF-tolerant
GWAS Catalog 26 unique SNPs / 52 rows
ClinVar 1486 records; 8 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance