CausalSentinel

Protein Dossier — RAD51D (DNA repair protein RAD51 homolog 4)

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) 0.0294 0.00537 4.15e-08 Wald ratio 1 trans 0.00381
Heel bone mineral density (BMD) T-score automated 0.0375 0.00694 6.72e-08 Wald ratio 1 trans 0.999
Forced expiratory volume in 1-second (FEV1) -0.0208 0.00464 7.37e-06 Wald ratio 1 trans NA
Forced vital capacity (FVC) -0.0195 0.0044 9.08e-06 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hypertension 0.0329 0.00886 2.04e-04 Wald ratio 1 trans NA
Birth weight -0.0215 0.00819 0.00865 Inverse variance weighted 2 trans NA
Birth weight -0.0215 0.00819 0.00865 Inverse variance weighted 2 trans NA
Eye problems or disorders: Diabetes related eye disease 0.148 0.0597 0.0133 Wald ratio 1 trans NA
Diagnoses - main ICD10: R04 Haemorrhage from respiratory passages 0.154 0.0643 0.0166 Wald ratio 1 trans NA
Diagnoses - main ICD10: K80 Cholelithiasis 0.0806 0.0345 0.0196 Wald ratio 1 trans NA
Sodium in urine 0.0118 0.00528 0.0256 Wald ratio 1 trans NA
Hearing difficulty or problems: Yes 0.0197 0.00909 0.0299 Wald ratio 1 trans NA
…and 86 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

2 association rows across 2 traits (2 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
CCL15 protein levels 2e-16 rs185961963 1 GCST90468567 no MR -> candidate analysis
CCL16 protein levels 2e-14 rs188753384 1 GCST90468568 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 205 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
Hereditary breast and ovarian cancer syndrome 0.867 established (curated) no MR -> candidate analysis
ovarian cancer 0.825 established (curated) MR: beta=-0.145, p=0.142 (trans)
hereditary breast ovarian cancer syndrome 0.866 established (curated) no MR -> candidate analysis
ovarian carcinoma 0.731 established (curated) no MR -> candidate analysis
RAD51D-related cancer predisposition 0.817 established (curated) no MR -> candidate analysis
hereditary neoplastic syndrome 0.946 established (curated) no MR -> candidate analysis
Inherited cancer-predisposing syndrome 0.946 established (curated) no MR -> candidate analysis
gastric cancer 0.859 established (curated) no MR -> candidate analysis
familial ovarian cancer 0.867 established (curated) no MR -> candidate analysis
breast cancer 0.824 established (curated) MR: beta=0.029, p=0.0306 (trans)
breast-ovarian cancer, familial, susceptibility to, 1 0.718 established (curated) no MR -> candidate analysis
Hereditary breast cancer 0.696 established (curated) no MR -> candidate analysis
hereditary breast carcinoma 0.696 established (curated) no MR -> candidate analysis
breast carcinoma 0.547 established (curated) no MR -> candidate analysis
colorectal cancer 0.559 established (curated) no MR -> candidate analysis

Of the 15 rows above, 13 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=7.7e-12, LOEUF=1.13 — LoF-tolerant
GWAS Catalog 20 unique SNPs / 40 rows
ClinVar 2130 records; 6 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance