MR feasibility tier: A — Published pQTL-MR estimates exist for this protein (retrieved below - not computed here).
| Outcome | beta | se | p | method | nSNP | cis/trans | coloc |
|---|---|---|---|---|---|---|---|
| Lung adenocarcinoma | 0.411 | 0.147 | 0.00522 | Wald ratio | 1 | trans | NA |
| Forearm bone mineral density | 0.216 | 0.0782 | 0.00581 | Wald ratio | 1 | trans | NA |
| Ulcerative colitis | -0.145 | 0.0616 | 0.0187 | Wald ratio | 1 | trans | NA |
| Total cholesterol | 0.044 | 0.0191 | 0.0211 | Wald ratio | 1 | trans | NA |
| Serum cystatin C (eGFRcys) | -0.0199 | 0.00896 | 0.0266 | Wald ratio | 1 | trans | NA |
| Lung cancer | 0.219 | 0.102 | 0.0315 | Wald ratio | 1 | trans | NA |
| Crohn’s disease | 0.122 | 0.0598 | 0.0414 | Wald ratio | 1 | trans | NA |
| Red blood cell count | -0.023 | 0.0113 | 0.0419 | Wald ratio | 1 | trans | NA |
| HDL cholesterol | 0.037 | 0.0183 | 0.0433 | Wald ratio | 1 | trans | NA |
| Rheumatoid arthritis | 0.227 | 0.113 | 0.0439 | Wald ratio | 1 | trans | NA |
| Neuroticism | -0.0312 | 0.0156 | 0.0455 | Wald ratio | 1 | trans | NA |
| Internalizing problems | -0.191 | 0.107 | 0.0743 | Wald ratio | 1 | trans | NA |
| …and 40 more outcomes (see JSON) |
No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).
65 association rows across 28 traits (55 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 |
|---|---|---|---|---|---|
| VCAN protein levels | 1e-94 | rs2441009 | 6 | GCST90471032 | no MR -> candidate analysis |
| DNA repair protein XRCC4 levels | 2e-22 | rs11953364 | 1 | GCST90250224 | no MR -> candidate analysis |
| XRCC4 protein levels | 2e-20 | rs1805377 | 1 | GCST90471085 | no MR -> candidate analysis |
| Cerebellar grey matter morphology (MOSTest) | 2e-17 | rs1478486 | 1 | GCST90728589 | no MR -> candidate analysis |
| IDP dMRI TBSS ICVF Middle cerebellar peduncle | 5e-17 | rs10473864 | 1 | GCST90004327 | no MR -> candidate analysis |
| heart rate (HR, mean, inv-normal transformed) | 8e-14 | rs17284253 | 1 | GCST90480666 | no MR -> candidate analysis |
| heart rate (HR, minimum, inv-normal transformed) | 4e-12 | rs17284253 | 1 | GCST90476341 | no MR -> candidate analysis |
| IDP dMRI TBSS ICVF Fornix cres+Stria terminalis R | 9e-12 | rs4343818 | 1 | GCST90004365 | no MR -> candidate analysis |
| Heel bone mineral density | 3e-11 | rs10474093 | 3 | GCST007066 | no MR -> candidate analysis |
| White matter microstructure (mean diusivities) | 7e-11 | rs2591453 | 20 | GCST009538 | no MR -> candidate analysis |
| White matter microstructure (radial diusivities) | 2e-10 | rs10055352 | 10 | GCST009540 | no MR -> candidate analysis |
| IDP dMRI TBSS ICVF Superior longitudinal fasciculus R | 3e-10 | rs10473864 | 1 | GCST90004367 | no MR -> candidate analysis |
| …and 16 more traits (see JSON) |
Top diseases by Open Targets association (of 286 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 |
|---|---|---|---|---|
| microcephalic primordial dwarfism-insulin resistance syndrome | 0.864 | — | established (curated) | no MR -> candidate analysis |
| short stature, microcephaly, and endocrine dysfunction | 0.911 | — | established (curated) | no MR -> candidate analysis |
| Non-acquired isolated growth hormone deficiency | 0.547 | — | established (curated) | no MR -> candidate analysis |
| androgenetic alopecia | 0.455 | — | common-variant locus | no MR -> candidate analysis |
| dyshidrosis | 0.443 | — | common-variant locus | no MR -> candidate analysis |
| multinodular goiter | 0.42 | — | common-variant locus | no MR -> candidate analysis |
| endometriosis | 0.391 | — | common-variant locus | no MR -> candidate analysis |
| rheumatoid arthritis | 0.375 | — | common-variant locus | MR: beta=0.227, p=0.0439 (trans) |
| head and neck cancer | 0.335 | — | common-variant locus | no MR -> candidate analysis |
| aging | 0.336 | — | common-variant locus | no MR -> candidate analysis |
| Abnormality of the gastrointestinal tract | 0.329 | — | common-variant locus | no MR -> candidate analysis |
| hereditary disease | 0.313 | — | established (curated) | no MR -> candidate analysis |
| skin neoplasm | 0.311 | — | common-variant locus | no MR -> candidate analysis |
| subarachnoid hemorrhage | 0.308 | — | common-variant locus | no MR -> candidate analysis |
| facial morphology | 0.297 | — | 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.
| Layer | Result |
|---|---|
| ChEMBL druggability | 0 known modulators (LIG4/XRCC4) |
| gnomAD constraint | pLI=1.8e-07, LOEUF=0.982 — LoF-tolerant |
| GWAS Catalog | 58 unique SNPs / 110 rows |
| ClinVar | 215 records; 3 pathogenic in sample of 30 |
| PharmGKB/ClinPGx | 3 clinical annotations across 4 drugs |
phenome — Top 30 of 286 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.chembl — ChEMBL target matched by text search on ‘XRCC4’ and resolved to ‘LIG4/XRCC4’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 215 ClinVar records for this gene; it is a sample, not a rate.gwas_traits — Top 20 of 28 traits by best p-value, aggregated from 65 association rows. These are GWAS ASSOCIATIONS (loci), not causal claims; mapped genes at a locus are not necessarily the effector gene.uniprot: https://www.uniprot.org/uniprotkb/Q13426 — UniProt release 2026_02 (10-June-2026)mr_outcomes: https://epigraphdb.org/pqtl/ — EpiGraphDB pQTL MR (Zheng et al., Nat Genet 2020) — pre-computed two-sample MR; retrieved, not computed by this agent; EpiGraphDB build 1.0, pQTL dataset v3.0phenome: https://platform.opentargets.org/target/ENSG00000152422/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL4296097/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/XRCC4 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/XRCC4 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=XRCC4%5Bgene%5D — ClinVar build Build260809-1055.1pharmgkb: https://www.pharmgkb.org/search?query=XRCC4 — ClinPGx clinicalAnnotation via https://api.clinpgx.org/v1/datagwas_traits: https://www.ebi.ac.uk/gwas/genes/XRCC4 — GWAS Catalog search API (live; release not exposed)