CausalSentinel

Protein Dossier — SURF1 (Surfeit locus protein 1)

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: D12 Benign neoplasm of colon rectum anus and anal canal 0.162 0.0553 0.00342 Wald ratio 1 trans NA
2hr glucose -0.141 0.0613 0.0217 Wald ratio 1 trans NA
Sleep duration 0.0134 0.00599 0.0256 Wald ratio 1 trans NA
Non-cancer illness code self-reported: deep venous thrombosis (dvt) 0.108 0.049 0.0273 Wald ratio 1 trans NA
Type 2 diabetes 0.068 0.0311 0.0285 Wald ratio 1 trans NA
Non-cancer illness code self-reported: hyperthyroidism or thyrotoxicosis 0.156 0.0768 0.0418 Wald ratio 1 trans NA
Non-cancer illness code self-reported: enlarged prostate -0.157 0.0773 0.0425 Wald ratio 1 trans NA
Diagnoses - main ICD10: R07 Pain in throat and chest -0.0722 0.0369 0.0502 Wald ratio 1 trans NA
Diagnoses - main ICD10: M16 Coxarthrosis [arthrosis of hip] 0.111 0.0574 0.0537 Wald ratio 1 trans NA
Years of schooling 0.0151 0.00805 0.0608 Wald ratio 1 trans NA
Diagnoses - main ICD10: Z09 Follow-up examination after treatment for conditions other than malignant neoplasms 0.103 0.0566 0.07 Wald ratio 1 trans NA
Non-cancer illness code self-reported: depression -0.0597 0.0336 0.0761 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

25 association rows across 24 traits (25 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
ISLR2 protein levels 2e-297 rs183853102 1 GCST90469629 no MR -> candidate analysis
IL3RA protein levels 9e-255 rs183853102 1 GCST90469596 no MR -> candidate analysis
PECAM1 protein levels 6e-239 rs183853102 1 GCST90470206 no MR -> candidate analysis
MUC2 protein levels 3e-221 rs183853102 2 GCST90469965 no MR -> candidate analysis
GP2 protein levels 1e-220 rs183853102 1 GCST90469382 no MR -> candidate analysis
EPHA4 protein levels 3e-211 rs183853102 1 GCST90469131 no MR -> candidate analysis
CDH17 protein levels 8e-197 rs183853102 1 GCST90468669 no MR -> candidate analysis
ROBO4 protein levels 2e-180 rs183853102 1 GCST90470491 no MR -> candidate analysis
ENG protein levels 4e-164 rs183853102 1 GCST90469108 no MR -> candidate analysis
CLEC1A protein levels 2e-79 rs183853102 1 GCST90468767 no MR -> candidate analysis
ADAM15 protein levels 7e-69 rs183853102 1 GCST90468217 no MR -> candidate analysis
CUZD1 protein levels 4e-58 rs183853102 1 GCST90468919 no MR -> candidate analysis
…and 12 more traits (see JSON)          

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

Top diseases by Open Targets association (of 215 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
Leigh syndrome 0.946 established (curated) no MR -> candidate analysis
Charcot-Marie-Tooth disease type 4K 0.861 established (curated) no MR -> candidate analysis
mitochondrial complex IV deficiency, nuclear type 22 0.963 established (curated) no MR -> candidate analysis
SURF1-related Charcot-Marie-Tooth disease type 4 0.608 established (curated) no MR -> candidate analysis
Isolated cytochrome C oxidase deficiency 0.94 established (curated) no MR -> candidate analysis
mitochondrial disease 0.699 established (curated) no MR -> candidate analysis
leigh syndrome due to mitochondrial complex iv deficiency 0.941 established (curated) no MR -> candidate analysis
hereditary disease 0.862 established (curated) no MR -> candidate analysis
cerebellar ataxia 0.669 established (curated) no MR -> candidate analysis
Muscle weakness 0.669 established (curated) no MR -> candidate analysis
Abnormal pyramidal sign 0.669 established (curated) no MR -> candidate analysis
Dysarthria 0.669 established (curated) no MR -> candidate analysis
fatal infantile encephalocardiomyopathy 0.559 established (curated) no MR -> candidate analysis

Of the 13 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=1.7e-19, LOEUF=1.69 — LoF-tolerant
GWAS Catalog 322 unique SNPs / 770 rows
ClinVar 865 records; 13 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance