CausalSentinel

Protein Dossier — BTD (Biotinidase)

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: N92 Excessive frequent and irregular menstruation -0.0834 0.027 0.00204 Wald ratio 1 cis NA
Non-cancer illness code self-reported: diverticular disease or diverticulitis -0.102 0.0374 0.00662 Wald ratio 1 cis NA
Clear cell ovarian cancer 0.165 0.0682 0.0156 Wald ratio 1 cis NA
Diagnoses - main ICD10: J33 Nasal polyp 0.104 0.0468 0.0257 Wald ratio 1 cis NA
Weight -0.00664 0.00315 0.035 Wald ratio 1 cis NA
Non-cancer illness code self-reported: migraine -0.0421 0.0215 0.0504 Wald ratio 1 cis NA
Sodium in urine -0.00642 0.00351 0.0676 Wald ratio 1 cis NA
Hearing difficulty or problems: Yes -0.0111 0.00623 0.075 Wald ratio 1 cis NA
Schizophrenia 0.0326 0.0187 0.0809 Wald ratio 1 cis NA
Diagnoses - main ICD10: M23 Internal derangement of knee 0.0396 0.0231 0.0859 Wald ratio 1 cis NA
Invasive mucinous ovarian cancer 0.113 0.0663 0.0878 Wald ratio 1 cis NA
Diagnoses - main ICD10: R07 Pain in throat and chest -0.0279 0.0164 0.0888 Wald ratio 1 cis NA
…and 64 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

90 association rows across 52 traits (66 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
Biotinidase levels 4e-682 rs13078881 4 GCST90246705 no MR -> candidate analysis
BTD protein levels 5e-204 rs7651039 9 GCST90468477 no MR -> candidate analysis
Serum levels of protein BTD 3e-126 rs71627145 2 GCST90090597 no MR -> candidate analysis
Cerebrospinal fluid protein BTD levels 1e-104 rs13092272 1 GCST90945077 no MR -> candidate analysis
Biotinidase (analyte X9269.7) levels 8e-51 rs35034250 1 GCST90427735 no MR -> candidate analysis
Biotinidase (analyte X15644.1) levels 9e-37 rs35617908 1 GCST90422778 no MR -> candidate analysis
X-18913 levels 6e-27 rs2470528 1 GCST90140504 no MR -> candidate analysis
Biotinidase level in Chronic kidney disease with hypertensio 1e-25 rs6807875 1 GCST90239282 no MR -> candidate analysis
Hematological traits (multi-trait analysis) 4e-23 rs6787119 1 GCST90838669 no MR -> candidate analysis
mean platelet volume (MPV, maximum, inv-norm transformed) 9e-23 rs2455815 1 GCST90479707 no MR -> candidate analysis
Metabolic syndrome 2e-22 rs2255248 1 GCST90444487 no MR -> candidate analysis
Mean platelet thrombocyte volume (UKB data field 30100) 2e-17 rs56263384 1 GCST90468087 no MR -> candidate analysis
…and 40 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 1415 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
biotinidase deficiency 0.918 established (curated) no MR -> candidate analysis
hereditary disease 0.886 established (curated) no MR -> candidate analysis
Optic neuropathy 0.438 established (curated) no MR -> candidate analysis
Global developmental delay 0.24 established (curated) no MR -> candidate analysis
Intellectual disability 0.228 established (curated) no MR -> candidate analysis
Generalized hypotonia 0.182 established (curated) no MR -> candidate analysis
cryptorchidism 0.182 established (curated) no MR -> candidate analysis
Macrocephaly 0.182 established (curated) no MR -> candidate analysis
diabetes mellitus 0.135 common-variant locus no MR -> candidate analysis
metabolic syndrome 0.118 common-variant locus no MR -> candidate analysis

Of the 10 rows above, 10 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 (Biotinidase)
gnomAD constraint pLI=0.00037, LOEUF=1.17 — LoF-tolerant
GWAS Catalog 97 unique SNPs / 194 rows
ClinVar 995 records; 9 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance