SIAH1
Chr 16ADsiah E3 ubiquitin protein ligase 1
Also known as: BURHAS, SIAH1A
The protein is an E3 ubiquitin ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins involved in apoptosis, transcription regulation, cell cycle control, and other cellular processes. Mutations cause Buratti-Harel syndrome, which follows autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (LOEUF = 0.499), suggesting intolerance to protein-disrupting mutations.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Highly missense-constrained (top ~0.1%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
87 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 4 | 15 | 0 | 19 |
Likely Pathogenic | 8 | 7 | 0 | 0 | 15 |
VUS | 5 | 29 | 4 | 0 | 38 |
Likely Benign | 0 | 0 | 0 | 6 | 6 |
Benign | 0 | 0 | 0 | 2 | 2 |
Conflicting | — | 1 | |||
| Total | 13 | 40 | 19 | 8 | 81 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SIAH1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools