SEPHS1
Chr 10ADselenophosphate synthetase 1
Also known as: SELD, SPS, SPS1, VERBRAS2
This protein functions as a core component of the zincore complex that stabilizes zinc finger transcription factors at DNA-binding sites to control gene expression, and plays an essential role in cellular redox homeostasis. Mutations cause Ververi-Brady syndrome 2, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants, indicating that functional copies are critical for normal development.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% 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
89 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 | 2 | 18 | 0 | 20 |
Likely Pathogenic | 0 | 1 | 1 | 0 | 2 |
VUS | 1 | 37 | 5 | 0 | 43 |
Likely Benign | 0 | 0 | 1 | 4 | 5 |
Benign | 0 | 0 | 1 | 1 | 2 |
Conflicting | — | 1 | |||
| Total | 1 | 40 | 26 | 5 | 73 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SEPHS1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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