SPEN
Chr 1ADspen family transcriptional repressor
Also known as: HIAA0929, MINT, RATARS, RBM15C, SHARP
This gene encodes a transcriptional repressor that regulates key developmental pathways including Notch signaling and serves as a nuclear matrix platform organizing transcriptional responses. Mutations cause Radio-Tartaglia syndrome, an autosomal dominant disorder characterized by intellectual disability, distinctive facial features, and skeletal abnormalities. The gene is highly constrained against loss-of-function variation (pLI=1, LOEUF=0.071), indicating that complete loss of protein function is likely incompatible with normal development.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
SPEN · 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