SOX5
Chr 12ADSRY-box transcription factor 5
Also known as: L-SOX5, L-SOX5B, L-SOX5F, LAMSHF
The SOX5 protein is a transcription factor that regulates embryonic development and cell fate determination, with particular involvement in chondrogenesis. Loss-of-function mutations cause Lamb-Shaffer syndrome, an autosomal dominant neurodevelopmental disorder. The gene is highly constrained against loss-of-function variants, indicating that haploinsufficiency is the mechanism underlying this condition.
Definitive — sufficient evidence for diagnostic panels
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).
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
300 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 | 30 | 2 | 24 | 0 | 56 |
Likely Pathogenic | 12 | 9 | 3 | 0 | 24 |
VUS | 3 | 139 | 22 | 3 | 167 |
Likely Benign | 2 | 17 | 5 | 7 | 31 |
Benign | 0 | 0 | 2 | 1 | 3 |
Conflicting | — | 3 | |||
| Total | 47 | 167 | 56 | 11 | 284 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SOX5 · 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
External Resources
Links to major genomics databases and tools