NSD1
Chr 5ADnuclear receptor binding SET domain protein 1
Also known as: ARA267, KMT3B, SOTOS, SOTOS1, STO
This protein functions as a histone methyltransferase that enhances androgen receptor transactivation and acts as a bifunctional transcriptional regulator in the nucleus. Mutations cause Sotos syndrome and Weaver syndrome through an autosomal dominant inheritance pattern. The pathogenic mechanism involves loss of function, as the protein is highly intolerant to loss-of-function variants.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
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
500 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 | 36 | 11 | 4 | 0 | 51 |
Likely Pathogenic | 22 | 13 | 3 | 0 | 38 |
VUS | 4 | 171 | 6 | 4 | 185 |
Likely Benign | 0 | 35 | 39 | 60 | 134 |
Benign | 0 | 9 | 43 | 3 | 55 |
Conflicting | — | 5 | |||
| Total | 62 | 239 | 95 | 67 | 468 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NSD1 · 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