NSD1 Gene (Nuclear Receptor Binding SET Domain Protein 1)
Key regulator of chromatin methylation implicated in Sotos syndrome and various cancers
Gene Information Card
| Symbol | NSD1 |
|---|---|
| Full Name | Nuclear Receptor Binding SET Domain Protein 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q35.3 |
| NCBI Gene ID | 64324 ncbi.nlm.nih.gov/gene/64324 |
| Ensembl ID | ENSG00000165671 |
| UniProt ID | Q96L73 |
| OMIM ID | 606681 |
| HGNC ID | 14234 |
| Aliases | ARA267, KMT3B, SOTOS, STO, PPP1R142 |
Description
NSD1 (Nuclear Receptor Binding SET Domain Protein 1) encodes a histone methyltransferase that specifically methylates histone H3 at lysine 36 (H3K36). It functions as a transcriptional regulator through chromatin modification and interaction with nuclear receptors. NSD1 is essential for normal development and growth regulation. Heterozygous loss-of-function mutations cause Sotos syndrome, an overgrowth disorder. NSD1 is also recurrently mutated in various cancers, including acute myeloid leukemia and neuroblastoma.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Sotos syndrome | Heterozygous loss-of-function mutations (nonsense, frameshift, deletions) lead to haploinsufficiency, disrupting H3K36 methylation and gene expression regulation during development. | OMIM #117550; multiple case series |
| Acute myeloid leukemia (AML) | Recurrent microdeletions and point mutations (e.g., R2017C) in NSD1, often with NUP98-NSD1 fusion, drive leukemogenesis via aberrant H3K36 methylation. | COSMIC; ClinVar; PMID: 23334668 |
| Neuroblastoma | NSD1 mutations (e.g., missense, frameshift) are found in high-risk neuroblastoma, potentially altering chromatin state and differentiation. | PMID: 27869827 |
| Beckwith-Wiedemann syndrome (mimic) | NSD1 deletions can phenocopy Beckwith-Wiedemann syndrome due to overlapping overgrowth features. | OMIM #130650 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 28.5 | High |
| Brain (cerebellum) | 15.2 | Medium |
| Kidney | 12.1 | Medium |
| Lung | 8.4 | Low |
| Liver | 5.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 18.7 | Embryonic kidney; moderate expression |
| K562 | 22.1 | Leukemia cell line; high expression |
| SH-SY5Y | 14.5 | Neuroblastoma; moderate expression |
| HepG2 | 9.8 | Hepatocellular carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.601C>T (p.R201*) | Nonsense | ~15% of Sotos syndrome | Loss of function; premature truncation |
| c.4562_4563del (p.L1521Rfs*3) | Frameshift | ~5% of Sotos syndrome | Loss of function; truncated protein |
| c.6050G>A (p.R2017C) | Missense | <1% in AML | Gain of function?; altered substrate specificity |
| Whole gene deletion | Deletion | ~10% of Sotos syndrome | Haploinsufficiency |
Mutation functional classification
Loss of Function (LOF)
Most Sotos syndrome mutations (nonsense, frameshift, deletions) result in haploinsufficiency, reducing H3K36 methyltransferase activity.
Gain of Function (GOF)
Rare missense mutations in AML (e.g., R2017C) may alter substrate specificity or increase activity, though evidence is limited.
Dominant Negative (DN)
Not clearly established; most pathogenic mutations are loss-of-function.
View complete mutation data：
Gene Ontology (GO)
| • protein binding (GO:0005515) | • nucleus (GO:0005634) |
| • zinc ion binding (GO:0008270) | • histone-lysine N-methyltransferase activity (GO:0018024) |
| • histone H3-K36 methylation (GO:0035098) | • histone methyltransferase activity (H3-K36 specific) (GO:0042800) |
| • regulation of transcription, DNA-templated (GO:0006355) |
Pathways
• Chromatin modifying enzymes (Reactome R-HSA-3247509)
• H3K36 methylation (Reactome R-HSA-3214847)
• Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors (Reactome R-HSA-8866907)
Protein Summary
NSD1 is a large multidomain protein (~2696 amino acids) containing a SET domain responsible for histone H3 lysine 36 methyltransferase activity, PHD fingers, PWWP domains, and a nuclear receptor interaction domain. It localizes to the nucleus and modifies chromatin to regulate gene expression. NSD1 interacts with nuclear receptors (e.g., retinoic acid receptor) and other transcription factors. Loss of NSD1 function leads to global reduction of H3K36me2, affecting developmental gene programs.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NSD1 Knockout HEK293 Cell Line | EDJ-KQ2666 | Human | 64324 | Details Get a Quote |
| NSD1 Knockout A-549 Cell Line | EDJ-KQ24838 | Human | 64324 | Details Get a Quote |
| NSD1 Knockout HCT 116 Cell Line | EDJ-KQ24840 | Human | 64324 | Details Get a Quote |
| NSD1 Knockout HeLa Cell Line | EDJ-KQ24841 | Human | 64324 | Details Get a Quote |
