NSD3 (Nuclear Receptor Binding SET Domain Protein 3)
A histone methyltransferase implicated in oncogenesis and developmental disorders
Gene Information Card
| Symbol | NSD3 |
|---|---|
| Full Name | Nuclear Receptor Binding SET Domain Protein 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 8p11.23 |
| NCBI Gene ID | 54974 ncbi.nlm.nih.gov/gene/54974 |
| Ensembl ID | ENSG00000147592 |
| UniProt ID | Q9BZ95 |
| OMIM ID | 607083 |
| HGNC ID | 12768 |
| Aliases | WHSC1L1, KMT3F, KMT3G, FLJ20353, MGC126562 |
Description
NSD3 (Nuclear Receptor Binding SET Domain Protein 3) encodes a histone methyltransferase that specifically methylates histone H3 at lysine 36 (H3K36me2). It is a member of the NSD (Nuclear Receptor Binding SET Domain) family and plays a critical role in chromatin regulation, transcriptional elongation, and DNA repair. NSD3 is frequently amplified or overexpressed in various cancers, particularly in lung squamous cell carcinoma and breast cancer, and is considered a potential oncogene. Germline mutations in NSD3 are associated with Wolf-Hirschhorn syndrome (WHS) and other developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Wolf-Hirschhorn syndrome | Haploinsufficiency of NSD3 contributes to the core phenotype, including intellectual disability and growth delay. | OMIM #194190; PMID: 25271085 |
| Lung squamous cell carcinoma | Amplification of the 8p11.23 region leads to NSD3 overexpression, driving tumorigenesis via H3K36me2-mediated transcriptional activation. | COSMIC; PMID: 24670642 |
| Breast cancer | NSD3 amplification and overexpression promote cell proliferation and metastasis through epigenetic reprogramming. | COSMIC; PMID: 28481359 |
| Acute myeloid leukemia | NSD3 fusions (e.g., NUP98-NSD3) result in aberrant H3K36 methylation and leukemogenesis. | COSMIC; PMID: 23334668 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.5 | Medium |
| Breast | 8.3 | Medium |
| Brain | 6.1 | Low |
| Testis | 15.2 | High |
| Bone marrow | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung carcinoma) | 14.7 | High expression |
| MCF7 (breast adenocarcinoma) | 9.2 | Medium expression |
| HEK293 (embryonic kidney) | 7.5 | Medium expression |
| K562 (leukemia) | 5.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Gln1142* | Nonsense | <0.1% | Loss of function; truncation of SET domain |
| p.Arg1157Trp | Missense | <0.1% | Likely loss of function; disrupts catalytic activity |
| NUP98-NSD3 fusion | Gene fusion | Rare in AML | Gain of function; constitutive H3K36me2 activity |
| Amplification (8p11.23) | Copy number gain | ~10% in lung SCC | Gain of function; overexpression |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations in the SET domain (e.g., p.Gln1142*, p.Arg1157Trp) lead to reduced H3K36 methyltransferase activity, contributing to developmental disorders like Wolf-Hirschhorn syndrome.
Gain of Function (GOF)
Gene amplification and NUP98-NSD3 fusions result in increased H3K36me2 levels and oncogenic transcriptional programs, driving cancer progression.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported for NSD3.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005515 – protein binding | • GO:0005634 – nucleus |
| • GO:0008270 – zinc ion binding | • GO:0018024 – histone H3K36 methyltransferase activity |
| • GO:0035098 – ESC/E(Z) complex | • GO:0045893 – positive regulation of transcription |
| • DNA-templated | • GO:0006325 – chromatin organization |
Pathways
• Histone methylation (H3K36me2)
• Chromatin remodeling
• Transcriptional elongation by RNA polymerase II
• DNA damage response
• Oncogenic signaling in lung and breast cancer
Protein Summary
NSD3 is a 1,437-amino-acid protein containing a SET domain, PHD fingers, and a PWWP domain. It functions as a histone methyltransferase that catalyzes the dimethylation of histone H3 at lysine 36 (H3K36me2), a mark associated with active transcription and elongation. NSD3 interacts with nuclear receptors and chromatin remodeling complexes. Its overexpression or fusion with NUP98 drives oncogenesis in multiple cancer types, while loss-of-function mutations cause neurodevelopmental phenotypes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NSD3 Knockout HEK293 Cell Line | EDJ-KQ2143 | Human | 54904 | Details Get a Quote |
| NSD3 Knockout HCT 116 Cell Line | EDJ-KQ21007 | Human | 54904 | Details Get a Quote |
| NSD3 Knockout A-549 Cell Line | EDJ-KQ22314 | Human | 54904 | Details Get a Quote |
| NSD3 Knockout HeLa Cell Line | EDJ-KQ22316 | Human | 54904 | Details Get a Quote |
| NSD3 Knockout HAP1 Cell Line | EDC08143 | Human | 54904 | Details Get a Quote |
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