NSD3
protein-codingnuclear receptor binding SET domain protein 3, the group of Lysine methyltransferases|PWWP domain containing|PHD finger proteins|SET domain containing
Gene summary
This gene is related to the Wolf-Hirschhorn syndrome candidate-1 gene and encodes a protein with PWWP (proline-tryptophan-tryptophan-proline) domains. This protein methylates histone H3 at lysine residues 4 and 27, which represses gene transcription. Two alternatively spliced variants have been described. [provided by RefSeq, May 2015]
- WHSC1L1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~112.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NSD3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_023034.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 10 | 2 | 13 | ||
| missense | 137 | 3 | 4 | 144 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 144 | 13 | 6 | 163 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_075447.1 | 23 | MANE Select | |
| Ensembl | ENSP00000313983.7 | 23 | MANE Select | |
| RefSeq | NP_060248.2 | 9 | Standard | |
| Ensembl | ENSP00000313410.3 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Lysine degradation - Homo sapiens (human)
- PKMTs methylate histone lysines
- Chromatin modifying enzymes
- Lysine metabolism
- Chromatin organization
Biological Process
- regulation of transcription, DNA-templated
- histone methylation
- histone lysine methylation
- positive regulation of transcription, DNA-templated
- positive regulation of histone H3-K36 trimethylation
Molecular Function
- transcription coactivator activity
- protein binding
- histone-lysine N-methyltransferase activity
- metal ion binding
- histone methyltransferase activity (H3-K36 specific)
Cellular Component
- chromatin
- nucleus
- nucleoplasm
- chromosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000317025
- Coding exons
- 23
- Length
- 112576
- Individuals with no LoFs
- 125738
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 125748
- p
- 0.0000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.73 | 483 | 775 | 0.623 | 0.0000408 | 9463 |
| Missense (PolyPhen) | 139 | 335.61 | 0.41418 | 3999 | ||
| Synonymous | 1.47 | 247 | 278 | 0.888 | 0.0000153 | 2639 |
| Loss of Function | 7.44 | 5 | 74.1 | 0.0674 | 0.00000398 | 928 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000056 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000054 | 0.000053 | rare |
| South Asian | 0.000037 | 0.000033 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Histone methyltransferase. Preferentially methylates 'Lys-4' and 'Lys-27' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation, while 'Lys-27' is a mark for transcriptional repression. {ECO:0000269|PubMed:16682010}.;
- Disease
- DISEASE: Note=A chromosomal aberration involving NSD3 is found in childhood acute myeloid leukemia. Translocation t(8;11)(p11.2;p15) with NUP98. {ECO:0000269|PubMed:11986249}.;
Recessive Scores
- pRec
- 0.0998
Intolerance Scores
- RVIS EVS
- -0.55
- RVIS percentile EVS
- 19.93
Essentials
- Essential (gene trap)
- N