NSD3

nuclear receptor binding SET domain protein 3, the group of Lysine methyltransferases|PWWP domain containing|PHD finger proteins|SET domain containing

Basic information

Region (hg38): 8:38269703-38382272

Previous symbols: [ "WHSC1L1" ]

Links

ENSG00000147548 ∙ NCBI:54904 ∙ OMIM:607083 ∙ HGNC:12767 ∙ Uniprot:Q9BZ95 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NSD3 gene.

• Inborn genetic diseases (16 variants)
• not provided (11 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NSD3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	2	4
missense			17	1	4	22
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	17	3	6

Variants in NSD3

This is a list of pathogenic ClinVar variants found in the NSD3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-38275750-C-T		not specified	Uncertain significance (Jan 19, 2022)
8-38275753-C-T		not specified	Uncertain significance (May 17, 2023)
8-38275853-C-G		not specified	Uncertain significance (Mar 07, 2024)
8-38276298-T-C		not specified	Uncertain significance (Dec 18, 2023)
8-38278361-G-A		not specified	Uncertain significance (Jan 23, 2024)
8-38278375-C-G		NSD3-related disorder	Likely benign (Apr 04, 2019)
8-38279537-T-C			Benign (Jun 26, 2018)
8-38279657-T-G		not specified	Uncertain significance (Jul 12, 2023)
8-38279664-G-A			Benign (May 03, 2018)
8-38281562-C-T		NSD3-related disorder	Likely benign (May 11, 2020)
8-38288548-G-C		not specified	Uncertain significance (Jul 14, 2021)
8-38288612-G-T		not specified	Uncertain significance (Oct 26, 2022)
8-38288672-T-G		not specified	Uncertain significance (Feb 28, 2023)
8-38288720-C-T		not specified	Uncertain significance (Mar 29, 2023)
8-38288746-A-G		not specified	Uncertain significance (Jan 24, 2023)
8-38289440-C-G		not specified	Uncertain significance (May 11, 2022)
8-38289478-T-C		not specified	Uncertain significance (Jan 18, 2023)
8-38289485-G-A		not specified	Uncertain significance (Jul 14, 2023)
8-38290568-A-G		not specified	Uncertain significance (Feb 28, 2023)
8-38290613-C-A		not specified	Uncertain significance (Aug 01, 2022)
8-38290632-G-A		NSD3-related disorder	Benign/Likely benign (Nov 21, 2022)
8-38295928-G-A		not specified	Uncertain significance (Jan 04, 2022)
8-38304631-T-C		not specified	Uncertain significance (Oct 25, 2023)
8-38304635-T-C			Benign (Apr 24, 2018)
8-38304680-C-T		not specified	Uncertain significance (Dec 30, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NSD3	protein_coding	protein_coding	ENST00000317025	23	112576

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	6.19e-9	125738	0	10	125748	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.73	483	775	0.623	0.0000408	9463
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000561	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000540	0.0000527
Middle Eastern	0.0000561	0.0000544
South Asian	0.0000373	0.0000327
Other	0.000165	0.000163

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: Lysine degradation - Homo sapiens (human);PKMTs methylate histone lysines;Chromatin modifying enzymes;Lysine metabolism;Chromatin organization (Consensus)

Recessive Scores

• pRec: 0.0998

Intolerance Scores

• rvis_EVS: -0.55
• rvis_percentile_EVS: 19.93

Haploinsufficiency Scores

• pHI: 0.419
• hipred: Y
• hipred_score: 0.728
• ghis: 0.568

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Nsd3
• Phenotype: homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• 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
• Cellular component: chromatin;nucleus;nucleoplasm;chromosome
• Molecular function: transcription coactivator activity;protein binding;histone-lysine N-methyltransferase activity;metal ion binding;histone methyltransferase activity (H3-K36 specific)