GeneBe

NSD1

nuclear receptor binding SET domain protein 1, the group of PWWP domain containing|PHD finger proteins|Lysine methyltransferases

Basic information

Region (hg38): 5:177131830-177300213

Previous symbols: [ "STO" ]

Links

ENSG00000165671 ∙ NCBI:64324 ∙ OMIM:606681 ∙ HGNC:14234 ∙ Uniprot:Q96L73 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • Sotos syndrome (Definitive), mode of inheritance: AD
  • Sotos syndrome 1 (Strong), mode of inheritance: AD
  • Sotos syndrome 1 (Strong), mode of inheritance: AD
  • Sotos syndrome 1 (Definitive), mode of inheritance: AD
  • Sotos syndrome (Supportive), mode of inheritance: AD
  • Sotos syndrome (Definitive), mode of inheritance: AD
  • Beckwith-Wiedemann syndrome due to NSD1 mutation (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Sotos syndrome 1; Weaver syndrome; Beckwith-Wiedemann syndromeADCardiovascular; Oncologic; RenalWhile only reported in the minority of individuals, individuals are at increased risk of malignancy, and recognition may allow prompt diagnosis and treatment; Surveillance for cardiac and renal complications may also be beneficial in order to allow prompt recognition and managementCardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal14148233; 4366187; 6324572; 3565472; 2319581; 1552397; 10507738; 10434127; 11146472; 11078573; 11813184; 11896389; 12464997; 12525543; 14517949; 14571271; 14997421; 15125616; 16010674; 15452385; 15362962; 15455365; 15365454; 16170239; 15942875; 15852475; 16222665; 16780628; 16329110; 17825104; 17480008; 17420391; 18304174; 19914434; 20101679; 20420030; 21677402; 21738022; 21834047; 22012791; 21342349; 20301652

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NSD1 gene.

  • not_provided (1678 variants)
  • Sotos_syndrome (851 variants)
  • Inborn_genetic_diseases (378 variants)
  • not_specified (152 variants)
  • NSD1-related_disorder (110 variants)
  • Beckwith-Wiedemann_syndrome (32 variants)
  • Acute_myeloid_leukemia (8 variants)
  • See_cases (8 variants)
  • Intellectual_disability (6 variants)
  • Weaver_syndrome (6 variants)
  • Neurodevelopmental_disorder (4 variants)
  • Neurodevelopmental_delay (2 variants)
  • Hereditary_spastic_paraplegia_8 (1 variants)
  • Abnormal_cerebral_morphology (1 variants)
  • Microcephaly (1 variants)
  • Delayed_speech_and_language_development (1 variants)
  • Marfanoid_habitus_and_intellectual_disability (1 variants)
  • Congenital_diaphragamitc_hernia (1 variants)
  • Scoliosis (1 variants)
  • Hypertelorism (1 variants)
  • High_anterior_hairline (1 variants)
  • Osteopenia (1 variants)
  • Delayed_gross_motor_development (1 variants)
  • Non-immune_hydrops_fetalis (1 variants)
  • Pointed_chin (1 variants)
  • Holoprosencephaly_2 (1 variants)
  • Global_developmental_delay (1 variants)
  • Tall_stature (1 variants)
  • Overgrowth (1 variants)
  • Choroid_plexus_carcinoma (1 variants)
  • Hereditary_cancer (1 variants)
  • High_forehead (1 variants)
  • Hypoplasia_of_the_corpus_callosum (1 variants)
  • Preeclampsia (1 variants)
  • Macrocephaly (1 variants)
  • Increased_body_weight (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NSD1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000022455.5. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
3
clinvar
1
clinvar
18
clinvar
319
clinvar
17
clinvar
 358
missense
57
clinvar
129
clinvar
783
clinvar
333
clinvar
38
clinvar
 1340
nonsense
131
clinvar
18
clinvar
3
clinvar
 152
start loss
0
frameshift
256
clinvar
51
clinvar
11
clinvar
1
clinvar
 319
splice donor/acceptor (+/-2bp)
31
clinvar
22
clinvar
2
clinvar
 55
Total 478 221 817 653 55

Highest pathogenic variant AF is 0.0000065720296

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
NSD1protein_codingprotein_codingENST00000439151 22167191
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.007.31e-15125741071257480.0000278
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense3.4110651.43e+30.7460.000079017650
Missense in Polyphen179418.120.428115206
Synonymous0.07795235250.9960.00002825309
Loss of Function9.3151110.04520.000006781380

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00002890.0000289
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.00004620.0000462
European (Non-Finnish)0.00004410.0000439
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Histone methyltransferase. Preferentially methylates 'Lys-36' of histone H3 and 'Lys-20' of histone H4 (in vitro). Transcriptional intermediary factor capable of both negatively or positively influencing transcription, depending on the cellular context. {ECO:0000269|PubMed:21196496}.;
Disease
DISEASE: Beckwith-Wiedemann syndrome (BWS) [MIM:130650]: A disorder characterized by anterior abdominal wall defects including exomphalos (omphalocele), pre- and postnatal overgrowth, and macroglossia. Additional less frequent complications include specific developmental defects and a predisposition to embryonal tumors. {ECO:0000269|PubMed:14997421}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=A chromosomal aberration involving NSD1 is found in childhood acute myeloid leukemia. Translocation t(5;11)(q35;p15.5) with NUP98.; DISEASE: Note=A chromosomal aberration involving NSD1 is found in an adult form of myelodysplastic syndrome (MDS). Insertion of NUP98 into NSD1 generates a NUP98-NSD1 fusion product. {ECO:0000269|PubMed:15382262}.;
Pathway
Lysine degradation - Homo sapiens (human);Histone Modifications;Pathways Affected in Adenoid Cystic Carcinoma;PKMTs methylate histone lysines;Chromatin modifying enzymes;AndrogenReceptor;Lysine metabolism;Chromatin organization (Consensus)

Recessive Scores

pRec
0.241

Intolerance Scores

loftool
0.00186
rvis_EVS
-1.55
rvis_percentile_EVS
3.24

Haploinsufficiency Scores

pHI
0.661
hipred
N
hipred_score
0.471
ghis
0.580

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.959

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Nsd1
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); embryo phenotype;

Gene ontology

Biological process
negative regulation of transcription by RNA polymerase II;regulation of histone H3-K36 methylation;regulation of transcription, DNA-templated;histone H3-K36 methylation;histone methylation;regulation of peptidyl-serine phosphorylation;histone H4-K20 methylation;positive regulation of transcription, DNA-templated;regulation of RNA polymerase II regulatory region sequence-specific DNA binding
Cellular component
chromatin;nucleus;nucleoplasm;chromosome
Molecular function
RNA polymerase II proximal promoter sequence-specific DNA binding;chromatin binding;transcription coregulator activity;transcription corepressor activity;protein binding;zinc ion binding;histone-lysine N-methyltransferase activity;estrogen receptor binding;histone methyltransferase activity (H4-K20 specific);retinoic acid receptor binding;retinoid X receptor binding;thyroid hormone receptor binding;histone methyltransferase activity (H3-K36 specific);androgen receptor binding