Developmental Brain Disorder Gene Database

LoF Variant Gene

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Tier

1

NSD1

HGNC:14234 (protein-coding gene)

nuclear receptor binding SET domain protein 1

Unique Cases:
54
Disorders:
ID, ASD, EP, ADHD, CP
Last Updated:
November 4, 2024

Summary
Cases
Publications
External

Gene Summary:

DBD Genes Classification
NSD1 is a High Confidence candidate gene classified as Tier 1. Tier 1 genes have three or more de novo pathogenic loss-of-function variants.
Gene Function
Histone methyltransferase that dimethylates Lys-36 of histone H3 (H3K36me2). Transcriptional intermediary factor capable of both negatively or positively influencing transcription, depending on the cellular context. {ECO:0000269|PubMed:21196496}. (Source: Uniprot)
Previous symbols
STO
Alias symbols
ARA267, FLJ22263, KMT3B
Chromosomal Location
5q35.3
Genomic Coordinates
GRCh37:chr5:176560080-176727214
GRCh38:chr5:177131835-177300213
Associated Disorders
Intellectual Disability, Autism, Epilepsy, Attention Deficit Hyperactivity Disorder, Cerebral Palsy

Predictive Scores:

HI Score (Decipher)

29.19

pLI (gnomAD)

1.00

LOEUF (gnomAD)

0.1

Classifications from External Sources:

SFARI Score (SFARI)

1

DDG2P Classification (DDG2P)

Definitive

ClinGen Classification (ClinGen)

Definitive1

GenCC Classification (GenCC)

Definitive5 Strong2 Supportive1

Publications:

Leventopoulos G et. al., Three novel mutations in greek sotos patients with rare clinical manifestations., Horm Res, 2009
Castronovo C et. al., A novel mosaic NSD1 intragenic deletion in a patient with an atypical phenotype., Am J Med Genet A, 2013
Sohn YB et. al., Clinical and genetic spectrum of 18 unrelated Korean patients with Sotos syndrome: frequent 5q35 microdeletion and identification of four novel NSD1 mutations., J Hum Genet, 2013
Lee H et. al., Clinical exome sequencing for genetic identification of rare Mendelian disorders., JAMA, 2014
Trujillano D et. al., Clinical exome sequencing: results from 2819 samples reflecting 1000 families., Eur J Hum Genet, 2017
Deciphering Developmental Disorders Study. et. al., Large-scale discovery of novel genetic causes of developmental disorders., Nature, 2015
Wu H et. al., Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort., Clin Genet, 2020
Grozeva D et. al., Targeted Next-Generation Sequencing Analysis of 1,000 Individuals with Intellectual Disability., Hum Mutat, 2015
Ji J et. al., A semiautomated whole-exome sequencing workflow leads to increased diagnostic yield and identification of novel candidate variants., Cold Spring Harb Mol Case Stud, 2019
Tei S et. al., The first Japanese familial Sotos syndrome with a novel mutation of the NSD1 gene., Kobe J Med Sci, 2006
Arteche-López A et. al., Towards a Change in the Diagnostic Algorithm of Autism Spectrum Disorders: Evidence Supporting Whole Exome Sequencing as a First-Tier Test., Genes (Basel), 2021
Tatton-Brown K et. al., Mutations in Epigenetic Regulation Genes Are a Major Cause of Overgrowth with Intellectual Disability., Am J Hum Genet, 2017
Hiraide T et. al., Genetic and phenotypic analysis of 101 patients with developmental delay or intellectual disability using whole-exome sequencing., Clin Genet, 2021
Lindstrand A et. al., Genome sequencing is a sensitive first-line test to diagnose individuals with intellectual disability., Genet Med, 2022
et. al., , ,

NCBI: Gene

Integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
NCBI: Gene

Gene Reviews

An international point-of-care resource for busy clinicians, provides clinically relevant and medically actionable information for inherited conditions in a standardized journal-style format, covering diagnosis, management, and genetic counseling for patients and their families.
Gene Reviews

DECIPHER

DECIPHER (DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources) is an interactive web-based database which incorporates a suite of tools designed to aid the interpretation of genomic variants. DECIPHER enhances clinical diagnosis by retrieving information from a variety of bioinformatics resources relevant to the variant found in the patient.
DECIPHER

SFARI

SFARI Gene is an evolving online database designed to permit quick entrée into the genetics of autism, and to help researchers track the ever-expanding genetic risk factors that emerge in the literature.
SFARI

ClinGen

ClinGen is a National Institutes of Health (NIH)-funded resource dedicated to building an authoritative central resource that defines the clinical relevance of genes and variants for use in precision medicine and research.
ClinGen

GenCC

The GenCC DB provides information pertaining to the validity of gene-disease relationships, with a current focus on Mendelian diseases.
GenCC

gnomAD

The Genome Aggregation Database (gnomAD) is a resource developed by an international coalition of investigators, with the goal of aggregating and harmonizing both exome and genome sequencing data from a wide variety of large-scale sequencing projects, and making summary data available for the wider scientific community.
gnomAD
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Autism & Developmental Medicine Institute