Developmental Brain Disorder Gene Database

LoF Variant Gene

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Tier

1

SETD5

HGNC:25566 (protein-coding gene)

SET domain containing 5

Unique Cases:
39
Disorders:
ID, ASD, EP, ADHD, CP
Last Updated:
November 4, 2024

Summary
Cases
Publications
External

Gene Summary:

DBD Genes Classification
SETD5 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
Chromatin regulator required for brain development: acts as a regulator of RNA elongation rate, thereby regulating neural stem cell (NSC) proliferation and synaptic transmission. May act by mediating trimethylation of 'Lys-36' of histone H3 (H3K36me3), which is essential to allow on-time RNA elongation dynamics. Also monomethylates 'Lys-9' of histone H3 (H3K9me1) in vitro. The relevance of histone methyltransferase activity is however subject to discussion. {ECO:0000250|UniProtKB:Q5XJV7}. (Source: Uniprot)
Previous symbols
No previous symbols
Alias symbols
FLJ10707, SETD5A
Chromosomal Location
3p25.3
Genomic Coordinates
GRCh37:chr3:9439384-9519838
GRCh38:chr3:9397615-9478154
Associated Disorders
Intellectual Disability, Autism, Epilepsy, Attention Deficit Hyperactivity Disorder, Cerebral Palsy

Predictive Scores:

HI Score (Decipher)

12.88

pLI (gnomAD)

1.00

LOEUF (gnomAD)

0.23

Classifications from External Sources:

SFARI Score (SFARI)

1

DDG2P Classification (DDG2P)

Definitive

ClinGen Classification (ClinGen)

Definitive1

GenCC Classification (GenCC)

Definitive2 Supportive1 Strong1

Publications:

Wang T et. al., Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders., Nat Commun, 2020
Kobayashi Y et. al., High prevalence of genetic alterations in early-onset epileptic encephalopathies associated with infantile movement disorders., Brain Dev, 2016
De Rubeis S et. al., Synaptic, transcriptional and chromatin genes disrupted in autism., Nature, 2014
Pinto D et. al., Convergence of genes and cellular pathways dysregulated in autism spectrum disorders., Am J Hum Genet, 2014
Halvardson J et. al., Mutations in HECW2 are associated with intellectual disability and epilepsy., J Med Genet, 2016
Grozeva D et. al., De novo loss-of-function mutations in SETD5, encoding a methyltransferase in a 3p25 microdeletion syndrome critical region, cause intellectual disability., Am J Hum Genet, 2014
Guo H et. al., Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model., Mol Autism, 2018
Powis Z et. al., Expansion and further delineation of the SETD5 phenotype leading to global developmental delay, variable dysmorphic features, and reduced penetrance., Clin Genet, 2018
Kuechler A et. al., Loss-of-function variants of SETD5 cause intellectual disability and the core phenotype of microdeletion 3p25.3 syndrome., Eur J Hum Genet, 2015
Liao LH et. al., Diagnosis of intellectual disability/global developmental delay via genetic analysis in a central region of China., Chin Med J (Engl), 2019
Fang YL et. al., A novel mutation in a common pathogenic gene (SETD5) associated with intellectual disability: A case report., Exp Ther Med, 2019
Wang T et. al., De novo genic mutations among a Chinese autism spectrum disorder cohort., Nat Commun, 2016
Grozeva D et. al., Targeted Next-Generation Sequencing Analysis of 1,000 Individuals with Intellectual Disability., Hum Mutat, 2015
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
Moreno-De-Luca A et. al., Molecular Diagnostic Yield of Exome Sequencing in Patients With Cerebral Palsy., JAMA, 2021
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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