Developmental Brain Disorder Gene Database

LoF Variant Gene

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Tier

1

IQSEC2

HGNC:29059 (protein-coding gene)

IQ motif and Sec7 domain ArfGEF 2

Unique Cases:
42
Disorders:
ID, ASD, EP, ADHD, CP
Last Updated:
January 24, 2024

Summary
Cases
Publications
External

Gene Summary:

DBD Genes Classification
IQSEC2 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
Is a guanine nucleotide exchange factor for the ARF GTP- binding proteins. {ECO:0000269|PubMed:26793055}. (Source: Uniprot)
Previous symbols
MRX1, MRX78, MRX18
Alias symbols
KIAA0522, BRAG1, IQ-ArfGEF
Chromosomal Location
Xp11.22
Genomic Coordinates
GRCh37:chrX:53262058-53350522
GRCh38:chrX:53225784-53321356
Associated Disorders
Intellectual Disability, Autism, Epilepsy, Attention Deficit Hyperactivity Disorder, Cerebral Palsy

Predictive Scores:

HI Score (Decipher)

26.16

pLI (gnomAD)

1.00

LOEUF (gnomAD)

0.13

Classifications from External Sources:

SFARI Score (SFARI)

1

DDG2P Classification (DDG2P)

Definitive

ClinGen Classification (ClinGen)

Definitive1

GenCC Classification (GenCC)

Definitive3 Supportive2 Strong1

Publications:

Zhou WZ et. al., Targeted resequencing of 358 candidate genes for autism spectrum disorder in a Chinese cohort reveals diagnostic potential and genotype-phenotype correlations., Hum Mutat, 2019
Barrie ES et. al., Genotype-phenotype correlation: Inheritance and variant-type infer pathogenicity in IQSEC2 gene., Eur J Med Genet, 2020
Accogli A et. al., Psychiatric features and variable neurodevelopment outcome in four females with IQSEC2 spectrum disorder., J Genet, 2020
Wayhelova M et. al., Novel familial IQSEC2 pathogenic sequence variant associated with neurodevelopmental disorders and epilepsy., Neurogenetics, 2020
Gandomi SK et. al., Diagnostic exome sequencing identifies two novel IQSEC2 mutations associated with X-linked intellectual disability with seizures: implications for genetic counseling and clinical diagnosis., J Genet Couns, 2014
Tzschach A et. al., Next-generation sequencing in X-linked intellectual disability., Eur J Hum Genet, 2015
Olson HE et. al., Mutations in epilepsy and intellectual disability genes in patients with features of Rett syndrome., Am J Med Genet A, 2015
Helbig KL et. al., Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy., Genet Med, 2016
Ewans LJ et. al., Whole-exome sequencing reanalysis at 12 months boosts diagnosis and is cost-effective when applied early in Mendelian disorders., Genet Med, 2018
Kim SY et. al., Dissecting the phenotypic and genetic spectrum of early childhood-onset generalized epilepsies., Seizure, 2019
Coe BP et. al., Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity., Nat Genet, 2019
Allen AS et. al., De novo mutations in epileptic encephalopathies., Nature, 2013
Berger SI et. al., Exome analysis of Smith-Magenis-like syndrome cohort identifies de novo likely pathogenic variants., Hum Genet, 2017
Ko A et. al., Targeted gene panel and genotype-phenotype correlation in children with developmental and epileptic encephalopathy., Epilepsy Res, 2018
Munnich A et. al., Impact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder., Mol Autism, 2019
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
Balciuniene J et. al., Use of a Dynamic Genetic Testing Approach for Childhood-Onset Epilepsy., JAMA Netw Open, 2019
Takata A et. al., Comprehensive analysis of coding variants highlights genetic complexity in developmental and epileptic encephalopathy., Nat Commun, 2019
Zou Q et. al., A case of intellectual disability reveals a novel mutation in IQSEC2 gene by whole exome sequencing., Psychiatr Genet, 2019
Moreno-De-Luca A et. al., Molecular Diagnostic Yield of Exome Sequencing in Patients With Cerebral Palsy., JAMA, 2021
Varesio C et. al., Diagnostic Yield and Cost-Effectiveness of "Dynamic" Exome Analysis in Epilepsy with Neurodevelopmental Disorders: A Tertiary-Center Experience in Northern Italy., Diagnostics (Basel), 2021
Brea-Fernández AJ et. al., Trio-based exome sequencing reveals a high rate of the de novo variants in intellectual disability., Eur J Hum Genet, 2022

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