Developmental Brain Disorder Gene Database

LoF Variant Gene





HGNC:8008 (protein-coding gene)

neurexin 1

Unique Cases:
Last Updated:
January 24, 2024

Gene Summary:

DBD Genes Classification
NRXN1 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
Neuronal cell surface protein involved in cell recognition and cell adhesion by forming intracellular junctions through binding to neuroligins. Plays a role in formation of synaptic junctions. {ECO:0000250|UniProtKB:P0DI97, ECO:0000250|UniProtKB:Q63373}. (Source: Uniprot)
Previous symbols
No previous symbols
Alias symbols
KIAA0578, Hs.22998
Chromosomal Location
Genomic Coordinates
Associated Disorders
Intellectual Disability, Autism, Epilepsy, Attention Deficit Hyperactivity Disorder

Predictive Scores:

HI Score (Decipher)


pLI (gnomAD)


LOEUF (gnomAD)


Classifications from External Sources:



DDG2P Classification (DDG2P)

No Classification

ClinGen Classification (ClinGen)


GenCC Classification (GenCC)

Limited1 Moderate2 Strong2 Definitive1


Husson T et. al., Rare genetic susceptibility variants assessment in autism spectrum disorder: detection rate and practical use., Transl Psychiatry, 2020
Sundaram SK et. al., Tourette syndrome is associated with recurrent exonic copy number variants., Neurology, 2010
Duong L et. al., Mutations in NRXN1 in a family multiply affected with brain disorders: NRXN1 mutations and brain disorders., Am J Med Genet B Neuropsychiatr Genet, 2012
Dabell MP et. al., Investigation of NRXN1 deletions: clinical and molecular characterization., Am J Med Genet A, 2013
Bremer A et. al., Copy number variation characteristics in subpopulations of patients with autism spectrum disorders., Am J Med Genet B Neuropsychiatr Genet, 2011
Béna F et. al., Molecular and clinical characterization of 25 individuals with exonic deletions of NRXN1 and comprehensive review of the literature., Am J Med Genet B Neuropsychiatr Genet, 2013
Ching MS et. al., Deletions of NRXN1 (neurexin-1) predispose to a wide spectrum of developmental disorders., Am J Med Genet B Neuropsychiatr Genet, 2010
Todarello G et. al., Incomplete penetrance of NRXN1 deletions in families with schizophrenia., Schizophr Res, 2014
Al-Mamari W et. al., Diagnostic Yield of Chromosomal Microarray Analysis in a Cohort of Patients with Autism Spectrum Disorders from a Highly Consanguineous Population., J Autism Dev Disord, 2015
Boone PM et. al., Detection of clinically relevant exonic copy-number changes by array CGH., Hum Mutat, 2010
Noor A et. al., Copy number variant study of bipolar disorder in Canadian and UK populations implicates synaptic genes., Am J Med Genet B Neuropsychiatr Genet, 2014
Walsh T et. al., Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia., Science, 2008
Vulto-van Silfhout AT et. al., Clinical significance of de novo and inherited copy-number variation., Hum Mutat, 2013
Iossifov I et. al., De novo gene disruptions in children on the autistic spectrum., Neuron, 2012
Al Shehhi M et. al., NRXN1 deletion syndrome; phenotypic and penetrance data from 34 families., Eur J Med Genet, 2019
De Rubeis S et. al., Synaptic, transcriptional and chromatin genes disrupted in autism., Nature, 2014
C Yuen RK et. al., Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder., Nat Neurosci, 2017
Levy D et. al., Rare de novo and transmitted copy-number variation in autistic spectrum disorders., Neuron, 2011
Pinto D et. al., Functional impact of global rare copy number variation in autism spectrum disorders., Nature, 2010
Pinto D et. al., Convergence of genes and cellular pathways dysregulated in autism spectrum disorders., Am J Hum Genet, 2014
Girirajan S et. al., Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder., Am J Hum Genet, 2013
Georgieva L et. al., De novo CNVs in bipolar affective disorder and schizophrenia., Hum Mol Genet, 2014
Shen Y et. al., Clinical genetic testing for patients with autism spectrum disorders., Pediatrics, 2010
Gai X et. al., Rare structural variation of synapse and neurotransmission genes in autism., Mol Psychiatry, 2012
Rujescu D et. al., Disruption of the neurexin 1 gene is associated with schizophrenia., Hum Mol Genet, 2009
Stojanovic JR et. al., Diagnostic and Clinical Utility of Clinical Exome Sequencing in Children With Moderate and Severe Global Developmental Delay / Intellectual Disability., J Child Neurol, 2020
Lal D et. al., Burden analysis of rare microdeletions suggests a strong impact of neurodevelopmental genes in genetic generalised epilepsies., PLoS Genet, 2015
Møller RS et. al., Exon-disrupting deletions of NRXN1 in idiopathic generalized epilepsy., Epilepsia, 2013
Coe BP et. al., Refining analyses of copy number variation identifies specific genes associated with developmental delay., Nat Genet, 2014
Gregor A et. al., Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1., BMC Med Genet, 2011
Gauthier J et. al., Truncating mutations in NRXN2 and NRXN1 in autism spectrum disorders and schizophrenia., Hum Genet, 2011
Zweier C et. al., CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in Drosophila., Am J Hum Genet, 2009
Leblond CS et. al., Both rare and common genetic variants contribute to autism in the Faroe Islands., NPJ Genom Med, 2019
Awadalla P et. al., Direct measure of the de novo mutation rate in autism and schizophrenia cohorts., Am J Hum Genet, 2010
Kushima I et. al., High-resolution copy number variation analysis of schizophrenia in Japan., Mol Psychiatry, 2017
Feliciano P et. al., Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes., NPJ Genom Med, 2019
Wallis M et. al., Dual genetic diagnoses: Atypical hand-foot-genital syndrome and developmental delay due to de novo mutations in HOXA13 and NRXN1., Am J Med Genet A, 2016
Vrijenhoek T et. al., Recurrent CNVs disrupt three candidate genes in schizophrenia patients., Am J Hum Genet, 2008
Roberts JL et. al., Chromosomal microarray analysis of consecutive individuals with autism spectrum disorders or learning disability presenting for genetic services., Gene, 2014
Purcell SM et. al., A polygenic burden of rare disruptive mutations in schizophrenia., Nature, 2014
Kong A et. al., Rate of de novo mutations and the importance of father's age to disease risk., Nature, 2012
Bermudez-Wagner K et. al., 2p16.3 microdeletion with partial deletion of the neurexin-1 gene in a female with developmental delays, short stature, and a congenital diaphragmatic hernia., Clin Dysmorphol, 2013
Agha Z et. al., A de novo microdeletion in NRXN1 in a Dutch patient with mild intellectual disability, microcephaly and gonadal dysgenesis., Genet Res (Camb), 2015
Schaaf CP et. al., Phenotypic spectrum and genotype-phenotype correlations of NRXN1 exon deletions., Eur J Hum Genet, 2012
Curran S et. al., NRXN1 deletions identified by array comparative genome hybridisation in a clinical case series - further understanding of the relevance of NRXN1 to neurodevelopmental disorders., J Mol Psychiatry, 2013

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.

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.


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.


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.


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.


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


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.
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