• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
NRXN1 (HGNC:8008) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
neurexin 1
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
KIAA0578, Hs.22998
%HI
0.81(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.25(Read more about gnomAD LOEUF score)
Cytoband
2p16.3
Genomic Coordinates
GRCh37/hg19: chr2:50145641-51259270 NCBI Ensembl UCSC
GRCh38/hg38: chr2:49918503-51032132 NCBI Ensembl UCSC
MANE Select Transcript
NM_001330078.2 ENST00000401669.7 (Read more about MANE Select)
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)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-3442
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
06/08/2021

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • Complex Neurodevelopmental Disorder Monarch
HI Evidence:
  • PUBMED: 20162629
    Wisniomiecka-Kowalnik et al. (2010) identified three families with NRXN1 rearrangements and autism spectrum disorder. A 380-kb deletion was identified in a woman with Asperger syndrome and in four of her children affected with autism, DD, and speech delay, but not in her unaffected child.
  • PUBMED: 18057082
    Zahir et al (2008) describe a de novo 321 kb deletion including only NRXN1 (exons 1-5 of a-form) in a child with DD, autism, unusual facies. Note: This is the same individual described in PMID:16909388 -Friedman et al (2006)
  • PUBMED: 20468056
    Ching et al (2010): 12 subjects of 3,540 referred for clinical aCGH were identified with exonic deletions of NRXN1. The phenotype of these individuals was variable and included autism, ID, language delays, and hypotonia. Comparing this cohort to a control population showed a statistically significant increase in NRXN1 deletion in cases versus controls (p=8.9x10(-7)). Further, two families were described with NRXN1 deletions (one exoninc, one of 5' regulatory region) that segregated with autism and ID in both families.
  • PUBMED: 21424692
    Gauthier et al., 2011. They identified a de novo heterozygous frameshift mutation in exon 22 of NRXN1, affecting the α and β isoform in a female with disorganised SCZ. The 4- nucleotide insertion led to a premature stop codon, with a truncated protein lacking the transmembrane region and cytoplasmic tail.
  • PUBMED: 27869829
    Marshall et al., 2017. It is the largest-to-date genome-wide schizophrenia cohort (21,094 cases; 20,227 controls). They assessed the contribution of CNV to the risk of SCZ. Odds ratio (95% CI) is 14.4 (4.2-46.9, cases: 35; controls: 3) for losses involving NRXN1 (majority are partial loss of the gene). A gene-based association test identified genome-wide significant association signals at 8 loci. NRXN1 got the third highest level of statistical support, was the only single-gene locus identified and was observed to have one of the highest odds ratios of all reported loci.
  • PUBMED: 24768552
    Pinto et al., 2014. Analyzed 2,446 ASD-affected families and confirmed exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and ID (odds ratio = 12.62, p=2.7E-15). Five de novo deletions involving NRXN1 were found in ASD patients.
HI Evidence Comments:
Heterozygous deletions of NRXN1 have been reported in individuals with autism, schizophrenia, and ID. Other PMIDs including: 21424692; 19557195, 18369103 describe both case reports and case-control studies supporting a role for the haploinsufficiency of NRXN1 in neurological phenotypes. Other PMIDs: 33191396, 29923609, 23533028, 24253858, 29703944, 24811917, 23505263. Compound heterozygosity reported in one individual with Pitt-Hopkins-like syndrome 2-severe ID, autistic behavior, dysmorphism.(PMID 19896112) Several intronic deletion polymorphisms, particularly in the longer isoform, have been reported in NRXN1 and are cataloged in DGV. Note that some NRXN1 variants have been inherited from reportedly normal parents, suggesting a role for reduced penetrance and variable expressivity.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000002.11) (NC_000002.12)