NRXN1

neurexin 1, the group of Neurexins|MicroRNA protein coding host genes

Basic information

Region (hg38): 2:49918503-51225575

Links

ENSG00000179915 ∙ NCBI:9378 ∙ OMIM:600565 ∙ HGNC:8008 ∙ Uniprot:P58400, Q9ULB1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 54.

Transcript ID	Protein ID	Coding exons	MANE Select	MANE Plus Clinical
ENST00000331040.9	ENSP00000489573.1	13	-	-
ENST00000342183.9	ENSP00000341184.5	6	-	-
ENST00000378262.7	ENSP00000367510.4	3	-	-
ENST00000401669.7	ENSP00000385017.2	22	yes	-

Phenotypes

GenCC

Source: genCC

• Pitt-Hopkins-like syndrome 2 (Moderate), mode of inheritance: AR
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD
• schizophrenia (Limited), mode of inheritance: Unknown
• chromosome 2p16.3 deletion syndrome (Strong), mode of inheritance: AD
• Pitt-Hopkins-like syndrome 2 (Strong), mode of inheritance: AR
• autism (Moderate), mode of inheritance: AD
• Pitt-Hopkins-like syndrome 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Schizophrenia 17; Pitt-Hopkins-like syndrome 2	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic	18369103; 17989066; 18945720; 19896112; 21424692

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NRXN1 gene.

• Pitt-Hopkins-like_syndrome_2 (1824 variants)
• not_provided (555 variants)
• Inborn_genetic_diseases (308 variants)
• not_specified (179 variants)
• NRXN1-related_disorder (60 variants)
• Chromosome_2p16.3_deletion_syndrome (41 variants)
• History_of_neurodevelopmental_disorder (8 variants)
• Intellectual_disability (8 variants)
• Autism_spectrum_disorder (5 variants)
• Complex_neurodevelopmental_disorder (3 variants)
• See_cases (2 variants)
• Obesity (1 variants)
• NRXN-related_disorder (1 variants)
• Gestational_diabetes_mellitus_uncontrolled (1 variants)
• Ovarian_dysgenesis_3 (1 variants)
• Schizophrenia_17 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NRXN1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001330078.2. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			15	545	7	567
missense	1		1036	33		1070
nonsense	15	13	4			32
start loss	1					1
frameshift	20	8	6			34
splice donor/acceptor (+/-2bp)	2	14	8			24
Total	39	35	1069	578	7

Highest pathogenic variant AF is 0.000014514209

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NRXN1	protein_coding	protein_coding	ENST00000404971	23	1114032

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125731	0	17	125748	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.56	681	897	0.759	0.0000541	10084
Missense in Polyphen		212	368.05	0.57601		4246
Synonymous	-3.35	451	369	1.22	0.0000253	3017
Loss of Function	6.44	10	66.8	0.150	0.00000378	796

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.00	0.00
East Asian	0.000178	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000803	0.0000703
Middle Eastern	0.000178	0.000163
South Asian	0.000138	0.000131
Other	0.000199	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Neuronal cell surface protein that may be involved in cell recognition and cell adhesion by forming intracellular junctions through binding to neuroligins. May play a role in formation or maintenance of synaptic junctions. May mediate intracellular signaling. May play a role in angiogenesis (By similarity). {ECO:0000250}.
• Pathway: Cell adhesion molecules (CAMs) - Homo sapiens (human);Extracellular matrix organization;Neuronal System;Neurexins and neuroligins;Non-integrin membrane-ECM interactions;Protein-protein interactions at synapses (Consensus)

Intolerance Scores

• loftool: 0.297
• rvis_EVS: -1.79
• rvis_percentile_EVS: 2.25

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.909

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Zebrafish Information Network

• Gene name: nrxn1a
• Affected structure: caudal vein plexus
• Phenotype tag: abnormal
• Phenotype quality: malformed

Gene ontology

• Biological process: neuron cell-cell adhesion;chemical synaptic transmission;neurotransmitter secretion;axon guidance;synapse assembly;learning;adult behavior;social behavior;vocal learning;neuromuscular process controlling balance;positive regulation of synapse assembly;positive regulation of synaptic transmission, glutamatergic;prepulse inhibition;vocalization behavior;positive regulation of synapse maturation;postsynaptic membrane assembly;gephyrin clustering involved in postsynaptic density assembly;neuroligin clustering involved in postsynaptic membrane assembly;postsynaptic density protein 95 clustering;regulation of synaptic vesicle cycle;regulation of postsynaptic density assembly;trans-synaptic signaling by endocannabinoid;synaptic membrane adhesion;regulation of presynapse assembly;positive regulation of excitatory postsynaptic potential;regulation of grooming behavior
• Cellular component: nucleolus;endoplasmic reticulum;plasma membrane;integral component of plasma membrane;cell surface;cell junction;nuclear membrane;vesicle;protein-containing complex;presynaptic membrane;neuronal cell body;Schaffer collateral - CA1 synapse;glutamatergic synapse;GABA-ergic synapse;integral component of presynaptic active zone membrane
• Molecular function: calcium channel regulator activity;calcium ion binding;protein binding;acetylcholine receptor binding;signaling receptor activity;cell adhesion molecule binding;neuroligin family protein binding