NRXN2

neurexin 2, the group of Neurexins

Basic information

Region (hg38): 11:64606174-64723197

Links

ENSG00000110076 ∙ NCBI:9379 ∙ OMIM:600566 ∙ HGNC:8009 ∙ Uniprot:P58401, Q9P2S2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autism (Strong), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NRXN2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NRXN2 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	21	10	36
missense			113	14	2	129
nonsense						0
start loss						0
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			2	1	2	5
non coding			1	2	21	24
Total	0	0	122	37	33

Variants in NRXN2

This is a list of pathogenic ClinVar variants found in the NRXN2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-64607248-G-C		not specified	Uncertain significance (May 28, 2024)
11-64607270-T-G			not provided (-)
11-64607295-CGA-C		Autism spectrum disorder;Schizophrenia	not provided (-)
11-64607348-G-A		not specified	Uncertain significance (May 24, 2023)
11-64607350-T-C		Intellectual disability • not specified	Uncertain significance (Feb 10, 2023)
11-64607403-C-T			Benign (Mar 29, 2018)
11-64607470-G-A		not specified	Uncertain significance (Jun 11, 2024)
11-64607473-C-T		not specified	Uncertain significance (Apr 23, 2024)
11-64607474-C-T		not specified	Uncertain significance (Aug 16, 2021)
11-64607488-C-A		not specified	Likely benign (May 31, 2016)
11-64607489-C-CT		Intellectual disability	Uncertain significance (Apr 20, 2020)
11-64607512-T-C		not specified	Likely benign (Apr 07, 2023)
11-64607522-C-G		not specified	Uncertain significance (Feb 27, 2023)
11-64607524-G-A		not specified	Uncertain significance (Jul 20, 2021)
11-64607558-G-T		not specified	Uncertain significance (Feb 16, 2023)
11-64607684-A-G		not specified	Likely benign (Apr 07, 2023)
11-64607710-C-T		not specified	Uncertain significance (Nov 08, 2022)
11-64607713-T-A		not specified	Uncertain significance (Jul 17, 2015)
11-64607734-G-C		NRXN2-related disorder	Uncertain significance (Jan 30, 2024)
11-64607740-G-T		not specified	Uncertain significance (Feb 16, 2023)
11-64607816-G-A		not specified	Uncertain significance (Feb 16, 2023)
11-64607880-G-T		not specified	Uncertain significance (Jun 24, 2022)
11-64607889-G-C			Uncertain significance (Jul 23, 2022)
11-64607890-TC-T			Uncertain significance (Jan 19, 2022)
11-64607895-C-A		NRXN2-related autism spectrum disorder	Uncertain significance (Apr 23, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NRXN2	protein_coding	protein_coding	ENST00000265459	22	117015

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000660	125736	0	12	125748	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.02	646	1.00e+3	0.643	0.0000694	10943
Missense in Polyphen		140	263.82	0.53067		2569
Synonymous	0.233	444	450	0.986	0.0000335	3652
Loss of Function	6.16	9	60.8	0.148	0.00000358	649

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000545	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000528	0.0000527
Middle Eastern	0.0000545	0.0000544
South Asian	0.0000658	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Neuronal cell surface protein that may be involved in cell recognition and cell adhesion.
• Pathway: Cell adhesion molecules (CAMs) - Homo sapiens (human);Neuronal System;Neurexins and neuroligins;Protein-protein interactions at synapses (Consensus)

Recessive Scores

• pRec: 0.102

Intolerance Scores

• loftool: 0.204
• rvis_EVS: -2.16
• rvis_percentile_EVS: 1.43

Haploinsufficiency Scores

• pHI: 0.242
• hipred: Y
• hipred_score: 0.651
• ghis: 0.603

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.861

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nrxn2
• Phenotype: growth/size/body region phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: nrxn2a
• Affected structure: CaP motoneuron
• Phenotype tag: abnormal
• Phenotype quality: truncated

Gene ontology

• Biological process: neuron cell-cell adhesion;signal transduction;chemical synaptic transmission;neurotransmitter secretion;synapse assembly;adult behavior;social behavior;vocal learning;vocalization behavior;postsynaptic membrane assembly;gephyrin clustering involved in postsynaptic density assembly;neuroligin clustering involved in postsynaptic membrane assembly;postsynaptic density protein 95 clustering
• Cellular component: plasma membrane;integral component of membrane;presynapse
• Molecular function: transmembrane signaling receptor activity;calcium channel regulator activity;metal ion binding;cell adhesion molecule binding;neuroligin family protein binding