NLGN2

neuroligin 2, the group of Neuroligins

Basic information

Region (hg38): 17:7404874-7419860

Links

ENSG00000169992 ∙ NCBI:57555 ∙ OMIM:606479 ∙ HGNC:14290 ∙ Uniprot:Q8NFZ4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NLGN2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NLGN2 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				34	12	46
missense			81	1	2	84
nonsense			3			3
start loss						0
frameshift			2			2
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region			1	1	1	3
non coding				4	3	7
Total	0	0	88	39	17

Variants in NLGN2

This is a list of pathogenic ClinVar variants found in the NLGN2 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-7408295-G-A		not specified	Uncertain significance (May 23, 2024)
17-7408313-G-A			Uncertain significance (Oct 30, 2023)
17-7408326-G-A			Uncertain significance (Jan 09, 2024)
17-7408333-G-A			Likely benign (Oct 07, 2024)
17-7408339-C-T			Likely benign (Jan 06, 2025)
17-7408349-G-GGCCTCGGCA			Uncertain significance (Aug 23, 2024)
17-7408392-C-T			Uncertain significance (Sep 27, 2022)
17-7408404-G-A		not specified	Uncertain significance (Jan 30, 2024)
17-7408419-G-T			Uncertain significance (Mar 22, 2023)
17-7408426-G-C			Uncertain significance (May 24, 2024)
17-7408431-A-G		not specified	Uncertain significance (Mar 28, 2024)
17-7408483-G-A			Benign (Nov 28, 2024)
17-7408492-GGGCGCCCGCCGCTTCCAGCCGCCTGA-G			Uncertain significance (Jun 08, 2023)
17-7408496-G-A		not specified	Uncertain significance (May 23, 2023)
17-7408500-G-A		not specified	Uncertain significance (Oct 16, 2023)
17-7408503-G-GCTTCCAGC			Uncertain significance (May 23, 2024)
17-7408532-T-TGGCCCGGCGTGC			Uncertain significance (Sep 12, 2024)
17-7408539-G-A			Uncertain significance (Mar 07, 2023)
17-7408549-C-T			Likely benign (Feb 03, 2023)
17-7408583-C-T			Likely benign (Apr 18, 2024)
17-7408628-G-A			Uncertain significance (Sep 24, 2018)
17-7408663-C-G			Uncertain significance (Jul 25, 2022)
17-7408664-C-T			Uncertain significance (Nov 02, 2020)
17-7408721-G-A			Benign (Nov 05, 2024)
17-7408722-C-T		NLGN2-related disorder	Likely benign (Jul 01, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NLGN2	protein_coding	protein_coding	ENST00000302926	7	14987

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000259	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.47	225	508	0.442	0.0000367	5271
Missense in Polyphen		83	300.88	0.27585		3091
Synonymous	0.278	234	239	0.977	0.0000194	1807
Loss of Function	4.50	0	23.6	0.00	0.00000102	277

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transmembrane scaffolding protein involved in cell-cell interactions via its interactions with neurexin family members. Mediates cell-cell interactions both in neurons and in other types of cells, such as Langerhans beta cells. Plays a role in synapse function and synaptic signal transmission, especially via gamma- aminobutyric acid receptors (GABA(A) receptors). Functions by recruiting and clustering synaptic proteins. Promotes clustering of postsynaptic GABRG2 and GPHN. Modulates signaling by inhibitory synapses, and thereby plays a role in controlling the ratio of signaling by excitatory and inhibitory synapses and information processing. Required for normal signal amplitude from inhibitory synapses, but is not essential for normal signal frequency. May promote the initial formation of synapses, but is not essential for this. In vitro, triggers the de novo formation of presynaptic structures. Mediates cell-cell interactions between Langerhans beta cells and modulates insulin secretion (By similarity). {ECO:0000250}.
• Pathway: Cell adhesion molecules (CAMs) - Homo sapiens (human);Neuronal System;Neurexins and neuroligins;Protein-protein interactions at synapses (Consensus)

Recessive Scores

• pRec: 0.113

Intolerance Scores

• rvis_EVS: -1.02
• rvis_percentile_EVS: 7.94

Haploinsufficiency Scores

• pHI: 0.310
• hipred: Y
• hipred_score: 0.662
• ghis: 0.647

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.767

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nlgn2
• Phenotype: growth/size/body region phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive 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); 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)

Gene ontology

• Biological process: regulation of respiratory gaseous exchange by neurological system process;neuron cell-cell adhesion;synapse assembly;sensory perception of pain;positive regulation of insulin secretion;positive regulation of synaptic transmission, GABAergic;protein localization to synapse;locomotory exploration behavior;cell-cell junction maintenance;synaptic vesicle endocytosis;modulation of chemical synaptic transmission;synapse organization;neuromuscular process controlling balance;positive regulation of synapse assembly;positive regulation of synaptic transmission, glutamatergic;terminal button organization;postsynaptic membrane assembly;presynaptic membrane assembly;gephyrin clustering involved in postsynaptic density assembly;postsynaptic density protein 95 clustering;positive regulation of inhibitory postsynaptic potential;cell-cell adhesion;presynapse assembly;positive regulation of protein localization to synapse;inhibitory synapse assembly;regulation of AMPA receptor activity;positive regulation of excitatory postsynaptic potential;positive regulation of synaptic vesicle clustering
• Cellular component: plasma membrane;integral component of plasma membrane;cell surface;membrane;cell junction;presynaptic membrane;synapse;postsynaptic membrane;inhibitory synapse;spanning component of membrane;glycinergic synapse;dopaminergic synapse;symmetric, GABA-ergic, inhibitory synapse;integral component of postsynaptic membrane;integral component of postsynaptic specialization membrane
• Molecular function: signaling receptor activity;neurexin family protein binding;identical protein binding;cell adhesion molecule binding