NLGN3

neuroligin 3, the group of Neuroligins

Basic information

Region (hg38): X:71144821-71175255

Links

ENSG00000196338 ∙ NCBI:54413 ∙ OMIM:300336 ∙ HGNC:14289 ∙ Uniprot:Q9NZ94 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• X-linked complex neurodevelopmental disorder (Moderate), mode of inheritance: XL
• autism, susceptibility to, X-linked 1 (Limited), mode of inheritance: Unknown
• X-linked complex neurodevelopmental disorder (Moderate), mode of inheritance: XL
• autism, susceptibility to, X-linked 1 (Strong), mode of inheritance: XL
• autism, susceptibility to, X-linked 1 (Moderate), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Autism, susceptibility to, X-linked 1	XL	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	Neurologic	12669065

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NLGN3 gene.

• not_provided (104 variants)
• Inborn_genetic_diseases (62 variants)
• not_specified (24 variants)
• Autism,_susceptibility_to,_X-linked_1 (14 variants)
• NLGN3-related_disorder (13 variants)
• Intellectual_disability (7 variants)
• Autism_spectrum_disorder (2 variants)
• X-linked_complex_neurodevelopmental_disorder (2 variants)
• Hypogonadotropic_hypogonadism (1 variants)
• Cone-rod_dystrophy (1 variants)
• Complex_neurodevelopmental_disorder (1 variants)
• See_cases (1 variants)
• Autistic_behavior (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NLGN3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000181303.2. 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			8	30	3	41
missense	2	5	121	5		133
nonsense	1		4			5
start loss			1			1
frameshift	1	1	4			6
splice donor/acceptor (+/-2bp)		2		1		3
Total	4	8	138	36	3

Highest pathogenic variant AF is 0.0000036427218

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NLGN3	protein_coding	protein_coding	ENST00000358741	7	26371

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.976	0.0236	125591	1	1	125593	0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.21	151	382	0.395	0.0000331	5517
Missense in Polyphen		51	191.59	0.2662		2733
Synonymous	0.674	157	168	0.934	0.0000153	1781
Loss of Function	3.77	2	20.3	0.0984	0.00000151	322

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000268	0.000199
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: Cell surface protein involved in cell-cell-interactions via its interactions with neurexin family members. Plays a role in synapse function and synaptic signal transmission, and may mediate its effects by clustering other synaptic proteins. May promote the initial formation of synapses, but is not essential for this. May also play a role in glia-glia or glia-neuron interactions in the developing peripheral nervous system (By similarity). {ECO:0000250, ECO:0000269|PubMed:15620359}.
• Disease: DISEASE: Asperger syndrome, X-linked, 1 (ASPGX1) [MIM:300494]: A syndrome with features similar to autism. Affected individuals exhibit qualitative impairment in social interaction, as manifest by impairment in the use of non-verbal behaviors such as eye-to- eye gaze, facial expression, body postures, and gestures, failure to develop appropriate peer relationships, and lack of social sharing or reciprocity. Patients also exhibit restricted, repetitive and stereotyped patterns of behavior, interests, and activities, including abnormal preoccupation with certain activities and inflexible adherence to routines or rituals. Asperger syndrome is primarily distinguished from autism by the higher cognitive abilities and a more normal and timely development of language and communicative phrases. {ECO:0000269|PubMed:12669065}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Cell adhesion molecules (CAMs) - Homo sapiens (human);Neuronal System;Neurexins and neuroligins;Protein-protein interactions at synapses (Consensus)

Recessive Scores

• pRec: 0.212

Intolerance Scores

• loftool: 0.165
• rvis_EVS: -0.54
• rvis_percentile_EVS: 20.54

Haploinsufficiency Scores

• pHI: 0.533
• hipred: Y
• hipred_score: 0.728
• ghis: 0.661

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.739

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nlgn3
• Phenotype: growth/size/body region phenotype; taste/olfaction phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system 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); normal 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); reproductive system phenotype

Gene ontology

• Biological process: regulation of respiratory gaseous exchange by neurological system process;receptor-mediated endocytosis;neuron cell-cell adhesion;synapse assembly;learning;visual learning;adult behavior;social behavior;synaptic vesicle endocytosis;axon extension;oligodendrocyte differentiation;modulation of chemical synaptic transmission;synapse organization;positive regulation of synapse assembly;positive regulation of synaptic transmission, glutamatergic;rhythmic synaptic transmission;excitatory postsynaptic potential;inhibitory postsynaptic potential;long-term synaptic potentiation;negative regulation of dendritic spine morphogenesis;vocalization behavior;negative regulation of excitatory postsynaptic potential;postsynaptic membrane assembly;presynaptic membrane assembly;presynapse assembly;regulation of long-term synaptic potentiation;regulation of NMDA receptor activity;regulation of terminal button organization;positive regulation of excitatory postsynaptic potential;positive regulation of synaptic vesicle clustering;positive regulation of AMPA receptor activity
• Cellular component: plasma membrane;integral component of plasma membrane;cell surface;cell junction;endocytic vesicle;synapse;excitatory synapse;spanning component of membrane;presynapse;symmetric, GABA-ergic, inhibitory synapse;asymmetric, glutamatergic, excitatory synapse;integral component of postsynaptic membrane
• Molecular function: protein binding;signaling receptor activity;neurexin family protein binding;cell adhesion molecule binding;scaffold protein binding