NLGN3

neuroligin 3, the group of Neuroligins

Basic information

Region (hg38): X:71144820-71175255

Links

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

Phenotypes

GenCC

Source: genCC

• autism, susceptibility to, X-linked 1 (Strong), mode of inheritance: XLR
• 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 (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 (65 variants)
• Inborn genetic diseases (47 variants)
• not specified (22 variants)
• Autism, susceptibility to, X-linked 1 (6 variants)
• NLGN3-related condition (3 variants)
• Intellectual disability (2 variants)
• Autism spectrum disorder (2 variants)
• Hypogonadotropic hypogonadism (1 variants)
• Complex neurodevelopmental disorder (1 variants)
• Intellectual disability;Autistic behavior (1 variants)
• See cases (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.

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			8	24	3	35
missense	1	2	67	3		73
nonsense	1		2			3
start loss			1			1
frameshift	1		1			2
inframe indel						0
splice donor/acceptor (+/-2bp)		1		1		2
splice region			1			1
non coding			3	3	1	7
Total	3	3	82	31	4

Variants in NLGN3

This is a list of pathogenic ClinVar variants found in the NLGN3 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-71147745-G-A		Inborn genetic diseases	Uncertain significance (Aug 16, 2016)
X-71147751-T-G			Uncertain significance (Jul 25, 2022)
X-71147759-C-T		not specified • Inborn genetic diseases	Conflicting classifications of pathogenicity (Nov 19, 2018)
X-71147769-C-T			Uncertain significance (Aug 26, 2014)
X-71147770-G-A		not specified	Likely benign (Jul 22, 2016)
X-71147775-C-T		not specified	Uncertain significance (Jul 29, 2019)
X-71147787-G-A		not specified	Uncertain significance (Mar 20, 2020)
X-71147797-C-T		Inborn genetic diseases	Likely benign (Oct 23, 2019)
X-71147800-G-A		Inborn genetic diseases	Likely benign (May 31, 2017)
X-71147842-G-C			Uncertain significance (Mar 22, 2023)
X-71147845-G-A		Inborn genetic diseases	Likely benign (Oct 23, 2019)
X-71147895-G-A			Uncertain significance (Apr 02, 2021)
X-71147909-G-A			Uncertain significance (Aug 05, 2022)
X-71147912-C-G		Intellectual disability	Uncertain significance (Apr 20, 2020)
X-71147912-C-T		Autism, susceptibility to, X-linked 1	Uncertain significance (Feb 05, 2021)
X-71147919-C-T		Inborn genetic diseases	Uncertain significance (Apr 29, 2021)
X-71147927-A-G			Uncertain significance (Nov 21, 2022)
X-71147958-T-TG		Inborn genetic diseases	Pathogenic (Jan 13, 2016)
X-71147971-C-T		Inborn genetic diseases	Likely benign (Nov 20, 2019)
X-71147975-G-A			Uncertain significance (Jun 20, 2022)
X-71147978-C-T		Inborn genetic diseases	Uncertain significance (Jan 26, 2018)
X-71147986-C-G		not specified	Uncertain significance (Dec 20, 2023)
X-71147990-G-A		Inborn genetic diseases	Uncertain significance (Jul 14, 2021)
X-71147993-A-C		Intellectual disability	Likely benign (Jan 01, 2019)
X-71147996-C-T			Uncertain significance (Jun 15, 2020)

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