NLGN1

neuroligin 1, the group of Neuroligins

Basic information

Region (hg38): 3:173396284-174294372

Links

ENSG00000169760 ∙ NCBI:22871 ∙ OMIM:600568 ∙ HGNC:14291 ∙ Uniprot:Q8N2Q7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autism, susceptibility to, 20 (Moderate), mode of inheritance: AD
• autism, susceptibility to, 20 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Autism, susceptibility to, 20	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	Neurologic	28841651; 30460678

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NLGN1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NLGN1 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			1	5	8	14
missense			42	10		52
nonsense			1			1
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2		2
non coding						0
Total	0	0	45	15	8

Variants in NLGN1

This is a list of pathogenic ClinVar variants found in the NLGN1 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-173604617-A-G			Uncertain significance (Dec 19, 2023)
3-173604651-C-A		Inborn genetic diseases	Uncertain significance (Jul 27, 2022)
3-173604666-G-A		Inborn genetic diseases	Uncertain significance (May 24, 2024)
3-173604669-G-A		Inborn genetic diseases	Uncertain significance (Sep 14, 2022)
3-173604672-T-A			Uncertain significance (May 14, 2020)
3-173604680-C-G		Inborn genetic diseases	Likely benign (Feb 16, 2023)
3-173604709-G-A		NLGN1-related disorder	Likely benign (Jul 01, 2019)
3-173604800-G-C		Inborn genetic diseases	Likely benign (Apr 07, 2023)
3-173604806-A-G		NLGN1-related disorder	Uncertain significance (Nov 29, 2023)
3-173604807-A-G		Inborn genetic diseases	Uncertain significance (Oct 29, 2021)
3-173604809-A-T		Inborn genetic diseases	Uncertain significance (May 24, 2024)
3-173604819-T-G		Inborn genetic diseases	Uncertain significance (Apr 13, 2022)
3-173604845-G-A		Inborn genetic diseases	Likely benign (Apr 01, 2024)
3-173604857-G-T		Inborn genetic diseases	Uncertain significance (Jun 13, 2023)
3-173604860-C-T			Uncertain significance (Jun 09, 2021)
3-173604864-C-T		Autism, susceptibility to, 20	risk factor (May 13, 2020)
3-173604876-G-A		Inborn genetic diseases	Likely benign (Nov 10, 2022)
3-173604893-G-C		Inborn genetic diseases	Uncertain significance (Jun 02, 2023)
3-173604896-C-T		See cases	Uncertain significance (Mar 29, 2021)
3-173604905-C-T		Inborn genetic diseases	Uncertain significance (Jul 11, 2023)
3-173604946-G-A		NLGN1-related disorder	Benign (Feb 20, 2019)
3-173605041-A-G		Inborn genetic diseases	Uncertain significance (Mar 01, 2023)
3-173605081-G-A		NLGN1-related disorder	Likely benign (Mar 26, 2019)
3-173800298-C-T		NLGN1-related disorder	Likely benign (Jan 04, 2022)
3-173800306-GAAAC-G		See cases	Uncertain significance (Oct 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NLGN1	protein_coding	protein_coding	ENST00000457714	5	890361

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.853	0.147	125685	0	11	125696	0.0000438

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.22	315	447	0.705	0.0000226	5389
Missense in Polyphen		162	265.91	0.60924		3226
Synonymous	0.320	158	163	0.968	0.00000845	1628
Loss of Function	4.06	5	28.3	0.177	0.00000133	376

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000407	0.000298
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000531	0.0000528
Middle Eastern	0.000109	0.000109
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 probably mediates its effects by recruiting and clustering other synaptic proteins. May promote the initial formation of synapses, but is not essential for this. In vitro, triggers the de novo formation of presynaptic structures. May be involved in specification of excitatory synapses. Required to maintain wakefulness quality and normal synchrony of cerebral cortex activity during wakefulness and sleep. {ECO:0000250|UniProtKB:Q99K10}.
• Pathway: Cell adhesion molecules (CAMs) - Homo sapiens (human);Ectoderm Differentiation;Serotonin and anxiety-related events;Neuronal System;Neurexins and neuroligins;Protein-protein interactions at synapses (Consensus)

Recessive Scores

• pRec: 0.135

Intolerance Scores

• loftool: 0.487
• rvis_EVS: -1.4
• rvis_percentile_EVS: 4.19

Haploinsufficiency Scores

• pHI: 0.342
• hipred: Y
• hipred_score: 0.638
• ghis: 0.613

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.794

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nlgn1
• 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; reproductive 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); growth/size/body region phenotype

Gene ontology

• Biological process: regulation of respiratory gaseous exchange by neurological system process;protein targeting;heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules;neuron cell-cell adhesion;nervous system development;synapse assembly;positive regulation of circadian sleep/wake cycle, wakefulness;synaptic vesicle targeting;calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules;neuronal signal transduction;neuron projection development;positive regulation of synaptic transmission, GABAergic;protein localization to synapse;establishment of protein localization;regulation of neuron differentiation;synaptic vesicle endocytosis;rhythmic process;cytoskeletal matrix organization at active zone;modulation of chemical synaptic transmission;protein homooligomerization;protein heterotetramerization;positive regulation of filopodium assembly;positive regulation of synapse assembly;positive regulation of synaptic transmission, glutamatergic;long-term synaptic potentiation;positive regulation of dendritic spine development;negative regulation of dendritic spine morphogenesis;cellular response to calcium ion;terminal button organization;synaptic vesicle clustering;postsynaptic membrane assembly;presynaptic membrane assembly;AMPA glutamate receptor clustering;NMDA glutamate receptor clustering;neurexin clustering involved in presynaptic membrane assembly;postsynaptic density protein 95 clustering;receptor localization to synapse;postsynaptic specialization assembly;retrograde trans-synaptic signaling by trans-synaptic protein complex;presynapse assembly;synaptic membrane adhesion;neuron projection arborization;positive regulation of ruffle assembly;positive regulation of synaptic vesicle endocytosis;positive regulation of protein localization to synapse;positive regulation of intracellular signal transduction;excitatory synapse assembly;positive regulation of presynaptic active zone assembly;positive regulation of synaptic vesicle exocytosis;regulation of NMDA receptor activity;regulation of AMPA receptor activity;positive regulation of excitatory postsynaptic potential;positive regulation of synaptic vesicle clustering
• Cellular component: Golgi apparatus;plasma membrane;integral component of plasma membrane;external side of plasma membrane;cell surface;postsynaptic density;NMDA selective glutamate receptor complex;cell junction;dendrite;filopodium tip;dendritic spine;dendritic shaft;synapse;excitatory synapse;spanning component of membrane;presynapse;postsynapse;asymmetric, glutamatergic, excitatory synapse;integral component of postsynaptic membrane;integral component of postsynaptic specialization membrane
• Molecular function: amyloid-beta binding;PDZ domain binding;signaling receptor activity;neurexin family protein binding;protein dimerization activity;cell adhesion molecule binding;scaffold protein binding