NLGN1

protein-coding

neuroligin 1, the group of Neuroligins

Gene summary

This gene encodes a member of a family of neuronal cell surface proteins. Members of this family may act as splice site-specific ligands for beta-neurexins and may be involved in the formation and remodeling of central nervous system synapses. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001365925.2

Inheritance

AR, AD

ClinVar variants

U:108B:28

Top phenotype

Autism, susceptibility to, 20

gnomAD constraint

pLI —, LoF o/e 0.18

Max pathogenic AF

—

Genomic locus

chr3:173,396,284-174,294,372

External References & Databases

Ensembl (ENSG00000169760)

Transcript & Mutation Effects

hg38 • Region Span ~898.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autism, susceptiblity toLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0020836

Submitter: PanelApp Australia

autism, susceptibility to, 20MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0030004

Submitter: Ambry Genetics

autism, susceptibility to, 20LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0030004

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Autism, susceptibility to, 20AD/AR

Manifestation: Neurologic

Intervention: General

Rationale: 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

Refs: 28841651; 30460678

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NLGN1 variants in ClinVar

7 Conditions Cataloged

Inborn genetic diseasesTotal: 87

not providedTotal: 21

NLGN1-related disorderTotal: 17

Autism, susceptibility to, 20Total: 13

not specifiedTotal: 4

See casesTotal: 2

Intellectual disability, X-linked 102Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001365925.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	9 clinvar	6 clinvar	17
missense			101 clinvar	13 clinvar		114
nonsense			5 clinvar			5
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	108	22	6	136

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 46 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001365925.2	RefSeq	NP_001352854.1	6	MANE Select
ENST00000695368.1	Ensembl	ENSP00000511841.1	6	MANE Select
NM_001365923.2	RefSeq	NP_001352852.1	6	Standard
NM_001365924.2	RefSeq	NP_001352853.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cell adhesion molecules (CAMs) - Homo sapiens (human)
Ectoderm Differentiation
Serotonin and anxiety-related events
Neuronal System
Neurexins and neuroligins

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

Molecular Function

amyloid-beta binding
PDZ domain binding
signaling receptor activity
neurexin family protein binding
protein dimerization activity

Cellular Component

Golgi apparatus
plasma membrane
integral component of plasma membrane
external side of plasma membrane
cell surface

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000457714
Coding exons: 5
Length: 890361
Individuals with no LoFs: 125685
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125696
p: 0.0000438

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.22	315	447	0.705	0.0000226	5389
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00041	0.00030	rare
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.135

Intolerance Scores

LoFtool: 0.487
RVIS EVS: -1.4
RVIS percentile EVS: 4.19

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.794

Gene Damage Prediction

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