NRXN3

protein-coding

neurexin 3, the group of Neurexins

Gene summary

This gene encodes a member of a family of proteins that function in the nervous system as receptors and cell adhesion molecules. Extensive alternative splicing and the use of alternative promoters results in multiple transcript variants and protein isoforms for this gene, but the full-length nature of many of these variants has not been determined. Transcripts that initiate from an upstream promoter encode alpha isoforms, which contain epidermal growth factor-like (EGF-like) sequences and laminin G domains. Transcripts initiating from the downstream promoter encode beta isoforms, which lack EGF-like sequences. Genetic variation at this locus has been associated with a range of behavioral phenotypes, including alcohol dependence and autism spectrum disorder. [provided by RefSeq, Dec 2012]

Previous symbols:

C14orf60

MANE transcript

NM_001330195.2

Inheritance

ClinVar variants

P:1U:156B:57

Top phenotype

NRXN3-related disorder

gnomAD constraint

pLI —, LoF o/e 0.02

Max pathogenic AF

—

Genomic locus

chr14:78,170,373-79,868,291

External References & Databases

Ensembl (ENSG00000021645)

UniProt (Q9HDB5, Q9Y4C0)

Transcript & Mutation Effects

hg38 • Region Span ~1,697.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autismLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005260

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NRXN3 variants in ClinVar

8 Conditions Cataloged

not specifiedTotal: 145

not providedTotal: 56

NRXN3-related disorderTotal: 53

Autism spectrum disorderTotal: 3

Relative macrocephalyTotal: 2

Short statureTotal: 2

AutismTotal: 1

NRXN3-associated neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001330195.2. 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				47 clinvar	4 clinvar	51
missense	1 clinvar		148 clinvar	5 clinvar		154
nonsense			1 clinvar			1
start loss						0
frameshift			3 clinvar	1 clinvar		4
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	1	0	156	53	4	214

Highest pathogenic variant AF is 0.0000018587775

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 67 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001330195.2	RefSeq	NP_001317124.1	20	MANE Select
ENST00000335750.7	Ensembl	ENSP00000338349.7	20	MANE Select
NM_001105250.3	RefSeq	NP_001098720.1	7	Standard
NM_001272020.2	RefSeq	NP_001258949.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cell adhesion molecules (CAMs) - Homo sapiens (human)
Neuronal System
Neurexins and neuroligins
Protein-protein interactions at synapses

Biological Process

neuron cell-cell adhesion
axon guidance
learning
adult behavior
social behavior

Molecular Function

signaling receptor activity
metal ion binding
cell adhesion molecule binding
neuroligin family protein binding

Cellular Component

plasma membrane
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000554719
Coding exons: 15
Length: 1622029
Individuals with no LoFs: 125741
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125745
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.44	409	657	0.623	0.0000402	7030
Missense (PolyPhen)		156	271.62	0.57433		2865
Synonymous	0.565	243	254	0.955	0.0000164	2065
Loss of Function	5.90	1	42.5	0.0235	0.00000221	494

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Neuronal cell surface protein that may be involved in cell recognition and cell adhesion. May play a role in angiogenesis (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.119

Intolerance Scores

LoFtool: 0.00234
RVIS EVS: -1.55
RVIS percentile EVS: 3.27

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.894

Gene Damage Prediction

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