NLGN4Y

protein-coding

neuroligin 4 Y-linked, the group of Neuroligins

Gene summary

This gene encodes a type I membrane protein that belongs to the family of neuroligins, which are cell adhesion molecules present at the postsynaptic side of the synapse, and may be essential for the formation of functional synapses. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Mar 2011]

MANE transcript

NM_001365588.1

Inheritance

ClinVar variants

U:39B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.33

Max pathogenic AF

—

Genomic locus

chrY:14,522,573-14,845,654

External References & Databases

Ensembl (ENSG00000165246)

Transcript & Mutation Effects

hg38 • Region Span ~323.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

male infertility with azoospermia or oligozoospermia due to single gene mutationLIMITED

Inheritance Pattern: YL

Disease ID:MONDO:0018393

Submitter: King Faisal Specialist Hospital and Research Center

Alhathal et al., 2020 (PMID: 32719396) reported a missense variant in a large male infertility cohort (n=285 infertile man and case–control fertile man). Gene is scored according to ClinGen classification. Limited with total score of 4. Single variant segregation (3 points), experimental evidence: testicular expression (1 points) (PMID: 27965440).

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NLGN4Y variants in ClinVar

1 Conditions Cataloged

not providedTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001365588.1. 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			7 clinvar	3 clinvar	1 clinvar	11
missense			21 clinvar			21
nonsense			4 clinvar			4
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	39	3	1	43

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 84 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001365588.1	RefSeq	NP_001352517.1	6	MANE Select
ENST00000684976.1	Ensembl	ENSP00000510011.1	6	MANE Select
NM_001164238.1	RefSeq	NP_001157710.1	4	Standard
NM_001206850.2	RefSeq	NP_001193779.1	4	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
learning
social behavior
synaptic vesicle endocytosis
modulation of chemical synaptic transmission

Molecular Function

protein binding
signaling receptor activity
neurexin family protein binding
cell adhesion molecule binding
scaffold protein binding

Cellular Component

plasma membrane
integral component of plasma membrane
cell surface
postsynaptic density
cell junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000355905
Coding exons: 5
Length: 323013
Individuals with no LoFs: 67952
Homozygous LoFs: 5
Heterozygous LoFs: 0
Defined: 67957
p: 0.0000368

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.42	118	170	0.694	0.0000287	5409
Missense (PolyPhen)		59	101	0.58413		2988
Synonymous	-0.986	92	80.7	1.14	0.0000148	1612
Loss of Function	1.85	3	8.98	0.334	0.00000142	321

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00042	0.00021	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000063	0.000031	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Putative neuronal cell surface protein involved in cell- cell-interactions.;

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.181

Gene Damage Prediction

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