NLGN4Y

Chr Y

neuroligin 4 Y-linked

Also known as: HNL4Y

NCBI Gene: 22829 ENSG00000165246 UniProt: Q8NFZ3 OMIM: 400028

This protein functions as a postsynaptic cell adhesion molecule that interacts with neurexins to facilitate cell-cell interactions essential for functional synapse formation. Mutations cause X-linked intellectual disability and autism spectrum disorders. The gene follows X-linked inheritance and shows relatively low constraint to loss-of-function variation.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

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LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in NLGN4Y?

gnomAD v4 · ~364k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

179 rare PASS variants

Rare truncating (LoF)

1 in 1,100

12 rare PASS variants

Rare synonymous (reference)

1 in 400

72 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NLGN4Y. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 8 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~270k	1 in 190	1 in 2,900
South Asian	~32k	1 in 270	≈ 1 in 8,300
Remaining (unassigned)	~14k	1 in 440	none seen
European (Finnish)	~13k	1 in 1,900	1 in 1,500
Admixed American	~9,517	1 in 390	≈ 1 in 2,700
East Asian	~9,494	1 in 400	none seen
African / African American	~8,924	1 in 250	none seen
Ashkenazi Jewish	~6,750	≈ 1 in 6,700	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 0 of 6 coding exons well covered in gnomAD exomes; exons 2, 3, 4, 5, 6 poorly covered; exon 7 marginal. Genomes: 0 of 6 (exons 2, 3, 4, 5, 6, 7 below).? see exons ↓