Intellectual disability syndromic and non-syndromic
Gene: NLGN4X

NLGN4X (neuroligin 4, X-linked)
EnsemblGeneIds (GRCh38): ENSG00000146938
EnsemblGeneIds (GRCh37): ENSG00000146938
OMIM: 300427, Gene2Phenotype
NLGN4X is in 7 panels

2 reviews

Krithika Murali (Victorian Clinical Genetics Services)

Green List (high evidence)

ClinGen ID/Autism GCEP 1/8/2018: Definitive association. Decision was made to lump into X-linked complex neurodevelopmental disorder encompassing autism spectrum disorders, intellectual disability, attention deficit hyperactivity disorder (ADHD), and/or cerebral palsy phenotypes.

Clinvar P/LP SNV's identified through clinical testing entries reviewed:
c.1747C>T (p.Arg583Trp) - dev delay, ASD, ADHD, cardiac defects, dysmorphism
c.625+1G>A - no disease assertion provided (2022 entry)
c.334dup (p.Gln112fs) - no clinical information
c.301C>T (p.Arg101Ter) - 3 entries - x1 ASD susceptibility disease assertion - reported in an individual with BCS1L variant also who had short stature, failure to thrive, rickets, Fanconi syndrome, delayed motor milestones, absent speech, developmental regression, intellectual disability, hypotonia, seizure disorder, gait ataxia, abnormal movements (laughing behavior and tongue protrusion), dysmorphic features, microcephaly, history of seizure disorder.

Decipher - LP c.456C>G; p.Tyr152Ter - cited in the literature PMID 26350204 - male XY with ID.
Created: 6 Dec 2022, 1:16 a.m. | Last Modified: 6 Dec 2022, 1:16 a.m.

Panel Version: 0.5079

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Intellectual developmental disorder, X-linked - MIM#300495

Publications

PMID:26350204
PMID:14963808
PMID:12669065
PMID:23352163
PMID:28263302
PMID:16648374

Created: 6 Dec 2022, 1:16 a.m.
Last Modified: 6 Dec 2022, 1:16 a.m.
Panel version: 0.5079

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Red List (low evidence)

Associations studies and cytogenetic reports linking with ID/autism; some conflicting; evidence for SNVs causing ID is from two families pre-dating genomic testing era.
Created: 24 Jan 2020, 1:06 a.m. | Last Modified: 24 Jan 2020, 1:06 a.m.

Panel Version: 0.1667

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Mental retardation, X-linked, MIM# 300495

Publications

Created: 24 Jan 2020, 1:06 a.m.
Last Modified: 24 Jan 2020, 1:06 a.m.
Panel version: 0.1667

Details

Mode of Inheritance

X-LINKED: hemizygous mutation in males, biallelic mutations in females

Sources

Expert Review Green
Genetic Health Queensland

Phenotypes

Mental retardation, X-linked, MIM# 300495

OMIM

300427

Clinvar variants

Variants in NLGN4X

Penetrance

None

Publications

Panels with this gene