autism, susceptibility to, X-linked 1

disease

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Also known as autism susceptibility, X-linked 1autism, susceptibility to, X-linked type 1AUTSX1

Summary

autism, susceptibility to, X-linked 1 (MONDO:0010321) is a disease caused by NLGN3 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: NLGN3 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 16

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autism, susceptibility to, X-linked 1
Mondo ID	MONDO:0010321
OMIM	300425
UMLS	C1845540
MedGen	335205
Is cancer (heuristic)	no

Also known as: autism susceptibility, X-linked 1 · autism, susceptibility to, X-linked 1 · autism, susceptibility to, X-linked type 1 · AUTSX1

Data availability: 16 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › autism, susceptiblity to › autism, susceptibility to, X-linked 1

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

16 retrieved; paginated sample, class counts are floors:

8 uncertain significance, 5 likely pathogenic, 1 risk factor, 1 pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1710287	NM_181303.2(NLGN3):c.611T>C (p.Val204Ala)	NLGN3	Pathogenic	no assertion criteria provided
1326919	NM_181303.2(NLGN3):c.913+1G>A	NLGN3	Likely pathogenic	no assertion criteria provided
1327915	NM_181303.2(NLGN3):c.1672A>G (p.Met558Val)	NLGN3	Likely pathogenic	no assertion criteria provided
1806399	NM_181303.2(NLGN3):c.2222T>G (p.Leu741Arg)	NLGN3	Likely pathogenic	criteria provided, single submitter
4082285	NM_181303.2(NLGN3):c.622G>A (p.Gly208Arg)	NLGN3	Likely pathogenic	criteria provided, single submitter
4292970	NM_181303.2(NLGN3):c.422_423del (p.Cys141fs)	NLGN3	Likely pathogenic	criteria provided, single submitter
11327	NM_181303.2(NLGN3):c.1411C>T (p.Arg471Cys)	NLGN3	risk factor	no assertion criteria provided
1028130	NM_181303.2(NLGN3):c.707A>G (p.Asn236Ser)	NLGN3	Uncertain significance	criteria provided, single submitter
1098690	NM_181303.2(NLGN3):c.806G>A (p.Ser269Asn)	NLGN3	Uncertain significance	criteria provided, single submitter
1706452	NM_181303.2(NLGN3):c.1384G>A (p.Ala462Thr)	NLGN3	Uncertain significance	criteria provided, single submitter
2442803	NM_181303.2(NLGN3):c.163C>T (p.Arg55Ter)	NLGN3	Uncertain significance	criteria provided, single submitter
3359009	NM_181303.2(NLGN3):c.1685C>T (p.Thr562Ile)	NLGN3	Uncertain significance	criteria provided, single submitter
3376319	NM_181303.2(NLGN3):c.2342A>G (p.His781Arg)	NLGN3	Uncertain significance	criteria provided, single submitter
4526621	NM_181303.2(NLGN3):c.415G>A (p.Glu139Lys)	NLGN3	Uncertain significance	criteria provided, single submitter
4796548	NM_181303.2(NLGN3):c.614A>G (p.Tyr205Cys)	NLGN3	Uncertain significance	criteria provided, single submitter
931307	NM_181303.2(NLGN3):c.913+11C>G	NLGN3	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
NLGN3	Strong	X-linked	X-linked complex neurodevelopmental disorder	5

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NLGN3	HGNC:14289	ENSG00000196338	Q9NZ94	Neuroligin-3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NLGN3	Neuroligin-3	Cell surface protein involved in cell-cell-interactions via its interactions with neurexin family members.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NLGN3	Other/Unknown	no		Nlgn, CarbesteraseB, Carboxylesterase_B_CS

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
prefrontal cortex	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NLGN3	181	broad	marker	cortical plate, ventricular zone, prefrontal cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NLGN3	2,122

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NLGN3	Q9NZ94	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Neurexins and neuroligins	1	196.9×	0.005	NLGN3

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
rhythmic synaptic transmission	1	4213.0×	0.003	NLGN3
postsynaptic membrane assembly	1	2407.4×	0.003	NLGN3
inhibitory postsynaptic potential	1	1685.2×	0.003	NLGN3
presynaptic membrane assembly	1	1685.2×	0.003	NLGN3
positive regulation of glutamate receptor signaling pathway	1	1532.0×	0.003	NLGN3
regulation of respiratory gaseous exchange by nervous system process	1	1296.3×	0.003	NLGN3
presynapse assembly	1	1203.7×	0.003	NLGN3
neuron cell-cell adhesion	1	991.3×	0.003	NLGN3
vocalization behavior	1	887.0×	0.003	NLGN3
positive regulation of synaptic transmission, glutamatergic	1	624.1×	0.004	NLGN3
positive regulation of excitatory postsynaptic potential	1	526.6×	0.004	NLGN3
axon extension	1	495.6×	0.004	NLGN3
adult behavior	1	468.1×	0.004	NLGN3
synaptic vesicle endocytosis	1	432.1×	0.004	NLGN3
learning	1	280.9×	0.005	NLGN3
synapse organization	1	280.9×	0.005	NLGN3
social behavior	1	271.8×	0.005	NLGN3
positive regulation of synapse assembly	1	244.2×	0.005	NLGN3
synapse assembly	1	230.8×	0.005	NLGN3
receptor-mediated endocytosis	1	221.7×	0.005	NLGN3
modulation of chemical synaptic transmission	1	183.2×	0.006	NLGN3
chemical synaptic transmission	1	77.3×	0.013	NLGN3

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NLGN3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	NLGN3

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
NLGN3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: NLGN3