Chromosome 2p16.3 deletion syndrome

Summary

Chromosome 2p16.3 deletion syndrome (MONDO:0013696) is a disease caused by NRXN1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: NRXN1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 43

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	chromosome 2p16.3 deletion syndrome
Mondo ID	MONDO:0013696
OMIM	614332
UMLS	C3808494
MedGen	814824
GARD	0024940
Is cancer (heuristic)	no

Also known as: chromosome 2P16.3 deletion syndrome · schizophrenia, susceptibility to, 17

Data availability: 43 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › psychiatric disorder › cognitive disorder › psychotic disorder › schizophrenia › chromosome 2p16.3 deletion syndrome

Related subtypes (17): paranoid schizophrenia, treatment-refractory schizophrenia, schizophrenia 1, schizophrenia 3, schizophrenia 5, schizophrenia 7, schizophrenia 8, schizophrenia 2, schizophrenia 10, schizophrenia 11, schizophrenia 12, schizophrenia 15, schizophrenia 16, early-onset schizophrenia, schizophrenia 19, schizophrenia 17, childhood-onset schizophrenia

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

43 retrieved; paginated sample, class counts are floors:

20 uncertain significance, 15 conflicting classifications of pathogenicity, 5 likely benign, 2 pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
3376541	GRCh38/hg38 2p16.3(chr2:50399054-50579740)x1	NRXN1	Pathogenic	criteria provided, single submitter
560057	Single allele	NRXN1	Pathogenic	criteria provided, single submitter
167390	NM_001330078.2(NRXN1):c.569A>G (p.Asn190Ser)	NRXN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
194930	NM_001330078.2(NRXN1):c.3499C>T (p.Arg1167Ter)	NRXN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
195130	NM_001330078.2(NRXN1):c.270G>T (p.Gln90His)	NRXN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
206232	NM_001330078.2(NRXN1):c.2190G>T (p.Gln730His)	NRXN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
206242	NM_001330078.2(NRXN1):c.2459G>A (p.Ser820Asn)	NRXN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
206245	NM_001330078.2(NRXN1):c.2533C>T (p.His845Tyr)	NRXN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
206264	NM_001330078.2(NRXN1):c.3365-109939C>T	NRXN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
206282	NM_001330078.2(NRXN1):c.4011G>C (p.Glu1337Asp)	NRXN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
282592	NM_138735.4(NRXN1):c.49GGC[11] (p.Gly17[11])	NRXN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
503668	NM_001330078.2(NRXN1):c.600C>T (p.Gly200=)	NRXN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
515773	NM_001330078.2(NRXN1):c.3375A>G (p.Thr1125=)	NRXN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
625988	NM_001330078.2(NRXN1):c.3365-109902C>T	NRXN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
93587	NM_001330078.2(NRXN1):c.1700T>G (p.Leu567Trp)	NRXN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
93592	NM_001330078.2(NRXN1):c.2605C>A (p.Leu869Met)	NRXN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
93599	NM_001330078.2(NRXN1):c.322C>T (p.Pro108Ser)	NRXN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1373921	NM_001330078.2(NRXN1):c.2509G>C (p.Gly837Arg)	NRXN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
206227	NM_001330078.2(NRXN1):c.302C>G (p.Ala101Gly)	NRXN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
206235	NM_001330078.2(NRXN1):c.262C>G (p.Arg88Gly)	NRXN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
206250	NM_001330078.2(NRXN1):c.2597T>C (p.Ile866Thr)	NRXN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
206265	NM_001330078.2(NRXN1):c.3407C>T (p.Thr1136Met)	NRXN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
206267	NM_001330078.2(NRXN1):c.3542A>G (p.His1181Arg)	NRXN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
206273	NM_001330078.2(NRXN1):c.4237G>A (p.Gly1413Ser)	NRXN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
206276	NM_001330078.2(NRXN1):c.1978G>A (p.Ala660Thr)	NRXN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2098170	NM_001330078.2(NRXN1):c.1753C>T (p.Arg585Trp)	NRXN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3024297	NM_001330078.2(NRXN1):c.314C>G (p.Ala105Gly)	NRXN1	Uncertain significance	criteria provided, single submitter
3068171	NM_001330078.2(NRXN1):c.4070C>G (p.Thr1357Ser)	NRXN1	Uncertain significance	criteria provided, single submitter
336550	NM_001330078.2(NRXN1):c.1546C>A (p.Leu516Ile)	NRXN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3586726	NM_001330078.2(NRXN1):c.504G>C (p.Lys168Asn)	NRXN1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 1 · 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
NRXN1	Strong	Autosomal dominant	chromosome 2p16.3 deletion syndrome	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NRXN1	Orphanet:600663	NRXN1-related severe neurodevelopmental disorder-motor stereotypies-chronic constipation-sleep-wake cycle disturbance

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
NRXN1	HGNC:8008	ENSG00000179915	P58400	Neurexin-1-beta	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NRXN1	Neurexin-1-beta	Neuronal cell surface protein involved in cell recognition and cell adhesion by forming intracellular junctions through binding to neuroligins.

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)
NRXN1	Other/Unknown	no		Laminin_G, Neurexin-like, ConA-like_dom_sf

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
middle temporal gyrus	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NRXN1	222	broad	marker	sural nerve, cortical plate, middle temporal gyrus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NRXN1	120

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NRXN1	P58400	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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×	0.006	NRXN1
Non-integrin membrane-ECM interactions	1	154.3×	0.006	NRXN1

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
obsolete positive regulation of cAMP-mediated signaling	1	16852.0×	0.001	NRXN1
protein-containing complex assembly involved in synapse maturation	1	16852.0×	0.001	NRXN1
positive regulation of presynaptic active zone assembly	1	16852.0×	0.001	NRXN1
guanylate kinase-associated protein clustering	1	8426.0×	0.001	NRXN1
neuroligin clustering involved in postsynaptic membrane assembly	1	5617.3×	0.001	NRXN1
positive regulation of neuromuscular synaptic transmission	1	5617.3×	0.001	NRXN1
negative regulation of filopodium assembly	1	3370.4×	0.001	NRXN1
gamma-aminobutyric acid receptor clustering	1	3370.4×	0.001	NRXN1
NMDA glutamate receptor clustering	1	3370.4×	0.001	NRXN1
gephyrin clustering involved in postsynaptic density assembly	1	3370.4×	0.001	NRXN1
AMPA selective glutamate receptor signaling pathway	1	3370.4×	0.001	NRXN1
postsynaptic density protein 95 clustering	1	2808.7×	0.001	NRXN1
neuronal signal transduction	1	2407.4×	0.001	NRXN1
postsynaptic membrane assembly	1	2407.4×	0.001	NRXN1
NMDA selective glutamate receptor signaling pathway	1	2407.4×	0.001	NRXN1
positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway	1	2407.4×	0.001	NRXN1
cerebellar granule cell differentiation	1	2106.5×	0.001	NRXN1
vocal learning	1	2106.5×	0.001	NRXN1
receptor localization to synapse	1	2106.5×	0.001	NRXN1
positive regulation of synapse maturation	1	1872.4×	0.001	NRXN1
presynaptic membrane assembly	1	1685.2×	0.001	NRXN1
positive regulation of fibroblast growth factor receptor signaling pathway	1	1532.0×	0.002	NRXN1
synaptic vesicle clustering	1	1404.3×	0.002	NRXN1
neuron cell-cell adhesion	1	991.3×	0.002	NRXN1
positive regulation of synaptic transmission, GABAergic	1	991.3×	0.002	NRXN1
vocalization behavior	1	887.0×	0.002	NRXN1
protein localization to synapse	1	766.0×	0.002	NRXN1
neurotransmitter secretion	1	702.2×	0.003	NRXN1
positive regulation of synaptic transmission, glutamatergic	1	624.1×	0.003	NRXN1
positive regulation of excitatory postsynaptic potential	1	526.6×	0.003	NRXN1

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
NRXN1	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	NRXN1

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)
NRXN1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.