NRXN1

Summary

NRXN1 (neurexin 1, HGNC:8008) is a protein-coding gene on chromosome 2p16.3, encoding Neurexin-1-beta (P58400). Neuronal cell surface protein involved in cell recognition and cell adhesion by forming intracellular junctions through binding to neuroligins. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a single-pass type I membrane protein that belongs to the neurexin family. Neurexins are cell-surface receptors that bind neuroligins to form Ca(2+)-dependent neurexin/neuroligin complexes at synapses in the central nervous system. This complex is required for efficient neurotransmission and is involved in the formation of synaptic contacts. Three members of this gene family have been studied in detail and are estimated to generate over 3,000 variants through the use of two alternative promoters (alpha and beta) and extensive alternative splicing in each family member. Recently, a third promoter (gamma) was identified for this gene in the 3’ region. Mutations in this gene are associated with Pitt-Hopkins-like syndrome-2 and may contribute to susceptibility to schizophrenia.

Source: NCBI Gene 9378 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 38
• Clinical variants (ClinVar): 2,679 total — 183 pathogenic, 53 likely-pathogenic
• Phenotypes (HPO): 20
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001330078

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8008
Approved symbol	NRXN1
Name	neurexin 1
Location	2p16.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0578, Hs.22998
Ensembl gene	ENSG00000179915
Ensembl biotype	protein_coding
OMIM	600565
Entrez	9378

Gene structure

Transcript identifiers

Ensembl transcripts: 65 — 33 protein_coding_CDS_not_defined, 26 protein_coding, 3 nonsense_mediated_decay, 3 retained_intron

ENST00000331040, ENST00000342183, ENST00000378262, ENST00000401669, ENST00000401710, ENST00000404971, ENST00000405472, ENST00000405581, ENST00000406316, ENST00000412315, ENST00000416262, ENST00000447773, ENST00000462791, ENST00000474354, ENST00000484192, ENST00000495871, ENST00000496792, ENST00000625320, ENST00000625672, ENST00000625891, ENST00000626192, ENST00000626249, ENST00000626899, ENST00000627198, ENST00000628364, ENST00000628515, ENST00000628761, ENST00000629717, ENST00000630431, ENST00000630543, ENST00000630656, ENST00000634412, ENST00000634431, ENST00000634764, ENST00000635126, ENST00000635164, ENST00000635264, ENST00000635310, ENST00000635519, ENST00000635834, ENST00000636066, ENST00000636104, ENST00000636298, ENST00000636342, ENST00000636345, ENST00000636599, ENST00000636736, ENST00000636818, ENST00000637006, ENST00000637021, ENST00000637151, ENST00000637207, ENST00000637368, ENST00000637459, ENST00000637472, ENST00000637511, ENST00000637605, ENST00000637653, ENST00000637679, ENST00000637889, ENST00000637906, ENST00000637975, ENST00000638037, ENST00000638060, ENST00000675235

RefSeq mRNA: 25 — MANE Select: NM_001330078 NM_001135659, NM_001320156, NM_001320157, NM_001330077, NM_001330078, NM_001330079, NM_001330081, NM_001330082, NM_001330083, NM_001330084, NM_001330085, NM_001330086, NM_001330087, NM_001330088, NM_001330089, NM_001330090, NM_001330091, NM_001330092, NM_001330093, NM_001330094, NM_001330095, NM_001330096, NM_001330097, NM_004801, NM_138735

CCDS: CCDS1845, CCDS46282, CCDS54360, CCDS82444, CCDS82445, CCDS82446, CCDS82447, CCDS82449, CCDS82450, CCDS82451, CCDS86838, CCDS86840

Canonical transcript exons

ENST00000401669 — 23 exons

Exon	Start	End
ENSE00000962769	50091323	50091494
ENSE00000962771	50053271	50053590
ENSE00001476882	50528625	50528651
ENSE00001552564	51031981	51032132
ENSE00001784876	49943704	49943791
ENSE00002171876	51027502	51029194
ENSE00002433390	50621226	50621249
ENSE00002446452	50921869	50921880
ENSE00002455897	50054955	50055044
ENSE00002482562	50925938	50925955
ENSE00003437132	50922658	50922687
ENSE00003496186	50620022	50620183
ENSE00003502853	50531227	50531430
ENSE00003517428	50506495	50506617
ENSE00003557927	50497333	50497714
ENSE00003610684	50552587	50553025
ENSE00003627205	50465442	50465561
ENSE00003641882	50538253	50538636
ENSE00003649136	50623314	50623615
ENSE00003655408	50472298	50472471
ENSE00003666351	50495905	50496095
ENSE00003667725	50236789	50236970
ENSE00003766693	49918503	49922251

Expression profiles

Bgee: expression breadth ubiquitous, 222 present calls, max score 99.14.

FANTOM5 (CAGE): breadth broad, TPM avg 16.2160 / max 1593.2512, expressed in 426 samples.

FANTOM5 promoters (39 alternative TSS)

Promoter ID	TPM avg	Samples expressed
28319	6.8377	304
28287	1.8351	160
28272	0.8733	91
28322	0.8071	152
28326	0.5842	130
28323	0.5212	116
28286	0.4500	95
28320	0.4123	120
28317	0.3998	95
28325	0.3872	104

Top tissues by expression

284 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	99.14	gold quality
cortical plate	UBERON:0005343	98.76	gold quality
middle temporal gyrus	UBERON:0002771	98.21	gold quality
superior frontal gyrus	UBERON:0002661	97.92	gold quality
parietal lobe	UBERON:0001872	97.86	gold quality
postcentral gyrus	UBERON:0002581	97.77	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.71	gold quality
entorhinal cortex	UBERON:0002728	97.67	gold quality
primary visual cortex	UBERON:0002436	97.43	gold quality
occipital lobe	UBERON:0002021	97.42	gold quality
ventricular zone	UBERON:0003053	97.10	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.99	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.92	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.84	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.79	gold quality
prefrontal cortex	UBERON:0000451	96.50	gold quality
pons	UBERON:0000988	96.25	gold quality
ganglionic eminence	UBERON:0004023	96.24	gold quality
cerebellar hemisphere	UBERON:0002245	96.12	gold quality
cerebellar cortex	UBERON:0002129	96.09	gold quality
buccal mucosa cell	CL:0002336	96.03	gold quality
cerebellum	UBERON:0002037	96.03	gold quality
frontal cortex	UBERON:0001870	96.01	gold quality
dorsal root ganglion	UBERON:0000044	95.86	gold quality
cerebral cortex	UBERON:0000956	95.84	gold quality
neocortex	UBERON:0001950	95.76	gold quality
frontal pole	UBERON:0002795	95.71	gold quality
orbitofrontal cortex	UBERON:0004167	95.69	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.54	gold quality
temporal lobe	UBERON:0001871	95.49	gold quality

Single-cell (SCXA)

Detected in 20 experiment(s), a significant marker in 17.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	9942.52
E-MTAB-11268	yes	9283.98
E-ANND-2	yes	6665.14
E-GEOD-137537	yes	2470.98
E-HCAD-56	yes	1642.53
E-MTAB-7316	yes	868.27
E-GEOD-135922	yes	788.92
E-CURD-79	yes	669.98
E-MTAB-11121	yes	562.07
E-HCAD-35	yes	72.64
E-HCAD-11	yes	36.48
E-MTAB-8410	yes	31.95
E-CURD-46	yes	17.78
E-HCAD-25	yes	16.69
E-HCAD-5	yes	15.24

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
DISC1	Repression
FOS	Activation
GRIN1	Activation
RAC1	Activation

Upstream regulators (CollecTRI, top): ASH1L, PHOX2A, TCF4

miRNA regulators (miRDB)

306 targeting NRXN1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• neurexin-1beta binds to neuroligin-1 in an interaction whose specificity depends on glycosylation, mRNA splicing and gene selection of neuroligin (PMID:14522992)
• Results report the solution structure of AF-6 PDZ domain and its interaction with the C-terminal peptides from Neurexin and Bcr. (PMID:15684424)
• the neurexin 1beta/neuroligin 1 complex has a role in synapse formation (PMID:15797875)
• Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia. (PMID:17989066)
• A number of rare sequence variants in the coding region of the alpha-neurexin 1 leader sequence and of an epidermal growth factor like domain, respectively, suggest that even subtle changes in NRXN1 might contribute to susceptibility to autism. (PMID:18179900)
• NRXN1 gene represents a strong candidate for involvement in the etiology of nicotine dependence. (PMID:18270208)
• the ultra-rare structural variants of the neurexin 1alpha gene are consistent with mutations predisposing to autism. (PMID:18490107)
• NRXN1 deletions affecting exons confer risk of schizophrenia. (PMID:18945720)
• The findings of studies to date provide strong evidence that deletions of NRXN1 confer a substantial increase in risk of schizophrenia. (PMID:19675094)
• NRXN1 is mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determines the level of a common synaptic protein in Drosophila. (PMID:19896112)
• Three-way translocation involving MLL, MLLT1, and a novel third partner, NRXN1, in a patient with acute lymphoblastic leukemia and t(2;19;11) (p12;p13.3;q23). (PMID:20113834)
• NRXN1 may be pathogenic in a wide variety of psychiatric diseases, including autism spectrum disorder, global developmental delay, anxiety, and depression. (PMID:20162629)
• In addition to chromosomal alterations disrupting the NRXN1alpha promoter, rare point mutations in the region may also be involved in SZ pathogenesis. (PMID:20347009)
• The rs6721498 and rs2193225 of NRXN1 were genotyped in 2516 Japanese with various smoking habits. (PMID:20414139)
• These data suggest that TCF4, NRXN1, and CNTNAP2 may participate in a biological pathway that is altered in patients with schizophrenia and other neuropsychiatric disorders. (PMID:20421335)
• Results suggest that unique conformational reshaping of the neuroligin 4 surface is required to permit neurexin 1beta association. (PMID:20543817)
• Schizophrenia patients antipsychotic response may be altered depending on the synaptic connectivity. NRXN1 deletions have also been associated with schizophrenia. observed a trend toward association of clozapine response with the rs12467557 (PMID:20860064)
• The results of this study do not suggest the existence of rare, highly penetrant NRXN1 mutations in patients with schizophrenia. (PMID:21288692)
• Truncating mutations in NRXN1 is associated with autism spectrum disorders and schizophrenia (PMID:21424692)
• findings suggest that NRXN1 might represent a major susceptibility gene for schizophrenia in Chinese Han population. (PMID:21477380)
• Presenilin/gamma-secretase regulates neurexin processing at synapses (PMID:21559374)
• a neural and cognitive susceptibility mechanism by which the NRXN1 gene confers risk for both schizophrenia and autism spectrum disorders (PMID:21687627)
• The mutational testing found a heterozygous deletion in NRXN1 in one patient. (PMID:21827697)
• These results suggest that the rs1045881 NRXN1 polymorphism may influence clozapine response. (PMID:21890328)
• Biallelic NRXN1 mutations result in a severe recessive mental retardation syndrome. (PMID:21964664)
• Neurexin-1alpha is a component of the beta-cell secretory machinery and contributes to secretory granule docking, most likely through interactions with granuphilin. (PMID:22235116)
• a possible gene-dose effect of NRXN1 mutations on type and severity of mental illness (PMID:22337556)
• This study demonistrated that there was a statistically significant association of neurexin-1 SNP P300P (rs2303298) with risk of autism in Chinese Han population. (PMID:22405623)
• The data reported here support a role for synaptic defects of neurexin-1beta in neurodevelopmental disorders. (PMID:22504536)
• Patients with exonic deletions in NRXN1 manifested intellectual disability, infantile hypotonia and ASDs. (PMID:22617343)
• In both human and mouse, NRXN1 is co-expressed with numerous cell signaling genes and known schizophrenia candidates. (PMID:22832527)
• Five genes have been directly disrupted in Tourette Syndrome by independent genomic rearrangements and copy number variations with unique breakpoints. (PMID:22948383)
• Expression levels of neurexin and neuroligin in ENS are significantly down-regulated in HSCR, which may be involved in the pathogenesis of HSCR. (PMID:23264101)
• We conclude that exon-disrupting deletions of NRXN1 represent a genetic risk factor in the genetically complex predisposition of common idiopathic generalized epilepsies (PMID:23294455)
• Deletions in both affected and control individuals were clustered in the 5’ portion of NRXN1. (PMID:23472757)
• study supports a pathogenic role for heterozygous exonic deletions of NRXN1 in neurodevelopmental disorders (PMID:23533028)
• The results are consistent with the proposal that rare CNVs play a role in TS aetiology and suggest a possible role for rearrangements in the COL8A1 and NRXN1 gene regions (PMID:23533600)
• based on in vitro models, NRXN1 deletions impact several biological processes during neurodevelopment, including synaptic adhesion and neuron differentiation. (PMID:23536886)
• alpha- or beta-NRXN-1 isoforms expressed under C. elegans nrx-1 promoter rescue impairment of exploratory behavior and sinusoidal postural movement in nrx-1 C elegans mutant. (PMID:23638761)
• The rs10187911(NRXN1 protein) on 2p16.3 was significantly associated with lung cancer development (dominant model, OR of TG or GG, 1.58, P = 0.025). (PMID:23772147)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nrxn1b	ENSDARG00000063635
mus_musculus	Nrxn1	ENSMUSG00000024109
rattus_norvegicus	Nrxn1	ENSRNOG00000050220

Paralogs (35): NRXN3 (ENSG00000021645), TLL1 (ENSG00000038295), CP (ENSG00000047457), DCBLD2 (ENSG00000057019), HEPH (ENSG00000089472), TLL2 (ENSG00000095587), NRP1 (ENSG00000099250), PCOLCE (ENSG00000106333), CNTNAP3 (ENSG00000106714), CUBN (ENSG00000107611), CNTNAP1 (ENSG00000108797), NRXN2 (ENSG00000110076), MEP1A (ENSG00000112818), NRP2 (ENSG00000118257), CUZD1 (ENSG00000138161), MFGE8 (ENSG00000140545), MEP1B (ENSG00000141434), PDGFC (ENSG00000145431), CNTNAP4 (ENSG00000152910), CNTNAP3B (ENSG00000154529), CNTNAP5 (ENSG00000155052), CDCP2 (ENSG00000157211), PCOLCE2 (ENSG00000163710), EDIL3 (ENSG00000164176), NETO1 (ENSG00000166342), BMP1 (ENSG00000168487), PDGFD (ENSG00000170962), NETO2 (ENSG00000171208), CNTNAP2 (ENSG00000174469), HEPHL1 (ENSG00000181333), F8 (ENSG00000185010), ASTL (ENSG00000188886), F5 (ENSG00000198734), MFRP (ENSG00000235718), CNTNAP3C (ENSG00000283378)

Protein

Protein identifiers

Neurexin-1-beta — P58400 (reviewed: P58400, Q9ULB1)

Alternative names: Neurexin I-beta

All UniProt accessions (25): P58400, Q9ULB1, A0A0D9SEJ1, A0A0D9SEM5, A0A0D9SEQ7, A0A0D9SF07, A0A0D9SF36, A0A0D9SFF4, A0A0D9SFY6, A0A0D9SG60, A0A0D9SG96, A0A0R4J2G7, A0A0U1RQP8, A0A0U1RR00, A0A0U1RRK7, A0A1B0GTL0, A0A1B0GU94, A0A1B0GUQ1, A0A1B0GUR2, A0A1B0GVF4, A0A1D5RMU6, A0A6Q8PFA2, E7EQN4, H0Y568, H7BYC7

UniProt curated annotations — full annotation on UniProt →

Function. Neuronal cell surface protein involved in cell recognition and cell adhesion by forming intracellular junctions through binding to neuroligins. Plays a role in formation of synaptic junctions. Functions as part of a trans-synaptic complex by binding to cerebellins and postsynaptic GRID1. This interaction helps regulate the activity of NMDA and AMPA receptors at hippocampal synapses without affecting synapse formation. NRXN1B-CBLN2-GRID1 complex transduce presynaptic signals into postsynaptic NMDAR response.

Subunit / interactions. The cytoplasmic C-terminal region binds to CASK. Binds NLGN1, NLGN2 and NLGN3, DAG1 (alpha-dystroglycan) and alpha-latrotoxin. Binding to neuroligins is calcium-dependent, and the binding preference ranks as follow: NLGN1 > NLGN4 » NLGN3 > NLGN2. Interacts with CBLN2 and more weakly with CBLN4. Interacts with CBLN1; interaction is CBLN1 hexamer form-dependent; CBLN1-binding is calcium-independent; isoform 1b does not interact with CBLN1. Interacts with CLSTN3. (Microbial infection) Interacts with Staphylococcus aureus protein SdrC; this interaction increases S.aureus adherence to cells.

Subcellular location. Presynaptic cell membrane.

Post-translational modifications. O-glycosylated; contains heparan sulfate. Heparan sulfate attachment is required for synapse development by mediating interactions with neuroligins.

Similarity. Belongs to the neurexin family.

Isoforms (7)

UniProt ID	Names	Canonical?
P58400-2	1b	yes
P58400-1	3b
Q9ULB1-1	1a
Q9ULB1-2	2a
Q9ULB1-3	3a
Q9ULB1-4	4
Q9ULB1-5	5

RefSeq proteins (25): NP_001129131, NP_001307085, NP_001307086, NP_001317006, NP_001317007, NP_001317008, NP_001317010, NP_001317011, NP_001317012, NP_001317013, NP_001317014, NP_001317015, NP_001317016, NP_001317017, NP_001317018, NP_001317019, NP_001317020, NP_001317021, NP_001317022, NP_001317023, NP_001317024, NP_001317025, NP_001317026, NP_004792, NP_620072 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001791	Laminin_G	Domain
IPR003585	Neurexin-like	Domain
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR027789	Syndecan/Neurexin_dom	Domain
IPR050372	Neurexin-related_CASP	Family
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000742	EGF	Domain

Pfam: PF00008, PF01034, PF02210

UniProt features (98 total): binding site 14, strand 14, disulfide bond 12, domain 10, splice variant 8, sequence conflict 8, glycosylation site 7, region of interest 7, topological domain 4, modified residue 3, signal peptide 2, chain 2, transmembrane region 2, turn 2, sequence variant 2, helix 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6NID	X-RAY DIFFRACTION	1.86
3B3Q	X-RAY DIFFRACTION	2.4
5Z8Y	X-RAY DIFFRACTION	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P58400-F1	68.53	0.39
AF-Q9ULB1-F1	82.67	0.60

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

P58400 (canonical)

Ligand- & substrate-binding residues (4): 158; 240; 242; 141

Post-translational modifications (3): 454, 455, 458

Glycosylation sites (2): 188, 350

Q9ULB1

Ligand- & substrate-binding residues (10): 329; 346; 407; 765; 782; 841; 1176; 1193; 1245; 1247

Disulfide bonds (12): 228–243, 245–255, 437–473, 643–672, 680–691, 685–700, 702–712, 883–891, 1052–1080, 1087–1098, 1092–1107, 1109–1119

Glycosylation sites (5): 125, 190, 790, 1223, 1355

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6794361	Neurexins and neuroligins
R-HSA-3000171	Non-integrin membrane-ECM interactions

MSigDB gene sets: 556 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GOBP_SYNAPTIC_VESICLE_LOCALIZATION, GNF2_RTN1, GOBP_POSITIVE_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_METENCEPHALON_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_COGNITION, GOBP_HETEROPHILIC_CELL_CELL_ADHESION, GOBP_BEHAVIOR, PAX4_01, CCAWYNNGAAR_UNKNOWN, GOBP_VESICLE_LOCALIZATION, GOBP_SYNAPSE_ASSEMBLY

GO Biological Process (52): angiogenesis (GO:0001525), heterophilic cell-cell adhesion (GO:0007157), neuron cell-cell adhesion (GO:0007158), signal transduction (GO:0007165), synapse assembly (GO:0007416), learning (GO:0007612), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), calcium-dependent cell-cell adhesion (GO:0016339), cerebellar granule cell differentiation (GO:0021707), neuronal signal transduction (GO:0023041), adult behavior (GO:0030534), neuron projection development (GO:0031175), positive regulation of synaptic transmission, GABAergic (GO:0032230), social behavior (GO:0035176), protein localization to synapse (GO:0035418), obsolete positive regulation of cAMP-mediated signaling (GO:0043950), establishment of protein localization (GO:0045184), positive regulation of fibroblast growth factor receptor signaling pathway (GO:0045743), neuron projection morphogenesis (GO:0048812), negative regulation of filopodium assembly (GO:0051490), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), positive regulation of synapse assembly (GO:0051965), positive regulation of synaptic transmission, glutamatergic (GO:0051968), positive regulation of ERK1 and ERK2 cascade (GO:0070374), cellular response to calcium ion (GO:0071277), vocalization behavior (GO:0071625), protein-containing complex assembly involved in synapse maturation (GO:0090126), synaptic vesicle clustering (GO:0097091), postsynaptic membrane assembly (GO:0097104), presynaptic membrane assembly (GO:0097105), gamma-aminobutyric acid receptor clustering (GO:0097112), NMDA glutamate receptor clustering (GO:0097114), gephyrin clustering involved in postsynaptic density assembly (GO:0097116), guanylate kinase-associated protein clustering (GO:0097117), neuroligin clustering involved in postsynaptic membrane assembly (GO:0097118), postsynaptic density protein 95 clustering (GO:0097119), receptor localization to synapse (GO:0097120), NMDA selective glutamate receptor signaling pathway (GO:0098989), AMPA selective glutamate receptor signaling pathway (GO:0098990)

GO Molecular Function (12): transmembrane signaling receptor activity (GO:0004888), signaling receptor binding (GO:0005102), type 1 fibroblast growth factor receptor binding (GO:0005105), metal ion binding (GO:0046872), calcium-dependent protein binding (GO:0048306), cell adhesion molecule binding (GO:0050839), neuroligin family protein binding (GO:0097109), calcium channel regulator activity (GO:0005246), calcium ion binding (GO:0005509), acetylcholine receptor binding (GO:0033130), signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (20): endoplasmic reticulum (GO:0005783), plasma membrane (GO:0005886), cell surface (GO:0009986), endocytic vesicle (GO:0030139), neuromuscular junction (GO:0031594), nuclear membrane (GO:0031965), vesicle (GO:0031982), presynaptic membrane (GO:0042734), neuronal cell body (GO:0043025), axonal growth cone (GO:0044295), protein complex involved in cell-cell adhesion (GO:0098635), presynapse (GO:0098793), trans-synaptic protein complex (GO:0098820), glutamatergic synapse (GO:0098978), GABA-ergic synapse (GO:0098982), nucleolus (GO:0005730), endomembrane system (GO:0012505), membrane (GO:0016020), cell projection (GO:0042995), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Protein-protein interactions at synapses	1
Extracellular matrix organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
synapse	4
cell-cell adhesion	3
protein binding	3
gene expression	2
regulation of gene expression	2
behavior	2
signaling receptor binding	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
nervous system development	1
cell junction assembly	1
synapse organization	1
learning or memory	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
cell differentiation in hindbrain	1
cerebellar granular layer formation	1
central nervous system neuron differentiation	1
glutamatergic neuron differentiation	1
signal transduction	1
neuron development	1
plasma membrane bounded cell projection organization	1
regulation of synaptic transmission, GABAergic	1
positive regulation of synaptic transmission	1
synaptic transmission, GABAergic	1
biological process involved in intraspecies interaction between organisms	1
protein localization to cell junction	1
establishment of localization	1
fibroblast growth factor receptor signaling pathway	1
positive regulation of signal transduction	1
regulation of fibroblast growth factor receptor signaling pathway	1
neuron projection development	1
plasma membrane bounded cell projection morphogenesis	1
signaling receptor activity	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

1 interactions, top by confidence:

BioGRID (119): ARHGAP26 (Affinity Capture-MS), TCEB3 (Affinity Capture-MS), ARHGAP10 (Affinity Capture-MS), TULP1 (Affinity Capture-MS), NLGN1 (Reconstituted Complex), Sytl1 (Reconstituted Complex), NLGN1 (Reconstituted Complex), NRXN1 (Proximity Label-MS), NRXN1 (Reconstituted Complex), NLGN1 (Reconstituted Complex), NLGN2 (Reconstituted Complex), NLGN3 (Reconstituted Complex), NRXN1 (Two-hybrid), NRXN1 (Affinity Capture-MS), NRXN1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A1XQX1, A1XQX3, A1XQY0, A8WGA3, C6K2K4, D0PRN2, D0PRN4, D4A1J9, E9PUN2, O13097, O42596, O73612, O73874, P0DI97, P52795, P52796, P58400, P58401, P98172, Q01974, Q0PMD2, Q17QD6, Q28142, Q28143, Q460M5, Q63373, Q63376, Q6NW40, Q6PCX7, Q6PFE7, Q7TQ33, Q80TG9, Q8BNJ6, Q8BXA0, Q8C985, Q8IYR6, Q8NC67, Q91590, Q96B86, Q96NI6

Diamond homologs: A1XQX0, A1XQX1, A1XQX2, A1XQX3, A1XQX8, A1XQY0, A1XQY1, A1XQY3, A6MFK7, D0PRN2, D0PRN3, D0PRN4, E9PUN2, E9Q7X7, P00741, P0DI97, P16294, P16296, P58400, P58401, Q07310, Q28142, Q28143, Q28146, Q3KN41, Q63372, Q63373, Q63374, Q63376, Q6P9K9, Q6SA95, Q8C985, Q9CS84, Q9DDD0, Q9HDB5, Q9P2S2, Q9ULB1, Q9Y4C0, O02768, O19183

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
NLGN3	“up-regulates activity”	NRXN1	binding
NLGN4Y	“up-regulates activity”	NRXN1	binding
NLGN1	“up-regulates activity”	NRXN1	binding
NLGN4X	“up-regulates activity”	NRXN1	binding
NLGN2	“up-regulates activity”	NRXN1	binding
DGC	“up-regulates activity”	NRXN1	binding
NRXN1	“up-regulates activity”	NLGN2	binding
NRXN1	“up-regulates activity”	DAG1	binding
NXPH1	up-regulates	NRXN1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

2679 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	183
Likely pathogenic	53
Uncertain significance	1324
Likely benign	812
Benign	124

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1074562	NC_000002.11:g.(?51148997)(51259192_?)del	Pathogenic
1299323	NM_001135659.3:c.(?-921)(931+1_932-1)del	Pathogenic
1339972	GRCh37/hg19 2p16.3(chr2:50991242-51158769)x1	Pathogenic
1340730	GRCh37/hg19 2p16.3(chr2:51118080-51348997)x1	Pathogenic
1341023	GRCh37/hg19 2p16.3(chr2:50871418-51603924)x1	Pathogenic
1341137	GRCh37/hg19 2p16.3(chr2:51193858-51433041)x1	Pathogenic
1341259	GRCh37/hg19 2p16.3(chr2:51002884-51257328)x1	Pathogenic
1383533	NM_001330078.2(NRXN1):c.4021_4022del (p.Thr1341fs)	Pathogenic
1387846	NC_000002.11:g.(?51148987)(51255411_?)del	Pathogenic
1390346	NM_001330078.2(NRXN1):c.772+1129_772+1132del	Pathogenic
1399605	NM_001330078.2(NRXN1):c.2386G>T (p.Glu796Ter)	Pathogenic
1451359	NM_001330078.2(NRXN1):c.601G>T (p.Glu201Ter)	Pathogenic
1452805	NC_000002.11:g.(?51253489)(51255411_?)del	Pathogenic
1452876	NM_001330078.2(NRXN1):c.2281dup (p.Arg761fs)	Pathogenic
1455324	NC_000002.11:g.(?50463907)(50464128_?)del	Pathogenic
145653	GRCh38/hg38 2p16.3(chr2:50915711-50999091)x1	Pathogenic
145992	GRCh38/hg38 2p16.3(chr2:51009862-51155675)x1	Pathogenic
146000	GRCh38/hg38 2p16.3(chr2:50944985-51024360)x1	Pathogenic
1460378	NC_000002.11:g.(?50692560)(50780183_?)del	Pathogenic
146244	GRCh38/hg38 2p16.3(chr2:50809966-51219735)x1	Pathogenic
146267	GRCh38/hg38 2p16.3(chr2:50754975-50999091)x1	Pathogenic
146354	GRCh38/hg38 2p16.3(chr2:50999032-51155734)x1	Pathogenic
146445	GRCh38/hg38 2p16.3(chr2:50856272-50999091)x1	Pathogenic
146472	GRCh38/hg38 2p16.3(chr2:50710306-50999091)x1	Pathogenic
148176	GRCh38/hg38 2p16.3(chr2:50999032-51087292)x1	Pathogenic
148717	GRCh38/hg38 2p16.3(chr2:50860917-51029929)x1	Pathogenic
149316	GRCh38/hg38 2p16.3(chr2:50953423-51131743)x1	Pathogenic
152099	GRCh38/hg38 2p16.3(chr2:50827235-50953482)x1	Pathogenic
1526563	GRCh37/hg19 2p16.3(chr2:50730130-50897456)	Pathogenic
1526574	GRCh37/hg19 2p16.3(chr2:50813343-50948464)	Pathogenic

SpliceAI

7429 predictions. Top by Δscore:

Variant	Effect	Δscore
2:49922248:TTGG:T	acceptor_gain	1.0000
2:49922249:TGG:T	acceptor_gain	1.0000
2:49922250:GG:G	acceptor_gain	1.0000
2:49922252:C:CC	acceptor_gain	1.0000
2:49922254:A:C	acceptor_gain	1.0000
2:49943790:GTC:G	acceptor_loss	1.0000
2:49943791:TC:T	acceptor_loss	1.0000
2:49943792:C:CC	acceptor_gain	1.0000
2:49943792:CTG:C	acceptor_loss	1.0000
2:50024042:T:TA	donor_gain	1.0000
2:50053587:CGCC:C	acceptor_gain	1.0000
2:50053589:CC:C	acceptor_gain	1.0000
2:50053590:CC:C	acceptor_gain	1.0000
2:50053591:C:CC	acceptor_gain	1.0000
2:50054949:TTTTA:T	donor_loss	1.0000
2:50054950:TTTAC:T	donor_loss	1.0000
2:50054951:TTAC:T	donor_loss	1.0000
2:50054952:TAC:T	donor_loss	1.0000
2:50054953:ACCT:A	donor_loss	1.0000
2:50055044:CCTT:C	acceptor_gain	1.0000
2:50055047:T:TC	acceptor_gain	1.0000
2:50091318:CTTA:C	donor_loss	1.0000
2:50091319:TTA:T	donor_loss	1.0000
2:50091320:TA:T	donor_loss	1.0000
2:50091322:C:G	donor_loss	1.0000
2:50091490:TGGTG:T	acceptor_gain	1.0000
2:50091491:GGTG:G	acceptor_gain	1.0000
2:50091492:GTG:G	acceptor_gain	1.0000
2:50091493:TG:T	acceptor_gain	1.0000
2:50091495:C:CC	acceptor_gain	1.0000

AlphaMissense

9934 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:49922122:A:G	L1419P	1.000
2:49922125:A:G	L1418P	1.000
2:49922125:A:T	L1418H	1.000
2:49922131:A:T	L1416H	1.000
2:49922138:A:G	C1414R	1.000
2:49922140:A:G	L1413P	1.000
2:49922143:G:T	A1412D	1.000
2:49922146:G:T	A1411D	1.000
2:49922149:G:T	A1410D	1.000
2:49922152:G:T	A1409D	1.000
2:49922161:C:T	G1406E	1.000
2:49922162:C:G	G1406R	1.000
2:49922162:C:T	G1406R	1.000
2:49943757:C:G	C1358S	1.000
2:49943758:A:G	C1358R	1.000
2:49943758:A:T	C1358S	1.000
2:50053509:A:G	L1267P	1.000
2:50053516:C:G	G1265R	1.000
2:50053521:A:C	F1263C	1.000
2:50053554:A:C	I1252R	1.000
2:50053554:A:T	I1252K	1.000
2:50053568:A:C	N1247K	1.000
2:50053568:A:T	N1247K	1.000
2:50053571:G:C	F1246L	1.000
2:50053571:G:T	F1246L	1.000
2:50053572:A:C	F1246C	1.000
2:50053572:A:G	F1246S	1.000
2:50053573:A:G	F1246L	1.000
2:50053575:A:T	I1245N	1.000
2:50053581:A:G	L1243P	1.000

dbSNP variants (sampled 300 via entrez): RS1000001 (2:50484504 G>A,T), RS1000001788 (2:50640839 T>C), RS1000003936 (2:50186621 T>C), RS1000005036 (2:50505621 A>T), RS1000006119 (2:50377349 T>A), RS1000018135 (2:50392822 A>T), RS1000018419 (2:50719161 CAT>C), RS1000018696 (2:50321447 C>A), RS1000019279 (2:50839968 G>A,T), RS1000019528 (2:50768189 C>T), RS1000019972 (2:50861216 G>A,T), RS1000022385 (2:50647796 T>A), RS1000023574 (2:50761000 T>G), RS1000024382 (2:50712000 T>C), RS1000030410 (2:50830266 G>A)

Disease associations

OMIM: gene MIM:600565 | disease phenotypes: MIM:614325, MIM:209850, MIM:238950, MIM:614332, MIM:621407, MIM:614324, MIM:181500

GenCC curated gene-disease

Disease	Classification	Inheritance
Pitt-Hopkins-like syndrome 2	Strong	Autosomal recessive
chromosome 2p16.3 deletion syndrome	Strong	Autosomal dominant
autism	Moderate	Autosomal dominant
schizophrenia	Limited	Unknown

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Definitive	AD

Mondo (12): Pitt-Hopkins-like syndrome 2 (MONDO:0013690), autism spectrum disorder (MONDO:0005258), intellectual disability (MONDO:0001071), autism (MONDO:0005260), hyperopia, high (MONDO:0009392), chromosome 2p16.3 deletion syndrome (MONDO:0013696), obesity disorder (MONDO:0011122), complex neurodevelopmental disorder (MONDO:0100038), schizophrenia 17 (MONDO:0800358), ovarian dysgenesis 3 (MONDO:0013689), schizophrenia (MONDO:0005090), neurodevelopmental disorder (MONDO:0700092)

Orphanet (9): OBSOLETE: Pitt-Hopkins-like syndrome (Orphanet:221150), NRXN1-related severe neurodevelopmental disorder-motor stereotypies-chronic constipation-sleep-wake cycle disturbance (Orphanet:600663), Obesity due to melanocortin 4 receptor deficiency (Orphanet:71529), Non-specific syndromic intellectual disability (Orphanet:528084), 46,XX gonadal dysgenesis (Orphanet:243), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Non rare obesity (Orphanet:521399), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

20 total (22 of 20 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000154	Wide mouth
HP:0000486	Strabismus
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001642	Pulmonic stenosis
HP:0002019	Constipation
HP:0002020	Gastroesophageal reflux
HP:0002136	Broad-based gait
HP:0002307	Drooling
HP:0002376	Developmental regression
HP:0002650	Scoliosis
HP:0002883	Hyperventilation
HP:0003745	Sporadic
HP:0010808	Protruding tongue
HP:0010864	Severe intellectual disability
HP:0011968	Feeding difficulties
HP:0100753	Schizophrenia
HP:0200134	Epileptic encephalopathy
HP:0000717	Autism
HP:0001513	Obesity

GWAS associations

38 associations (top):

Study	Trait	p-value
GCST000754_7	Personality dimensions	9.000000e-06
GCST000785_1	Longevity	1.000000e-06
GCST001531_16	Temperament	1.000000e-06
GCST001823_4	Metabolite levels (HVA/MHPG ratio)	4.000000e-06
GCST002598_36	Educational attainment	5.000000e-06
GCST002685_1	Refractive astigmatism	3.000000e-07
GCST002685_6	Refractive astigmatism	4.000000e-08
GCST002951_2	Response to zileuton treatment in asthma (FEV1 change interaction)	4.000000e-06
GCST003264_1028	Post bronchodilator FEV1/FVC ratio	3.000000e-06
GCST003264_755	Post bronchodilator FEV1/FVC ratio	2.000000e-07
GCST004198_2	Severe gingival inflammation	4.000000e-06
GCST004649_2	Isovolumetric relaxation time	6.000000e-06
GCST004749_92	Lung cancer in ever smokers	7.000000e-06
GCST004765_19	Total cholesterol change in response to fenofibrate in statin-treated type 2 diabetes	1.000000e-07
GCST004904_223	Body mass index	5.000000e-09
GCST006624_94	Systolic blood pressure	1.000000e-08
GCST007267_91	Systolic blood pressure	6.000000e-10
GCST007325_81	General risk tolerance (MTAG)	8.000000e-10
GCST007467_3	Word spelling	1.000000e-06
GCST007565_213	Morning person	3.000000e-17
GCST007565_27	Morning person	5.000000e-14
GCST007565_80	Morning person	6.000000e-16
GCST007565_85	Morning person	2.000000e-14
GCST007576_337	Chronotype	3.000000e-17
GCST007576_367	Chronotype	2.000000e-08
GCST007576_368	Chronotype	5.000000e-14
GCST008595_22	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	2.000000e-08
GCST008953_2	Chromosomal aberration frequency (chromatid type)	2.000000e-06
GCST009218_41	Lateral ventricle temporal horn volume	7.000000e-10
GCST009218_42	Lateral ventricle temporal horn volume	3.000000e-08

EFO canonical traits (21, from GWAS)

EFO ID	Trait name
EFO:0004365	personality trait
EFO:0004825	temperament and character inventory
EFO:0005131	HVA measurement
EFO:0005133	MHPG measurement
EFO:0004784	self reported educational attainment
EFO:0005921	FEV change measurement
EFO:0004713	FEV/FVC ratio
EFO:0008204	left ventricular diastolic function measurement
EFO:0007806	total cholesterol change measurement
EFO:0004340	body mass index
EFO:0006335	systolic blood pressure
EFO:0008579	risk-taking behaviour
EFO:0005301	reading and spelling ability
EFO:0008328	chronotype measurement
EFO:0004337	intelligence
EFO:0009862	chromatid-type aberration frequency
EFO:0009262	nicotine dependence symptom count
EFO:0004530	triglyceride measurement
EFO:0008255	particulate matter air pollution measurement
EFO:0005670	smoking initiation
EFO:0009749	age at first sexual intercourse measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
C565497	Hyperopia, High (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

3 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs10490162	Efficacy	3	antipsychotics	Schizophrenia
rs12467557	Efficacy	3	antipsychotics	Schizophrenia
rs4971678	Efficacy	3	duloxetine	Major Depressive Disorder

PharmGKB variants

8 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2193225	NRXN1		0.00	0
rs6721498	NRXN1		0.00	0
rs10490162	NRXN1	3	1.75	1	antipsychotics
rs12467557	NRXN1	3	1.75	1	antipsychotics
rs985919	NRXN1		0.00	0
rs1882296	NRXN1		0.00	0
rs10865246	NRXN1		0.00	0
rs4971678	NRXN1	3	0.00	1	duloxetine

CTD chemical–gene interactions

42 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	8
Benzo(a)pyrene	increases expression, increases methylation	2
Nickel	decreases expression	2
Rotenone	decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
Particulate Matter	increases methylation, affects methylation, decreases expression, decreases reaction	2
bisphenol F	affects cotreatment, decreases methylation	1
methylmercuric chloride	decreases expression	1
bisphenol A	affects methylation	1
trichostatin A	increases expression	1
sodium arsenite	affects methylation	1
CGP 52608	affects binding, increases reaction	1
deguelin	decreases expression	1
fenpyroximate	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
pyrimidifen	decreases expression	1
thifluzamide	decreases expression	1
pyrachlostrobin	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
bisphenol S	affects cotreatment, decreases methylation, affects methylation	1
picoxystrobin	decreases expression	1
Decitabine	decreases expression, decreases reaction, increases methylation	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetylcysteine	decreases expression, decreases reaction, increases methylation	1
Air Pollutants	affects expression, increases abundance	1
Aldicarb	affects reaction, increases response to substance, decreases response to substance	1
Antimycin A	decreases expression	1
Arsenic	affects methylation	1
Diethylhexyl Phthalate	decreases expression	1

Cellosaurus cell lines

31 cell lines: 31 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E4XB	MLUi001-A	Induced pluripotent stem cell	Male
CVCL_E4XC	MLUi001-B	Induced pluripotent stem cell	Male
CVCL_E4XD	MLUi001-C	Induced pluripotent stem cell	Male
CVCL_E4XE	MLUi001-D	Induced pluripotent stem cell	Male
CVCL_E4XF	MLUi001-E	Induced pluripotent stem cell	Male
CVCL_E4XG	MLUi001-F	Induced pluripotent stem cell	Male
CVCL_E4XH	MLUi001-G	Induced pluripotent stem cell	Male
CVCL_E4XI	MLUi001-H	Induced pluripotent stem cell	Male
CVCL_E4XJ	MLUi001-I	Induced pluripotent stem cell	Male
CVCL_E4XK	MLUi001-J	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

599 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety