NFIB

Summary

NFIB (nuclear factor I B, HGNC:7785) is a protein-coding gene on chromosome 9p23-p22.3, encoding Nuclear factor 1 B-type (O00712). Transcriptional activator of GFAP, essential for proper brain development. It is haploinsufficient (ClinGen: sufficient evidence).

Enables DNA-binding transcription activator activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and transcription regulator inhibitor activity. Involved in brain development and regulation of DNA-templated transcription. Located in fibrillar center and nucleoplasm.

Source: NCBI Gene 4781 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic complex neurodevelopmental disorder (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 15
• Clinical variants (ClinVar): 208 total — 20 pathogenic, 17 likely-pathogenic
• Phenotypes (HPO): 25
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 27 downstream targets (CollecTRI)
• MANE Select transcript: NM_001190737

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7785
Approved symbol	NFIB
Name	nuclear factor I B
Location	9p23-p22.3
Locus type	gene with protein product
Status	Approved
Aliases	NFI-RED, NFIB2, NFIB3
Ensembl gene	ENSG00000147862
Ensembl biotype	protein_coding
OMIM	600728
Entrez	4781

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 31 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000380921, ENST00000380924, ENST00000380934, ENST00000380953, ENST00000380959, ENST00000397575, ENST00000397579, ENST00000397581, ENST00000493697, ENST00000543693, ENST00000606230, ENST00000632375, ENST00000633317, ENST00000635877, ENST00000636057, ENST00000636063, ENST00000636432, ENST00000636735, ENST00000637640, ENST00000637742, ENST00000638165, ENST00000646622, ENST00000877583, ENST00000877584, ENST00000877585, ENST00000877586, ENST00000877587, ENST00000877588, ENST00000877589, ENST00000877590, ENST00000959941, ENST00000959942, ENST00000959943, ENST00000959944

RefSeq mRNA: 29 — MANE Select: NM_001190737 NM_001190737, NM_001190738, NM_001282787, NM_001369458, NM_001369459, NM_001369460, NM_001369461, NM_001369462, NM_001369463, NM_001369464, NM_001369465, NM_001369466, NM_001369467, NM_001369468, NM_001369469, NM_001369470, NM_001369471, NM_001369472, NM_001369473, NM_001369474, NM_001369475, NM_001369476, NM_001369477, NM_001369478, NM_001369479, NM_001369480, NM_001369481, NM_001429577, NM_005596

CCDS: CCDS55291, CCDS55292, CCDS6474, CCDS65007, CCDS94382, CCDS94383, CCDS94384, CCDS94385, CCDS94386, CCDS94387, CCDS94388, CCDS94389, CCDS94390

Canonical transcript exons

ENST00000380953 — 11 exons

Exon	Start	End
ENSE00001088861	14125632	14125766
ENSE00001088863	14120440	14120624
ENSE00001088870	14146689	14146807
ENSE00001374815	14306989	14307520
ENSE00001486924	14112999	14113081
ENSE00001486931	14116208	14116346
ENSE00001486934	14313482	14314141
ENSE00001663148	14081848	14088326
ENSE00003466662	14150145	14150265
ENSE00003475198	14155825	14155893
ENSE00003477927	14179727	14179780

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.1980 / max 1391.1312, expressed in 1439 samples.

FANTOM5 promoters (26 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100000	13.0560	1170
99996	10.0981	1215
99968	2.2235	805
99999	1.5612	678
99994	1.5158	554
99991	0.9681	400
100002	0.4826	205
99992	0.3527	156
100005	0.3478	184
99993	0.3279	147

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pericardium	UBERON:0002407	99.56	gold quality
epithelium of mammary gland	UBERON:0003244	99.56	gold quality
mammary duct	UBERON:0001765	99.54	gold quality
urethra	UBERON:0000057	99.48	gold quality
nipple	UBERON:0002030	99.47	gold quality
parietal pleura	UBERON:0002400	99.44	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.41	gold quality
saphenous vein	UBERON:0007318	99.36	gold quality
vena cava	UBERON:0004087	99.33	gold quality
synovial joint	UBERON:0002217	99.25	gold quality
pleura	UBERON:0000977	99.20	gold quality
cardia of stomach	UBERON:0001162	99.19	gold quality
penis	UBERON:0000989	99.14	gold quality
ganglionic eminence	UBERON:0004023	99.12	gold quality
cortical plate	UBERON:0005343	98.92	gold quality
germinal epithelium of ovary	UBERON:0001304	98.90	gold quality
pylorus	UBERON:0001166	98.88	gold quality
visceral pleura	UBERON:0002401	98.88	gold quality
skin of hip	UBERON:0001554	98.87	gold quality
parotid gland	UBERON:0001831	98.85	gold quality
superficial temporal artery	UBERON:0001614	98.71	gold quality
upper arm skin	UBERON:0004263	98.55	gold quality
seminal vesicle	UBERON:0000998	98.54	gold quality
lower lobe of lung	UBERON:0008949	98.53	gold quality
renal medulla	UBERON:0000362	98.45	gold quality
medial globus pallidus	UBERON:0002477	98.41	gold quality
hair follicle	UBERON:0002073	98.36	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.25	gold quality
body of tongue	UBERON:0011876	98.24	gold quality
globus pallidus	UBERON:0001875	98.23	gold quality

Single-cell (SCXA)

Detected in 32 experiment(s), a significant marker in 29.

Experiment	Marker?	Max mean expression
E-GEOD-75140	yes	18411.84
E-ANND-2	yes	2867.76
E-HCAD-5	yes	2815.84
E-MTAB-10485	yes	2562.81
E-MTAB-8894	yes	1344.95
E-MTAB-11121	yes	1226.69
E-GEOD-93593	yes	1080.79
E-CURD-6	yes	1035.49
E-GEOD-81608	yes	545.87
E-GEOD-124472	yes	455.72
E-CURD-114	yes	311.32
E-MTAB-10287	yes	64.93
E-GEOD-134144	yes	42.67
E-GEOD-135922	yes	39.97
E-HCAD-10	yes	39.45

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

27 targets.

Target	Regulation
ANOS1	Repression
CCL2	Activation
CDKN1A	Activation
COL2A1
CYP3A7	Repression
EPHA4	Activation
EPHA5	Activation
EPHA8	Activation
ETV5	Repression
EZH2	Repression
FABP7	Activation
FOXO6	Repression
GAS6	Repression
ID3	Repression
MAPK1
MBP	Activation
NEUROD1	Activation
NEUROD4	Activation
NFIX	Unknown
RBFOX3	Activation
ROBO1	Activation
SLIT1	Activation
STAT5A	Activation
TRIB3
TSHB
WFDC2	Unknown
WNT5A	Repression

JASPAR motifs

Motif	Name	Family
MA1643.1	NFIB	Nuclear factor 1
MA1643.2	NFIB	Nuclear factor 1

JASPAR matrix evidence (PMIDs): PMID:23332764

Upstream regulators (CollecTRI, top): ESR1, MYB

miRNA regulators (miRDB)

316 targeting NFIB, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-371B-5P	99.99	75.34	4759
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
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4775	99.98	75.00	6394

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 40)

• expression of NFI-B2 impairs CD4 transcription on CDd4-positive primary T-lymphocytes and cell lines in HIV-1 infection (PMID:12639247)
• C-terminal domain of the nuclear factor I-B2 isoform is glycosylated and transactivates the WAP gene in tumor cells (PMID:17511965)
• the rearrangement of NFIB might be associated with deep-seated lipomas, such as retroperitoneal or gastro-intestinal lipomas (PMID:18663748)
• Knockdown of NFIB and NFIC expression using siRNA decreased and increased IGFBP5 expression, respectively. (PMID:18809517)
• lipomas containing NFIB rearrangements may be related to peculiar clinicohistologic features, including large size, deep situation, infiltration of surrounding muscles, or precocious occurrence. (PMID:19837271)
• The MYB-NFIB fusion is a hallmark of adenoid cystic carcinomas (ACC) and deregulation of the expression of MYB and its target genes is a key oncogenic event in the pathogenesis of ACC.[MYB-NFIB fusion prtoein] (PMID:19841262)
• The the MYB-NFIB fusion characterizes a subset of ACCs and contributes to MYB overexpression. (PMID:20702610)
• these results suggest that NFIB is a novel and specific biomarker for oxaliplatin resistance in human cancers (PMID:21087353)
• study revealed that miRNA (miRs-372/373) can promote HBV expression through a pathway involving the transcription factor (PMID:21608007)
• study demonstrates that benign sporadic, dermal cylindromas express the MYB-NFIB gene fusion (PMID:21618541)
• Functional studies indicate that NFIB regulates cell viability and proliferation during transformation (PMID:21764851)
• 1 of the 9 Polymorphous low-grade adenocarcinomas (PLGA) expressed the adenoid cystic carcinoma-associated MYB-NFIB gene fusion; findings indicate that the PLGA genome is genetically stable (PMID:21901247)
• Tissue microarray results from invasive breast cancer patients, and the immunohistochemistry results showed a significant association between NFIB expression and nuclear grade, estrogen receptor, and HER2 expression status. (PMID:21925980)
• study concludes conclude that: t(6;9) results in complex genetic and molecular alterations in adenoid cystic carcinoma (ACC); MYB-NFIB gene fusion may not always be associated with chimeric transcript formation; noncanonical MYB-NFIB gene fusions occur in a subset of tumors; high MYB expression correlates with worse patient survival (PMID:21976542)
• The data demonstrates that the autism spectrum disorder-associated A-C intronic haplotype of the ENGRAILED2 gene is a transcriptional activator, and both CUX1 and NFIB mediate this activity. (PMID:22180456)
• Explored copy number alterations rearrangements in adenoid cystic carcinoma. 86% of the tumors expressed MYB-NFIB fusion transcripts and 97% overexpressed MYB mRNA. (PMID:22505352)
• Increased expression of NF1B is associated with pilocytic astrocytoma. (PMID:23161775)
• Further studies also discovered a conserved feedback regulatory circuitry formed by NFIB and miR-365 in cutaneous squamous cell carcinoma development (PMID:24949940)
• TGF-beta-mediated suppression of ANT2 through NF1/Smad4 complexes contributes to oxidative stress and DNA damage during induction of cellular senescence. (PMID:25220407)
• multivariate analysis co-overexpression of NFIB, RANK and RANKL significantly increased the risk of metastasis with an odds ratio of 13.59 (PMID:25764026)
• These data suggest that germline genetic variation at rs7034162 is important in osteosarcoma metastasis and that NFIB is an osteosarcoma metastasis susceptibility gene. (PMID:26084801)
• Our study defines new molecular subclasses of ACC characterized by MYBL1 rearrangements and 5’-NFIB gene fusions. (PMID:26631609)
• In benign prostatic hyperplasia, luminal NFIB loss correlated with more severe disease. in androgen-dependent LNCaP prostate cancer cells demonstrated that 64.3% of NFIB binding sites are associated with AR and FOXA1 binding sites. (PMID:26677878)
• we report that the transcription factor NFIB is associated with significantly improved survival in glioblastoma (PMID:27083054)
• Expression of the MYB-NFIB fusion oncogene in mammary tissue resulted in hyperplastic glands that developed into adenocarcinoma. (PMID:27213588)
• low expression of NFIB was significantly associated with biologically more aggressive subtypes and, ultimately, poorer survival in lung adenocarcinoma patients (PMID:27357447)
• High NFIB levels are associated with expansive growth of a poorly differentiated and almost exclusively E-cadherin (CDH1)-negative invasive tumor cell population. (PMID:27373156)
• A trend toward superior PFS was noted with the MYB/NFIB rearrangement, although this was not statistically significant. NGS revealed three tumors with 4q12 amplification, producing increased copies of axitinib-targeted genes PDGFR/KDR/KIT. (PMID:27566443)
• NFIB-associated gene rearrangement is a frequent genetic event in vulvar adenoid cystic carcinomas. Chromosome translocations involving NFIB but with an intact MYB indicate the presence of novel oncogenic mechanisms for the development of adenoid cystic carcinomas of the vulva. (PMID:27662035)
• Studies indicate the role of nuclear factor one (NFIs) as epigenetic regulators in cancer. (PMID:28076901)
• Data indicate that NFIB protein increases EZH2 protein expression downstream of BRN2 protein, which further decreases MITF protein levels. (PMID:28119061)
• Both cases harbored the MYB-NFIB gene fusion as demonstrated by FISH and RNA-sequencing (PMID:28210977)
• Study highlighted the paradoxical involvement of NFIB in both the inhibition and promotion of tumor development as well as progression in different malignancies; especially between different tumor subtypes within a single organ system, such as in lung, brain and skin,which corroborates its diverse and distinct roles in specific tissues and cell types. [review] (PMID:28596133)
• Studied role of miR-30d in tumor invasiveness and migration in non-small lung cancer (NSCLC). Found miR-30d suppressed cell migration and invasion by directly targeting nuclear factor I B (NFIB) in NSCLC. (PMID:28861760)
• Breast adenoid cystic carcinomas probably constitute a convergent phenotype, whereby activation of MYB and MYBL1 and their downstream targets can be driven by the MYB-NFIB fusion gene, MYBL1 rearrangements, MYB amplification, or other yet to be identified mechanisms. (PMID:29149504)
• Salivary gland ACC cases expressing the MYB-NFIB chimeric gene showed significantly higher blood vessels density compared to non-expressing cases, and suggested that higher VEGF production capability in the former cases may be the cause. The findings also suggested that MYB-NFIB chimeric gene expression may be related to the onset age of ACC. (PMID:29243184)
• High NFIB expression correlates with lymph node metastasis and poor differentiation in tumors of patients with esophagogastric junction adenocarcinoma (EJA) predicting poor outcome. (PMID:29577671)
• This study confirmed the association of SNP rs1324183 in MPDZ-NF1B with keratoconus and revealed the association of this SNP with keratoconus severity and corneal parameters. It is thus a putative genetic marker for monitoring the progression of keratoconus to a severe form and facilitating early intervention. (PMID:30002070)
• High NF1B expression is associated with cell growth, aggressiveness, metastasis in gastric cancer. (PMID:30015981)
• Nuclear factor I/B (NFIB) is overexpressed in colorectal cancer (CRC) tissues. (PMID:30320939)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nfib	ENSMUSG00000008575
rattus_norvegicus	Nfib	ENSRNOG00000009795
drosophila_melanogaster	NfI	FBGN0042696
caenorhabditis_elegans		WBGENE00003592

Paralogs (3): NFIX (ENSG00000008441), NFIC (ENSG00000141905), NFIA (ENSG00000162599)

Protein

Protein identifiers

Nuclear factor 1 B-type — O00712 (reviewed: O00712)

Alternative names: CCAAT-box-binding transcription factor, Nuclear factor I/B, TGGCA-binding protein

All UniProt accessions (18): O00712, A0A0A0MRX8, A0A1B0GTC1, A0A1B0GU97, A0A1B0GVN4, A0A1B0GW37, A0A1B0GWB8, A0A1B0GWI9, A0A1B0GWJ4, A0A2R8Y7V8, Q5VW26, Q5VW27, Q5VW28, Q5VW30, Q5VW31, Q5W0Y9, U3KPY9, U3KQE8

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional activator of GFAP, essential for proper brain development. Recognizes and binds the palindromic sequence 5’-TTGGCNNNNNGCCAA-3’ present in viral and cellular promoters and in the origin of replication of adenovirus type 2. These proteins are individually capable of activating transcription and replication.

Subunit / interactions. Binds DNA as a homodimer.

Subcellular location. Nucleus.

Disease relevance. Macrocephaly, acquired, with impaired intellectual development (MACID) [MIM:618286] An autosomal dominant disorder characterized by postnatal macrocephaly and borderline to mild intellectual disability. Additional variable neurodevelopmental features include muscular hypotonia, motor and speech delay, attention deficit disorder, autism spectrum disorder, and behavioral abnormalities. Some patients present corpus callosum dysgenesis. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.

Similarity. Belongs to the CTF/NF-I family.

Isoforms (6)

UniProt ID	Names	Canonical?
O00712-1	1	yes
O00712-3	2
O00712-2	3, NFI-B3
O00712-4	4
O00712-5	5
O00712-6	6

RefSeq proteins (29): NP_001177666, NP_001177667, NP_001269716, NP_001356387, NP_001356388, NP_001356389, NP_001356390, NP_001356391, NP_001356392, NP_001356393, NP_001356394, NP_001356395, NP_001356396, NP_001356397, NP_001356398, NP_001356399, NP_001356400, NP_001356401, NP_001356402, NP_001356403, NP_001356404, NP_001356405, NP_001356406, NP_001356407, NP_001356408, NP_001356409, NP_001356410, NP_001416506, NP_005587 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000647	CTF/NFI	Family
IPR003619	MAD_homology1_Dwarfin-type	Domain
IPR019548	CTF/NFI_DNA-bd_N	Domain
IPR019739	CTF/NFI_DNA-bd_CS	Conserved_site
IPR020604	CTF/NFI_DNA-bd-dom	Domain

Pfam: PF00859, PF03165, PF10524

UniProt features (34 total): modified residue 9, splice variant 6, sequence variant 6, sequence conflict 5, region of interest 3, compositionally biased region 2, chain 1, DNA-binding region 1, short sequence motif 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9W7S	X-RAY DIFFRACTION	2.3
9W7W	X-RAY DIFFRACTION	2.81

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00712-F1	68.17	0.40

Functional residue map

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

Post-translational modifications (9): 292, 295, 312, 328, 333, 335, 388, 264, 286

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-73980	RNA Polymerase III Transcription Termination
R-HSA-749476	RNA Polymerase III Abortive And Retractive Initiation

MSigDB gene sets: 0 (showing top):

GO Biological Process (45): negative regulation of transcription by RNA polymerase II (GO:0000122), tissue homeostasis (GO:0001894), chondrocyte differentiation (GO:0002062), glandular epithelial cell differentiation (GO:0002067), DNA replication (GO:0006260), regulation of transcription by RNA polymerase II (GO:0006357), brain development (GO:0007420), response to wounding (GO:0009611), response to bacterium (GO:0009617), glial cell differentiation (GO:0010001), exit from mitosis (GO:0010458), gene expression (GO:0010467), glial cell proliferation (GO:0014009), stem cell population maintenance (GO:0019827), principal sensory nucleus of trigeminal nerve development (GO:0021740), glial cell fate specification (GO:0021780), cell proliferation in forebrain (GO:0021846), anterior commissure morphogenesis (GO:0021960), hindbrain development (GO:0030902), regeneration (GO:0031099), negative regulation of DNA binding (GO:0043392), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), neuron fate specification (GO:0048665), retina development in camera-type eye (GO:0060041), club cell differentiation (GO:0060486), type I pneumocyte differentiation (GO:0060509), type II pneumocyte differentiation (GO:0060510), salivary gland cavitation (GO:0060662), cell differentiation involved in salivary gland development (GO:0060689), lung ciliated cell differentiation (GO:0061141), commissural neuron axon guidance (GO:0071679), stem cell proliferation (GO:0072089), negative regulation of miRNA transcription (GO:1902894), negative regulation of stem cell proliferation (GO:2000647), negative regulation of mesenchymal cell proliferation involved in lung development (GO:2000791), negative regulation of epithelial cell proliferation involved in lung morphogenesis (GO:2000795), regulation of DNA-templated transcription (GO:0006355), cell population proliferation (GO:0008283), regulation of gene expression (GO:0010468)

GO Molecular Function (9): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), transcription regulator inhibitor activity (GO:0140416), sequence-specific double-stranded DNA binding (GO:1990837), double-stranded DNA binding (GO:0003690), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515)

GO Cellular Component (5): chromatin (GO:0000785), fibrillar center (GO:0001650), nucleus (GO:0005634), nucleoplasm (GO:0005654), cerebellar mossy fiber (GO:0044300)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RNA Polymerase III Transcription	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
cell differentiation	2
regulation of DNA-templated transcription	2
gliogenesis	2
anatomical structure development	2
transcription regulator activity	2
negative regulation of DNA-templated transcription	1
multicellular organismal-level homeostasis	1
anatomical structure homeostasis	1
cartilage development	1
columnar/cuboidal epithelial cell differentiation	1
DNA metabolic process	1
DNA biosynthetic process	1
central nervous system development	1
animal organ development	1
head development	1
response to stress	1
response to other organism	1
mitotic cell cycle phase transition	1
mitotic nuclear division	1
macromolecule biosynthetic process	1
cell population proliferation	1
multicellular organismal process	1
maintenance of cell number	1
trigeminal sensory nucleus development	1
cell fate specification	1
glial cell fate commitment	1
forebrain development	1
neural precursor cell proliferation	1
telencephalon development	1
central nervous system projection neuron axonogenesis	1
brain development	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1

Protein interactions and networks

STRING

1610 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NFIB	SLC1A3	P43003	721
NFIB	F5H6H0	F5H6H0	693
NFIB	MPDZ	O75970	682
NFIB	LNX1	Q8TBB1	664
NFIB	MYBL1	P10243	598
NFIB	CEBPA	P49715	581
NFIB	CRTC1	Q6UUV9	576
NFIB	FHIT	P49789	549
NFIB	JUND	P17535	523
NFIB	ZDHHC21	Q8IVQ6	520
NFIB	PAX6	P26367	519
NFIB	PDCD4	Q53EL6	506
NFIB	RAD51B	O15315	500
NFIB	NF1	P21359	494
NFIB	JUN	P05412	492

IntAct

92 interactions, top by confidence:

A	B	Type	Score
NFIC	NFIB	psi-mi:“MI:0915”(physical association)	0.690
NFIB	NFIC	psi-mi:“MI:0914”(association)	0.690
NFIC	NFIB	psi-mi:“MI:0914”(association)	0.690
NFIC	NFIB	psi-mi:“MI:2364”(proximity)	0.690
NFIA	NFIB	psi-mi:“MI:0914”(association)	0.570
NFIX	NFIB	psi-mi:“MI:0914”(association)	0.570
NFIB	TBXT	psi-mi:“MI:0915”(physical association)	0.470
NFIB	ETV7	psi-mi:“MI:0915”(physical association)	0.470
NFIB	EN1	psi-mi:“MI:0915”(physical association)	0.470
NFIB	LHX2	psi-mi:“MI:0915”(physical association)	0.470
NFIB	ELK3	psi-mi:“MI:0915”(physical association)	0.470
NFIB	FOXL1	psi-mi:“MI:0915”(physical association)	0.470
NFIB	KLF3	psi-mi:“MI:0915”(physical association)	0.470
NFIB	ERG	psi-mi:“MI:0915”(physical association)	0.470
NFIB	GATA2	psi-mi:“MI:0915”(physical association)	0.470
NFIB	LHX4	psi-mi:“MI:0915”(physical association)	0.470
NFIB	SOX10	psi-mi:“MI:0915”(physical association)	0.470
NFIB	TLX2	psi-mi:“MI:0915”(physical association)	0.470
NFIB	PAX2	psi-mi:“MI:0915”(physical association)	0.470
NFIB	SOX2	psi-mi:“MI:0915”(physical association)	0.470
NFIB	SOX15	psi-mi:“MI:0915”(physical association)	0.470
NFIB	TLX3	psi-mi:“MI:0915”(physical association)	0.470
NFIB	PAX6	psi-mi:“MI:0915”(physical association)	0.470
NFIB	SOX5	psi-mi:“MI:0915”(physical association)	0.470
NFIB	SOX17	psi-mi:“MI:0915”(physical association)	0.470
NFIB	PAX7	psi-mi:“MI:0915”(physical association)	0.470
NFIB	SOX6	psi-mi:“MI:0915”(physical association)	0.470
NFIB	SP7	psi-mi:“MI:0915”(physical association)	0.470
NFIB	PAX8	psi-mi:“MI:0915”(physical association)	0.470

BioGRID (794): NFIB (Affinity Capture-MS), NFIB (Affinity Capture-RNA), NFIB (Affinity Capture-MS), NFIB (Affinity Capture-MS), NFIB (Affinity Capture-MS), NFIB (Affinity Capture-MS), NFIB (Affinity Capture-MS), NFIA (Affinity Capture-MS), NFIX (Affinity Capture-MS), NFIC (Affinity Capture-MS), NFIB (Affinity Capture-RNA), NFIA (Two-hybrid), NFIX (Two-hybrid), NFIB (Affinity Capture-MS), NFIB (Proximity Label-MS)

ESM2 similar proteins: A2AVJ0, F4IXJ7, F5H9W9, O00712, O41804, O75603, P09265, P0CK37, P0CK38, P0CO74, P0CO75, P13622, P13623, P17924, P17926, P21740, P36714, P53963, P70255, P70257, P97454, P97863, Q00041, Q01769, Q02362, Q02780, Q04360, Q0VCL6, Q14938, Q1HVH2, Q1PDC6, Q2HR75, Q3KSU1, Q4JQW5, Q56I99, Q56XX3, Q5K2K5, Q5K2K6, Q5R6H7, Q6AYM7

Diamond homologs: O00712, P08651, P09414, P13622, P13623, P14057, P17923, P17924, P17926, P21999, P70255, P70257, P97863, Q02780, Q0VCL6, Q12857, Q14938, Q5H9N3, Q90932

SIGNOR signaling

21 interactions.

A	Effect	B	Mechanism
NFIB	“down-regulates quantity by repression”	EZH2	“transcriptional regulation”
FOXA1	up-regulates	NFIB	binding
NFIB	“down-regulates activity”	NFIC	binding
NFIB	“down-regulates activity”	NFIB	binding
NFIB	“down-regulates activity”	NFIX	binding
NFIB	“up-regulates quantity”	NFIX	“transcriptional regulation”
NFIB	“down-regulates quantity”	ANOS1	“transcriptional regulation”
NFIB	“down-regulates quantity”	ID3	“transcriptional regulation”
NFIB	“down-regulates quantity”	ETV5	“transcriptional regulation”
NFIB	“down-regulates quantity”	FOXO6	“transcriptional regulation”
NFIB	“down-regulates quantity”	GAS6	“transcriptional regulation”
NFIB	“down-regulates quantity”	WNT5A	“transcriptional regulation”
NFIB	“up-regulates quantity”	NEUROD1	“transcriptional regulation”
NFIB	“up-regulates quantity”	NEUROD4	“transcriptional regulation”
NFIB	“up-regulates quantity”	SLIT1	“transcriptional regulation”
NFIB	“up-regulates quantity”	ROBO1	“transcriptional regulation”
NFIB	“up-regulates quantity”	EPHA4	“transcriptional regulation”
NFIB	“up-regulates quantity”	EPHA5	“transcriptional regulation”
NFIB	“up-regulates quantity”	EPHA8	“transcriptional regulation”
NFIB	“up-regulates quantity”	RBFOX3	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 67 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Deactivation of the beta-catenin transactivating complex	6	33.3×	5e-06
TCF dependent signaling in response to WNT	6	16.8×	8e-05
Signaling by WNT	6	16.0×	9e-05
Nervous system development	7	7.2×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
cartilage development	6	23.6×	2e-05
inner ear morphogenesis	5	23.5×	9e-05
cell fate commitment	5	23.1×	9e-05
positive regulation of miRNA transcription	5	22.7×	1e-04
anatomical structure morphogenesis	9	19.6×	1e-07
transcription by RNA polymerase II	14	15.4×	6e-11
animal organ morphogenesis	5	15.0×	5e-04
neuron differentiation	8	12.5×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	20
Likely pathogenic	17
Uncertain significance	114
Likely benign	23
Benign	3

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1209855	GRCh37/hg19 9p23(chr9:13862493-14155897)x1	Pathogenic
1341289	GRCh37/hg19 9p22.3(chr9:14303821-14446948)x1	Pathogenic
1710235	NM_001190737.2(NFIB):c.1073del (p.Arg358fs)	Pathogenic
1800541	NM_001190737.2(NFIB):c.870C>A (p.Tyr290Ter)	Pathogenic
1805131	NM_001190737.2(NFIB):c.93_94del (p.Trp31fs)	Pathogenic
2499088	NM_001190737.2(NFIB):c.844G>T (p.Glu282Ter)	Pathogenic
2499576	NM_001190737.2(NFIB):c.686-2A>G	Pathogenic
2576943	NM_001190737.2(NFIB):c.364C>T (p.Arg122Ter)	Pathogenic
2692348	NM_001190737.2(NFIB):c.26dup (p.Gln10fs)	Pathogenic
3376240	NM_001190737.2(NFIB):c.870C>G (p.Tyr290Ter)	Pathogenic
3377174	NM_001190737.2(NFIB):c.816del (p.Thr274fs)	Pathogenic
4086014	GRCh37/hg19 9p23(chr9:14088196-14136675)x1	Pathogenic
4682738	GRCh37/hg19 9p23-22.3(chr9:13594876-14543548)x1	Pathogenic
495138	t(6;9)(q23.3;p22.3)	Pathogenic
560024	NM_001190737.2(NFIB):c.109C>T (p.Arg37Ter)	Pathogenic
560025	NM_001190737.2(NFIB):c.341A>C (p.Lys114Thr)	Pathogenic
560028	NM_001190737.2(NFIB):c.758_759dup (p.Asn254Ter)	Pathogenic
560029	NM_001190737.2(NFIB):c.1063_1076del (p.Ile355fs)	Pathogenic
562132	GRCh37/hg19 9p23-22.2(chr9:13739630-18023839)x1	Pathogenic
980896	GRCh37/hg19 9p23(chr9:14067538-14159969)x1	Pathogenic
1184959	NM_001190737.2(NFIB):c.367C>T (p.Gln123Ter)	Likely pathogenic
1324803	NM_001190737.2(NFIB):c.152del (p.Lys51fs)	Likely pathogenic
1709684	NM_001190737.2(NFIB):c.951del (p.Lys318fs)	Likely pathogenic
1806041	NM_001190737.2(NFIB):c.340A>G (p.Lys114Glu)	Likely pathogenic
2430344	NM_001190737.2(NFIB):c.389_399del (p.Leu130fs)	Likely pathogenic
3065166	NM_001190737.2(NFIB):c.1465C>T (p.Gln489Ter)	Likely pathogenic
3067743	NM_001190737.2(NFIB):c.377_378del (p.Lys126fs)	Likely pathogenic
3197505	NM_001190737.2(NFIB):c.1061-1G>C	Likely pathogenic
3338460	GRCh37/hg19 9p23(chr9:14088188-14102587)x1	Likely pathogenic
3342513	NM_001190737.2(NFIB):c.330C>A (p.Asp110Glu)	Likely pathogenic

SpliceAI

4944 predictions. Top by Δscore:

Variant	Effect	Δscore
9:14120620:GATGA:G	acceptor_gain	1.0000
9:14120622:TGA:T	acceptor_gain	1.0000
9:14120623:GA:G	acceptor_gain	1.0000
9:14120623:GAC:G	acceptor_loss	1.0000
9:14120624:AC:A	acceptor_loss	1.0000
9:14120625:C:CA	acceptor_loss	1.0000
9:14120625:C:CC	acceptor_gain	1.0000
9:14120626:T:G	acceptor_loss	1.0000
9:14137431:T:A	donor_gain	1.0000
9:14139807:T:A	donor_gain	1.0000
9:14146684:CTCA:C	donor_loss	1.0000
9:14146685:TCA:T	donor_loss	1.0000
9:14146686:CA:C	donor_loss	1.0000
9:14146687:A:T	donor_loss	1.0000
9:14155819:ACTT:A	donor_loss	1.0000
9:14155820:CTT:C	donor_loss	1.0000
9:14155821:TT:T	donor_loss	1.0000
9:14155822:TACT:T	donor_loss	1.0000
9:14155823:A:AC	donor_gain	1.0000
9:14155823:A:T	donor_loss	1.0000
9:14155823:ACTT:A	donor_gain	1.0000
9:14155824:C:CG	donor_gain	1.0000
9:14155824:CT:C	donor_gain	1.0000
9:14155824:CTT:C	donor_gain	1.0000
9:14155824:CTTC:C	donor_gain	1.0000
9:14155891:AACCT:A	acceptor_loss	1.0000
9:14155893:CCT:C	acceptor_loss	1.0000
9:14155894:CT:C	acceptor_loss	1.0000
9:14155895:T:G	acceptor_loss	1.0000
9:14176364:G:C	donor_gain	1.0000

AlphaMissense

3224 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:14150259:A:T	I231K	1.000
9:14155842:A:G	L223P	1.000
9:14155856:G:C	F218L	1.000
9:14155856:G:T	F218L	1.000
9:14155857:A:C	F218C	1.000
9:14155857:A:G	F218S	1.000
9:14155858:A:G	F218L	1.000
9:14307021:T:A	D177V	1.000
9:14307024:A:G	L176P	1.000
9:14307024:A:T	L176H	1.000
9:14307033:A:T	V173D	1.000
9:14307039:A:T	V171E	1.000
9:14307047:A:C	H168Q	1.000
9:14307047:A:T	H168Q	1.000
9:14307048:T:C	H168R	1.000
9:14307054:G:C	P166R	1.000
9:14307054:G:T	P166Q	1.000
9:14307060:A:T	V164D	1.000
9:14307062:A:C	C163W	1.000
9:14307063:C:A	C163F	1.000
9:14307063:C:G	C163S	1.000
9:14307063:C:T	C163Y	1.000
9:14307064:A:C	C163G	1.000
9:14307064:A:G	C163R	1.000
9:14307064:A:T	C163S	1.000
9:14307080:G:C	C157W	1.000
9:14307081:C:A	C157F	1.000
9:14307081:C:G	C157S	1.000
9:14307081:C:T	C157Y	1.000
9:14307082:A:G	C157R	1.000

dbSNP variants (sampled 300 via entrez): RS1000004752 (9:14469456 T>A,C), RS1000012506 (9:14383687 A>T), RS1000023865 (9:14227836 A>G), RS1000025630 (9:14349626 A>C), RS1000029970 (9:14098780 G>A), RS1000033061 (9:14205454 T>C), RS1000039985 (9:14117313 G>A), RS1000047439 (9:14268316 G>A,C), RS1000059344 (9:14450160 C>T), RS1000060388 (9:14257336 G>C), RS1000060703 (9:14154099 A>G), RS1000066192 (9:14383855 C>T), RS1000067801 (9:14347975 C>T), RS1000072323 (9:14450353 C>G), RS1000077038 (9:14449964 A>T)

Disease associations

OMIM: gene MIM:600728 | disease phenotypes: MIM:618286, MIM:181500

GenCC curated gene-disease

Disease	Classification	Inheritance
macrocephaly, acquired, with impaired intellectual development	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
syndromic complex neurodevelopmental disorder	Definitive	AD

Mondo (7): macrocephaly, acquired, with impaired intellectual development (MONDO:0032658), schizophrenia (MONDO:0005090), syndromic complex neurodevelopmental disorder (MONDO:0800439), autism spectrum disorder (MONDO:0005258), neurodevelopmental disorder (MONDO:0700092), intellectual disability (MONDO:0001071), adenoid cystic carcinoma (MONDO:0004971)

Orphanet (3): NON RARE IN EUROPE: Schizophrenia (Orphanet:3140), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

25 total (26 of 25 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000256	Macrocephaly
HP:0000276	Long face
HP:0000343	Long philtrum
HP:0000348	High forehead
HP:0000446	Narrow nasal bridge
HP:0000463	Anteverted nares
HP:0000494	Downslanted palpebral fissures
HP:0000581	Blepharophimosis
HP:0000717	Autism
HP:0000718	Aggressive behavior
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001270	Motor delay
HP:0001274	Agenesis of corpus callosum
HP:0002119	Ventriculomegaly
HP:0007018	Attention deficit hyperactivity disorder
HP:0012741	Unilateral cryptorchidism
HP:0033725	Thin corpus callosum
HP:0034054	Probst bundles
HP:0045075	Sparse eyebrow
HP:0100710	Impulsivity
HP:0100753	Schizophrenia

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST001868_6	Alzheimer’s disease biomarkers	2.000000e-06
GCST002978_1	Metastasis at diagnosis in osteosarcoma	1.000000e-09
GCST002978_2	Metastasis at diagnosis in osteosarcoma	3.000000e-08
GCST004860_144	Alcoholic chronic pancreatitis	2.000000e-06
GCST004952_37	Ankle injury	5.000000e-08
GCST005194_245	Coronary artery disease	4.000000e-06
GCST007445_12	Factor VIII levels	2.000000e-10
GCST007445_48	Factor VIII levels	3.000000e-10
GCST008595_132	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	1.000000e-10
GCST009028_41	Adverse response to drug	4.000000e-07
GCST009616_1	HDL cholesterol levels x thiazide or thiazide-like diuretics use interaction	7.000000e-07
GCST010242_113	HDL cholesterol levels	2.000000e-08
GCST010988_390	Adult body size	2.000000e-13
GCST90002403_605	Red blood cell count	5.000000e-09
GCST90013407_176	Liver enzyme levels (gamma-glutamyl transferase)	2.000000e-10

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0005194	amyloid-beta measurement
EFO:0004953	date of diagnosis
EFO:0007675	metastasis measurement
EFO:1002021	ankle injury
EFO:0004630	factor VIII measurement
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0009658	adverse effect
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004305	erythrocyte count
EFO:0004532	serum gamma-glutamyl transferase measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D003528	Carcinoma, Adenoid Cystic	C04.557.470.200.025.220
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs28379954	Metabolism/PK	3	clozapine	Schizophrenia
rs7858	Efficacy	3	methylphenidate	Attention Deficit Disorder with Hyperactivity

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7858	NFIB	3	0.00	1	methylphenidate
rs28379954	NFIB	3	0.00	1	clozapine
rs10961381	NFIB		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression	5
Estradiol	decreases expression, affects expression, affects cotreatment, increases expression	4
Cadmium Chloride	decreases expression, increases abundance, increases expression	4
bisphenol A	affects cotreatment, decreases methylation, decreases expression, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance	3
Tobacco Smoke Pollution	decreases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	3
manganese chloride	decreases expression, increases abundance, increases expression, affects cotreatment	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	decreases expression	2
Arsenic	decreases expression, increases abundance, affects cotreatment	2
Cisplatin	affects cotreatment, decreases expression	2
Manganese	decreases expression, increases abundance, increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Progesterone	affects cotreatment, increases expression	2
Cyclosporine	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
ethylbenzene	increases expression	1
titanium dioxide	decreases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
2-xylene	increases expression	1
potassium chromate(VI)	decreases expression	1
nickel sulfate	decreases expression	1
coumarin	decreases phosphorylation	1

Cellosaurus cell lines

8 cell lines: 3 embryonic stem cell, 3 cancer cell line, 2 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A4N0	SEES3-1V human NFIB, clone1	Embryonic stem cell	Male
CVCL_A4N1	SEES3-1V human NFIB, clone2	Embryonic stem cell	Male
CVCL_A4N2	SEES3-1V human NFIB, clone3	Embryonic stem cell	Male
CVCL_C4UW	UM-HACC-2A	Cancer cell line	Female
CVCL_D1XR	Abcam A-549 NFIB KO	Cancer cell line	Male
CVCL_D2C1	Abcam HCT 116 NFIB KO	Cancer cell line	Male
CVCL_E3D2	MSA-21 pB-rtTA(#4)-NFIB-mKate2	Induced pluripotent stem cell	Male
CVCL_E3D3	MSA-23 pB-rtTA(#4)-NFIB-mKate2	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

300 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