ZFHX3

Summary

ZFHX3 (zinc finger homeobox 3, HGNC:777) is a protein-coding gene on chromosome 16q22.2-q22.3, encoding Zinc finger homeobox protein 3 (Q15911). Transcriptional regulator which can act as an activator or a repressor.

This gene encodes a transcription factor with multiple homeodomains and zinc finger motifs, and regulates myogenic and neuronal differentiation. The encoded protein suppresses expression of the alpha-fetoprotein gene by binding to an AT-rich enhancer motif. The protein has also been shown to negatively regulate c-Myb, and transactivate the cell cycle inhibitor cyclin-dependent kinase inhibitor 1A (also known as p21CIP1). This gene is reported to function as a tumor suppressor in several cancers, and sequence variants of this gene are also associated with atrial fibrillation. Multiple transcript variants expressed from alternate promoters and encoding different isoforms have been found for this gene.

Source: NCBI Gene 463 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Definitive, GenCC) — +5 more curated relationships
• GWAS associations: 61
• Clinical variants (ClinVar): 956 total — 21 pathogenic, 16 likely-pathogenic
• Phenotypes (HPO): 15
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 10 cancer types
• Transcription factor: yes — 20 downstream targets (CollecTRI)
• MANE Select transcript: NM_006885

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:777
Approved symbol	ZFHX3
Name	zinc finger homeobox 3
Location	16q22.2-q22.3
Locus type	gene with protein product
Status	Approved
Aliases	ZNF927, FLJ26184
Ensembl gene	ENSG00000140836
Ensembl biotype	protein_coding
OMIM	104155
Entrez	463

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding_CDS_not_defined, 3 protein_coding, 1 retained_intron

ENST00000268489, ENST00000358463, ENST00000397992, ENST00000558842, ENST00000563625, ENST00000641018, ENST00000641077, ENST00000641206, ENST00000642085

RefSeq mRNA: 3 — MANE Select: NM_006885 NM_001164766, NM_001386735, NM_006885

CCDS: CCDS10908, CCDS54035

Canonical transcript exons

ENST00000268489 — 10 exons

Exon	Start	End
ENSE00000945261	72889731	72889962
ENSE00001033169	72811577	72811777
ENSE00001033177	72811905	72812038
ENSE00001033184	72793255	72798714
ENSE00001033196	72800027	72800129
ENSE00001147763	73047752	73048128
ENSE00001171638	72957427	72960194
ENSE00001199804	72829779	72829859
ENSE00001199831	72782885	72788848
ENSE00003584866	72950469	72950965

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 97.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.6533 / max 182.0932, expressed in 1663 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158085	3.2952	1377
158086	1.7266	927
158084	1.2459	756
158091	0.9768	465
158079	0.9714	646
158089	0.7314	435
158082	0.6476	387
158088	0.3960	211
158078	0.3328	168
158083	0.2939	144

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
saphenous vein	UBERON:0007318	97.68	gold quality
buccal mucosa cell	CL:0002336	97.27	gold quality
synovial joint	UBERON:0002217	96.17	gold quality
tendon of biceps brachii	UBERON:0008188	95.88	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.76	gold quality
pericardium	UBERON:0002407	94.68	gold quality
urethra	UBERON:0000057	94.15	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.73	gold quality
dorsal root ganglion	UBERON:0000044	93.66	gold quality
trigeminal ganglion	UBERON:0001675	93.66	gold quality
cauda epididymis	UBERON:0004360	92.76	gold quality
endometrium epithelium	UBERON:0004811	92.73	gold quality
lower lobe of lung	UBERON:0008949	92.65	gold quality
seminal vesicle	UBERON:0000998	92.60	gold quality
penis	UBERON:0000989	92.05	gold quality
renal medulla	UBERON:0000362	91.82	gold quality
sural nerve	UBERON:0015488	91.75	gold quality
tendon	UBERON:0000043	90.96	gold quality
layer of synovial tissue	UBERON:0007616	90.83	gold quality
secondary oocyte	CL:0000655	90.65	gold quality
corpus epididymis	UBERON:0004359	90.62	gold quality
ventral tegmental area	UBERON:0002691	90.39	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.35	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	89.52	gold quality
medial globus pallidus	UBERON:0002477	89.26	gold quality
substantia nigra pars compacta	UBERON:0001965	89.23	gold quality
tibia	UBERON:0000979	89.19	gold quality
caput epididymis	UBERON:0004358	88.82	gold quality
mammary duct	UBERON:0001765	88.49	gold quality
calcaneal tendon	UBERON:0003701	88.28	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-MTAB-11268	yes	6403.77
E-HCAD-56	yes	1781.91
E-GEOD-75140	yes	803.63
E-MTAB-11121	yes	621.06
E-MTAB-10662	yes	419.74
E-GEOD-93593	yes	339.90
E-MTAB-8142	yes	38.92
E-HCAD-35	yes	30.92
E-HCAD-5	yes	28.17
E-GEOD-135922	yes	25.30
E-CURD-114	yes	8.08
E-HCAD-25	yes	7.60
E-MTAB-8410	yes	4.51
E-MTAB-8060	no	450.68
E-MTAB-3929	no	212.88

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

20 targets.

Target	Regulation
ADIPOQ
AFP	Repression
ANPEP	Unknown
CAT
CCND1	Repression
CDKN1A	Activation
COL3A1	Activation
ESR1
ITGA8	Activation
MUC5AC	Repression
MYB	Repression
MYOD1	Repression
MYOG	Repression
NES	Repression
NEUROD1	Activation
PDGFRB	Activation
POU1F1
PROP1
TSHB
ZFHX3

Upstream regulators (CollecTRI, top): ATM, CREB1, ESR1, HMGA2, PGR, ZFHX3

miRNA regulators (miRDB)

312 targeting ZFHX3, 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-3613-3P	100.00	76.36	7965
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883

Literature-anchored findings (GeneRIF, showing 40)

• Aberrant expression of ATBF1 induces the expression of various factors that are otherwise suppressed, and this somehow determines the biological features of Alpha-fetoprotein producing gastric cancer. (PMID:14654895)
• In conclusion, ATBF1 can suppress the IL-6-mediated cellular response by acting together with PIAS3. (PMID:14715251)
• ATBF1-A mRNA has a role in lymph node metastasis of breast neoplasms (PMID:15671546)
• Somatic mutations of the transcription factor ATBF1 is associated with human prostate cancer (PMID:15750593)
• Two somatic mutations (shortening of a polypyrimidine tract [Poly(T)n] and a deletion beginning at codon 3381 (3381del)) were each observed in multiple prostate cancer samples and both appear to have an impact on ATBF1 gene function and expression. (PMID:16637072)
• ATBF1 plays a role in breast cancer through transcriptional downregulation rather than mutations. (PMID:16932943)
• Results indicate that ATBF1 in the nucleus negatively regulates the MUC5AC gene in gastric cancer by binding to an AT motif-like element in the MUC5AC promoter. (PMID:17330845)
• Genetic alterations of the ATBF1 gene is associated with gastric cancer (PMID:17671116)
• The ATBF1 gene may contribute to the development of hepatocellular carcinomas via transcriptional down-regulation of mRNA expression, but not by genetic or epigenetic alterations. (PMID:18312352)
• ATBF1 and NQO1 as candidate targets for allelic loss at chromosome arm 16q in breast cancer: absence of somatic ATBF1 mutations and no role for the C609T NQO1 polymorphism. (PMID:18416817)
• ATBF1-A mRNA levels are regulated at the transcriptional stage, but not by genetic mechanisms, deletions (LOH), or mutations. (PMID:18796146)
• Prostate cancer linkage to the same region of 16q23 has been observed by others and the region contains several strong candidate genes including the known prostate cancer tumor suppressor genes ATBF1 and WWOX. (PMID:19035517)
• A variant in the ZFHX3 gene on chromosome 16q22, rs7193343-T, associated significantly with atrial fibrillation (odds ratio OR = 1.21, P = 1.4 x 10(-10)). (PMID:19597491)
• Meta-analyses of 896 prevalent (15,768 referents) and 2,517 incident (21,337 referents) atrial fibrillation (AF) cases identified a new locus for AF (ZFHX3, rs2106261, risk ratio RR = 1.19; P = 2.3 x 10(-7)). (PMID:19597492)
• ATBF1 associates with RUNX3 and translocates to the nucleus in response to TGF-beta signal transduction and might function in the nucleus as tumor suppressor and transcriptional regulator. (PMID:20599712)
• Using DirectDNA sequencing analysis, we detected ATBF1, CYLD, PARK2 and WNT9A mutations in stomach and colorectal cancers (PMID:20854080)
• A novel signaling pathway that links ATM via CREB to the transcription factor ZFHX3, which in turn promotes survival of neurons by inducing expression of platelet-derived growth factor receptor beta, is reported. (PMID:20876357)
• Our results indicate that the s2106261 SNP in ZFHX3 confers a significant risk of atrial fibrillation in a Chinese Han population. (PMID:21107608)
• gen up-regulates ATBF1 transcription but causes its protein degradation in estrogen receptor-alpha-positive breast cancer cells (PMID:21367855)
• Levels of ATBF1 protein in breast tumors are positively correlated with the levels of estrogen-responsive finger protein (EFP). (PMID:22452784)
• Nuclear localization of ATBF1 is frequently interrupted in HNSCC, and the interruption is significantly associated with the progression of HNSCC (PMID:22791392)
• 3 loci from related cardiovascular genomewide studies were significant: PHACTR1 in large-vessel disease (P=2.63e(-6)), PITX2 in cardioembolic stroke (P=4.78e(-8)), and ZFHX3 in cardioembolic stroke (P=5.50e(-7)). (PMID:23042660)
• A polymorphism in the ZFHX3 gene, encoding a cardiac transcription factor, was associated with increased AF risk in HF patients, and the genetic association with AF was more pronounced in HF patients than in the general population. (PMID:23132824)
• Suppression of ZFHX3 expression in tumor cells decreases the survival rate among patients with NSCLC. (PMID:23144151)
• These findings suggest that ATBF1 plays a crucial role in the Progesterone-progesterone receptors signaling pathway in mammary epithelial cells. (PMID:23159610)
• findings indicate that Atbf1 plays a role in the development of pubertal mammary gland likely by modulating the function of estrogen-ER signaling in luminal cells and by modulating gene expression in basal cells (PMID:23251482)
• based on observations, nuclear ATBF1 staining was associated with low malignancy profiles of skin cancer (PMID:23317484)
• nuclear localization and SUMOylation are important for the transcription factor function of ATBF1, and that ATBF1 could cooperate with PML NBs to regulate protein SUMOylation in different biological processes. (PMID:24651376)
• Two SNPs (rs2106261, rs6499600) located in gene ZFHX3 showed significant associations with atrial fibrillation in a Chinese Han population. (PMID:24983873)
• Study found increased levels of ATBF1 in the cytoplasm of hippocampal pyramidal neurons in Alzheimer’s disease brains and that ATBF1 binds to the C-terminal of A-beta-PP, increasing the steady state levels of A-beta-PP and resulting in increased A-beta production (PMID:25079792)
• A missense mutation in ZFHX3 results in damage to the ZFHX3 protein structure in patients with extreme atrial fibrillation. (PMID:25391453)
• ZFHX3 transcription is regulated in a transcript-specific fashion by independent cis-acting transcribed polymorphisms. (PMID:25539802)
• The CAA repeat polymorphism in exon 9 of the ZFHX3 gene contributes to the Coronary heart disease susceptibility in the Chinese population. (PMID:25797214)
• In a Caucasian population, genetic variant rs7193343 SNP in ZFHX3 gene is associated with risk of atrial fibrillation. (PMID:26112950)
• The results suggest an additive effect of ZFHX3 and PTEN deletions on the development and progression of prostate neoplasia (PMID:26233892)
• Both ZFHX3 and PITX2c regulate expression of NPPA, TBX5 and NKX2.5. (PMID:26267381)
• ZFHX3 defects are associated with poor outcome in endometroid endometrial cancer. (PMID:26330387)
• using in vitro prolactin induced lactogenic differentiation in an HC11 mouse cell model and an in vivo conditional knockout mouse model we showed that mouse Zfhx3 is essential for mouse mammary epithelial cell differentiation and mouse mammary gland development at the lactation stage through regulation of prolactin receptor expression and the downstream Jak2-Stat5 signaling pathway. (PMID:27129249)
• Nuclear localization of AT-motif binding factor 1 (ATBF1) indicates better prognosis of urothelial carcinoma. (PMID:27756245)
• We showed that the ZFHX3 polymorphism, rs2106261 (A allele), was a risk marker for atrial fibrillation (A)F and AF-related phenotypes. (PMID:28007413)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	zfhx3b	ENSDARG00000103057
mus_musculus	Zfhx3	ENSMUSG00000038872
rattus_norvegicus	Zfhx3	ENSRNOG00000014452

Paralogs (20): FHL1 (ENSG00000022267), LMO3 (ENSG00000048540), LHX5 (ENSG00000089116), ZFHX4 (ENSG00000091656), LHX2 (ENSG00000106689), LHX6 (ENSG00000106852), LHX3 (ENSG00000107187), LHX4 (ENSG00000121454), LMO2 (ENSG00000135363), ZFHX2 (ENSG00000136367), LMX1B (ENSG00000136944), LMO4 (ENSG00000143013), LHX9 (ENSG00000143355), CRIP3 (ENSG00000146215), LHX8 (ENSG00000162624), LMX1A (ENSG00000162761), LMO1 (ENSG00000166407), CRIP2 (ENSG00000182809), CRIP1 (ENSG00000213145), LHX1 (ENSG00000273706)

Protein

Protein identifiers

Zinc finger homeobox protein 3 — Q15911 (reviewed: Q15911)

Alternative names: AT motif-binding factor 1, AT-binding transcription factor 1, Alpha-fetoprotein enhancer-binding protein, Zinc finger homeodomain protein 3

All UniProt accessions (1): Q15911

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional regulator which can act as an activator or a repressor. Inhibits the enhancer element of the AFP gene by binding to its AT-rich core sequence. In concert with SMAD-dependent TGF-beta signaling can repress the transcription of AFP via its interaction with SMAD2/3. Regulates the circadian locomotor rhythms via transcriptional activation of neuropeptidergic genes which are essential for intercellular synchrony and rhythm amplitude in the suprachiasmatic nucleus (SCN) of the brain. Regulator of myoblasts differentiation through the binding to the AT-rich sequence of MYF6 promoter and promoter repression. Down-regulates the MUC5AC promoter in gastric cancer. In association with RUNX3, up-regulates CDKN1A promoter activity following TGF-beta stimulation. Inhibits estrogen receptor (ESR1) function by selectively competing with coactivator NCOA3 for binding to ESR1 in ESR1-positive breast cancer cells.

Subunit / interactions. Interacts with FNBP3. Interacts with ALKBH4 and PIAS3. Interacts with ESR1. Interacts with RUNX3. Interacts with TRIM25. Interacts with SMAD2 and SMAD3.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Not found in normal gastric mucosa but found in gastric carcinoma cells (at protein level). Expression is higher in ER-positive breast tumors than ER-negative breast tumors (at protein level).

Post-translational modifications. Hyperphosphorylation protects ZFHX3 from calpain/CAPN1-mediated degradation. Ubiquitinated, leading to its proteasomal degradation. Nuclear localization is essential for its sumoylation.

Disease relevance. Atrial fibrillation, familial, 8 (ATFB8) [MIM:613055] A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure. Disease susceptibility is associated with variants affecting the gene represented in this entry. An intronic C-to-A transversion (rs12931021) correlates with decreased ZFHX3 expression and increased risk of atrial fibrillation. Spinocerebellar ataxia 4 (SCA4) [MIM:600223] A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA4 is characterized by the onset of balance disturbances and gait and limb ataxia usually in the fourth decade, although earlier onset in the teens or twenties has been reported. There is evidence of genetic anticipation within families. Inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry. SCA4 is caused by heterozygous triplet repeat expansions in the poly-Gly tract. Affected individuals have expansions ranging from 42 to 74 repeats, while the number of repeats ranges from 14 to 26 in the general population. Patient-derived cells have increased ZFHX3 protein levels and show features of abnormal autophagy.

Polymorphism. The poly-Gly region is polymorphic due to GGC triplet repeat expansions ranging from 14 to 26 repeats in the general population.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15911-1	A	yes
Q15911-2	B

RefSeq proteins (3): NP_001158238, NP_001373664, NP_008816* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR003604	Matrin/U1-like-C_Znf_C2H2	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR013087	Znf_C2H2_type	Domain
IPR017970	Homeobox_CS	Conserved_site
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR051968	ZnFinger_Homeobox_TR	Family

Pfam: PF00046, PF00096, PF24056

UniProt features (129 total): compositionally biased region 30, zinc finger region 23, region of interest 20, modified residue 16, sequence variant 10, helix 9, sequence conflict 5, mutagenesis site 4, DNA-binding region 4, cross-link 4, chain 1, turn 1, short sequence motif 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
2DA1	SOLUTION NMR
2DA2	SOLUTION NMR
2DA3	SOLUTION NMR

Predicted structure (AlphaFold)

No AlphaFold model available for Q15911 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

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 (20): 426, 428, 533, 571, 1197, 1204, 1590, 2625, 2786, 2795, 2892, 2896, 3409, 3432, 3593, 3677, 2349, 2806, 2806, 3258

Mutagenesis-validated functional residues (4):

Position	Phenotype
2349	loss of sumoylation.
2615–2617	loss of nuclear localization.
2806	loss of sumoylation.
3258	loss of sumoylation.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8941855	RUNX3 regulates CDKN1A transcription

MSigDB gene sets: 450 (showing top): GOBP_CIRCADIAN_RHYTHM, CREL_01, FREAC2_01, BENPORATH_ES_WITH_H3K27ME3, GOBP_BEHAVIOR, chr16q22, GCANCTGNY_MYOD_Q6, SP3_Q3, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_NEUROGENESIS, RACCACAR_AML_Q6, GOBP_CIRCADIAN_REGULATION_OF_GENE_EXPRESSION, CACCAGC_MIR138, COUP_01, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION

GO Biological Process (13): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), muscle organ development (GO:0007517), circadian regulation of gene expression (GO:0032922), negative regulation of myoblast differentiation (GO:0045662), positive regulation of myoblast differentiation (GO:0045663), regulation of neuron differentiation (GO:0045664), positive regulation of cell adhesion (GO:0045785), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), response to transforming growth factor beta (GO:0071559), regulation of locomotor rhythm (GO:1904059)

GO Molecular Function (11): transcription cis-regulatory region binding (GO:0000976), 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 repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), enzyme binding (GO:0019899), nucleic acid binding (GO:0003676), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), cytoplasm (GO:0005737), nuclear body (GO:0016604)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Transcriptional regulation by RUNX3	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
DNA-templated transcription	2
regulation of gene expression	2
myoblast differentiation	2
regulation of myoblast differentiation	2
binding	2
negative regulation of DNA-templated transcription	1
regulation of RNA biosynthetic process	1
animal organ development	1
muscle structure development	1
circadian rhythm	1
negative regulation of cell differentiation	1
positive regulation of cell differentiation	1
neuron differentiation	1
regulation of cell differentiation	1
cell adhesion	1
regulation of cell adhesion	1
positive regulation of cellular process	1
positive regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
response to growth factor	1
regulation of circadian rhythm	1
locomotor rhythm	1
regulation of behavior	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
transition metal ion binding	1
protein binding	1

Protein interactions and networks

STRING

1496 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZFHX3	POU1F1	P28069	848
ZFHX3	PITX2	Q99697	720
ZFHX3	KCNN3	Q9UGI6	717
ZFHX3	PIAS3	Q9Y6X2	712
ZFHX3	SYNPO2L	Q9H987	692
ZFHX3	TBX3	O15119	635
ZFHX3	TSHB	P01222	588
ZFHX3	ATM	Q13315	579
ZFHX3	KMT2C	Q8NEZ4	575
ZFHX3	RUNX3	Q13761	571
ZFHX3	SLC20A2	Q08357	549
ZFHX3	NKX2-5	P52952	537
ZFHX3	CUX2	O14529	531
ZFHX3	PRRX1	P54821	527
ZFHX3	NAALADL2	Q58DX5	525

IntAct

33 interactions, top by confidence:

A	B	Type	Score
SYNGAP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
TRPS1	MTA2	psi-mi:“MI:0914”(association)	0.530
ZFHX3	ALKBH4	psi-mi:“MI:0915”(physical association)	0.370
WRAP53	STK24	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
MYC		psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	POM121C	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	POTEF	psi-mi:“MI:0914”(association)	0.350
ZFHX3	CCS	psi-mi:“MI:0914”(association)	0.350
ZFHX3	TRAF7	psi-mi:“MI:0914”(association)	0.350
FEV	TAF4	psi-mi:“MI:2364”(proximity)	0.270
FOXL1	PGRMC1	psi-mi:“MI:2364”(proximity)	0.270
GATA2	BCL9	psi-mi:“MI:2364”(proximity)	0.270
HNF1B	BCL9	psi-mi:“MI:2364”(proximity)	0.270
LHX2	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
NFIX	TAF4	psi-mi:“MI:2364”(proximity)	0.270
PAX6	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
PAX7	BCL9	psi-mi:“MI:2364”(proximity)	0.270
PAX9	BCL9	psi-mi:“MI:2364”(proximity)	0.270
SOX2	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
SOX5	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
SOX6	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
TBR1	BCL9	psi-mi:“MI:2364”(proximity)	0.270
TEAD1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
TLX1	BCL9	psi-mi:“MI:2364”(proximity)	0.270
TLX2	IGF2BP3	psi-mi:“MI:2364”(proximity)	0.270
TLX3	BCL9	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (120): KRT40 (Two-hybrid), NINL (Two-hybrid), ZFHX3 (Affinity Capture-MS), ZFHX3 (Reconstituted Complex), ZFHX3 (Affinity Capture-RNA), ZFHX3 (Two-hybrid), ZFHX3 (Affinity Capture-RNA), ZFHX3 (Two-hybrid), ZFHX3 (Affinity Capture-MS), ZFHX3 (Affinity Capture-MS), ZFHX3 (Affinity Capture-MS), ZFHX3 (Affinity Capture-MS), ZFHX3 (Affinity Capture-MS), ZFHX3 (Affinity Capture-RNA), ZFHX3 (Affinity Capture-MS)

ESM2 similar proteins: A0A5E4M3Q4, A0JPB4, A1L1R6, A1Z9R4, A4IFJ6, B0X9H6, G5EBU4, G5EFF4, M9PBE2, O08900, O08961, O13089, O62537, O62538, O62541, O73590, P05084, P07247, P08155, P13361, P17789, P22265, P23803, P25932, P28166, P34303, P42282, Q01778, Q05192, Q15911, Q22024, Q2M1K9, Q59E55, Q5T0B9, Q61329, Q6DBW0, Q7M3M8, Q80TS5, Q86UP3, Q8I7Z8

Diamond homologs: A0A1L8FFY5, A0A1W2PPF3, A0JNI8, A1L0Z1, A1L2U9, A2PZF9, B0XS89, B1WAZ8, B1WBU4, G5EBU4, G5EC36, G5EE86, G5EEA1, O60315, O62836, O73590, P08048, P09088, P10925, P17010, P17012, P20154, P20662, P20912, P28166, P29674, P31362, P31363, P34764, P34765, P36197, P36198, P36200, P37137, P37275, P42571, P48742, P49335, P50458, P52739

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
ZFHX3	“down-regulates quantity by repression”	AFP	“transcriptional regulation”
TRIM25	“down-regulates quantity by destabilization”	ZFHX3	polyubiquitination
ATM	“up-regulates activity”	ZFHX3	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 40 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.

GO biological processes:

GO term	Partners	Fold	FDR
transcription by RNA polymerase II	8	14.8×	8e-06
chromatin remodeling	6	11.5×	6e-04
brain development	5	10.5×	3e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 10 cancer types — BLCA, BRCA, DLBCLNOS, HCC, OS, PCM, PRAD, UCEC, VULVA, WDTC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	16
Uncertain significance	635
Likely benign	137
Benign	88

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
2671874	NM_006885.4:c.10519GGC[42-74]	Pathogenic
2828030	NM_006885.4(ZFHX3):c.3512dup (p.Asp1172fs)	Pathogenic
3390581	NM_006885.4(ZFHX3):c.3628C>T (p.Arg1210Ter)	Pathogenic
3473192	NM_006885.4(ZFHX3):c.5497G>T (p.Glu1833Ter)	Pathogenic
3724519	NM_006885.4(ZFHX3):c.5179C>T (p.Gln1727Ter)	Pathogenic
4082602	NM_006885.4(ZFHX3):c.10231_10234del (p.Asp3411fs)	Pathogenic
4082882	NM_006885.4(ZFHX3):c.709C>T (p.Arg237Ter)	Pathogenic
4205117	NM_006885.4(ZFHX3):c.3767del (p.Leu1256fs)	Pathogenic
4531619	NM_006885.4(ZFHX3):c.4132C>T (p.Gln1378Ter)	Pathogenic
4607405	NM_006885.4(ZFHX3):c.314dup (p.Pro106fs)	Pathogenic
4607406	NM_006885.4(ZFHX3):c.5689G>T (p.Glu1897Ter)	Pathogenic
4607413	NM_006885.4(ZFHX3):c.2095_2096delinsTGC (p.Gly699fs)	Pathogenic
4607420	NM_006885.4(ZFHX3):c.1604T>A (p.Leu535Ter)	Pathogenic
4607423	NM_006885.4(ZFHX3):c.5512C>T (p.Gln1838Ter)	Pathogenic
4759510	NM_006885.4(ZFHX3):c.10853C>A (p.Pro3618Gln)	Pathogenic
4759512	NM_006885.4(ZFHX3):c.4122TGC[1] (p.Ala1376del)	Pathogenic
4759513	NM_006885.4(ZFHX3):c.10455G>T (p.Lys3485Asn)	Pathogenic
4814234	NM_006885.4(ZFHX3):c.2655del (p.Gln885fs)	Pathogenic
4827743	NM_006885.4(ZFHX3):c.7768_7783del (p.Ser2590fs)	Pathogenic
4828860	NM_006885.4(ZFHX3):c.3646G>T (p.Glu1216Ter)	Pathogenic
58646	GRCh38/hg38 16q22.1-24.3(chr16:70514631-90081985)x3	Pathogenic
1805305	NM_006885.4(ZFHX3):c.3355C>T (p.Arg1119Ter)	Likely pathogenic
1805351	NM_006885.4(ZFHX3):c.6040C>T (p.Gln2014Ter)	Likely pathogenic
1805363	NM_006885.4(ZFHX3):c.5749G>T (p.Glu1917Ter)	Likely pathogenic
1805417	NM_006885.4(ZFHX3):c.8002C>T (p.Arg2668Ter)	Likely pathogenic
2536717	NM_006885.4(ZFHX3):c.5858G>T (p.Gly1953Val)	Likely pathogenic
3346537	NM_006885.4(ZFHX3):c.2287dup (p.Glu763fs)	Likely pathogenic
3349897	NM_006885.4(ZFHX3):c.5697dup (p.Glu1900fs)	Likely pathogenic
3372126	NM_006885.4(ZFHX3):c.4834G>T (p.Glu1612Ter)	Likely pathogenic
3376146	NM_006885.4(ZFHX3):c.2143C>T (p.Arg715Ter)	Likely pathogenic

SpliceAI

3806 predictions. Top by Δscore:

Variant	Effect	Δscore
16:72800018:GATAC:G	donor_loss	1.0000
16:72800023:TGA:T	donor_loss	1.0000
16:72800024:GA:G	donor_loss	1.0000
16:72800025:A:AC	donor_gain	1.0000
16:72800025:A:C	donor_loss	1.0000
16:72800026:C:A	donor_loss	1.0000
16:72800026:C:CC	donor_gain	1.0000
16:72800026:CCAGG:C	donor_gain	1.0000
16:72800037:T:A	donor_gain	1.0000
16:72800127:CAC:C	acceptor_gain	1.0000
16:72800128:ACC:A	acceptor_loss	1.0000
16:72800129:CCT:C	acceptor_loss	1.0000
16:72800130:C:CC	acceptor_gain	1.0000
16:72811575:A:AC	donor_gain	1.0000
16:72811576:C:A	donor_loss	1.0000
16:72811576:C:CC	donor_gain	1.0000
16:72811576:CCGT:C	donor_gain	1.0000
16:72811773:TACAT:T	acceptor_gain	1.0000
16:72811775:CAT:C	acceptor_gain	1.0000
16:72811776:AT:A	acceptor_gain	1.0000
16:72811777:TC:T	acceptor_loss	1.0000
16:72811778:C:CC	acceptor_gain	1.0000
16:72811778:CTGTG:C	acceptor_loss	1.0000
16:72811900:CTCA:C	donor_loss	1.0000
16:72811902:CA:C	donor_loss	1.0000
16:72811904:C:CT	donor_loss	1.0000
16:72811904:CCTG:C	donor_gain	1.0000
16:72812034:CGATG:C	acceptor_gain	1.0000
16:72812038:GC:G	acceptor_loss	1.0000
16:72812039:C:CA	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000001239 (16:73488245 G>A,T), RS1000003746 (16:73417005 C>A), RS1000004466 (16:73596429 T>A), RS1000007754 (16:72810231 G>A,C), RS1000016393 (16:73429649 T>C), RS1000017442 (16:72938695 T>C), RS1000018870 (16:73519881 T>G), RS1000019595 (16:72971839 T>A), RS1000021503 (16:72832411 A>G), RS1000027624 (16:73693826 C>T), RS1000030201 (16:73181043 G>A), RS1000033090 (16:73424886 T>A), RS1000035948 (16:73497107 C>G,T), RS1000036416 (16:73620137 A>G,T), RS1000038237 (16:73006779 G>A)

Disease associations

OMIM: gene MIM:104155 | disease phenotypes: MIM:621500, MIM:613055, MIM:600223, MIM:308350, MIM:176807

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Definitive	Autosomal dominant
spinocerebellar ataxia type 4	Strong	Autosomal dominant
genetic developmental and epileptic encephalopathy	Strong	Autosomal recessive
neurodevelopmental disorder	Strong	Autosomal dominant
syndromic complex neurodevelopmental disorder	Strong	Autosomal dominant
epilepsy	Limited	Autosomal recessive

Mondo (12): neurodevelopmental disorder (MONDO:0700092), epilepsy, idiopathic generalized 20 (MONDO:0980988), autism spectrum disorder (MONDO:0005258), atrial fibrillation, familial, 8 (MONDO:0013100), spinocerebellar ataxia type 4 (MONDO:0010847), intellectual disability (MONDO:0001071), genetic developmental and epileptic encephalopathy (MONDO:0100062), prostate cancer, hereditary (MONDO:0700275), syndromic intellectual disability (MONDO:0000508), epilepsy (MONDO:0005027), complex neurodevelopmental disorder (MONDO:0100038), syndromic complex neurodevelopmental disorder (MONDO:0800439)

Orphanet (6): Spinocerebellar ataxia type 4 (Orphanet:98765), Familial prostate cancer (Orphanet:1331), Rare genetic syndromic intellectual disability (Orphanet:183763), Moyamoya angiopathy (Orphanet:477768), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

15 total (15 of 15 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000763	Sensory neuropathy
HP:0001260	Dysarthria
HP:0001265	Hyporeflexia
HP:0001272	Cerebellar atrophy
HP:0001284	Areflexia
HP:0001442	Typified by somatic mosaicism
HP:0002073	Progressive cerebellar ataxia
HP:0002406	Limb dysmetria
HP:0002936	Distal sensory impairment
HP:0003487	Babinski sign
HP:0003581	Adult onset
HP:0005110	Atrial fibrillation
HP:0007772	Impaired smooth pursuit
HP:0012125	Prostate cancer

GWAS associations

61 associations (top):

Study	Trait	p-value
GCST000266_7	Multiple sclerosis (severity)	6.000000e-06
GCST000314_1	Kawasaki disease	2.000000e-06
GCST000445_1	Atrial fibrillation	2.000000e-15
GCST000446_2	Atrial fibrillation	1.000000e-10
GCST000975_5	LDL cholesterol	5.000000e-06
GCST001499_3	Atrial fibrillation	3.000000e-16
GCST001639_34	Metabolite levels	7.000000e-12
GCST001706_5	Stroke (ischemic)	2.000000e-08
GCST002563_18	Hypospadias	1.000000e-18
GCST003084_10	Glucocorticoid-induced osteonecrosis	1.000000e-06
GCST003257_2	Ischemic stroke (cardioembolic)	2.000000e-10
GCST003992_14	Photic sneeze reflex	4.000000e-09
GCST004286_7	Midgestational circulating levels of PBDEs (fetal genetic effect)	2.000000e-07
GCST004295_10	Atrial fibrillation	8.000000e-32
GCST004296_8	Atrial fibrillation	1.000000e-14
GCST004297_20	Atrial fibrillation	4.000000e-24
GCST004300_5	Incident atrial fibrillation	4.000000e-08
GCST004301_4	Prevalent atrial fibrillation	1.000000e-19
GCST004352_6	Early onset atrial fibrillation	3.000000e-30
GCST004373_19	Atrial fibrillation	1.000000e-35
GCST004904_122	Body mass index	3.000000e-09
GCST004904_5	Body mass index	3.000000e-08
GCST006061_161	Atrial fibrillation	3.000000e-100
GCST006061_162	Atrial fibrillation	2.000000e-76
GCST006110_7	Nose morphology	8.000000e-06
GCST006146_3	Behavioural changes in frontotemporal lobe dementia	7.000000e-06
GCST006414_31	Atrial fibrillation	5.000000e-91
GCST006414_44	Atrial fibrillation	7.000000e-09
GCST006483_40	Lung function (FVC)	6.000000e-10
GCST006483_41	Lung function (FVC)	8.000000e-06

EFO canonical traits (20, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004723	coronary artery calcification
EFO:1001493	cardiac embolism
EFO:0007887	autosomal dominant compelling helio-ophthalmic outburst syndrome
EFO:0007959	fetal genotype effect measurement
EFO:0007961	polybrominated biphenyl measurement
EFO:0007962	polybrominated diphenyl ether measurement
EFO:0007964	gestational serum measurement
EFO:0004340	body mass index
EFO:0004312	vital capacity
EFO:0009270	heel bone mineral density
EFO:0008579	risk-taking behaviour
EFO:0004318	smoking behavior
EFO:0008328	chronotype measurement
EFO:0007820	cognitive behavioural therapy
EFO:0010390	sphingomyelin 14:0 measurement
EFO:1001976	cardioembolic stroke
EFO:0006919	cardiovascular event measurement
EFO:0004346	neuroimaging measurement
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
C567802	Atrial Fibrillation, Familial, 8 (supp.)
C537243	Prostate cancer, familial (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression, decreases methylation	7
Benzo(a)pyrene	affects methylation, decreases expression	5
trichostatin A	affects cotreatment, increases expression	3
entinostat	decreases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Aflatoxin B1	affects methylation, decreases methylation	2
aristolochic acid I	decreases expression	1
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
terbufos	increases methylation	1
arsenite	increases methylation	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	increases expression	1
coumarin	affects phosphorylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects 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
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
bisphenol S	decreases methylation	1
Resveratrol	affects cotreatment, decreases expression	1
Troglitazone	increases expression	1
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1
Cadmium	decreases expression, increases abundance	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E3GB	HCI-EC-23	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	PHASE4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	PHASE4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	PHASE4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	PHASE4	COMPLETED	RNS® System LTT Study
NCT00610532	PHASE4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357	PHASE4	COMPLETED	Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630	PHASE4	COMPLETED	Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968	PHASE4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150	PHASE4	COMPLETED	A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958	PHASE4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	PHASE4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989	PHASE4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884	PHASE4	COMPLETED	The Safety of Intravenous Lacosamide
NCT00869622	PHASE4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987	PHASE4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00952081	PHASE4	COMPLETED	A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients
NCT01118455	PHASE4	TERMINATED	Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures
NCT01127165	PHASE4	COMPLETED	Low and High Dose Zonisamide in Children as Monotherapy
NCT01127256	PHASE4	COMPLETED	Comparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation
NCT01140867	PHASE4	COMPLETED	Open-label, Multi-center Trial of Zonisamide as Adjunctive Therapy in Patients With Uncontrolled Partial Epilepsy
NCT01175954	PHASE4	COMPLETED	Cognitive and Behavioral Effects of Lacosamide
NCT01229735	PHASE4	COMPLETED	Levetiracetam Versus Topiramate as Adjunctive Therapy to Evaluate Efficacy and Safety in Subjects With Refractory Partial Onset Seizures
NCT01244724	PHASE4	TERMINATED	Lexapro for Major Depression in Patients With Epilepsy