TCF12

Summary

TCF12 (transcription factor 12, HGNC:11623) is a protein-coding gene on chromosome 15q21.3, encoding Transcription factor 12 (Q99081). Transcriptional regulator. It is haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene is a member of the basic helix-loop-helix (bHLH) E-protein family that recognizes the consensus binding site (E-box) CANNTG. This encoded protein is expressed in many tissues, among them skeletal muscle, thymus, B- and T-cells, and may participate in regulating lineage-specific gene expression through the formation of heterodimers with other bHLH E-proteins. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined.

Source: NCBI Gene 6938 — RefSeq curated summary.

At a glance

• Gene–disease (curated): TCF12-related craniosynostosis (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 13
• Clinical variants (ClinVar): 561 total — 90 pathogenic, 43 likely-pathogenic
• Phenotypes (HPO): 45
• Druggable target: yes
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 2 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 60 downstream targets (CollecTRI)
• MANE Select transcript: NM_207037

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11623
Approved symbol	TCF12
Name	transcription factor 12
Location	15q21.3
Locus type	gene with protein product
Status	Approved
Aliases	HEB, HTF4, HsT17266, bHLHb20, p64
Ensembl gene	ENSG00000140262
Ensembl biotype	protein_coding
OMIM	600480
Entrez	6938

Gene structure

Transcript identifiers

Ensembl transcripts: 55 — 40 protein_coding, 13 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000267811, ENST00000333725, ENST00000343827, ENST00000438423, ENST00000537840, ENST00000543579, ENST00000557843, ENST00000557947, ENST00000558210, ENST00000558908, ENST00000559216, ENST00000559609, ENST00000559703, ENST00000559710, ENST00000560190, ENST00000560191, ENST00000560506, ENST00000560764, ENST00000560836, ENST00000560887, ENST00000560948, ENST00000561152, ENST00000561235, ENST00000561346, ENST00000561420, ENST00000561449, ENST00000561454, ENST00000569880, ENST00000888320, ENST00000888321, ENST00000888322, ENST00000888323, ENST00000888324, ENST00000888325, ENST00000888326, ENST00000888327, ENST00000888328, ENST00000888329, ENST00000888330, ENST00000888331, ENST00000888332, ENST00000934194, ENST00000934195, ENST00000934196, ENST00000934197, ENST00000934198, ENST00000934199, ENST00000945986, ENST00000945987, ENST00000945988, ENST00000945989, ENST00000945990, ENST00000945991, ENST00000945992, ENST00000945993

RefSeq mRNA: 18 — MANE Select: NM_207037 NM_001306219, NM_001306220, NM_001322151, NM_001322152, NM_001322154, NM_001322156, NM_001322157, NM_001322158, NM_001322159, NM_001322161, NM_001322162, NM_001322164, NM_001322165, NM_003205, NM_207036, NM_207037, NM_207038, NM_207040

CCDS: CCDS10159, CCDS10160, CCDS42042, CCDS76760, CCDS76761

Canonical transcript exons

ENST00000333725 — 21 exons

Exon	Start	End
ENSE00001857959	56918644	56918906
ENSE00003473844	57166402	57166466
ENSE00003474900	57192158	57192293
ENSE00003489614	57251350	57251423
ENSE00003503784	57197773	57197825
ENSE00003520324	57253262	57253468
ENSE00003523777	57232291	57232430
ENSE00003524068	57243472	57243550
ENSE00003558492	57232712	57232856
ENSE00003568449	56921026	56921098
ENSE00003569678	57273030	57273262
ENSE00003605283	57263112	57263274
ENSE00003606443	57063750	57063823
ENSE00003621902	57262094	57262208
ENSE00003623588	57231152	57231257
ENSE00003630817	57234043	57234107
ENSE00003635680	57282445	57282598
ENSE00003636796	57252421	57252492
ENSE00003647364	56919892	56919988
ENSE00003651986	57091789	57091891
ENSE00003899694	57286157	57289853

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.2584 / max 723.7019, expressed in 1817 samples.

FANTOM5 promoters (18 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146803	18.3902	1800
146831	11.7229	829
146804	4.3309	1322
146808	1.2798	561
146809	1.1222	605
146830	1.0343	480
146801	0.7411	462
146802	0.7045	434
207531	0.2555	75
146807	0.2418	95

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
periodontal ligament	UBERON:0008266	98.02	gold quality
ventricular zone	UBERON:0003053	97.64	gold quality
ganglionic eminence	UBERON:0004023	97.60	gold quality
hair follicle	UBERON:0002073	97.53	gold quality
colonic epithelium	UBERON:0000397	97.34	gold quality
calcaneal tendon	UBERON:0003701	96.89	gold quality
stromal cell of endometrium	CL:0002255	96.88	gold quality
embryo	UBERON:0000922	96.83	gold quality
endometrium	UBERON:0001295	96.57	gold quality
corpus callosum	UBERON:0002336	96.51	gold quality
adrenal tissue	UBERON:0018303	96.39	gold quality
cranial nerve II	UBERON:0000941	96.01	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.02	gold quality
skin of hip	UBERON:0001554	94.97	gold quality
upper leg skin	UBERON:0004262	94.75	gold quality
mucosa of stomach	UBERON:0001199	94.28	gold quality
gall bladder	UBERON:0002110	94.25	gold quality
endocervix	UBERON:0000458	94.10	gold quality
tendon	UBERON:0000043	93.89	gold quality
uterus	UBERON:0000995	93.85	gold quality
medial globus pallidus	UBERON:0002477	93.39	gold quality
caput epididymis	UBERON:0004358	93.28	gold quality
sural nerve	UBERON:0015488	93.02	gold quality
urinary bladder	UBERON:0001255	92.83	gold quality
globus pallidus	UBERON:0001875	92.81	gold quality
cauda epididymis	UBERON:0004360	92.79	gold quality
rectum	UBERON:0001052	92.73	gold quality
endothelial cell	CL:0000115	92.67	gold quality
body of uterus	UBERON:0009853	92.50	gold quality
ovary	UBERON:0000992	92.48	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-75140	yes	950.89
E-HCAD-35	yes	97.73
E-HCAD-25	yes	50.11
E-GEOD-93593	yes	7.19
E-ANND-3	yes	6.81
E-CURD-112	no	2.59

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

60 targets.

Target	Regulation
ACSL5
ANK3
APEX1
BDNF
CAT
CBFA2T3
CD4	Unknown
CD8A
CDH1	Repression
CDH17
CNTN2
DSP
EIF3K
FGFR1
FN1
GABRB3
GAP43
GNAS
ID2
IFNA1
IFNG
INS
KDM1A
KDM1B
KDM3A
KMT5A
KRT27
KRT9
LCK
LEFTY1	Unknown

JASPAR motifs

Motif	Name	Family
MA1648.1	TCF12	E2A
MA1648.2	TCF12	E2A

JASPAR matrix evidence (PMIDs): PMID:8163514

Upstream regulators (CollecTRI, top): CBFA2T3, MYC, NOTCH1, RUNX1, TCF12, ZNF652

miRNA regulators (miRDB)

300 targeting TCF12, 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-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-559	99.95	72.28	3609

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 40)

• two alternative acceptor sites for mRNA splicing yield two distinguishable transcripts (HTF4a and HTF4b) which differ in their 5’ untranslated region but share identical coding sequences. (PMID:12826747)
• study identifes E proteins(HEB, E2A) as AML1-ETO targets whose dysregulation may be important for t(8;21) leukemogenesis, as well as an E protein silencing mechanism that is distinct from that associated with differentiation-inhibitory proteins (PMID:15333839)
• dHAND/E-protein (E2A, ME2, and ALF1) heterodimers have distinct DNA binding specificities (PMID:15351717)
• CBFA2T3 interacts with ZNF652 to repress HEB expression, and in addition CBFA2T3 interacts with the HEB protein to inhibit its activator function. (PMID:18456661)
• The DNA binding profile of the E-protein HEB was grossly rearranged upon expression of AML1/ETO, and the fusion protein was found to co-localize with both AML1 and HEB on many of its regulated targets (PMID:19043539)
• T cell development is impaired by Id2, most likely by sequestering HEB, whereas NK cell development is promoted by increasing a pool of CD1a-CD5+ NK cell progenitors, which together with IL-15 differentiate into mature NK cells (PMID:20483740)
• As a first exploitation of this unique cohort, we identify three novel candidate dyslexia genes, ZNF280D and TCF12 at 15q21, and PDE7B at 6q23.3, by molecular mapping of the familial translocation with the 15q21 breakpoint. (PMID:20798984)
• HEB and E2A-bind the SCA motif at regions overlapping SMAD2/3 and FOXH1 (PMID:21828274)
• TCF12 functioned as a transcriptional repressor of E-cadherin and its overexpression was significantly correlated with the occurrence of CRC metastasis. (PMID:22130667)
• haploinsufficiency of TCF12 causes coronal synostosis in humans and that severe bilateral coronal synostosis occurs in mice with 50% of the wild-type dosage of both the Tcf12 and Twist1 genes highlights the key role of TCF12 acting with TWIST1. (PMID:23354436)
• the CD91/IKK/NF-kappaB signaling cascade is involved in secreted HSP90alpha-induced TCF12 expression, leading to E-cadherin down-regulation and enhanced CRC cell migration/invasion (PMID:23386606)
• In t(8;21) leukemia cells, the two E proteins, HEB and E2A, function as components of the stable AML1-ETO-containing transcription factor complex (AETFC). The AETFC components cooperatively regulate gene expression and contribute to leukemogenesis. (PMID:23812588)
• Within the AETFC complex, AML1-ETO oligomerization is required for a specific interaction between the oligomerized NHR2 domain and a novel NHR2-binding (N2B) motif in E proteins, including HEB and E2A. Disruption of this interaction by point mutations abrogates AML1-ETO-induced hematopoietic stem/progenitor cell self-renewal and leukemogenesis. (PMID:23812588)
• several familial cases of coronal synostosis associated with mutations in TCF12 (PMID:24736737)
• Studies suggest that transcription factor 12 (TCF12) should be included in level 2 genetic testing. (PMID:25271085)
• show that these mutations compromise TCF12 transcriptional activity and are associated with a more aggressive tumour type (PMID:26068201)
• Two novel translocations leading to the inactivation of RUNX1 and its partners SIN3A and TCF12 in myeloid leukemia. (PMID:26671595)
• HDAC1 promoted migration and invasion of gallbladder tumor cells by binding with TCF12 to promote epithelial mesenchymal transformation. (PMID:27092878)
• Study describes the identification of three large inherited intragenic exon deletions in TCF12 using whole-genome sequencing and one large inherited duplication using targeted TCF12 sequencing in patients with craniosynostosis. (PMID:27158814)
• Heb expression is regulated by Med19 in breast cancer cells. (PMID:27572702)
• HEB may be involved in GBM cell proliferation, as HEB silencing reduced proliferation in cells cultured as monolayers or neurospheres. Furthermore, the results suggested a potential role for HEB in the maintenance of GBM stem cells, as HEB silencing affected the differentiation capacity of cells. (PMID:27779678)
• enforced expression of transcription factor 12 suppressed cell proliferation, migration, and invasion in vitro and inhibited tumor growth in vivo. In conclusion, transcription factor 12 protein may be a novel molecule which plays a critical role in prostate cancer progression and patients’ prognosis, suggesting it might be a promising therapeutic target for prostate cancer therapy (PMID:28651494)
• These results identify HEB as a critical regulator of human mesodermal and hematopoietic specification. (PMID:28803914)
• Pathogenic or likely pathogenic variants in non-FGFR genes were identified in 43 individuals, with diagnostic yields of 14% and 15% in retrospective and prospective cohorts, respectively. Variants were identified most frequently in TCF12 (N = 22) and EFNB1 (N = 8), typically in individuals with nonsyndromic coronal craniosynostosis or TWIST1-negative clinically suspected Saethre-Chotzen syndrome. (PMID:29215649)
• directly interacts with AML1-ETO, confers new DNA-binding capacity to the AML1-ETO-containing transcription factor complex, and is essential for leukemogenesis (PMID:30593567)
• The results suggest that TCF12 is a poor prognostic factor of ovarian cancer (PMID:31311684)
• SNHG1/miR-556-5p/TCF12 feedback loop enhances the tumorigenesis of meningioma through Wnt signaling pathway. (PMID:31692066)
• Study demonstrates that TCF12 is a direct target of miR26a, and upregulation of miR26a resulted in TCF12 inhibition in epithelial ovarian cancer (OC) cells. Furthermore, the proliferation, migration and invasion were inhibited and apoptosis was induced by miR26a upregulation in OC cells. These results indicated that miR26a may act as a tumor suppressor in OC, and TCF12 targeting by miR26a. (PMID:31789414)
• Circ_0000388 Exerts Oncogenic Function in Cervical Cancer Cells by Regulating miR-337-3p/TCF12 Axis. (PMID:32119786)
• Proliferation and migration of hepatocellular carcinoma are accelerated by LINC01287 via the miR-559/TCF12 axis. (PMID:32572916)
• TCF12 haploinsufficiency causes autosomal dominant Kallmann syndrome and reveals network-level interactions between causal loci. (PMID:32620954)
• Neurodevelopmental, Cognitive, and Psychosocial Outcomes for Individuals With Pathogenic Variants in the TCF12 Gene and Associated Craniosynostosis. (PMID:33904513)
• miR-218-5p inhibits the malignant progression of glioma via targeting TCF12. (PMID:34121515)
• Long non-coding RNA GLIDR accelerates the tumorigenesis of lung adenocarcinoma by miR-1270/TCF12 axis. (PMID:34369267)
• Evaluation of dental maturity in Muenke syndrome, Saethre-Chotzen syndrome, and TCF12-related craniosynostosis. (PMID:34424951)
• Craniofacial morphology and growth in Muenke syndrome, Saethre-Chotzen syndrome, and TCF12-related craniosynostosis. (PMID:34904178)
• Auricles Anomalies in Patients With a TCF12 Gene Mutation. (PMID:35994750)
• RNA-binding protein DHX9 promotes glioma growth and tumor-associated macrophages infiltration via TCF12. (PMID:36377508)
• Circular RNA hsa_circ_0002938 (circCRIM1) promotes the progression of esophageal squamous cell carcinoma by upregulating transcription factor 12. (PMID:36916930)
• Nuclear Tubulin Enhances CXCR4 Transcription and Promotes Chemotaxis Through TCF12 Transcription Factor in human Hematopoietic Stem Cells. (PMID:37067645)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tcf12	ENSDARG00000004714
mus_musculus	Tcf12	ENSMUSG00000032228
rattus_norvegicus	Tcf12	ENSRNOG00000057754
drosophila_melanogaster	da	FBGN0267821
caenorhabditis_elegans	hlh-2	WBGENE00001949

Paralogs (2): TCF3 (ENSG00000071564), TCF4 (ENSG00000196628)

Protein

Protein identifiers

Transcription factor 12 — Q99081 (reviewed: Q99081)

Alternative names: Class B basic helix-loop-helix protein 20, DNA-binding protein HTF4, E-box-binding protein, Transcription factor HTF-4

All UniProt accessions (9): Q99081, B4DGI9, B4DZP2, F5GY10, H0YML2, H0YNP8, H0YNQ5, H3BNF4, H3BRK2

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional regulator. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5’-CANNTG-3’). May be involved in the functional network that regulates the development of the GnRH axis.

Subunit / interactions. Efficient DNA binding requires dimerization with another bHLH protein. Forms homo- or heterooligomers with myogenin, E12 and ITF2 proteins. Interacts with PTF1A. Interacts with NEUROD2. Interacts with RUNX1T1. Interacts with AML1-MTG8/ETO (via nervy homology region 2 in oligomerized form). Interacts with BHLHA9. Interacts with ZNF652; inhibiting TCF12 transcription factor activity.

Subcellular location. Nucleus.

Tissue specificity. Expressed in several tissues and cell types including skeletal muscle, thymus, and a B-cell line.

Disease relevance. Craniosynostosis 3 (CRS3) [MIM:615314] A primary abnormality of skull growth involving premature fusion of one or more cranial sutures. The growth velocity of the skull often cannot match that of the developing brain resulting in an abnormal head shape and, in some cases, increased intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability. The disease is caused by variants affecting the gene represented in this entry. Hypogonadotropic hypogonadism 26 with or without anosmia (HH26) [MIM:619718] A form of hypogonadotropic hypogonadism, a group of disorders characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone, and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). HH26 is characterized by micropenis and cryptorchidism at birth in male patients, and absent puberty and anosmia in male or female patients. Some affected individuals also exhibit craniosynostosis. Inheritance can be autosomal dominant or autosomal recessive. 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.

Induction. Expression is repressed by ZNF652 and CBFA2T3.

Isoforms (4)

UniProt ID	Names	Canonical?
Q99081-1	1, a	yes
Q99081-2	2, b
Q99081-3	3, c
Q99081-4	4

RefSeq proteins (18): NP_001293148, NP_001293149, NP_001309080, NP_001309081, NP_001309083, NP_001309085, NP_001309086, NP_001309087, NP_001309088, NP_001309090, NP_001309091, NP_001309093, NP_001309094, NP_003196, NP_996919, NP_996920, NP_996921, NP_996923 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011598	bHLH_dom	Domain
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily
IPR051098	NeuroDiff_E-box_TFs	Family

Pfam: PF00010

UniProt features (60 total): compositionally biased region 16, modified residue 11, region of interest 9, cross-link 6, splice variant 5, sequence variant 4, mutagenesis site 3, chain 1, domain 1, short sequence motif 1, sequence conflict 1, helix 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4JOL	X-RAY DIFFRACTION	2.91
2KNH	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99081-F1	51.13	0.11

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 (17): 47, 67, 79, 98, 116, 313, 333, 540, 557, 558, 559, 110, 181, 519, 550, 609, 653

Mutagenesis-validated functional residues (3):

Position	Phenotype
187	decreases interaction with runx1t1.
191	decreases interaction with runx1t1.
192	decreases interaction with runx1t1.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-525793	Myogenesis
R-HSA-8939236	RUNX1 regulates transcription of genes involved in differentiation of HSCs
R-HSA-9031628	NGF-stimulated transcription
R-HSA-9764725	Negative Regulation of CDH1 Gene Transcription
R-HSA-9839394	TGFBR3 expression
R-HSA-9943411	CHD1 and CHD2 subfamily

MSigDB gene sets: 584 (showing top): AGGAAGC_MIR5163P, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, TAATAAT_MIR126, GAANYNYGACNY_UNKNOWN, NKX25_02, GCANCTGNY_MYOD_Q6, GOBP_POSITIVE_REGULATION_OF_NEURON_DIFFERENTIATION, MORF_ATRX, RIZ_ERYTHROID_DIFFERENTIATION_CCNE1, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, TATTATA_MIR374, GOBP_NEUROGENESIS, RACCACAR_AML_Q6, TAL1ALPHAE47_01, HNF1_Q6

GO Biological Process (11): regulation of transcription by RNA polymerase II (GO:0006357), immune response (GO:0006955), nervous system development (GO:0007399), muscle organ development (GO:0007517), gene expression (GO:0010467), positive regulation of gene expression (GO:0010628), cell differentiation (GO:0030154), positive regulation of neuron differentiation (GO:0045666), positive regulation of transcription by RNA polymerase II (GO:0045944), response to gonadotropin-releasing hormone (GO:0097210), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (17): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), cis-regulatory region sequence-specific DNA binding (GO:0000987), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), cAMP response element binding (GO:0035497), bHLH transcription factor binding (GO:0043425), SMAD binding (GO:0046332), protein heterodimerization activity (GO:0046982), E-box binding (GO:0070888), HMG box domain binding (GO:0071837), DNA-binding transcription factor binding (GO:0140297), sequence-specific double-stranded DNA binding (GO:1990837), transcription cis-regulatory region binding (GO:0000976), DNA binding (GO:0003677), protein binding (GO:0005515), protein dimerization activity (GO:0046983)

GO Cellular Component (7): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), cytoplasm (GO:0005737), nuclear speck (GO:0016607), RNA polymerase II transcription regulator complex (GO:0090575)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Developmental Biology	1
Transcriptional regulation by RUNX1	1
Nuclear Events (kinase and transcription factor activation)	1
Regulation of CDH1 Gene Transcription	1
Signaling by TGFBR3	1
CHD chromatin remodelers	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
transcription cis-regulatory region binding	2
RNA polymerase II cis-regulatory region sequence-specific DNA binding	2
protein binding	2
immune system process	1
response to stimulus	1
system development	1
animal organ development	1
muscle structure development	1
macromolecule biosynthetic process	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
cellular developmental process	1
neuron differentiation	1
positive regulation of cell differentiation	1
regulation of neuron differentiation	1
positive regulation of DNA-templated transcription	1
response to peptide hormone	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	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
positive regulation of transcription by RNA polymerase II	1
transcription regulator activity	1
DNA-binding transcription factor binding	1
protein dimerization activity	1
protein domain specific binding	1
transcription factor binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1

Protein interactions and networks

STRING

1542 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TCF12	TAL1	P17542	900
TCF12	TAF15	Q92804	835
TCF12	NR4A3	Q92570	816
TCF12	MYOG	P15173	788
TCF12	TWIST1	Q15672	767
TCF12	RUNX1	Q01196	758
TCF12	TCF21	O43680	753
TCF12	MYOD1	P15172	752
TCF12	RUNX1T1	Q06455	747
TCF12	NEUROD1	Q13562	730
TCF12	EWSR1	Q01844	704
TCF12	HDAC1	Q13547	703
TCF12	MYC	P01106	690
TCF12	NR4A2	P43354	673
TCF12	LDB1	Q86U70	662

IntAct

207 interactions, top by confidence:

A	B	Type	Score
SGF29	NDC80	psi-mi:“MI:0914”(association)	0.840
TCF12	TAL1	psi-mi:“MI:0915”(physical association)	0.830
NEUROG3	TCF12	psi-mi:“MI:0915”(physical association)	0.800
TCF12	NEUROG3	psi-mi:“MI:0915”(physical association)	0.800
ID2	TCF4	psi-mi:“MI:0914”(association)	0.800
ID2	TCF12	psi-mi:“MI:0915”(physical association)	0.750
ID3	TCF12	psi-mi:“MI:0915”(physical association)	0.740
TCF12	HEXIM2	psi-mi:“MI:0915”(physical association)	0.740
TCF12	ID3	psi-mi:“MI:0915”(physical association)	0.740
HEXIM2	TCF12	psi-mi:“MI:0915”(physical association)	0.740
HEXIM2	AHCYL1	psi-mi:“MI:0914”(association)	0.740
TAL1	TCF4	psi-mi:“MI:0914”(association)	0.690
TCF12	PSMA1	psi-mi:“MI:0915”(physical association)	0.670
CDKN2C	TCF12	psi-mi:“MI:0915”(physical association)	0.670
TCF12	QARS1	psi-mi:“MI:0915”(physical association)	0.670
TCF12	ASCL4	psi-mi:“MI:0915”(physical association)	0.670
TCF12	TWIST2	psi-mi:“MI:0915”(physical association)	0.670
TCF12	SPG21	psi-mi:“MI:0915”(physical association)	0.670
OSGIN1	TCF12	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (229): TCF12 (Two-hybrid), TCF12 (Two-hybrid), TCF12 (Two-hybrid), TCF12 (Two-hybrid), TCF12 (Two-hybrid), TCF12 (Two-hybrid), TCF12 (Two-hybrid), TCF12 (Two-hybrid), TSNAX (Two-hybrid), STK16 (Two-hybrid), MAPKBP1 (Two-hybrid), ARMC8 (Two-hybrid), EDRF1 (Two-hybrid), CRCP (Two-hybrid), OSGIN1 (Two-hybrid)

ESM2 similar proteins: A0A087WPF7, A0A0R4IBL7, O09000, O54972, O70305, O75081, O75376, P15806, P15881, P15884, P15923, P21677, P30985, P51514, P98180, Q05AQ8, Q14157, Q14687, Q1LY51, Q2VPM4, Q3U3C9, Q4KKX4, Q4VCS5, Q566L4, Q5F3B1, Q5SFM8, Q5T6F2, Q60722, Q60974, Q61286, Q62655, Q6DIH5, Q7ZWN6, Q7ZXS3, Q80X50, Q86YP4, Q8BZ47, Q8CHY6, Q8IXK0, Q8VHG2

Diamond homologs: A0A0R4IBL7, G5EEG9, P11420, P15806, P15881, P15884, P15923, P21677, P30985, P51514, P98180, Q01978, Q28772, Q60420, Q60722, Q61286, Q62655, Q90683, Q91605, Q99081

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
NOTCH1	“up-regulates quantity by expression”	TCF12	“transcriptional regulation”
TCF12	“up-regulates quantity by expression”	NOTCH3	“transcriptional regulation”
TCF12	“up-regulates quantity by expression”	PTCRA	“transcriptional regulation”
TCF12	“form complex”	MYOD/HEB	binding
ID1	“down-regulates activity”	TCF12	binding
ID2	“down-regulates activity”	TCF12	binding
ID3	“down-regulates activity”	TCF12	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 121 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
TGFBR3 expression	5	31.3×	2e-04
Myogenesis	5	26.1×	2e-04
Signaling by TGFBR3	5	25.2×	2e-04
Gastrulation	5	17.8×	8e-04
Somitogenesis	5	16.0×	1e-03
Signaling by TGFB family members	7	11.1×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
developmental process	6	36.8×	2e-06
negative regulation of osteoblast differentiation	7	18.8×	1e-05
skeletal muscle cell differentiation	6	18.8×	1e-04
forebrain development	5	16.0×	2e-03
positive regulation of neuron differentiation	6	10.8×	2e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 2 cancer types — GBM, LGGNOS.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	90
Likely pathogenic	43
Uncertain significance	255
Likely benign	85
Benign	49

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1013375	NM_207037.2(TCF12):c.662dup (p.Ala222fs)	Pathogenic
1064628	NM_207037.2(TCF12):c.1261-3C>G	Pathogenic
1077132	NM_207037.2(TCF12):c.207del (p.Tyr70fs)	Pathogenic
1176991	NM_207037.2(TCF12):c.998C>G (p.Ser333Ter)	Pathogenic
1203498	NM_207037.2(TCF12):c.1267C>T (p.Arg423Ter)	Pathogenic
127269	NM_207037.2(TCF12):c.1000_1001del (p.Gln334fs)	Pathogenic
127270	NM_207037.2(TCF12):c.1071del (p.Ser358fs)	Pathogenic
127271	NM_207037.2(TCF12):c.1366dup (p.Ile456fs)	Pathogenic
1301270	NM_207037.2(TCF12):c.1882T>C (p.Cys628Arg)	Pathogenic
1328799	NM_207037.2(TCF12):c.825+1G>A	Pathogenic
1335906	NM_207037.2(TCF12):c.826-2A>G	Pathogenic
1335907	NM_207037.2(TCF12):c.1528dup (p.Thr510fs)	Pathogenic
1335908	NM_207037.2(TCF12):c.1270dup (p.Met424fs)	Pathogenic
1335909	NM_207037.2(TCF12):c.596dup (p.Asn200fs)	Pathogenic
1335910	NM_207037.2(TCF12):c.445del (p.Ser149fs)	Pathogenic
1344584	NM_207037.2(TCF12):c.1643_1647del (p.Glu548fs)	Pathogenic
1447552	NM_207037.2(TCF12):c.1836dup (p.Arg613fs)	Pathogenic
1678717	NM_207037.2(TCF12):c.1127G>A (p.Trp376Ter)	Pathogenic
1691163	NM_207037.2(TCF12):c.722C>A (p.Ser241Ter)	Pathogenic
1691342	NM_207037.2(TCF12):c.1703_1711del (p.Ser568_Lys571delinsTer)	Pathogenic
1691343	NM_207037.2(TCF12):c.707_710delinsCCC (p.Asp236fs)	Pathogenic
1810542	NM_207037.2(TCF12):c.1495del (p.Ser499fs)	Pathogenic
1955530	NM_207037.2(TCF12):c.1346dup (p.Leu449fs)	Pathogenic
2109165	NM_207037.2(TCF12):c.1180_1181insG (p.His394fs)	Pathogenic
2128244	NM_207037.2(TCF12):c.1804_1805del (p.Arg602fs)	Pathogenic
2152246	NM_207037.2(TCF12):c.1867G>T (p.Glu623Ter)	Pathogenic
2427773	NC_000015.9:g.(?57458580)(57545686_?)del	Pathogenic
2429445	NM_207037.2(TCF12):c.457G>T (p.Gly153Trp)	Pathogenic
2636319	NM_207037.2(TCF12):c.1073C>G (p.Ser358Ter)	Pathogenic
2693285	NM_207037.2(TCF12):c.1589T>A (p.Leu530Ter)	Pathogenic

SpliceAI

6529 predictions. Top by Δscore:

Variant	Effect	Δscore
15:56919959:GAGC:G	donor_gain	1.0000
15:56919984:G:GG	donor_gain	1.0000
15:56919984:GTGCG:G	donor_loss	1.0000
15:56919986:GCG:G	donor_gain	1.0000
15:56919987:CGGTA:C	donor_loss	1.0000
15:56919989:G:GA	donor_loss	1.0000
15:56919989:G:GG	donor_gain	1.0000
15:56919990:T:G	donor_loss	1.0000
15:56921021:TGCA:T	acceptor_loss	1.0000
15:56921022:GCA:G	acceptor_loss	1.0000
15:56921023:CAGAT:C	acceptor_loss	1.0000
15:56921024:A:AG	acceptor_gain	1.0000
15:56921024:A:C	acceptor_loss	1.0000
15:56921024:AGAT:A	acceptor_gain	1.0000
15:56921025:G:A	acceptor_loss	1.0000
15:56921025:G:GA	acceptor_gain	1.0000
15:56921025:GA:G	acceptor_gain	1.0000
15:56921025:GAT:G	acceptor_gain	1.0000
15:56921025:GATG:G	acceptor_gain	1.0000
15:56921025:GATGT:G	acceptor_gain	1.0000
15:56921097:AGGTA:A	donor_loss	1.0000
15:56921099:G:GG	donor_gain	1.0000
15:56921100:T:A	donor_loss	1.0000
15:57063744:TTTTA:T	acceptor_loss	1.0000
15:57063745:TTTA:T	acceptor_loss	1.0000
15:57063746:TTAG:T	acceptor_loss	1.0000
15:57063747:TAGG:T	acceptor_loss	1.0000
15:57063748:AGGT:A	acceptor_loss	1.0000
15:57063822:GA:G	donor_gain	1.0000
15:57063824:G:GG	donor_gain	1.0000

AlphaMissense

4609 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:56919963:T:A	L17Q	1.000
15:56919963:T:C	L17P	1.000
15:56919972:T:A	L20Q	1.000
15:56919972:T:C	L20P	1.000
15:56919975:T:C	L21P	1.000
15:56919980:T:C	F23L	1.000
15:56919981:T:C	F23S	1.000
15:56919981:T:G	F23C	1.000
15:56919982:C:A	F23L	1.000
15:56919982:C:G	F23L	1.000
15:56921029:T:C	F27L	1.000
15:56921031:T:A	F27L	1.000
15:56921031:T:G	F27L	1.000
15:57234100:T:C	L343S	1.000
15:57234100:T:G	L343W	1.000
15:57253293:T:A	L407Q	1.000
15:57253293:T:C	L407P	1.000
15:57253301:G:C	A410P	1.000
15:57253305:T:A	I411N	1.000
15:57253305:T:C	I411T	1.000
15:57253305:T:G	I411S	1.000
15:57253314:T:A	L414Q	1.000
15:57253314:T:C	L414P	1.000
15:57253314:T:G	L414R	1.000
15:57253317:G:C	R415P	1.000
15:57253326:C:A	A418D	1.000
15:57273089:G:C	R578T	1.000
15:57273089:G:T	R578M	1.000
15:57273090:G:C	R578S	1.000
15:57273090:G:T	R578S	1.000

dbSNP variants (sampled 300 via entrez): RS1000016294 (15:56950346 C>T), RS1000016920 (15:57101784 T>C), RS1000035226 (15:56923690 G>T), RS1000042461 (15:57084320 A>G), RS1000048111 (15:57101580 C>T), RS1000051392 (15:57145142 G>A,T), RS1000065570 (15:57064827 A>G), RS1000068184 (15:57028519 C>T), RS1000070929 (15:56955317 C>A,T), RS1000073230 (15:57227244 A>G), RS1000098730 (15:57028251 G>A), RS1000099268 (15:57257144 A>C,G), RS1000105488 (15:56992256 G>A), RS1000112884 (15:57080901 A>G), RS1000123732 (15:57107466 C>T)

Disease associations

OMIM: gene MIM:600480 | disease phenotypes: MIM:615314, MIM:619718, MIM:123100

GenCC curated gene-disease

Disease	Classification	Inheritance
TCF12-related craniosynostosis	Definitive	Autosomal dominant
hypogonadotropic hypogonadism 26 with or without anosmia	Strong	Autosomal dominant
Kallmann syndrome	Strong	Autosomal dominant
isolated plagiocephaly	Supportive	Autosomal dominant
isolated brachycephaly	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
TCF12-related craniosynostosis	Definitive	AD

Mondo (8): TCF12-related craniosynostosis (MONDO:0014128), hypogonadotropic hypogonadism 26 with or without anosmia (MONDO:0030534), craniosynostosis (MONDO:0015469), Kallmann syndrome (MONDO:0018800), intellectual disability (MONDO:0001071), autism spectrum disorder (MONDO:0005258), (MONDO:0018113), (MONDO:0018114)

Orphanet (8): OBSOLETE: Isolated plagiocephaly (Orphanet:35098), Non-syndromic bicoronal craniosynostosis (Orphanet:35099), Craniosynostosis-facial dysmorphism-brachydactyly syndrome (Orphanet:672979), Craniosynostosis (Orphanet:1531), Kallmann syndrome (Orphanet:478), Male infertility with azoospermia or oligozoospermia due to single gene mutation (Orphanet:399805), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

45 total (30 of 45 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000047	Hypospadias
HP:0000054	Micropenis
HP:0000248	Brachycephaly
HP:0000294	Low anterior hairline
HP:0000316	Hypertelorism
HP:0000337	Broad forehead
HP:0000365	Hearing impairment
HP:0000458	Anosmia
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000520	Proptosis
HP:0000689	Dental malocclusion
HP:0000691	Microdontia
HP:0000699	Diastema
HP:0000717	Autism
HP:0000729	Autistic behavior
HP:0000739	Anxiety
HP:0000823	Delayed puberty
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0000954	Single transverse palmar crease
HP:0001156	Brachydactyly
HP:0001249	Intellectual disability
HP:0001338	Partial agenesis of the corpus callosum
HP:0001382	Joint hypermobility
HP:0001822	Hallux valgus
HP:0002516	Increased intracranial pressure

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST004599_177	Mean platelet volume	2.000000e-18
GCST004904_3	Body mass index	2.000000e-08
GCST006065_27	Glaucoma (primary open-angle)	8.000000e-09
GCST006661_89	Male-pattern baldness	1.000000e-09
GCST007328_60	Alcohol consumption (drinks per week)	5.000000e-08
GCST007673_16	3-month functional outcome in ischaemic stroke (modified Rankin score)	4.000000e-06
GCST009379_203	Type 2 diabetes	4.000000e-08
GCST010173_103	Triglyceride levels	7.000000e-09
GCST010204_197	Low density lipoprotein cholesterol levels	4.000000e-17
GCST010243_236	Apolipoprotein B levels	5.000000e-10
GCST010245_37	LDL cholesterol levels	2.000000e-09
GCST90002395_172	Mean platelet volume	6.000000e-33
GCST90011770_69	Glaucoma (primary open-angle)	1.000000e-12

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0009603	stroke outcome severity measurement
EFO:0004530	triglyceride measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004615	apolipoprotein B measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D003398	Craniosynostoses	C05.116.099.370.894.232; C05.660.207.240; C05.660.906.364; C16.131.621.207.240; C16.131.621.906.364
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D017436	Kallmann Syndrome	C12.050.351.875.253.096.750; C12.200.706.316.096.750; C12.800.316.096.750; C16.131.939.316.096.750; C16.320.467; C19.391.119.096.750; C19.391.482.600

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067123 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression, increases stability	5
Benzo(a)pyrene	decreases expression, decreases methylation	4
Valproic Acid	increases expression, decreases expression, increases methylation, affects cotreatment	4
trichostatin A	affects expression, increases expression	2
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment, increases expression	2
Acrolein	affects cotreatment, increases expression, increases oxidation, increases abundance	2
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases expression, increases oxidation	2
Formaldehyde	decreases expression	2
Methotrexate	increases expression, affects response to substance	2
Ozone	affects cotreatment, increases expression, increases oxidation, increases abundance	2
Tretinoin	decreases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases expression, increases oxidation, increases abundance, affects cotreatment	1
bisphenol A	affects methylation, decreases methylation, affects cotreatment	1
geraniol	increases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	decreases expression	1
indirubin	decreases expression	1
coumarin	decreases phosphorylation	1
beta-methylcholine	affects expression	1
dimethylarsinous acid	decreases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Venlafaxine Hydrochloride	decreases expression	1
Irinotecan	decreases expression	1
Resveratrol	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652606	Binding	Binding affinity to human TCF12 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A7B6	SEES3-1V human TCF12, clone1	Embryonic stem cell	Male
CVCL_A7B7	SEES3-1V human TCF12, clone2	Embryonic stem cell	Male
CVCL_A7B8	SEES3-1V human TCF12, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01403532	PHASE4	COMPLETED	Sequential Therapy for Hypogonadotropic Hypogonadism
NCT02880280	PHASE4	UNKNOWN	Human Menopausal Gonadotropin Combining With Human Chorionic Gonadotropin Treat Congenital Hypogonadotropic Hypogonadism
NCT03687606	PHASE4	UNKNOWN	Efficacy and Safety of Long Term Use of hCG or hCG Plus hMG in Males With Isolated Hypogonadotropic Hypogonadism (IHH)
NCT00722436	PHASE4	TERMINATED	Tranexamic Acid for Craniofacial Surgery
NCT02188576	PHASE4	COMPLETED	The Efficacy and Population Pharmacokinetics of Tranexamic Acid for Craniosynostosis Surgery
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
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