GTF3C3

Summary

GTF3C3 (general transcription factor IIIC subunit 3, HGNC:4666) is a protein-coding gene on chromosome 2q33.1, encoding General transcription factor 3C polypeptide 3 (Q9Y5Q9). Involved in RNA polymerase III-mediated transcription. It is a selective cancer dependency (DepMap: 50.7% of cell lines).

The protein encoded by this gene is part of the TFIIIC2 complex, which binds to the promoters of small nuclear and cytoplasmic RNA genes in order to recruit RNA polymerase III. The TFIIIC2 complex is composed of six subunits. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 9330 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 126 total — 9 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 111
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 50.7% of screened cell lines
• MANE Select transcript: NM_012086

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4666
Approved symbol	GTF3C3
Name	general transcription factor IIIC subunit 3
Location	2q33.1
Locus type	gene with protein product
Status	Approved
Aliases	TFiiiC2-102, TFIIIC102
Ensembl gene	ENSG00000119041
Ensembl biotype	protein_coding
OMIM	604888
Entrez	9330

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 15 protein_coding, 4 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000263956, ENST00000409364, ENST00000416690, ENST00000435252, ENST00000448087, ENST00000448539, ENST00000451088, ENST00000455546, ENST00000466862, ENST00000470386, ENST00000481098, ENST00000651042, ENST00000897137, ENST00000897138, ENST00000897139, ENST00000897140, ENST00000897141, ENST00000929326, ENST00000929327, ENST00000929328, ENST00000929329, ENST00000951329

RefSeq mRNA: 2 — MANE Select: NM_012086 NM_001206774, NM_012086

CCDS: CCDS2316, CCDS56153

Canonical transcript exons

ENST00000263956 — 18 exons

Exon	Start	End
ENSE00000803107	196785441	196785588
ENSE00000803112	196776427	196776629
ENSE00000803113	196776010	196776111
ENSE00000803114	196775116	196775251
ENSE00000803115	196772916	196773153
ENSE00000803116	196771748	196771938
ENSE00000803117	196769915	196770039
ENSE00000964845	196784857	196784929
ENSE00000964846	196780559	196780662
ENSE00000964847	196778896	196779067
ENSE00000964848	196766565	196766717
ENSE00001217477	196763035	196764685
ENSE00003502493	196789204	196789369
ENSE00003531201	196797797	196797908
ENSE00003569650	196791337	196791460
ENSE00003594644	196792956	196793152
ENSE00003672109	196789879	196790070
ENSE00003847472	196799510	196799683

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 94.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.9020 / max 514.0123, expressed in 1800 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
33045	23.9242	1797
33044	0.7678	467
33043	0.1326	34
33042	0.0775	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	94.31	gold quality
adrenal tissue	UBERON:0018303	93.13	gold quality
colonic epithelium	UBERON:0000397	91.53	gold quality
sural nerve	UBERON:0015488	90.37	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.95	gold quality
body of pancreas	UBERON:0001150	89.80	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.25	gold quality
stromal cell of endometrium	CL:0002255	89.17	gold quality
rectum	UBERON:0001052	88.93	gold quality
right uterine tube	UBERON:0001302	88.63	gold quality
ventricular zone	UBERON:0003053	88.45	gold quality
skin of abdomen	UBERON:0001416	88.08	gold quality
right ovary	UBERON:0002118	88.04	gold quality
nerve	UBERON:0001021	88.01	gold quality
pancreas	UBERON:0001264	88.01	gold quality
tibial nerve	UBERON:0001323	88.01	gold quality
ganglionic eminence	UBERON:0004023	87.91	gold quality
skin of leg	UBERON:0001511	87.87	gold quality
left ovary	UBERON:0002119	87.86	gold quality
body of uterus	UBERON:0009853	87.80	gold quality
islet of Langerhans	UBERON:0000006	87.75	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.58	gold quality
right adrenal gland	UBERON:0001233	87.38	gold quality
ovary	UBERON:0000992	87.29	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.29	gold quality
minor salivary gland	UBERON:0001830	87.15	gold quality
zone of skin	UBERON:0000014	87.10	gold quality
monocyte	CL:0000576	87.08	gold quality
ectocervix	UBERON:0012249	87.08	gold quality
embryo	UBERON:0000922	87.07	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.93
E-MTAB-6142	no	212.95

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting GTF3C3, 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-3924	100.00	72.09	2394
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-4744	99.01	69.91	1581
HSA-MIR-487A-5P	98.85	69.37	993
HSA-MIR-487B-5P	98.85	69.48	987
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-299-5P	98.56	71.14	1140
HSA-MIR-4445-5P	97.21	66.16	832
HSA-MIR-1178-5P	95.83	64.12	504

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 50.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• DEDD and FLAME-3 form nuclear complexes with TFIIIC102 (PMID:11965497)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gtf3c3	ENSDARG00000043247
mus_musculus	Gtf3c3	ENSMUSG00000041303
rattus_norvegicus	Gtf3c3	ENSRNOG00000002091
drosophila_melanogaster	CG8950	FBGN0034186
caenorhabditis_elegans		WBGENE00014114

Protein

Protein identifiers

General transcription factor 3C polypeptide 3 — Q9Y5Q9 (reviewed: Q9Y5Q9)

Alternative names: Transcription factor IIIC 102 kDa subunit, Transcription factor IIIC subunit gamma

All UniProt accessions (7): Q9Y5Q9, A0A494C1S7, F8WC64, H0YFI7, H7BZV8, H7C0C0, H7C143

UniProt curated annotations — full annotation on UniProt →

Function. Involved in RNA polymerase III-mediated transcription. Integral, tightly associated component of the DNA-binding TFIIIC2 subcomplex that directly binds tRNA and virus-associated RNA promoters.

Subunit / interactions. Part of the TFIIIC subcomplex TFIIIC2, consisting of six subunits, GTF3C1, GTF3C2, GTF3C3, GTF3C4, GTF3C5 and GTF3C6. Interacts with BRF1 and TBP.

Subcellular location. Nucleus.

Disease relevance. Neurodevelopmental disorder with dysmorphic facies, brain anomalies, and seizures (NEDFBS) [MIM:621201] An autosomal recessive neurodevelopmental disorder characterized by developmental delay, intellectual disability, microcephaly, facial dysmorphism, seizures, motor impairments, and brain and cerebellar abnormalities. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. May be due to exon skipping.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y5Q9-1	1	yes
Q9Y5Q9-2	2, Short

RefSeq proteins (2): NP_001193703, NP_036218* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR039340	Tfc4/TFIIIC-102/Sfc4	Family

Pfam: PF13181

UniProt features (34 total): repeat 11, sequence variant 10, compositionally biased region 3, modified residue 3, splice variant 2, sequence conflict 2, initiator methionine 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8CLK	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y5Q9-F1	80.51	0.41

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 (3): 2, 43, 282

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-749476	RNA Polymerase III Abortive And Retractive Initiation
R-HSA-76061	RNA Polymerase III Transcription Initiation From Type 1 Promoter
R-HSA-76066	RNA Polymerase III Transcription Initiation From Type 2 Promoter
R-HSA-74158	RNA Polymerase III Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-76046	RNA Polymerase III Transcription Initiation

MSigDB gene sets: 169 (showing top): GOBP_TRNA_METABOLIC_PROCESS, GOBP_TRANSCRIPTION_BY_RNA_POLYMERASE_III, GOBP_RRNA_TRANSCRIPTION, PATIL_LIVER_CANCER, WANG_LMO4_TARGETS_DN, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, DODD_NASOPHARYNGEAL_CARCINOMA_UP, WOOD_EBV_EBNA1_TARGETS_UP, GOCC_NUCLEAR_ENVELOPE, GOCC_TRANSCRIPTION_REGULATOR_COMPLEX, GOCC_NUCLEOLUS, GOCC_NUCLEAR_MEMBRANE, BOYAULT_LIVER_CANCER_SUBCLASS_G3_UP, GOCC_ORGANELLE_ENVELOPE, BIOCARTA_RNAPOL3_PATHWAY

GO Biological Process (3): transcription by RNA polymerase III (GO:0006383), 5S class rRNA transcription by RNA polymerase III (GO:0042791), tRNA transcription by RNA polymerase III (GO:0042797)

GO Molecular Function (3): RNA polymerase III general transcription initiation factor activity (GO:0000995), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (6): transcription factor TFIIIC complex (GO:0000127), fibrillar center (GO:0001650), nucleoplasm (GO:0005654), nuclear membrane (GO:0031965), nucleus (GO:0005634), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
RNA Polymerase III Transcription	2
RNA Polymerase III Transcription Initiation	2
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase III	3
cellular anatomical structure	3
DNA-templated transcription	1
rRNA transcription	1
tRNA transcription	1
general transcription initiation factor activity	1
nucleic acid binding	1
binding	1
RNA polymerase III transcription regulator complex	1
nucleolus	1
nuclear lumen	1
nucleus	1
nuclear envelope	1
organelle membrane	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1806 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GTF3C3	GTF3C5	Q9Y5Q8	976
GTF3C3	GTF3C4	Q9UKN8	952
GTF3C3	GTF3C1	Q12789	916
GTF3C3	BRF1	Q92994	870
GTF3C3	GTF3C2	Q8WUA4	819
GTF3C3	SATB2	Q9UPW6	695
GTF3C3	HOXD1	Q9GZZ0	669
GTF3C3	BDP1	A6H8Y1	667
GTF3C3	COL5A2	P05997	649
GTF3C3	GTF3C6	Q969F1	647
GTF3C3	DEDD2	Q8WXF8	584
GTF3C3	CCDC150	Q8NCX0	559
GTF3C3	IDH1	O75874	548
GTF3C3	POLR3C	Q9BUI4	544
GTF3C3	COL3A1	P02461	538

IntAct

362 interactions, top by confidence:

A	B	Type	Score
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
FBL	NOP56	psi-mi:“MI:0914”(association)	0.800
GTF3C3	MYC	psi-mi:“MI:0915”(physical association)	0.750
HTT	GTF3C3	psi-mi:“MI:0915”(physical association)	0.670
GTF3C3	POLR3D	psi-mi:“MI:0914”(association)	0.640
AURKB	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
GTF3C3	ANXA8	psi-mi:“MI:0915”(physical association)	0.560
CBLB	GTF3C3	psi-mi:“MI:0915”(physical association)	0.560
CSNK1D	GTF3C3	psi-mi:“MI:0915”(physical association)	0.560
	GTF3C3	psi-mi:“MI:0915”(physical association)	0.560
NVL	GTF3C3	psi-mi:“MI:0915”(physical association)	0.560
POLR2E	GTF3C3	psi-mi:“MI:0915”(physical association)	0.560
PTPRS	GTF3C3	psi-mi:“MI:0915”(physical association)	0.560
RPS4X	GTF3C3	psi-mi:“MI:0915”(physical association)	0.560
VHL	GTF3C3	psi-mi:“MI:0915”(physical association)	0.560
BAG6	GTF3C3	psi-mi:“MI:0915”(physical association)	0.560
SEM1	GTF3C3	psi-mi:“MI:0915”(physical association)	0.560
DPF1	GTF3C3	psi-mi:“MI:0915”(physical association)	0.560
GTF3C3	SAP30	psi-mi:“MI:0915”(physical association)	0.560
GTF3C3	USP2	psi-mi:“MI:0915”(physical association)	0.560
TIMM44	GTF3C3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (293): GTF3C3 (Affinity Capture-MS), GTF3C3 (Affinity Capture-MS), GTF3C3 (Affinity Capture-MS), GTF3C3 (Affinity Capture-MS), GTF3C3 (Affinity Capture-MS), GTF3C3 (Affinity Capture-MS), BRD7 (Co-fractionation), GTF3C3 (Co-fractionation), GTF3C3 (Co-fractionation), GTF3C3 (Co-fractionation), GTF3C5 (Co-fractionation), POLR2A (Co-fractionation), SMARCA4 (Co-fractionation), SMARCC2 (Co-fractionation), GTF3C3 (Affinity Capture-MS)

ESM2 similar proteins: A0A8M3B525, A2AHJ4, A5PJP6, B0KWU8, B2RYM5, B5X8M4, E1C3P4, E9Q4Z2, O00763, O42611, O94967, O95630, P46736, P46737, P48553, Q15386, Q15542, Q3TLI0, Q4VA72, Q5KSL6, Q5R558, Q5R9L6, Q5RAQ5, Q5VVJ2, Q641K1, Q66GV6, Q66H62, Q69Z66, Q6RI45, Q6WKZ8, Q76N33, Q7M757, Q80U95, Q8BPM2, Q8CGF6, Q8IVH8, Q8QFR2, Q8TAT6, Q8VDD9, Q8W206

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
GTF3C3	“form complex”	TFIIIC	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	3
Uncertain significance	75
Likely benign	12
Benign	2

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
3899890	NM_012086.5(GTF3C3):c.1436A>G (p.Tyr479Cys)	Pathogenic
3899892	NM_012086.5(GTF3C3):c.2419C>T (p.Arg807Cys)	Pathogenic
3899893	NM_012086.5(GTF3C3):c.503C>T (p.Ala168Val)	Pathogenic
3899894	NM_012086.5(GTF3C3):c.2420G>A (p.Arg807His)	Pathogenic
3899895	GTF3C3, LEU423PRO	Pathogenic
3899896	NM_012086.5(GTF3C3):c.1279G>T (p.Val427Phe)	Pathogenic
3899897	NM_012086.5(GTF3C3):c.514T>G (p.Cys172Gly)	Pathogenic
3899898	NM_012086.5(GTF3C3):c.2149C>T (p.Arg717Ter)	Pathogenic
3899899	NM_012086.5(GTF3C3):c.1525G>A (p.Ala509Thr)	Pathogenic
3233390	NM_012086.5(GTF3C3):c.1390+3A>G	Likely pathogenic
4685097	NM_012086.5(GTF3C3):c.538C>T (p.Pro180Ser)	Likely pathogenic
4819553	NM_012086.5(GTF3C3):c.1708C>T (p.Arg570Ter)	Likely pathogenic

SpliceAI

3685 predictions. Top by Δscore:

Variant	Effect	Δscore
2:196769910:ATTAC:A	donor_loss	1.0000
2:196769911:TTACC:T	donor_loss	1.0000
2:196769912:TACCT:T	donor_loss	1.0000
2:196769914:CCTG:C	donor_loss	1.0000
2:196772912:TCAC:T	donor_loss	1.0000
2:196772913:CA:C	donor_loss	1.0000
2:196772914:ACCT:A	donor_loss	1.0000
2:196773050:AG:A	donor_gain	1.0000
2:196775110:TATTA:T	donor_loss	1.0000
2:196775111:ATTAC:A	donor_loss	1.0000
2:196775112:TTACC:T	donor_loss	1.0000
2:196775113:TA:T	donor_loss	1.0000
2:196775114:ACCT:A	donor_loss	1.0000
2:196775115:CCTTT:C	donor_loss	1.0000
2:196776404:T:TA	donor_gain	1.0000
2:196779074:C:CT	acceptor_gain	1.0000
2:196780557:A:AC	donor_gain	1.0000
2:196780558:C:CC	donor_gain	1.0000
2:196784834:T:A	donor_gain	1.0000
2:196784926:TTAT:T	acceptor_gain	1.0000
2:196784927:TATC:T	acceptor_loss	1.0000
2:196785436:CCTA:C	donor_loss	1.0000
2:196785438:TA:T	donor_loss	1.0000
2:196785439:A:AC	donor_gain	1.0000
2:196785439:ACCT:A	donor_gain	1.0000
2:196785440:C:CC	donor_gain	1.0000
2:196785440:CCT:C	donor_gain	1.0000
2:196785440:CCTC:C	donor_gain	1.0000
2:196785442:T:TA	donor_gain	1.0000
2:196785458:A:AC	donor_gain	1.0000

AlphaMissense

5843 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:196771901:A:G	W703R	1.000
2:196771901:A:T	W703R	1.000
2:196789948:A:G	W220R	1.000
2:196789948:A:T	W220R	1.000
2:196790040:A:G	L189P	1.000
2:196791390:G:T	A161D	1.000
2:196791406:C:G	A156P	1.000
2:196791411:C:T	G154D	1.000
2:196791412:C:A	G154C	1.000
2:196791412:C:G	G154R	1.000
2:196771789:C:T	G740E	0.999
2:196771838:G:T	R724S	0.999
2:196771845:G:C	F721L	0.999
2:196771845:G:T	F721L	0.999
2:196771847:A:G	F721L	0.999
2:196772916:C:A	R690M	0.999
2:196773063:C:G	R641P	0.999
2:196776089:C:G	R539P	0.999
2:196776524:A:G	L499P	0.999
2:196776533:A:G	L496P	0.999
2:196776596:G:T	A475D	0.999
2:196776625:A:C	C465W	0.999
2:196776627:A:G	C465R	0.999
2:196778898:G:T	A463E	0.999
2:196778899:C:G	A463P	0.999
2:196778907:A:G	L460P	0.999
2:196778913:A:T	V458D	0.999
2:196778946:A:G	L447P	0.999
2:196778955:A:G	L444P	0.999
2:196779012:A:G	L425P	0.999

dbSNP variants (sampled 300 via entrez): RS1000053424 (2:196784819 G>C), RS1000175949 (2:196787661 CCT>C), RS1000233299 (2:196792602 G>A), RS1000252303 (2:196799885 T>C), RS1000403395 (2:196772523 G>A), RS1000412793 (2:196780219 T>C), RS1000521809 (2:196792850 T>C), RS1000632797 (2:196787464 C>G), RS1000646201 (2:196763797 A>G), RS1000657043 (2:196770733 T>G), RS1000746280 (2:196778369 T>C), RS1000799969 (2:196778764 A>T), RS1000884847 (2:196778688 C>G), RS1000933538 (2:196764089 T>C), RS1000950529 (2:196787180 C>G)

Disease associations

OMIM: gene MIM:604888 | disease phenotypes: MIM:612313, MIM:621201

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal recessive
genetic developmental and epileptic encephalopathy	Limited	Autosomal recessive

Mondo (4): neurodevelopmental disorder (MONDO:0700092), chromosome 2q32-q33 deletion syndrome (MONDO:0012864), neurodevelopmental disorder with dysmorphic facies, brain anomalies, and seizures (MONDO:0978301), genetic developmental and epileptic encephalopathy (MONDO:0100062)

Orphanet (2): 2q32q33 deletion syndrome (Orphanet:251019), SATB2-associated syndrome due to a pathogenic variant (Orphanet:576283)

HPO phenotypes

111 total (30 of 111 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000175	Cleft palate
HP:0000179	Thick lower lip vermilion
HP:0000201	Pierre-Robin sequence
HP:0000252	Microcephaly
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000294	Low anterior hairline
HP:0000311	Round face
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000324	Facial asymmetry
HP:0000341	Narrow forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000414	Bulbous nose
HP:0000431	Wide nasal bridge
HP:0000445	Wide nose
HP:0000455	Broad nasal tip
HP:0000488	Retinopathy
HP:0000494	Downslanted palpebral fissures
HP:0000527	Long eyelashes
HP:0000565	Esotropia
HP:0000574	Thick eyebrow
HP:0000582	Upslanted palpebral fissure
HP:0000637	Long palpebral fissure

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
C567350	Chromosome 2q32-Q33 Deletion Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066302 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.02	Kd	963	nM	CHEMBL5653589
6.02	ED50	963	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148475: Binding affinity to human GTF3C3 incubated for 45 mins by Kinobead based pull down assay	kd	0.9629	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	5
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Tobacco Smoke Pollution	increases expression	2
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
salinomycin	decreases expression	1
arsenite	affects binding, decreases reaction	1
cobaltous chloride	increases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Caffeine	affects phosphorylation	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Formaldehyde	increases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Ribonucleotides	affects binding	1
Tretinoin	decreases expression	1
Vincristine	increases expression	1
Cyclosporine	increases expression	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	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
CHEMBL5651517	Binding	Binding affinity to human GTF3C3 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

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT06719141	PHASE3	RECRUITING	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE)
NCT06908226	PHASE3	ENROLLING_BY_INVITATION	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT05626634	PHASE2	COMPLETED	Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT06700811	PHASE1	RECRUITING	Ketogenic Diet for Prevention of Epileptic Spasms in Infantile Onset Genetic Epilepsies
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT05364021	PHASE1/PHASE2	COMPLETED	Study to Investigate LP352 in Subjects With Developmental and Epileptic Encephalopathies
NCT06983158	PHASE1/PHASE2	SUSPENDED	A Clinical Trial of CAP-002 Gene Therapy in Pediatric Patients With Syntaxin-Binding Protein 1 (STXBP1) Encephalopathy
NCT04937062	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Phenylbutyrate for Monogenetic Developmental and Epileptic Encephalopathy
NCT06149663	Not specified	AVAILABLE	Intermediate-Size Expanded Access Protocol (EAP) for LP352
NCT06380192	Not specified	RECRUITING	Developmental and Epileptic Encephalopathy of Genetic Etiology: Natural History Through Reuse of Clinical Data
NCT07396883	Not specified	NOT_YET_RECRUITING	Developmental and Epileptic Encephalopathies Diagnosed Via Long-read Genome Sequencing
NCT07531511	Not specified	NOT_YET_RECRUITING	SLC6A1-NDD Prospective Longitudinal Natural History Study
NCT07585643	Not specified	NOT_YET_RECRUITING	IBIS - Investigating Reliability of BIS and SEDLINE Monitoring in Children With Developmental and Epileptic Encephalopathies (DEE).
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP