UBTF

Summary

UBTF (upstream binding transcription factor, HGNC:12511) is a protein-coding gene on chromosome 17q21.31, encoding Nucleolar transcription factor 1 (P17480). Recognizes the ribosomal RNA gene promoter and activates transcription mediated by RNA polymerase I (Pol I) through cooperative interactions with the transcription factor SL1/TIF-IB complex. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

This gene encodes a member of the HMG-box DNA-binding protein family. The encoded protein plays a critical role in ribosomal RNA transcription as a key component of the pre-initiation complex, mediating the recruitment of RNA polymerase I to rDNA promoter regions. The encoded protein may also play important roles in chromatin remodeling and pre-rRNA processing, and its activity is regulated by both phosphorylation and acetylation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. Pseudogenes of this gene are located on the short arm of chromosomes 3, 11 and X and the long arm of chromosome 11.

Source: NCBI Gene 7343 — RefSeq curated summary.

At a glance

• Gene–disease (curated): childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 10
• Clinical variants (ClinVar): 15 total
• Phenotypes (HPO): 48
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_014233

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12511
Approved symbol	UBTF
Name	upstream binding transcription factor
Location	17q21.31
Locus type	gene with protein product
Status	Approved
Aliases	UBF, NOR-90, UBF1, UBF2
Ensembl gene	ENSG00000108312
Ensembl biotype	protein_coding
OMIM	600673
Entrez	7343

Gene structure

Transcript identifiers

Ensembl transcripts: 80 — 75 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000302904, ENST00000343638, ENST00000393606, ENST00000436088, ENST00000526094, ENST00000527034, ENST00000529042, ENST00000529373, ENST00000529383, ENST00000529947, ENST00000530828, ENST00000531368, ENST00000533177, ENST00000537550, ENST00000704740, ENST00000704741, ENST00000704742, ENST00000704746, ENST00000905765, ENST00000905766, ENST00000905767, ENST00000905768, ENST00000905769, ENST00000905770, ENST00000905771, ENST00000905772, ENST00000905773, ENST00000905774, ENST00000905775, ENST00000905776, ENST00000905777, ENST00000905778, ENST00000905779, ENST00000905780, ENST00000905781, ENST00000905782, ENST00000905783, ENST00000905784, ENST00000905785, ENST00000905786, ENST00000905787, ENST00000905788, ENST00000905789, ENST00000905790, ENST00000905791, ENST00000905792, ENST00000905793, ENST00000905794, ENST00000905795, ENST00000905796, ENST00000905797, ENST00000905798, ENST00000931833, ENST00000931834, ENST00000931835, ENST00000931836, ENST00000931837, ENST00000931838, ENST00000931839, ENST00000931840, ENST00000931841, ENST00000931842, ENST00000931843, ENST00000931844, ENST00000931845, ENST00000962301, ENST00000962302, ENST00000962303, ENST00000962304, ENST00000962305, ENST00000962306, ENST00000962307, ENST00000962308, ENST00000962309, ENST00000962310, ENST00000962311, ENST00000962312, ENST00000962313, ENST00000962314, ENST00000962315

RefSeq mRNA: 3 — MANE Select: NM_014233 NM_001076683, NM_001076684, NM_014233

CCDS: CCDS11480, CCDS42346

Canonical transcript exons

ENST00000436088 — 21 exons

Exon	Start	End
ENSE00000732399	44212344	44212454
ENSE00000732403	44211606	44211747
ENSE00000732411	44210792	44210947
ENSE00000732414	44210318	44210473
ENSE00000854236	44209352	44209541
ENSE00000854238	44210124	44210234
ENSE00000854241	44211039	44211152
ENSE00000854242	44211290	44211331
ENSE00000854244	44211873	44212006
ENSE00000854246	44213218	44213282
ENSE00000854247	44215654	44215809
ENSE00001386283	44218172	44218296
ENSE00001608256	44205040	44207367
ENSE00001641708	44219445	44219675
ENSE00003497919	44216529	44216704
ENSE00003596962	44207699	44207770
ENSE00003600864	44207454	44207597
ENSE00003660135	44209645	44209733
ENSE00003660509	44207864	44207911
ENSE00003674711	44212819	44212939
ENSE00003682889	44215906	44215989

Expression profiles

Bgee: expression breadth ubiquitous, 268 present calls, max score 96.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.7207 / max 247.5100, expressed in 1822 samples.

FANTOM5 promoters (19 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166339	15.6703	1806
166342	5.3246	1568
166334	3.9848	1509
166332	2.4901	1438
166340	1.3269	954
166343	1.0629	418
166329	0.9694	364
166337	0.7694	533
166335	0.7166	464
166330	0.6778	346

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	96.58	gold quality
cortical plate	UBERON:0005343	96.47	gold quality
ganglionic eminence	UBERON:0004023	96.17	gold quality
granulocyte	CL:0000094	95.90	gold quality
right lobe of thyroid gland	UBERON:0001119	95.89	gold quality
ventricular zone	UBERON:0003053	95.73	gold quality
right coronary artery	UBERON:0001625	95.26	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.15	gold quality
cerebellar hemisphere	UBERON:0002245	95.03	gold quality
cerebellar cortex	UBERON:0002129	94.96	gold quality
left lobe of thyroid gland	UBERON:0001120	94.95	gold quality
ectocervix	UBERON:0012249	94.70	gold quality
body of uterus	UBERON:0009853	94.68	gold quality
right uterine tube	UBERON:0001302	94.64	gold quality
calcaneal tendon	UBERON:0003701	94.64	gold quality
apex of heart	UBERON:0002098	94.60	gold quality
right lobe of liver	UBERON:0001114	94.59	gold quality
endocervix	UBERON:0000458	94.57	gold quality
thyroid gland	UBERON:0002046	94.54	gold quality
lymph node	UBERON:0000029	94.48	gold quality
metanephros cortex	UBERON:0010533	94.48	gold quality
left uterine tube	UBERON:0001303	94.45	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.37	gold quality
body of pancreas	UBERON:0001150	94.28	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.09	gold quality
popliteal artery	UBERON:0002250	94.04	gold quality
tibial artery	UBERON:0007610	94.03	gold quality
lower esophagus	UBERON:0013473	94.03	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.03	gold quality
right ovary	UBERON:0002118	93.93	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.95
E-GEOD-124858	no	39.86

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

9 targets.

Target	Regulation
CCND1	Activation
CREBBP
MMP3
POLI
POLR1A
POLR1E
RPS6KB1
TAF1A
TAF1B	Unknown

Upstream regulators (CollecTRI, top): MXD1, MYC

miRNA regulators (miRDB)

86 targeting UBTF, 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-8485	100.00	77.57	4731
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• The three-dimensional solution structure of the first high mobility group (HMG) box domain in upstream binding factor has been determined by multidimensional NMR. (PMID:11969401)
• we have identified an interaction between UBF and TAF1, a factor involved in the transcription of cell cycle and growth regulatory genes. Coimmunoprecipitation and protein-protein interaction assays confirmed that TAF1 binds to UBF. (PMID:12498690)
• The DNA binding affinity of UBF’s fifth box domain (HMG box 5) is found to be much weaker than that of the first HMG box domain (HMG box 1). (PMID:12590579)
• Data show that both UBF1 and UBF2 activate RNA polymerase II-regulated, beta-catenin-responsive promoters. (PMID:12748295)
• Proto-Oncogene Proteins c-myc activated transcription from the UBF promoter (PMID:15282543)
• results suggest that extensive binding of UBF is responsible for formation and maintenance of the secondary constriction at active NORs, and that UBF mediates recruitment of the pol I machinery to nucleoli independently of promoter elements (PMID:15598984)
• Data suggest that the A state of human upstream binding factor HMG Box1 could represent a potential folding intermediate on protein folding pathway. (PMID:15752694)
• A potential protein-folding pathway is proposed for upstream binding factor HMG box 1 domain based on the early stages of its pH 2.1 unfolded state characterized by multidimensional heteronuclear magnetic resonance spectroscopy. (PMID:15924431)
• SL1 directs preinitiation complex formation, functioning in core promoter binding, RNA polymerase I recruitment, and UBF stabilization. (PMID:15970593)
• model for CAST/hPAF49 function in which the network of interactions of Pol I-specific subunits with UBF facilitates conformational changes of the polymerase, leading to stabilization of the Pol I-template complex and, thereby, activation of transcription (PMID:16809778)
• UBF activates transcription in the transition between initiation and elongation, at promoter escape by RNA polymerase I (Pol I). (PMID:16858408)
• Upon p14ARF overexpression, UBF was found hypophosphorylated, thus unable to efficiently recruit the transcription complex, these data define a new p53-independent pathway that could regulate cell cycle through the negative control of rRNA transcription. (PMID:16924243)
• GdmCl-induced equilibrium unfolding transition of HMG box 5 of hUBF was monitored by both circular dichroism and fluorescence spectra. A cooperative two-state unfolding process was observed (PMID:17260958)
• possible sites in hUBF HMG box 5 that may interact with the first bromodomain of TAF1 were proposed (PMID:17505112)
• transcription factor UBF binds extensively across rDNA throughout the cell cycle, resulting in a specialized form of chromatin that is the hallmark of active nucleolar organizer regions (PMID:17699751)
• found a small but significant difference between the emerging daughter cells in the number of UBF-loaded NORs (PMID:18502146)
• The authors propose that UBF is recruited to the replication compartments to aid replication of HSV-1 DNA. (PMID:19088274)
• The established differential localization of UBF in nucleoli of HeLa cells has a functional meaning. It reflects both the level of rRNA synthesis activities and the architectural role of UBF in nucleoli of these cells. (PMID:19393134)
• these results implicate a fluid helix-turn-helix folding model of hUBF Box-5. (PMID:19452555)
• central repeated domain of treacle binds with RNA polymerase I, while that the treacle C-terminus is involved in rDNA promoter recognition and UBF recruitment. (PMID:19527688)
• depletion of upstream binding factor (UBF; an rRNA transcription factor) decreased the chromatin binding affinity of B23, which in turn led to an increase in histone density at the r-chromatin (PMID:20713446)
• UBF is expressed widely by human multiple fetal tissue,s and the expression level is very high in HL-60 cells. (PMID:21162312)
• hALP binds the upstream binding factor (UBF) in vivo and in vitro (PMID:21177859)
• Downregulation of RUNX2 expression reduces the localization of HDAC1 to the nucleolar periphery and also decreases the association between HDAC1 and UBF. (PMID:22393235)
• PIP2 depletion reduces Pol I transcription. (PMID:23591814)
• p14ARF fails to prevent E7-mediated UBF1 phosphorylation, but could facilitate nucleolar pRb inactivation by targeting E7 to the nucleolus. (PMID:24798431)
• we have uncovered a novel role for UBTF1 and UBTF2 in maintaining genome stability through coordinating the expression of highly transcribed Pol I (UBTF1 activity) and Pol II genes (UBTF2 activity). (PMID:25452314)
• This study provides some compelling evidences in support of HBx-elicited and c-Myc-mediated increase in UBF levels that abets oncogenic onslaught in hepatic cells by increasing rDNA transcription and ribosome biogenesis. (PMID:25890091)
• These results suggest that UBF can inhibit gene expression from viral DNA prior to its replication. (PMID:25965800)
• TP53INP2 promotes ribosome biogenesis through facilitating rRNA synthesis at the nucleolus (PMID:27172002)
• RINT-1 interacts with MSP58 and UBF within nucleoli and plays a role in ribosomal gene transcription. (PMID:27530925)
• In seven unrelated affected individuals, all suffering from developmental regression starting at 2.5-7 years, the authors identified a heterozygous variant, c.628G>A in UBTF, encoding p.Glu210Lys in UBF, which occurred de novo in all cases. (PMID:28777933)
• Study demonstrated that HMG box 1, the linker region between the HMG boxes and C-terminal acidic region (AR), and the AR cooperatively regulate the nucleolar localization of UBF. (PMID:28874518)
• Data underscore the importance of including UBTF E210K in the differential diagnosis of neuroregression and suggest that mainly gain-of-function mechanisms contribute to the pathogenesis of the UBTF E210K neuroregression syndrome. (PMID:29300972)
• mutant SEC23B binds to UBF transcription factor, with increased UBF transcription factor binding at the ribosomal DNA promoter. Our data indicate SEC23B has potential non-canonical COPII-independent function, particularly within the ribosome biogenesis pathway, and that may contribute to the pathogenesis of cancer-predisposition. (PMID:29893852)
• These results demonstrate the role of pNO40 in ribosomal RNA biosynthesis regulation by compromising UBF function in ribosomal DNA transcription activation with subsequent ribosomal RNA synthesis inhibition. (PMID:31217076)
• Protein kinase Ciota promotes UBF1-ECT2 binding on ribosomal DNA to drive rRNA synthesis and transformed growth of non-small-cell lung cancer cells. (PMID:32350115)
• Enhancer retargeting of CDX2 and UBTF::ATXN7L3 define a subtype of high-risk B-progenitor acute lymphoblastic leukemia. (PMID:35192684)
• Concurrent CDX2 cis-deregulation and UBTF::ATXN7L3 fusion define a novel high-risk subtype of B-cell ALL. (PMID:35316324)
• UBTF-internal tandem duplication as a novel poor prognostic factor in pediatric acute myeloid leukemia. (PMID:36448876)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ubtf	ENSDARG00000035066
mus_musculus	Ubtf	ENSMUSG00000020923
rattus_norvegicus	Ubtf	ENSRNOG00000020937
caenorhabditis_elegans	hmg-3	WBGENE00001973
caenorhabditis_elegans		WBGENE00001974

Paralogs (20): HMGB3 (ENSG00000029993), HMG20B (ENSG00000064961), SP100 (ENSG00000067066), SMARCE1 (ENSG00000073584), SP140 (ENSG00000079263), TOX4 (ENSG00000092203), HMGXB4 (ENSG00000100281), TOX3 (ENSG00000103460), TFAM (ENSG00000108064), HMGB1P1 (ENSG00000124097), TOX2 (ENSG00000124191), SP110 (ENSG00000135899), HMG20A (ENSG00000140382), SSRP1 (ENSG00000149136), HMGB2 (ENSG00000164104), HMGB4 (ENSG00000176256), SP140L (ENSG00000185404), HMGB1 (ENSG00000189403), TOX (ENSG00000198846), UBTFL1 (ENSG00000255009)

Protein

Protein identifiers

Nucleolar transcription factor 1 — P17480 (reviewed: P17480)

Alternative names: Autoantigen NOR-90, Upstream-binding factor 1

All UniProt accessions (5): P17480, A0A994J4N4, E9PKP7, E9PLT2, E9PMM2

UniProt curated annotations — full annotation on UniProt →

Function. Recognizes the ribosomal RNA gene promoter and activates transcription mediated by RNA polymerase I (Pol I) through cooperative interactions with the transcription factor SL1/TIF-IB complex. It binds specifically to the upstream control element and can activate Pol I promoter escape.

Subunit / interactions. Homodimer. Part of Pol I pre-initiation complex (PIC), in which Pol I core assembles with RRN3 and promoter-bound UTBF and SL1/TIF-IB complex. Interacts with TOP2A in the context of Pol I complex. Interacts with TBP. Interacts with TAF1A. Interacts with RASL11A. Binds to IRS1 and PIK3CA. Interacts with DHX33. Interacts with PHF6. Interacts with CEBPA (isoform 1 and isoform 4). Interacts with DDX11. Interacts with NOP53. Interacts with ALKBH2.

Subcellular location. Nucleus. Nucleolus.

Post-translational modifications. Phosphorylated and activated by PIK3CA.

Disease relevance. Neurodegeneration, childhood-onset, with brain atrophy (CONDBA) [MIM:617672] An autosomal dominant neurodegenerative disease with onset in childhood, characterized by progressive cortical atrophy, developmental delay, developmental regression, loss of motor skills and ambulation, absence of language, and intellectual disability. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
P17480-1	UBF1, Long	yes
P17480-2	UBF2, Short

RefSeq proteins (3): NP_001070151, NP_001070152, NP_055048* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009071	HMG_box_dom	Domain
IPR029215	HMG_box_5	Domain
IPR036910	HMG_box_dom_sf	Homologous_superfamily
IPR051762	UBF1	Family

Pfam: PF00505, PF09011, PF14887

UniProt features (42 total): modified residue 14, helix 8, DNA-binding region 6, region of interest 5, compositionally biased region 3, strand 2, chain 1, splice variant 1, sequence variant 1, turn 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
2HDZ	X-RAY DIFFRACTION	2
1K99	SOLUTION NMR
1L8Y	SOLUTION NMR
1L8Z	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17480-F1	78.52	0.44

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 (14): 1, 201, 273, 336, 364, 389, 412, 433, 435, 484, 495, 546, 584, 638

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-427413	NoRC negatively regulates rRNA expression
R-HSA-73728	RNA Polymerase I Promoter Opening
R-HSA-73762	RNA Polymerase I Transcription Initiation
R-HSA-73772	RNA Polymerase I Promoter Escape
R-HSA-73863	RNA Polymerase I Transcription Termination

MSigDB gene sets: 310 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, MYOGENIN_Q6, PAX4_01, REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION_INITIATION, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, AP4_Q6, AP2_Q3, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, CAGCTG_AP4_Q5, YY1_02, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GENTILE_UV_HIGH_DOSE_DN, GENTILE_UV_RESPONSE_CLUSTER_D5, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_INTRACELLULAR_GLUCOSE_HOMEOSTASIS

GO Biological Process (4): transcription by RNA polymerase I (GO:0006360), transcription initiation at RNA polymerase I promoter (GO:0006361), positive regulation of transcription by RNA polymerase I (GO:0045943), RNA polymerase I preinitiation complex assembly (GO:0001188)

GO Molecular Function (8): RNA polymerase I core promoter sequence-specific DNA binding (GO:0001164), RNA polymerase I cis-regulatory region sequence-specific DNA binding (GO:0001165), RNA polymerase I general transcription initiation factor activity (GO:0001181), chromatin binding (GO:0003682), RNA binding (GO:0003723), scaffold protein binding (GO:0097110), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (4): fibrillar center (GO:0001650), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
RNA Polymerase I Promoter Clearance	3
Negative epigenetic regulation of rRNA expression	1
RNA Polymerase I Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase I	3
RNA polymerase I transcription regulatory region sequence-specific DNA binding	2
binding	2
nucleic acid binding	2
cellular anatomical structure	2
nuclear lumen	2
DNA-templated transcription	1
DNA-templated transcription initiation	1
regulation of transcription by RNA polymerase I	1
positive regulation of DNA-templated transcription	1
transcription initiation at RNA polymerase I promoter	1
transcription preinitiation complex assembly	1
core promoter sequence-specific DNA binding	1
RNA polymerase I preinitiation complex assembly	1
general transcription initiation factor activity	1
protein binding	1
nucleolus	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2754 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBTF	POLI	Q9UNA4	962
UBTF	RRN3	Q9NYV6	934
UBTF	FBL	P22087	908
UBTF	SIRT7	Q9NRC8	903
UBTF	TAF1A	Q15573	900
UBTF	POLR1E	Q9GZS1	895
UBTF	TCOF1	Q13428	876
UBTF	TBP	P20226	844
UBTF	POLR1A	O95602	820
UBTF	POLR1G	O15446	806
UBTF	NPM1	P06748	803
UBTF	NOAZFP	Q9Y3S2	792
UBTF	NUCLEOLIN	P19338	787
UBTF	CHD4	Q14839	756
UBTF	MCRS1	Q96EZ8	736

IntAct

140 interactions, top by confidence:

A	B	Type	Score
MED19	MED19	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
MYBBP1A	NPM1	psi-mi:“MI:0403”(colocalization)	0.710
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
RAP1GDS1	DIRAS1	psi-mi:“MI:0914”(association)	0.640
SET	UBTF	psi-mi:“MI:0915”(physical association)	0.640
UBTF	SET	psi-mi:“MI:0915”(physical association)	0.640
UBTF	SET	psi-mi:“MI:0407”(direct interaction)	0.640
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
SUMO1	CBX4	psi-mi:“MI:0914”(association)	0.600
HEMGN	NPM1	psi-mi:“MI:0914”(association)	0.600
UBTF	RUNX2	psi-mi:“MI:0915”(physical association)	0.560
RUNX2	UBTF	psi-mi:“MI:0914”(association)	0.560
UBTF	CEBPA	psi-mi:“MI:0915”(physical association)	0.560
EDA	AP3B1	psi-mi:“MI:0914”(association)	0.530
PIP4K2A	AP3B1	psi-mi:“MI:0914”(association)	0.530
PES1	AP3B1	psi-mi:“MI:0914”(association)	0.530
PTGER3	PIK3R2	psi-mi:“MI:0914”(association)	0.530
MDK	SETD1A	psi-mi:“MI:0914”(association)	0.530
RSBN1	SETD1A	psi-mi:“MI:0914”(association)	0.530
H1-4	RRP8	psi-mi:“MI:0914”(association)	0.530
HDGFL2	CDC7	psi-mi:“MI:0914”(association)	0.530
SULF2	UBTF	psi-mi:“MI:0914”(association)	0.530

BioGRID (321): KAT2B (Co-localization), UBTF (Affinity Capture-MS), UBTF (Affinity Capture-MS), UBTF (Affinity Capture-MS), UBTF (Affinity Capture-MS), UBTF (Affinity Capture-MS), UBTF (Affinity Capture-MS), UBTF (Affinity Capture-MS), AP3M1 (Co-fractionation), RTF1 (Co-fractionation), UBTF (Affinity Capture-MS), UBTF (Synthetic Lethality), UBTF (Affinity Capture-MS), UBTF (Proximity Label-MS), UBTF (Protein-peptide)

ESM2 similar proteins: A9RA84, B0CM99, B1MTB0, B2RPK0, F4K4Y5, O23063, O24591, O49595, O49596, O49597, O64702, P09429, P0CO24, P0CO25, P12682, P15308, P17480, P25976, P25977, P26585, P27347, P35659, P40267, P40619, P40620, P40621, P40622, P63158, P63159, P91753, P93047, Q08IE6, Q1PEP5, Q42344, Q4R844, Q6AXS3, Q6V9I6, Q6YKA4, Q7TNV0, Q84JB7

Diamond homologs: P0CB47, P0CB48, P17480, P25976, P25977, P25979, P25980, P40626, Q0II87, Q3USZ2, Q5D144, A4QNP0, A9RA84, B0CM99, B1MTB0, B2RPK0, B7SBD2, O04235, O15347, O15405, O49596, O54879, O64702, O94842, O94900, P07746, P09429, P10103, P11632, P11633, P11873, P12682, P17741, P26583, P26584, P26585, P30681, P33417, P40618, P40619

SIGNOR signaling

19 interactions.

A	Effect	B	Mechanism
MAPK1	down-regulates	UBTF	phosphorylation
MAPK3	down-regulates	UBTF	phosphorylation
PHF6	down-regulates	UBTF	binding
CyclinE/CDK2	up-regulates	UBTF	phosphorylation
CyclinA2/CDK2	up-regulates	UBTF	phosphorylation
UBTF	“up-regulates quantity by expression”	rRNA_transcription	“transcriptional regulation”
“SL1 complex”	“up-regulates activity”	UBTF	binding
UBTF	“up-regulates activity”	“RNA Polymerase I”	binding
MYC	“up-regulates quantity by expression”	UBTF	“transcriptional regulation”
MXD1	“down-regulates quantity by repression”	UBTF	“transcriptional regulation”
Gbeta	down-regulates	UBTF	phosphorylation
ERK1/2	down-regulates	UBTF	phosphorylation
CDK2	“up-regulates activity”	UBTF	phosphorylation
CyclinD/CDK4	“up-regulates activity”	UBTF	phosphorylation
CyclinE/CDK2	“up-regulates activity”	UBTF	phosphorylation
UBTF	up-regulates	Proliferation
RB1	“down-regulates activity”	UBTF	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 161 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
chromatin remodeling	12	6.6×	3e-04
positive regulation of gene expression	14	4.1×	3e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	7
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

3054 predictions. Top by Δscore:

Variant	Effect	Δscore
17:44207363:TCATT:T	acceptor_gain	1.0000
17:44207364:CATT:C	acceptor_gain	1.0000
17:44207364:CATTC:C	acceptor_gain	1.0000
17:44207365:ATT:A	acceptor_gain	1.0000
17:44207366:TT:T	acceptor_gain	1.0000
17:44207368:C:CC	acceptor_gain	1.0000
17:44207368:CTGGG:C	acceptor_loss	1.0000
17:44207369:T:A	acceptor_loss	1.0000
17:44207375:G:C	acceptor_gain	1.0000
17:44207375:G:GC	acceptor_gain	1.0000
17:44207450:CCACC:C	donor_loss	1.0000
17:44207451:CACC:C	donor_loss	1.0000
17:44207452:ACC:A	donor_loss	1.0000
17:44207453:C:CA	donor_loss	1.0000
17:44207457:AT:A	donor_gain	1.0000
17:44207457:ATCC:A	donor_gain	1.0000
17:44207458:T:TA	donor_gain	1.0000
17:44207463:AT:A	donor_gain	1.0000
17:44207464:T:TA	donor_gain	1.0000
17:44207476:T:TA	donor_gain	1.0000
17:44207539:T:TA	donor_gain	1.0000
17:44207593:GACTC:G	acceptor_gain	1.0000
17:44207595:CTC:C	acceptor_gain	1.0000
17:44207597:CC:C	acceptor_loss	1.0000
17:44207597:CCT:C	acceptor_gain	1.0000
17:44207598:C:CC	acceptor_gain	1.0000
17:44207598:C:T	acceptor_gain	1.0000
17:44207598:CTTGG:C	acceptor_loss	1.0000
17:44207599:T:C	acceptor_gain	1.0000
17:44207599:T:TC	acceptor_gain	1.0000

AlphaMissense

5136 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:44209360:A:G	W633R	1.000
17:44209360:A:T	W633R	1.000
17:44209368:A:G	L630P	1.000
17:44209381:A:C	Y626D	1.000
17:44209401:G:T	A619D	1.000
17:44209421:C:A	K612N	1.000
17:44209421:C:G	K612N	1.000
17:44209445:C:A	W604C	1.000
17:44209445:C:G	W604C	1.000
17:44209446:C:G	W604S	1.000
17:44209447:A:G	W604R	1.000
17:44209447:A:T	W604R	1.000
17:44209449:C:G	R603P	1.000
17:44209455:C:A	G601V	1.000
17:44209455:C:T	G601D	1.000
17:44209456:C:G	G601R	1.000
17:44209458:A:C	I600S	1.000
17:44209458:A:T	I600N	1.000
17:44209466:C:A	M597I	1.000
17:44209466:C:G	M597I	1.000
17:44209466:C:T	M597I	1.000
17:44209467:A:C	M597R	1.000
17:44209467:A:G	M597T	1.000
17:44209467:A:T	M597K	1.000
17:44209470:C:G	R596P	1.000
17:44209471:G:T	R596S	1.000
17:44209494:A:G	L588P	1.000
17:44209509:A:G	L583P	1.000
17:44209509:A:T	L583Q	1.000
17:44209512:A:G	L582P	1.000

dbSNP variants (sampled 300 via entrez): RS1000025061 (17:44221386 G>A,T), RS1000078563 (17:44220661 C>T), RS1000193031 (17:44206813 G>T), RS1000281464 (17:44209981 G>A), RS1000476443 (17:44206981 C>A), RS1000879427 (17:44219315 C>G,T), RS1000897055 (17:44218831 A>C,G), RS1000910467 (17:44219563 C>G,T), RS1001078544 (17:44217338 G>A), RS1001544571 (17:44220957 C>T), RS1001575611 (17:44221090 CAAAA>C,CAAA,CAAAAA), RS1001690020 (17:44222687 C>A), RS1001814215 (17:44216949 C>A,T), RS1001862885 (17:44208037 T>A), RS1002145867 (17:44208353 C>T)

Disease associations

OMIM: gene MIM:600673 | disease phenotypes: MIM:617672

GenCC curated gene-disease

Disease	Classification	Inheritance
childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder	Definitive	Autosomal dominant
neurodevelopmental disorder	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder	Definitive	AD

Mondo (2): childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder (MONDO:0044701), neurodevelopmental disorder (MONDO:0700092)

Orphanet (1): Childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder (Orphanet:500180)

HPO phenotypes

48 total (30 of 48 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000252	Microcephaly
HP:0000708	Atypical behavior
HP:0000718	Aggressive behavior
HP:0000729	Autistic behavior
HP:0000752	Hyperactivity
HP:0000768	Pectus carinatum
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001268	Mental deterioration
HP:0001272	Cerebellar atrophy
HP:0001300	Parkinsonism
HP:0001332	Dystonia
HP:0001344	Absent speech
HP:0002015	Dysphagia
HP:0002059	Cerebral atrophy
HP:0002063	Rigidity
HP:0002066	Gait ataxia
HP:0002071	Abnormality of extrapyramidal motor function
HP:0002072	Chorea
HP:0002079	Hypoplasia of the corpus callosum
HP:0002119	Ventriculomegaly
HP:0002120	Cerebral cortical atrophy
HP:0002180	Neurodegeneration
HP:0002187	Profound intellectual disability
HP:0002353	EEG abnormality
HP:0002376	Developmental regression

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST005992_24	Mean corpuscular hemoglobin concentration	2.000000e-18
GCST006479_127	Diverticular disease	2.000000e-10
GCST007294_181	Body fat distribution (trunk fat ratio)	2.000000e-09
GCST007294_25	Body fat distribution (trunk fat ratio)	2.000000e-08
GCST007295_33	Body fat distribution (leg fat ratio)	4.000000e-11
GCST007295_66	Body fat distribution (leg fat ratio)	2.000000e-10
GCST008103_24	Bipolar disorder	2.000000e-08
GCST009325_54	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	6.000000e-10
GCST012126_13	hemolysis of donated blood (osmotic)	5.000000e-08
GCST012135_13	hemolysis of donated blood (osmotic)	4.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0009959	diverticular disease
EFO:0004341	body fat distribution
EFO:0009473	hemolysis

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725047 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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
7.17	Kd	67	nM	MOLIBRESIB
7.05	IC50	90	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 7 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179091: Binding affinity against UBTF (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0670	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	5
trichostatin A	affects expression, decreases expression	2
cobaltous chloride	decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	increases expression	1
bisphenol A	decreases expression	1
beta-lapachone	increases expression, decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	decreases phosphorylation	1
cadmium sulfate	decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation, increases ADP-ribosylation	1
abrine	decreases expression	1
bisphenol S	increases expression	1
NSC 689534	decreases expression, affects binding	1
(+)-JQ1 compound	decreases expression	1
Vorinostat	decreases expression	1
Acetaminophen	decreases expression	1
Clozapine	decreases expression	1
Copper	decreases expression, affects binding	1
Doxorubicin	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Haloperidol	decreases expression	1
Hydrogen Peroxide	affects cotreatment, decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697126	Binding	Inhibition of UBTF (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A7R8	SEES3-1V human UBTF, clone1	Embryonic stem cell	Male
CVCL_A7R9	SEES3-1V human UBTF, clone2	Embryonic stem cell	Male
CVCL_A7S0	SEES3-1V human UBTF, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

202 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,
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
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
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
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
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice