TOX4

Summary

TOX4 (TOX high mobility group box family member 4, HGNC:20161) is a protein-coding gene on chromosome 14q11.2, encoding TOX high mobility group box family member 4 (O94842). Transcription factor that modulates cell fate reprogramming from the somatic state to the pluripotent and neuronal fate. It is a selective cancer dependency (DepMap: 23.3% of cell lines).

Predicted to enable chromatin DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in chromatin and chromosome, telomeric region. Part of PTW/PP1 phosphatase complex.

Source: NCBI Gene 9878 — RefSeq curated summary.

At a glance

• Gene–disease (curated): bone marrow failure syndrome (Moderate, GenCC)
• GWAS associations: 9
• Clinical variants (ClinVar): 157 total — 1 pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 23.3% of screened cell lines
• MANE Select transcript: NM_014828

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20161
Approved symbol	TOX4
Name	TOX high mobility group box family member 4
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	LCP1
Ensembl gene	ENSG00000092203
Ensembl biotype	protein_coding
OMIM	614032
Entrez	9878

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 9 protein_coding, 4 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000416256, ENST00000447695, ENST00000448790, ENST00000455138, ENST00000455393, ENST00000457430, ENST00000463119, ENST00000473176, ENST00000487242, ENST00000494242, ENST00000613005, ENST00000613569, ENST00000673643, ENST00000673911, ENST00000853129, ENST00000911770, ENST00000911771

RefSeq mRNA: 2 — MANE Select: NM_014828 NM_001303523, NM_014828

CCDS: CCDS32043

Canonical transcript exons

ENST00000448790 — 9 exons

Exon	Start	End
ENSE00001707408	21496546	21499170
ENSE00003582219	21492296	21492376
ENSE00003599479	21495229	21495392
ENSE00003607897	21489173	21489403
ENSE00003611083	21477496	21477564
ENSE00003664670	21487451	21487693
ENSE00003671695	21492508	21493257
ENSE00003752378	21477195	21477284
ENSE00003895992	21488590	21488850

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 97.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.9247 / max 186.5970, expressed in 1811 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
138535	22.9247	1811

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	97.05	gold quality
olfactory bulb	UBERON:0002264	95.22	gold quality
islet of Langerhans	UBERON:0000006	94.86	gold quality
stromal cell of endometrium	CL:0002255	94.68	gold quality
gastrocnemius	UBERON:0001388	94.63	gold quality
bone marrow cell	CL:0002092	94.39	gold quality
type B pancreatic cell	CL:0000169	94.20	silver quality
muscle of leg	UBERON:0001383	94.13	gold quality
smooth muscle tissue	UBERON:0001135	93.68	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.35	gold quality
monocyte	CL:0000576	93.12	gold quality
leukocyte	CL:0000738	93.11	gold quality
mononuclear cell	CL:0000842	93.10	gold quality
tonsil	UBERON:0002372	93.02	gold quality
popliteal artery	UBERON:0002250	93.00	gold quality
muscle organ	UBERON:0001630	92.98	gold quality
tibial artery	UBERON:0007610	92.98	gold quality
blood	UBERON:0000178	92.92	gold quality
prefrontal cortex	UBERON:0000451	92.84	gold quality
esophagus mucosa	UBERON:0002469	92.83	gold quality
esophagus	UBERON:0001043	92.71	gold quality
sural nerve	UBERON:0015488	92.53	gold quality
skin of leg	UBERON:0001511	92.47	gold quality
ganglionic eminence	UBERON:0004023	92.42	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.37	gold quality
lower esophagus	UBERON:0013473	92.36	gold quality
heart left ventricle	UBERON:0002084	92.30	gold quality
rectum	UBERON:0001052	92.22	gold quality
cardiac ventricle	UBERON:0002082	92.21	gold quality
aorta	UBERON:0000947	92.19	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

85 targeting TOX4, 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-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-3618	99.69	68.57	1012
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-586	99.65	70.40	2051

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 23.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 9)

• the coordinated spatial and temporal regulation of LCP1 and PNUTS may be a novel mechanism to control the expression of genes that are critical for certain physiological and pathological processes. (PMID:19293638)
• mammalian Wdr82 functions in a variety of cellular processes; PTW/PP1 phosphatase complex (PNUTS, Tox4, Wdr82, PP1) has a role in the regulation of chromatin structure during the transition from mitosis into interphase (PMID:20516061)
• interaction between TOX4 and platinated DNA (PMID:21184731)
• Compared with TOX4, expression of TOX1, TOX2 and TOX3 in normal lung was 25, 44, and 88%lower, respectively, supporting the premise that reduced promoter activity confers increased susceptibility to methylation during lung carcinogenesis. (PMID:22496870)
• The formation of vasculogenic mimicry is inhibited by reducing the expression of Mig-7 in gastric cancer cells. (PMID:23127401)
• a regulation of LEDGF interaction with chromatin by cellular partners of its PWWP domain could be involved in several processes linked to LEDGF tethering properties, such as lentiviral integration, DNA repair or transcriptional regulation (PMID:24312278)
• TOX4, an insulin receptor-independent regulator of hepatic glucose production, is activated in diabetic liver. (PMID:34914893)
• TOX4 facilitates promoter-proximal pausing and C-terminal domain dephosphorylation of RNA polymerase II in human cells. (PMID:35365735)
• Migration-inducing gene-7 promotes glioma cell proliferation and invasiveness via activating the MAPK signaling pathway. (PMID:37789777)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	tox4a	ENSDARG00000002031
danio_rerio	tox4b	ENSDARG00000100163
mus_musculus	Tox4	ENSMUSG00000016831
rattus_norvegicus	Tox4	ENSRNOG00000012844
caenorhabditis_elegans	hmg-3	WBGENE00001973
caenorhabditis_elegans		WBGENE00001974

Paralogs (20): HMGB3 (ENSG00000029993), HMG20B (ENSG00000064961), SP100 (ENSG00000067066), SMARCE1 (ENSG00000073584), SP140 (ENSG00000079263), HMGXB4 (ENSG00000100281), TOX3 (ENSG00000103460), TFAM (ENSG00000108064), UBTF (ENSG00000108312), 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

TOX high mobility group box family member 4 — O94842 (reviewed: O94842)

All UniProt accessions (8): O94842, A0A669KA85, A0A669KB71, C9J919, C9JNL1, F8WBE8, F8WC04, F8WCL8

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that modulates cell fate reprogramming from the somatic state to the pluripotent and neuronal fate. In liver, controls the expression of hormone-regulated gluconeogenic genes such as G6PC1 and PCK1. This regulation is independent of the insulin receptor activation. Also acts as a regulatory component of protein phosphatase 1 (PP1) complexes. Component of the PNUTS-PP1 protein phosphatase complex, a PP1 complex that regulates RNA polymerase II transcription pause-release. PNUTS-PP1 also plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase.

Subunit / interactions. Component of the PNUTS-PP1 phosphatase complex, composed of PPP1R10/PNUTS, TOX4, WDR82 and PPP1CA or PPP1CB or PPP1CC. Interacts with PPP1R10/PNUTS. Interacts with FOXO1 and CREB1 (increased by cAMP); FOXO1 and CREB1 are required for full induction of TOX4-dependent activity and the interactions are inhibited by insulin.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Expressed in liver (at protein level).

Activity regulation. In liver, recruited to target gene promoters following treatment with dexamethasone and cAMP. Binding is decreased in presence of insulin.

Induction. Expression is highly induced in diabetic liver.

Isoforms (3)

UniProt ID	Names	Canonical?
O94842-1	1	yes
O94842-2	2
O94842-3	3

RefSeq proteins (2): NP_001290452, NP_055643* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009071	HMG_box_dom	Domain
IPR036910	HMG_box_dom_sf	Homologous_superfamily
IPR051365	TOX_HMG-box_domain	Family

Pfam: PF00505

UniProt features (27 total): modified residue 13, compositionally biased region 5, region of interest 3, splice variant 2, chain 1, DNA-binding region 1, sequence conflict 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9CI7	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O94842-F1	55.51	0.17

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 (13): 176, 178, 181, 182, 313, 315, 481, 533, 550, 552, 560, 562, 567

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 522 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, MCLACHLAN_DENTAL_CARIES_UP, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, MODULE_45, AAGCCAT_MIR135A_MIR135B, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, GOCC_RUFFLE, MODULE_16, GOMF_GTPASE_BINDING, CCATCCA_MIR432

GO Biological Process (4): RNA polymerase II promoter clearance (GO:0001111), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of transcription elongation by RNA polymerase II (GO:0032968), regulation of transcription elongation by RNA polymerase II (GO:0034243)

GO Molecular Function (3): chromatin DNA binding (GO:0031490), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), PTW/PP1 phosphatase complex (GO:0072357), chromosome, telomeric region (GO:0000781), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
transcription elongation by RNA polymerase II	2
promoter clearance during DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of DNA-templated transcription, elongation	1
regulation of transcription elongation by RNA polymerase II	1
positive regulation of transcription by RNA polymerase II	1
regulation of DNA-templated transcription elongation	1
DNA binding	1
chromatin binding	1
nucleic acid binding	1
binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1
protein phosphatase type 1 complex	1
chromosomal region	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1628 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TOX4	WDR82	Q6UXN9	882
TOX4	PPP1R10	Q96QC0	660
TOX4	PSIP1	O75475	589
TOX4	MB21D2	Q8IYB1	548
TOX4	CDCA7L	Q96GN5	496
TOX4	RNF212B	A8MTL3	456
TOX4	SUPT16H	Q9Y5B9	450
TOX4	RBMX2	Q9Y388	447
TOX4	CHD8	Q9HCK8	439
TOX4	SALL2	Q9Y467	415
TOX4	OR10G3	Q8NGC4	408
TOX4	OR10G2	Q8NGC3	406
TOX4	GIGYF2	Q6Y7W6	392
TOX4	STARD3NL	O95772	391
TOX4	EPDR1	Q9UM22	390

IntAct

163 interactions, top by confidence:

A	B	Type	Score
TBX6	TOX4	psi-mi:“MI:0915”(physical association)	0.780
TOX4	TBX6	psi-mi:“MI:0915”(physical association)	0.780
PPP1CB	CCDC85C	psi-mi:“MI:0914”(association)	0.750
PPP1CB	CCDC85C	psi-mi:“MI:2364”(proximity)	0.750
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
PPP1CC	CCDC85C	psi-mi:“MI:2364”(proximity)	0.740
FNDC3B	TOX4	psi-mi:“MI:0915”(physical association)	0.720
TOX4	ZMYND19	psi-mi:“MI:0915”(physical association)	0.720
TOX4	FNDC3B	psi-mi:“MI:0915”(physical association)	0.720
BANP	TOX4	psi-mi:“MI:0915”(physical association)	0.720
TOX4	BANP	psi-mi:“MI:0915”(physical association)	0.720
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
PPP1CA	CCDC85C	psi-mi:“MI:2364”(proximity)	0.670
TOX4	ATXN1	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (202): TOX4 (Affinity Capture-MS), TOX4 (Two-hybrid), BANP (Two-hybrid), MYL7 (Two-hybrid), FNDC3B (Two-hybrid), GEMIN6 (Two-hybrid), ZMYND19 (Two-hybrid), TOX4 (Affinity Capture-MS), TOX4 (Two-hybrid), TOX4 (Proximity Label-MS), TOX4 (Affinity Capture-MS), TOX4 (Affinity Capture-MS), TOX4 (Affinity Capture-MS), TOX4 (Affinity Capture-MS), TOX4 (Affinity Capture-MS)

ESM2 similar proteins: A0A8C0NGY6, A0A8I3PQN6, A1L1N5, A2BEA6, A2ICN5, A2VDZ3, A4QNP0, D6C652, F1LYL9, H2LBU8, O18896, O94842, P19484, P23899, P27889, P35680, P46936, P46937, P46938, P48436, P61753, P61754, Q02078, Q03365, Q04887, Q0P5K4, Q1L8J7, Q2EJA0, Q2LE08, Q2MJT0, Q32NJ6, Q4VYR7, Q571K4, Q5R6A9, Q5RER5, Q5XGD9, Q62431, Q6GQD7, Q7YRJ7, Q7ZXH3

Diamond homologs: A4QNP0, B2RPK0, B7SBD2, O15347, O15405, O54879, O94842, O94900, P0CO24, P0CO25, P11632, P11633, P11873, P12682, P40618, Q0P5K4, Q32L31, Q4IQX3, Q4PBZ9, Q4WY33, Q5B995, Q5R6A9, Q66JW3, Q6BRB4, Q6CC79, Q6CVH3, Q6DJL0, Q6IRR0, Q75B82, Q76IQ7, Q7S045, Q80W03, Q8BU11, Q96NM4, Q99PM1, Q9UVL1, Q9YH06, A9RA84, B0CM99, B1MTB0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 108 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
Pausing and recovery of Tat-mediated HIV elongation	5	25.9×	5e-05
Tat-mediated HIV elongation arrest and recovery	5	25.9×	5e-05
HIV elongation arrest and recovery	5	24.4×	5e-05
Pausing and recovery of HIV elongation	5	24.4×	5e-05
HIV Transcription Elongation	5	23.6×	5e-05
mRNA Polyadenylation	17	21.0×	9e-16
mRNA Splicing - Minor Pathway	6	18.9×	4e-05
mRNA Splicing	12	18.6×	1e-10

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal snRNP assembly	5	31.9×	2e-04
mRNA splicing, via spliceosome	14	14.1×	7e-10
RNA splicing	8	7.8×	2e-03
mRNA processing	8	6.9×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	116
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
981804	NM_002298.5(LCP1):c.1122C>A (p.Tyr374Ter)	Pathogenic

SpliceAI

4544 predictions. Top by Δscore:

Variant	Effect	Δscore
13:46127721:TATC:T	acceptor_loss	1.0000
13:46127722:ATCTA:A	acceptor_loss	1.0000
13:46127723:TCTAA:T	acceptor_loss	1.0000
13:46127724:C:CA	acceptor_loss	1.0000
13:46127724:C:CC	acceptor_gain	1.0000
13:46127725:T:C	acceptor_loss	1.0000
13:46130809:CGTA:C	donor_gain	1.0000
13:46130810:GTA:G	donor_loss	1.0000
13:46130811:TAC:T	donor_loss	1.0000
13:46130812:A:AC	donor_gain	1.0000
13:46130812:A:C	donor_loss	1.0000
13:46130813:C:CA	donor_gain	1.0000
13:46130813:CT:C	donor_gain	1.0000
13:46130813:CTT:C	donor_gain	1.0000
13:46130813:CTTT:C	donor_gain	1.0000
13:46130813:CTTTG:C	donor_gain	1.0000
13:46130936:GTCC:G	acceptor_loss	1.0000
13:46130938:CCTA:C	acceptor_gain	1.0000
13:46130938:CCTAT:C	acceptor_loss	1.0000
13:46130939:C:CC	acceptor_gain	1.0000
13:46130939:C:CG	acceptor_loss	1.0000
13:46130940:T:G	acceptor_loss	1.0000
13:46134121:TTTTA:T	donor_loss	1.0000
13:46134122:TTTAC:T	donor_loss	1.0000
13:46134123:TTA:T	donor_loss	1.0000
13:46134124:TA:T	donor_loss	1.0000
13:46134125:A:AG	donor_loss	1.0000
13:46134126:CCT:C	donor_loss	1.0000
13:46134162:C:A	donor_gain	1.0000
13:46134249:ACCT:A	acceptor_loss	1.0000

AlphaMissense

4026 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:21489260:C:T	P223S	1.000
14:21489261:C:A	P223H	1.000
14:21489268:A:C	K225N	1.000
14:21489268:A:T	K225N	1.000
14:21489269:C:T	P226S	1.000
14:21489270:C:A	P226Q	1.000
14:21489270:C:G	P226R	1.000
14:21489273:T:A	V227D	1.000
14:21489279:C:A	A229E	1.000
14:21489281:T:A	Y230N	1.000
14:21489281:T:C	Y230H	1.000
14:21489281:T:G	Y230D	1.000
14:21489282:A:G	Y230C	1.000
14:21489284:G:C	A231P	1.000
14:21489285:C:A	A231D	1.000
14:21489290:T:A	F233I	1.000
14:21489290:T:C	F233L	1.000
14:21489290:T:G	F233V	1.000
14:21489291:T:C	F233S	1.000
14:21489291:T:G	F233C	1.000
14:21489292:C:A	F233L	1.000
14:21489292:C:G	F233L	1.000
14:21489293:T:A	F234I	1.000
14:21489293:T:C	F234L	1.000
14:21489293:T:G	F234V	1.000
14:21489294:T:C	F234S	1.000
14:21489294:T:G	F234C	1.000
14:21489295:T:A	F234L	1.000
14:21489295:T:G	F234L	1.000
14:21489297:G:C	R235P	1.000

dbSNP variants (sampled 300 via entrez): RS1000199939 (14:21480577 C>T), RS1000373945 (14:21498838 C>T), RS1000401178 (14:21495542 G>A), RS1000421889 (14:21478885 C>T), RS1000478235 (14:21487391 T>C), RS1000723956 (14:21498492 G>A,C), RS1000925697 (14:21479617 C>A,T), RS1001028814 (14:21480340 A>C), RS1001090633 (14:21476397 T>C), RS1001294350 (14:21476608 G>A,C), RS1001378184 (14:21480029 C>T), RS1001801062 (14:21490292 C>T), RS1001892833 (14:21496465 CAAAAA>C,CAAA,CAAAA,CAAAAAA,CAAAAAAA,CAAAAAAAA), RS1001924169 (14:21496250 G>A), RS1002027231 (14:21475823 C>A,G)

Disease associations

OMIM: gene MIM:614032 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
bone marrow failure syndrome	Moderate	Autosomal dominant

Mondo (2): hereditary breast ovarian cancer syndrome (MONDO:0003582), bone marrow failure syndrome (MONDO:0000159)

Orphanet (1): Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001766_1	Non-alcoholic fatty liver disease histology (other)	3.000000e-06
GCST003155_30	Systemic lupus erythematosus	6.000000e-07
GCST006585_2666	Blood protein levels	2.000000e-07
GCST012488_43	L1-L4 bone mineral density x serum urate levels interaction	4.000000e-06
GCST012490_459	Femur bone mineral density x serum urate levels interaction	5.000000e-10
GCST90002388_448	Lymphocyte count	2.000000e-14
GCST90002395_154	Mean platelet volume	2.000000e-09
GCST90002401_57	Platelet distribution width	1.000000e-10
GCST90002402_213	Platelet count	3.000000e-10

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0007701	spine bone mineral density
EFO:0004587	lymphocyte count
EFO:0007984	platelet component distribution width
EFO:0004309	platelet count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067464 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Valproic Acid	decreases expression, increases expression	2
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
beta-lapachone	increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
Zoledronic Acid	increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Arsenic	increases expression, increases abundance	1
Caffeine	increases phosphorylation	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ethyl Methanesulfonate	increases expression	1
Hydrogen Peroxide	affects expression	1
Methyl Methanesulfonate	increases expression	1
Selenium	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Vitamin E	increases expression	1
Aflatoxin B1	decreases methylation	1
Copper Sulfate	increases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697601	Binding	Inhibition of TOX4 (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

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00774527	PHASE3	COMPLETED	Comparison of Cy-Atg Vs Cy-Flu-Atg for the Conditioning Therapy in Allo-HCT
NCT02393508	PHASE3	UNKNOWN	The Impact of Red Cell Age on Product Utilization in the Chronically Transfused Outpatient Population
NCT06940570	PHASE3	SUSPENDED	Methadone as an Alternative Treatment for Children Underdoing HSCT
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT01050439	PHASE2	TERMINATED	Unrelated Donor Transplant for Malignant and Non-Malignant Disorders
NCT01596699	PHASE2	TERMINATED	Pilot Trial of Clofarabine Added to Standard Busulfan and Fludarabine for Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation
NCT01757145	PHASE2	UNKNOWN	Eltrombopag for Enhancing Platelet Engraftment in Adult Patients Undergoing Cord Blood Transplantation
NCT02224872	PHASE2	COMPLETED	Transplantation of Partially Mismatched Related or Matched Unrelated Bone Marrow for Patients With Refractory Severe Aplastic Anemia
NCT02277639	PHASE2	COMPLETED	Reduced Intensity Conditioning Using CD3+/CD19+ Depletion for Non Malignant Transplantable Diseases
NCT02349906	PHASE2	COMPLETED	Treosulfan-based Versus Busulfan-based Conditioning in Paediatric Patients With Non-malignant Diseases
NCT02722668	PHASE2	COMPLETED	UCB Transplant for Hematological Diseases Using a Non Myeloablative Prep
NCT04356469	PHASE2	RECRUITING	TCR Alpha Beta T-cell Depleted Haploidentical HCT in the Treatment of Non-Malignant Hematological Disorders in Children
NCT04558736	PHASE2	RECRUITING	Haploidentical HCT for Severe Aplastic Anemia
NCT04965597	PHASE2	COMPLETED	Treosulfan-Based Conditioning Regimen Before a Blood or Bone Marrow Transplant for the Treatment of Bone Marrow Failure Diseases (BMT CTN 1904)
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT07585136	PHASE1	NOT_YET_RECRUITING	Stem Cell Mobilization and Apheresis for Life-threatening Blood Disorders
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT01419704	PHASE1/PHASE2	WITHDRAWN	Phase I/II Pilot Study of Mixed Chimerism to Treat Hemoglobinopathies
NCT01966367	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation
NCT02055456	PHASE1/PHASE2	COMPLETED	Nandrolone Decanoate in the Treatment of Telomeropathies
NCT02337595	PHASE1/PHASE2	COMPLETED	Memory T-cell Infusion to Improve Immunity After TCR-alpha/Beta Depleted Hematopoietic Stem Cell Transplantation
NCT03128996	PHASE1/PHASE2	RECRUITING	Reduced Intensity Conditioning and Familial HLA-Mismatched BMT for Non-Malignant Disorders
NCT03513328	PHASE1/PHASE2	COMPLETED	Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation
NCT02356653	EARLY_PHASE1	RECRUITING	Expanded Access Protocol Using CD3+/CD19+ Depleted PBSC
NCT02928991	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Fludarabine Based RIC for Bone Marrow Failure Syndromes
NCT06787560	EARLY_PHASE1	RECRUITING	CD7 CAR-T Cell Sequential Allo-HSCT for Non-malignant Blood and Immune System Diseases
NCT00315419	Not specified	UNKNOWN	Identifying Characteristics of Bone Marrow Failure Syndromes
NCT00897260	Not specified	COMPLETED	Umbilical Cord Blood Transplantation As Treatment Of Adult Patients With Hematologic Disorders
NCT02720679	Not specified	RECRUITING	Investigation of the Genetics of Hematologic Diseases
NCT02958462	Not specified	RECRUITING	Pre-myeloid Cancer and Bone Marrow Failure Clinic Study
NCT03145545	Not specified	AVAILABLE	Expanded Access Protocol Using Alpha/Beta T and CD19+ Depleted PBSC
NCT04781790	Not specified	RECRUITING	French National Registry of Bone Marrow Failures