TOE1

Summary

TOE1 (target of EGR1, exonuclease, HGNC:15954) is a protein-coding gene on chromosome 1p34.1, encoding Target of EGR1 protein 1 (Q96GM8). Inhibits cell growth rate and cell cycle. It is a selective cancer dependency (DepMap: 61.6% of cell lines).

Enables poly(A)-specific ribonuclease activity and snRNA binding activity. Involved in snRNA 3’-end processing. Located in Cajal body and cytoplasm. Implicated in pontocerebellar hypoplasia type 7.

Source: NCBI Gene 114034 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pontocerebellar hypoplasia type 7 (Strong, GenCC)
• Clinical variants (ClinVar): 257 total — 10 pathogenic, 19 likely-pathogenic
• Phenotypes (HPO): 66
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 61.6% of screened cell lines
• MANE Select transcript: NM_025077

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15954
Approved symbol	TOE1
Name	target of EGR1, exonuclease
Location	1p34.1
Locus type	gene with protein product
Status	Approved
Aliases	hCaf1z, TOE-1
Ensembl gene	ENSG00000132773
Ensembl biotype	protein_coding
OMIM	613931
Entrez	114034

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000372090, ENST00000460057, ENST00000471337, ENST00000477731, ENST00000495703, ENST00000874144, ENST00000874145, ENST00000874146, ENST00000938490, ENST00000938491

RefSeq mRNA: 1 — MANE Select: NM_025077 NM_025077

CCDS: CCDS521

Canonical transcript exons

ENST00000372090 — 8 exons

Exon	Start	End
ENSE00000905992	45342843	45343002
ENSE00001548144	45340170	45340304
ENSE00001813606	45343082	45343973
ENSE00003472555	45341073	45341215
ENSE00003483282	45341949	45342107
ENSE00003524434	45341303	45341343
ENSE00003607426	45341473	45341569
ENSE00003685409	45342384	45342643

Expression profiles

Bgee: expression breadth ubiquitous, 268 present calls, max score 90.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.0648 / max 250.1828, expressed in 1775 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2683	5.1686	1569
2684	3.4543	1045
2680	2.2461	866
2679	1.4623	855
2682	0.6601	294
2685	0.5873	346
2681	0.4862	207

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	90.35	gold quality
olfactory bulb	UBERON:0002264	90.24	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.26	gold quality
cervix squamous epithelium	UBERON:0006922	86.03	gold quality
parotid gland	UBERON:0001831	85.90	gold quality
mucosa of transverse colon	UBERON:0004991	83.84	gold quality
right lobe of thyroid gland	UBERON:0001119	83.45	gold quality
left testis	UBERON:0004533	83.45	gold quality
granulocyte	CL:0000094	83.43	gold quality
right testis	UBERON:0004534	83.36	gold quality
smooth muscle tissue	UBERON:0001135	83.14	gold quality
rectum	UBERON:0001052	82.90	gold quality
tongue squamous epithelium	UBERON:0006919	82.81	silver quality
testis	UBERON:0000473	82.76	gold quality
ventricular zone	UBERON:0003053	82.66	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.53	gold quality
lymph node	UBERON:0000029	82.41	gold quality
left lobe of thyroid gland	UBERON:0001120	81.91	gold quality
spleen	UBERON:0002106	81.59	gold quality
endothelial cell	CL:0000115	81.54	gold quality
thymus	UBERON:0002370	81.37	silver quality
left uterine tube	UBERON:0001303	81.34	gold quality
thyroid gland	UBERON:0002046	81.32	gold quality
cervix epithelium	UBERON:0004801	81.15	silver quality
nasal cavity epithelium	UBERON:0005384	81.01	silver quality
transverse colon	UBERON:0001157	80.95	gold quality
small intestine Peyer’s patch	UBERON:0003454	80.52	gold quality
body of stomach	UBERON:0001161	80.17	gold quality
left ovary	UBERON:0002119	80.02	gold quality
body of uterus	UBERON:0009853	79.96	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.68

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, MYOD1

miRNA regulators (miRDB)

23 targeting TOE1, 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-548C-3P	99.99	74.01	7587
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-367-5P	98.84	67.18	902
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-499B-5P	98.35	68.39	988
HSA-MIR-1267	98.24	69.05	837
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-552-3P	96.68	64.12	1026
HSA-MIR-764	94.16	64.85	656

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 61.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 7)

• TOE1 has a role in the growth inhibitory activity of Egr1 (PMID:12562764)
• Antiviral potency of TOE1 and its cell-penetrating capability have been identified to lie within a 35-amino-acid region containing the nuclear localization sequence (PMID:26056259)
• Human cells with reduced levels of TOE1 accumulated 3’-end-extended pre-snRNA. (PMID:28092684)
• PARN and TOE1 do not modulate the length of mRNA poly(A) tails. Rather, they promote the maturation of nuclear small non-coding RNAs (ncRNAs). PARN and TOE1 act redundantly on some ncRNAs, most prominently small Cajal body-specific RNAs (scaRNAs). (PMID:29669292)
• Our study highlights a mechanistic link between TOE1 mutation, improper hTR processing and telomere dysfunction in diseases such as Pontocerebella Hypoplasia Type 7 . (PMID:30371886)
• Novel compound heterozygous missense variants in TOE1 gene associated with pontocerebellar hypoplasia type 7. (PMID:36738896)
• Genetic and prenatal diagnosis of a Chinese pedigree with pathogenic TOE1 variants causing pontocerebellar hypoplasia type 7. (PMID:37635087)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	toe1	ENSDARG00000077544
mus_musculus	Toe1	ENSMUSG00000028688
rattus_norvegicus	Toe1	ENSRNOG00000017561
caenorhabditis_elegans		WBGENE00013265

Paralogs (2): PARN (ENSG00000140694), PNLDC1 (ENSG00000146453)

Protein

Protein identifiers

Target of EGR1 protein 1 — Q96GM8 (reviewed: Q96GM8)

All UniProt accessions (1): Q96GM8

UniProt curated annotations — full annotation on UniProt →

Function. Inhibits cell growth rate and cell cycle. Induces CDKN1A expression as well as TGF-beta expression. Mediates the inhibitory growth effect of EGR1. Involved in the maturation of snRNAs and snRNA 3’-tail processing.

Subunit / interactions. Interacts with U1, U2, U4, U5 and U6 snRNAs.

Subcellular location. Nucleus. Nucleolus. Nucleus speckle.

Tissue specificity. Widely expressed.

Disease relevance. Pontocerebellar hypoplasia 7 (PCH7) [MIM:614969] A form of pontocerebellar hypoplasia, a group of related disorders characterized by underdevelopment of the pons and the cerebellum. Pontocerebellar hypoplasia also causes impaired growth of other parts of the brain, leading to an unusually small head size. PCH7 patients manifest delayed psychomotor development, hypotonia, breathing abnormalities, and gonadal abnormalities. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the CAF1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96GM8-1	1	yes
Q96GM8-2	2

RefSeq proteins (1): NP_079353* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000571	Znf_CCCH	Domain
IPR006941	RNase_CAF1	Family
IPR012337	RNaseH-like_sf	Homologous_superfamily
IPR036397	RNaseH_sf	Homologous_superfamily
IPR051181	CAF1_poly(A)_ribonucleases	Family

Pfam: PF00642, PF04857

UniProt features (33 total): sequence variant 13, modified residue 4, region of interest 4, sequence conflict 3, helix 2, initiator methionine 1, chain 1, splice variant 1, zinc finger region 1, strand 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2FC6	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96GM8-F1	79.16	0.63

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 (4): 5, 358, 428, 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 252 (showing top): GOMF_RNA_NUCLEASE_ACTIVITY, GOMF_NUCLEASE_ACTIVITY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, PUJANA_CHEK2_PCC_NETWORK, MUELLER_PLURINET, chr1p34, GARCIA_TARGETS_OF_FLI1_AND_DAX1_DN, FISCHER_DREAM_TARGETS, GOMF_EXONUCLEASE_ACTIVITY, GOBP_SNRNA_PROCESSING, GOCC_NUCLEAR_SPECK, GOCC_CAJAL_BODY, GOCC_NUCLEAR_BODY, GOCC_RIBONUCLEOPROTEIN_GRANULE

GO Biological Process (2): snRNA 3’-end processing (GO:0034472), RNA metabolic process (GO:0016070)

GO Molecular Function (7): 3’-5’-RNA exonuclease activity (GO:0000175), poly(A)-specific ribonuclease activity (GO:0004535), zinc ion binding (GO:0008270), snRNA binding (GO:0017069), nucleic acid binding (GO:0003676), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (7): nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), Cajal body (GO:0015030), nuclear body (GO:0016604), nuclear speck (GO:0016607), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
nuclear lumen	2
cellular anatomical structure	2
intracellular membraneless organelle	2
nuclear ribonucleoprotein granule	2
snRNA processing	1
RNA 3’-end processing	1
nucleic acid metabolic process	1
3’-5’ exonuclease activity	1
RNA exonuclease activity, producing 5’-phosphomonoesters	1
3’-5’-RNA exonuclease activity	1
transition metal ion binding	1
RNA binding	1
cation binding	1
intracellular anatomical structure	1
nucleoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1502 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TOE1	ANGEL2	Q5VTE6	834
TOE1	TSEN54	Q7Z6J9	674
TOE1	MUTYH	Q9UIF7	561
TOE1	RARS2	Q5T160	529
TOE1	CNOT7	Q9UIV1	499
TOE1	CNOT8	Q9UFF9	499
TOE1	EXOSC3	Q9NQT5	491
TOE1	GEMIN4	P57678	475
TOE1	PARN	O95453	474
TOE1	TSEN15	Q8WW01	472
TOE1	TSEN34	Q9BSV6	472
TOE1	GEMIN5	Q8TEQ6	470
TOE1	TSEN2	Q8NCE0	469
TOE1	CNOT6	Q9ULM6	466
TOE1	GEMIN8	Q9NWZ8	462

IntAct

170 interactions, top by confidence:

A	B	Type	Score
IFIT1	IFIT3	psi-mi:“MI:0914”(association)	0.920
SNRPF	GEMIN2	psi-mi:“MI:0914”(association)	0.910
IFIT2	IFIT3	psi-mi:“MI:0914”(association)	0.780
SNRPE	GEMIN2	psi-mi:“MI:0914”(association)	0.770
SART3	PRPF4	psi-mi:“MI:0914”(association)	0.730
SNRPG	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SNRPB	PRMT5	psi-mi:“MI:0914”(association)	0.670
H1-1	RRP8	psi-mi:“MI:0914”(association)	0.640
SNRPA1	HTATSF1	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
SNRNP70	GEMIN2	psi-mi:“MI:0914”(association)	0.640
SNRPA1	U2SURP	psi-mi:“MI:0914”(association)	0.640
GABARAP	IPO5	psi-mi:“MI:0914”(association)	0.590
TP53	TOE1	psi-mi:“MI:0914”(association)	0.580
TOE1	TP53	psi-mi:“MI:0914”(association)	0.580
TP53	TOE1	psi-mi:“MI:0407”(direct interaction)	0.580
APP	TOE1	psi-mi:“MI:0915”(physical association)	0.560
KSR2	POLR3A	psi-mi:“MI:0914”(association)	0.530
H1-6	ZNF724	psi-mi:“MI:0914”(association)	0.530
H1-4	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
RPS2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
SNRPE	PRMT5	psi-mi:“MI:0914”(association)	0.530
SNRPN	PRMT5	psi-mi:“MI:0914”(association)	0.530

BioGRID (195): TOE1 (Affinity Capture-MS), TOE1 (Affinity Capture-MS), TOE1 (Affinity Capture-MS), TOE1 (Affinity Capture-MS), TOE1 (Affinity Capture-MS), TOE1 (Co-fractionation), TOE1 (Affinity Capture-MS), TOE1 (Affinity Capture-MS), TOE1 (Affinity Capture-MS), TOE1 (Affinity Capture-MS), TOE1 (Affinity Capture-MS), TOE1 (Affinity Capture-MS), TOE1 (Affinity Capture-MS), TOE1 (Affinity Capture-MS), TOE1 (Affinity Capture-MS)

ESM2 similar proteins: A0JMH2, A1L251, A2ARP1, A7Z050, D3ZEY4, E7FCP8, E9QAM5, O00562, O35954, O42412, O95822, P0C644, P0C7A1, P12617, P16386, P40935, P49898, P49899, P52824, P53370, P54310, P70563, Q17QN2, Q2KI24, Q3URQ7, Q499U8, Q5EU90, Q5I0I8, Q5RAR6, Q5RDF1, Q5TGY1, Q5U2N3, Q5XIL6, Q68J42, Q6P5E8, Q6PD24, Q6PFW1, Q80YU0, Q8BX80, Q8CH40

Diamond homologs: Q17QN2, Q5RAR6, Q90ZA1, Q96GM8, Q9D2E2, Q5R6R6, Q8NA58

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 171 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
Metabolism of non-coding RNA	9	47.6×	3e-12
SARS-CoV-2 modulates host translation machinery	15	28.0×	2e-16
Formation of Senescence-Associated Heterochromatin Foci (SAHF)	5	28.0×	7e-06
SARS-CoV-1 modulates host translation machinery	9	23.1×	3e-09
Eukaryotic Translation Initiation	8	20.6×	5e-08
Cap-dependent Translation Initiation	8	20.6×	5e-08
mRNA Splicing	22	20.1×	5e-21
mRNA Polyadenylation	27	19.8×	8e-26

GO biological processes:

GO term	Partners	Fold	FDR
U2-type prespliceosome assembly	12	47.4×	2e-15
spliceosomal snRNP assembly	12	44.1×	4e-15
negative regulation of DNA recombination	6	42.7×	3e-07
RNA splicing, via transesterification reactions	9	35.5×	3e-10
chromosome condensation	6	32.0×	2e-06
spliceosomal complex assembly	7	26.7×	5e-07
mRNA splicing, via spliceosome	30	17.4×	6e-26
positive regulation of mRNA splicing, via spliceosome	5	17.2×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	19
Uncertain significance	125
Likely benign	68
Benign	9

Top pathogenic / likely-pathogenic (29)

Variant ID	HGVS	Classification
1455307	NC_000001.10:g.(?45805881)(45809328_?)del	Pathogenic
1986984	NM_025077.4(TOE1):c.668del (p.Pro223fs)	Pathogenic
3000338	NM_025077.4(TOE1):c.805G>T (p.Glu269Ter)	Pathogenic
3624127	NM_025077.4(TOE1):c.505C>T (p.Gln169Ter)	Pathogenic
3653619	NM_025077.4(TOE1):c.626dup (p.Ser210fs)	Pathogenic
417749	NM_025077.4(TOE1):c.518T>G (p.Val173Gly)	Pathogenic
417751	NM_025077.4(TOE1):c.957C>A (p.His319Gln)	Pathogenic
523872	NM_025077.4(TOE1):c.733G>T (p.Glu245Ter)	Pathogenic
524117	NM_025077.4(TOE1):c.940_941del (p.Gln314fs)	Pathogenic
849146	NM_025077.4(TOE1):c.448C>T (p.Gln150Ter)	Pathogenic
1275738	NM_025077.4(TOE1):c.551G>T (p.Arg184Leu)	Likely pathogenic
1279928	NM_025077.4(TOE1):c.237-2A>G	Likely pathogenic
1325214	NM_025077.4(TOE1):c.1018C>T (p.Arg340Ter)	Likely pathogenic
1676460	NM_025077.4(TOE1):c.544C>T (p.Arg182Ter)	Likely pathogenic
1687385	NM_025077.4(TOE1):c.1062del (p.Thr355fs)	Likely pathogenic
1690619	NM_025077.4(TOE1):c.1172del (p.Asn391fs)	Likely pathogenic
2630730	NM_025077.4(TOE1):c.908_910del (p.Phe303del)	Likely pathogenic
3074953	NM_001128425.2(MUTYH):c.36+1G>T	Likely pathogenic
4082531	NM_025077.4(TOE1):c.373_374del (p.Leu125fs)	Likely pathogenic
4813066	NM_025077.4(TOE1):c.764del (p.Asn255fs)	Likely pathogenic
690333	NM_025077.4(TOE1):c.937C>G (p.Pro313Ala)	Likely pathogenic
690334	NM_025077.4(TOE1):c.957C>T (p.His319=)	Likely pathogenic
690335	NM_025077.4(TOE1):c.955C>T (p.His319Tyr)	Likely pathogenic
690336	NM_025077.4(TOE1):c.219G>C (p.Arg73Ser)	Likely pathogenic
690337	NM_025077.4(TOE1):c.716T>C (p.Phe239Ser)	Likely pathogenic
690339	NM_025077.4(TOE1):c.693T>A (p.Tyr231Ter)	Likely pathogenic
690340	NM_025077.4(TOE1):c.1487C>T (p.Ser496Phe)	Likely pathogenic
930764	NM_025077.4(TOE1):c.913-2A>G	Likely pathogenic
985544	NM_025077.4(TOE1):c.539T>A (p.Leu180Gln)	Likely pathogenic

SpliceAI

1222 predictions. Top by Δscore:

Variant	Effect	Δscore
1:45341193:C:G	donor_gain	1.0000
1:45341301:A:AG	acceptor_gain	1.0000
1:45341302:G:GG	acceptor_gain	1.0000
1:45341340:ACCA:A	donor_gain	1.0000
1:45341341:CCA:C	donor_gain	1.0000
1:45341342:CA:C	donor_gain	1.0000
1:45341343:AGT:A	donor_loss	1.0000
1:45341344:G:GG	donor_gain	1.0000
1:45341344:G:T	donor_loss	1.0000
1:45341944:CCCAG:C	acceptor_loss	1.0000
1:45341947:A:AG	acceptor_gain	1.0000
1:45341947:AG:A	acceptor_gain	1.0000
1:45341947:AGG:A	acceptor_gain	1.0000
1:45341947:AGGGT:A	acceptor_gain	1.0000
1:45341948:G:GT	acceptor_gain	1.0000
1:45341948:GG:G	acceptor_gain	1.0000
1:45341948:GGG:G	acceptor_gain	1.0000
1:45341948:GGGT:G	acceptor_gain	1.0000
1:45341948:GGGTG:G	acceptor_gain	1.0000
1:45342065:GCA:G	donor_gain	1.0000
1:45342068:G:GG	donor_gain	1.0000
1:45342106:AGGTA:A	donor_loss	1.0000
1:45342107:GGTAG:G	donor_loss	1.0000
1:45342108:GT:G	donor_loss	1.0000
1:45342378:A:AG	acceptor_gain	1.0000
1:45342379:T:G	acceptor_gain	1.0000
1:45342382:A:AG	acceptor_gain	1.0000
1:45342382:AG:A	acceptor_gain	1.0000
1:45342382:AGG:A	acceptor_gain	1.0000
1:45342382:AGGGT:A	acceptor_gain	1.0000

AlphaMissense

3362 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:45342033:T:C	F140L	1.000
1:45342035:C:A	F140L	1.000
1:45342035:C:G	F140L	1.000
1:45341309:A:C	S68R	0.999
1:45341311:T:A	S68R	0.999
1:45341311:T:G	S68R	0.999
1:45341313:G:A	G69E	0.999
1:45341511:C:A	A92D	0.999
1:45342034:T:C	F140S	0.999
1:45342580:A:T	K230I	0.999
1:45341307:T:C	L67P	0.998
1:45341312:G:A	G69R	0.998
1:45341312:G:C	G69R	0.998
1:45341312:G:T	G69W	0.998
1:45341489:T:G	Y85D	0.998
1:45341520:G:C	R95P	0.998
1:45342037:T:C	L141P	0.998
1:45342464:T:A	N191K	0.998
1:45342464:T:G	N191K	0.998
1:45342466:G:A	G192D	0.998
1:45342544:T:C	L218P	0.998
1:45342573:G:C	D228H	0.998
1:45342574:A:C	D228A	0.998
1:45342574:A:T	D228V	0.998
1:45342581:A:C	K230N	0.998
1:45342581:A:T	K230N	0.998
1:45341205:C:A	A62D	0.997
1:45341211:A:C	D64A	0.997
1:45341211:A:T	D64V	0.997
1:45341305:G:C	E66D	0.997

dbSNP variants (sampled 300 via entrez): RS1001144609 (1:45339009 C>T), RS1002321565 (1:45342684 A>G), RS1002637086 (1:45342032 G>A), RS1002653774 (1:45344271 T>C,G), RS1002914081 (1:45344452 C>G,T), RS1002995018 (1:45342425 G>A,C), RS1003275266 (1:45338190 T>C), RS1003985418 (1:45339998 C>T), RS1004038100 (1:45341929 C>A), RS1004840661 (1:45339708 T>C), RS1004992920 (1:45338682 G>A,C), RS1005046708 (1:45338394 G>A,T), RS1006118734 (1:45340894 A>G,T), RS1006142932 (1:45344285 C>T), RS1007156298 (1:45341554 G>T)

Disease associations

OMIM: gene MIM:613931 | disease phenotypes: MIM:614969, MIM:613659, MIM:608456

GenCC curated gene-disease

Disease	Classification	Inheritance
pontocerebellar hypoplasia type 7	Strong	Autosomal recessive

Mondo (4): pontocerebellar hypoplasia type 7 (MONDO:0013993), gastric cancer (MONDO:0001056), familial adenomatous polyposis 2 (MONDO:0012041), hereditary neoplastic syndrome (MONDO:0015356)

Orphanet (4): Pontocerebellar hypoplasia type 7 (Orphanet:284339), Inherited cancer-predisposing syndrome (Orphanet:140162), Attenuated familial adenomatous polyposis (Orphanet:220460), MUTYH-related polyposis (Orphanet:247798)

HPO phenotypes

66 total (30 of 66 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000054	Micropenis
HP:0000062	Ambiguous genitalia
HP:0000133	Gonadal dysgenesis
HP:0000151	Aplasia of the uterus
HP:0000215	Thick upper lip vermilion
HP:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000253	Progressive microcephaly
HP:0000286	Epicanthus
HP:0000336	Prominent supraorbital ridges
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000431	Wide nasal bridge
HP:0000455	Broad nasal tip
HP:0000582	Upslanted palpebral fissure
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000657	Oculomotor apraxia
HP:0000664	Synophrys
HP:0000729	Autistic behavior
HP:0000768	Pectus carinatum
HP:0000954	Single transverse palmar crease
HP:0001007	Hirsutism
HP:0001010	Hypopigmentation of the skin
HP:0001249	Intellectual disability
HP:0001250	Seizure

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
C563924	Colorectal Adenomatous Polyposis, Autosomal Recessive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725065 (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

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

pChembl	Type	Value	Unit	Molecule
5.08	IC50	8340	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 6 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	2179038: Inhibition of TOE1 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	8.3400	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
FR900359	affects phosphorylation	1
pirinixic acid	affects binding, increases activity, increases expression	1
deoxynivalenol	increases expression	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
ferrous chloride	decreases expression	1
nivalenol	increases expression	1
CGP 52608	increases reaction, affects binding	1
K 7174	decreases expression	1
abrine	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Leflunomide	decreases expression	1
Benzo(a)pyrene	increases expression	1
Caffeine	decreases phosphorylation	1
Coumestrol	increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Diethylhexyl Phthalate	increases abundance, increases methylation	1
Ivermectin	decreases expression	1
Manganese	decreases expression, increases abundance	1
Methyl Methanesulfonate	increases expression	1
Nickel	increases expression	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, decreases 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
CHEMBL5697768	Binding	Inhibition of TOE1 (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)

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

Trial	Phase	Status	Title
NCT00365508	PHASE4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00558155	PHASE4	COMPLETED	The Impact of Immunostimulating Nutrition on the Outcome of Surgery
NCT00576940	PHASE4	COMPLETED	Standard and Immunostimulating Enteral Nutrition in Surgical Patients
NCT00666978	PHASE4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT01038154	PHASE4	UNKNOWN	Study to Evaluate the Efficacy of Pravastatin on Survival and Recurrence of Advanced Gastroesophageal Cancer
NCT01234272	PHASE4	COMPLETED	Comparison of the Analgesic Effect Between Intrathecal Morphine and IV-fentanyl Patient Controlled Analgesia (ITM-IVPCA) and Epidural PCA (PCEA) in Patients Undergoing Gastrectomy -Randomized Allocation Study-
NCT01260194	PHASE4	TERMINATED	A Study of Herceptin (Trastuzumab) in Combination With Standard Chemotherapy in Patients With HER Positive Metastatic Gastric Cancer
NCT01271582	PHASE4	UNKNOWN	Investigation of Association Between UGT1A1 Polymorphisms and Irinotecan Toxicity in Korean Patients
NCT01401075	PHASE4	COMPLETED	RCT With Adjuvant Mistletoe Treatment in Gastric Cancer Patients
NCT01471756	PHASE4	COMPLETED	Improving Complete Endoscopic Mucosal Resection (EMR) of Colorectal Neoplasia
NCT01766765	PHASE4	UNKNOWN	Early Jejunostomy Nutrition Minimizes Time to Chemotherapy
NCT01910948	PHASE4	UNKNOWN	Perioperative Application of Omega-3 Polyunsaturated Fatty Acids in Gastric Cancer Patients
NCT01927328	PHASE4	UNKNOWN	Iron Replacement in Oesophagogastric Neoplasia
NCT01962272	PHASE4	COMPLETED	The Effect of Nutritional Counseling for Cancer Patients
NCT01962376	PHASE4	UNKNOWN	Preoperative Chemotherapy With Bevacizumab For Potentially Resectable Gastric Cancer With Liver Metastasis
NCT02047994	PHASE4	RECRUITING	Multicentric Randomized Study of H. Pylori Eradication and Pepsinogen Testing for Prevention of Gastric Cancer Mortality
NCT02235246	PHASE4	COMPLETED	The Effect of Perioperative Intravenous Magnesium on Pain After Endoscopic Submucosal Dissection for Gastric Neoplasm: Prospective Randomized Double-blind Placebo Controlled Study
NCT02366819	PHASE4	SUSPENDED	Genetic Analysis-Guided Irinotecan Hydrochloride Dosing of mFOLFIRINOX in Treating Patients With Locally Advanced Gastroesophageal or Stomach Cancer
NCT02401971	PHASE4	UNKNOWN	Irinotecan Plus Thalidomide in Second Line Advanced Gastric Cancer
NCT02458573	PHASE4	COMPLETED	Comparison of the Effects of Continuous Epidural Analgesia and Continuous Intravenous Analgesia on Postoperative Bowel Movement in Patients Undergoing Laparoscopic Gastrectomy
NCT02638584	PHASE4	COMPLETED	Effects of Ilaprazole on Ulcer Healing Rate and Prevention of Gastrointestinal Bleeding in the Patients Undergone ESD.
NCT02776527	PHASE4	UNKNOWN	A Clinical Trial of Maintenance Treatment of Apatinib in Advanced Gastric Cancer Patients Have Completed Postoprative Adjuvant Chemotherapy
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03550482	PHASE4	COMPLETED	Oncoxin® and Quality of Life in Cancer Patients
NCT03609892	PHASE4	COMPLETED	Helicobacter Rescue Therapy With Berberine Plus Amoxicillin Quadruple Therapy Versus Tetracycline Plus Furazolidone Quadruple Therapy
NCT03642093	PHASE4	UNKNOWN	HOPE - A Study to Evaluate the Effect of a Prehabilitation Program on GI Cancer Patients Planning to Undergo Surgery
NCT03733639	PHASE4	UNKNOWN	Tisseel® as a Reinforcement of Esophagojejunal Anastomoses
NCT04168346	PHASE4	NOT_YET_RECRUITING	Preoperative Intravenous Iron Therapy in Patients With Gastric Cancer
NCT04209933	PHASE4	COMPLETED	Helicobacter Pylori Eradication With Different Bismuth Quadruple Therapies
NCT04591028	PHASE4	WITHDRAWN	A Study to Evaluate Indocyanine Green Lymphangiography to Improve Lymphadenectomy in Gastric Cancer Patients
NCT04607057	PHASE4	UNKNOWN	Supplemental Parenteral Nutrition During Postgastrectomy in Nutritionally at Risk Patient
NCT04660123	PHASE4	COMPLETED	A Real World Study of Bismuth Colloidal Pectin Granules Quadruple Therapy for H. Pylori Eradication
NCT04678492	PHASE4	COMPLETED	Helicobacter Rescue Therapy With High-dose Esomeprazole and Amoxicillin Dual Therapy Versus Bismuth-containing Quadruple Therapy
NCT04697186	PHASE4	COMPLETED	Helicobacter Pylori Eradication With Berberine Plus Amoxicillin Triple Therapy Versus Bismuth-containing Quadruple Therapy
NCT05029453	PHASE4	UNKNOWN	Apatinib Combined With Chemotherapy Versus Chemotherapy in Second-line Gastric Cancer Receiving Prior Anti-PD-1 Therapy
NCT05183126	PHASE4	RECRUITING	Pharmacokinetic Study of Skeletal Muscle Area-based Paclitaxel Infusion in Patients With Cancer
NCT05354856	PHASE4	TERMINATED	The Effect of Chemoradiotherapy on Gastric Perfusion in Patients With Gastric Cancer.
NCT05410535	PHASE4	COMPLETED	To Evaluate Efficacy of Ursodeoxycholic Acid (UDCA) for the Prevention of Gallstone Formation After Gasterectomy
NCT05498766	PHASE4	NOT_YET_RECRUITING	Effect and Safety of Huaier Granule Versus SOX Regimen in Gastric Cancer Patients
NCT05518929	PHASE4	COMPLETED	Hypoxia During Gastroenterological Endoscope Procedures Sedated With Ciprofol In Overweight Or Obesity Patients