SELENOI

Summary

SELENOI (selenoprotein I, HGNC:29361) is a protein-coding gene on chromosome 2p23.3, encoding Ethanolaminephosphotransferase 1 (Q9C0D9). Ethanolaminephosphotransferase that catalyzes the transfer of phosphoethanolamine (PE) from CDP-ethanolamine to lipid acceptors, the final step in the synthesis of PE via the ‘Kennedy’ pathway.

The multi-pass transmembrane protein encoded by this gene belongs to the CDP-alcohol phosphatidyltransferase class-I family. It catalyzes the transfer of phosphoethanolamine from CDP-ethanolamine to diacylglycerol to produce phosphatidylethanolamine, which is involved in the formation and maintenance of vesicular membranes, regulation of lipid metabolism, and protein folding. This protein is a selenoprotein, containing the rare selenocysteine (Sec) amino acid at its active site. Sec is encoded by the UGA codon, which normally signals translation termination. The 3’ UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 85465 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spastic paraplegia 81, autosomal recessive (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 70 total — 4 pathogenic
• Phenotypes (HPO): 37
• Druggable target: yes
• MANE Select transcript: NM_033505

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29361
Approved symbol	SELENOI
Name	selenoprotein I
Location	2p23.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1724, SELI, SEPI
Ensembl gene	ENSG00000138018
Ensembl biotype	protein_coding
OMIM	607915
Entrez	85465

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000260585, ENST00000442141, ENST00000447170, ENST00000462301

RefSeq mRNA: 1 — MANE Select: NM_033505 NM_033505

CCDS: CCDS46240

Canonical transcript exons

ENST00000260585 — 10 exons

Exon	Start	End
ENSE00000932361	26373367	26373629
ENSE00000932362	26375040	26375148
ENSE00000962966	26364832	26364940
ENSE00000962967	26367146	26367220
ENSE00000962968	26383299	26383347
ENSE00001136464	26346143	26346289
ENSE00001506673	26386354	26386536
ENSE00001535481	26389005	26395885
ENSE00003460690	26364302	26364370
ENSE00003788867	26384959	26385139

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 95.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.6999 / max 297.9161, expressed in 1813 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19261	30.6249	1813
19262	1.0750	601

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	95.52	gold quality
jejunal mucosa	UBERON:0000399	94.30	gold quality
pancreatic ductal cell	CL:0002079	92.78	silver quality
tibialis anterior	UBERON:0001385	92.59	silver quality
secondary oocyte	CL:0000655	92.31	gold quality
middle temporal gyrus	UBERON:0002771	91.92	gold quality
upper arm skin	UBERON:0004263	90.81	silver quality
cerebellar vermis	UBERON:0004720	90.56	gold quality
islet of Langerhans	UBERON:0000006	89.15	gold quality
adrenal tissue	UBERON:0018303	89.07	gold quality
calcaneal tendon	UBERON:0003701	88.43	gold quality
buccal mucosa cell	CL:0002336	88.03	gold quality
endothelial cell	CL:0000115	87.88	silver quality
cortical plate	UBERON:0005343	87.83	gold quality
esophagus squamous epithelium	UBERON:0006920	87.22	gold quality
bone marrow cell	CL:0002092	85.81	gold quality
duodenum	UBERON:0002114	85.70	gold quality
Brodmann (1909) area 23	UBERON:0013554	85.68	gold quality
prefrontal cortex	UBERON:0000451	85.19	gold quality
Brodmann (1909) area 46	UBERON:0006483	85.12	gold quality
upper leg skin	UBERON:0004262	84.82	gold quality
corpus callosum	UBERON:0002336	84.63	gold quality
deltoid	UBERON:0001476	84.59	silver quality
liver	UBERON:0002107	84.35	gold quality
skin of hip	UBERON:0001554	84.13	gold quality
epithelial cell of pancreas	CL:0000083	83.95	silver quality
jejunum	UBERON:0002115	83.72	gold quality
tendon	UBERON:0000043	83.59	gold quality
colonic epithelium	UBERON:0000397	83.45	gold quality
ventricular zone	UBERON:0003053	83.38	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.77

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 8)

• These studies define the first human disorder arising due to defective CDP-ethanolamine biosynthesis and provide new insight into the role of Kennedy pathway components in human neurological function (PMID:28052917)
• intracellular localization of human selenoprotein SelI and the degree of expression of its gene in different human tumor cell lines (PMID:29101747)
• the indispensable role of EPT1 in the myelination process and neurodevelopment, and in the maintenance of normal homeostasis of ether-linked phospholipids in humans (PMID:29500230)
• Accessing the transcriptional status of selenoproteins in skin cancer-derived cell lines. (PMID:32142958)
• Roles for Selenoprotein I and Ethanolamine Phospholipid Synthesis in T Cell Activation. (PMID:34681834)
• Selenoprotein I (selenoi) as a critical enzyme in the central nervous system. (PMID:36007576)
• A novel homozygous synonymous splicing variant in SELENOI gene causes spastic paraplegia 81. (PMID:36942482)
• Biology and Roles in Diseases of Selenoprotein I Characterized by Ethanolamine Phosphotransferase Activity and Antioxidant Potential. (PMID:36963501)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	selenoi	ENSDARG00000060484
mus_musculus	Selenoi	ENSMUSG00000075703
rattus_norvegicus	Selenoi	ENSRNOG00000059295
drosophila_melanogaster	CG7149	FBGN0031948
drosophila_melanogaster	CG33116	FBGN0053116
caenorhabditis_elegans	ept-1	WBGENE00018797

Paralogs (2): CHPT1 (ENSG00000111666), CEPT1 (ENSG00000134255)

Protein

Protein identifiers

Ethanolaminephosphotransferase 1 — Q9C0D9 (reviewed: Q9C0D9)

Alternative names: Selenoprotein I

All UniProt accessions (3): Q9C0D9, C9JAG1, C9JEZ2

UniProt curated annotations — full annotation on UniProt →

Function. Ethanolaminephosphotransferase that catalyzes the transfer of phosphoethanolamine (PE) from CDP-ethanolamine to lipid acceptors, the final step in the synthesis of PE via the ‘Kennedy’ pathway. PE is the second most abundant phospholipid of membranes in mammals and is involved in various membrane-related cellular processes. The enzyme is critical for the synthesis of several PE species and also catalyzes the synthesis of plasmanyl-PE, a lipid required for proper myelination and neurodevelopment, from 1-alkyl-2-acylglycerol.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Widely expressed. Abundant in brain, placenta, liver and pancreas, followed by heart, skeletal muscle, lung and kidney. In brain it is strongly expressed in cerebellum, followed by the occipital pole and the frontal lobe.

Disease relevance. Spastic paraplegia 81, autosomal recessive (SPG81) [MIM:618768] A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG81 is a complicated form characterized by white matter abnormalities, hypomyelination with progressive white matter loss, delayed motor development, progressive spasticity, and impaired intellectual development and speech delay. Additional features may include bifid uvula, microcephaly, seizures, and variable ocular anomalies. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Phospholipid metabolism; phosphatidylethanolamine biosynthesis; phosphatidylethanolamine from ethanolamine: step 3/3.

Similarity. Belongs to the CDP-alcohol phosphatidyltransferase class-I family.

RefSeq proteins (1): NP_277040* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000462	CDP-OH_P_trans	Family
IPR014472	CHOPT	Family
IPR043130	CDP-OH_PTrfase_TM_dom	Homologous_superfamily
IPR048254	CDP_ALCOHOL_P_TRANSF_CS	Conserved_site

Pfam: PF01066

Enzyme classification (BRENDA):

• EC 2.7.8.1 — ethanolaminephosphotransferase (BRENDA: 17 organisms, 70 substrates, 58 inhibitors, 34 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

12 substrates with measured Km, best-characterized 12. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
CDP-ETHANOLAMINE	0.0006–1800	15
CDP-CHOLINE	0.036–10.7	4
1,2-DIOLEOYLGLYCEROL	0.0118–0.147	2
CMP	0.04–0.14	2
1-ALKYL-2-ACYL-SN-GLYCEROL	1.9	1
1-ARACHIDOYL-2-OCTADECENOYLGLYCEROL	0.182	1
1-DODECANOYL-2-OCTADECENOYLGLYCEROL	0.111	1
1-HEPTADECANOYL-2-OCTADECENOYLGLYCEROL	0.12	1
1-NONADECANOYL-2-OCTADECENOYLGLYCEROL	0.128	1
1-OCTADECANOYL-2-OCTADECENOYLGLYCEROL	0.167	1
1-PENTADECANOYL-2-OCTADECENOYLGLYCEROL	0.114	1
DIACYLGLYCEROL	0.063	1

Catalyzed reactions (Rhea), 2 shown:

• CDP-ethanolamine + a 1,2-diacyl-sn-glycerol = a 1,2-diacyl-sn-glycero-3-phosphoethanolamine + CMP + H(+) (RHEA:32943)
• 1-O-alkyl-2-acyl-sn-glycerol + CDP-ethanolamine = a 1-O-alkyl-2-acyl-sn-glycero-3-phosphoethanolamine + CMP + H(+) (RHEA:36187)

UniProt features (15 total): transmembrane region 10, initiator methionine 1, chain 1, non-standard amino acid 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for Q9C0D9 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

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 (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1483213	Synthesis of PE

MSigDB gene sets: 287 (showing top): RNGTGGGC_UNKNOWN, GCM_MAP4K4, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, TGCGCANK_UNKNOWN, GCM_GSPT1, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, TGCACTT_MIR519C_MIR519B_MIR519A, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, TGACCTY_ERR1_Q2, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, BONCI_TARGETS_OF_MIR15A_AND_MIR16_1, GCM_BCL2L1, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS

GO Biological Process (7): phosphatidylethanolamine biosynthetic process (GO:0006646), ether lipid biosynthetic process (GO:0008611), myelination (GO:0042552), lipid metabolic process (GO:0006629), lipid biosynthetic process (GO:0008610), phospholipid biosynthetic process (GO:0008654), glycerophospholipid biosynthetic process (GO:0046474)

GO Molecular Function (4): ethanolaminephosphotransferase activity (GO:0004307), metal ion binding (GO:0046872), transferase activity (GO:0016740), phosphotransferase activity, for other substituted phosphate groups (GO:0016780)

GO Cellular Component (4): endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lipid biosynthetic process	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
phosphatidylethanolamine metabolic process	1
glycerophospholipid biosynthetic process	1
ether lipid metabolic process	1
glycerol ether biosynthetic process	1
axon ensheathment	1
primary metabolic process	1
lipid metabolic process	1
biosynthetic process	1
phospholipid metabolic process	1
organophosphate biosynthetic process	1
glycerophospholipid metabolic process	1
phospholipid biosynthetic process	1
glycerolipid biosynthetic process	1
CDP-alcohol phosphatidyltransferase activity	1
cation binding	1
catalytic activity	1
transferase activity, transferring phosphorus-containing groups	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

852 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SELENOI	SELENOO	Q9BVL4	839
SELENOI	SELENOS	Q9BQE4	826
SELENOI	SELENOT	P62341	823
SELENOI	SELENOF	O60613	814
SELENOI	SELENOK	Q9Y6D0	811
SELENOI	SEPHS2	Q99611	809
SELENOI	SELENOH	Q8IZQ5	807
SELENOI	SELENOV	P59797	796
SELENOI	PCYT2	Q99447	795
SELENOI	ETNK1	Q9HBU6	790
SELENOI	SELENON	Q9NZV5	787
SELENOI	SELENOM	Q8WWX9	778
SELENOI	MSRB1	Q9NZV6	743
SELENOI	ETNK2	Q9NVF9	733
SELENOI	SELENOW	P63302	730

IntAct

13 interactions, top by confidence:

A	B	Type	Score
PPAT	SELENOI	psi-mi:“MI:0915”(physical association)	0.370
M	TM9SF1	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
COPB2	ESYT2	psi-mi:“MI:0914”(association)	0.350
RAB2A	TOMM40	psi-mi:“MI:0914”(association)	0.350
TMED10	PGRMC1	psi-mi:“MI:0914”(association)	0.350
VAPA	ESYT2	psi-mi:“MI:0914”(association)	0.350
VAPB	ESYT2	psi-mi:“MI:0914”(association)	0.350
TCTN3	TMEM120B	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (35): EPT1 (Two-hybrid), EPT1 (Two-hybrid), EPT1 (Proximity Label-MS), EPT1 (Affinity Capture-RNA), EPT1 (Positive Genetic), EPT1 (Protein-RNA), ACSL5 (Two-hybrid), CSNK2B (Two-hybrid), EPT1 (Proximity Label-MS), EPT1 (Proximity Label-MS), EPT1 (Negative Genetic), EPT1 (Affinity Capture-MS), EPT1 (Affinity Capture-MS), EPT1 (Affinity Capture-RNA), EPT1 (Proximity Label-MS)

ESM2 similar proteins: B0S4Q1, B9EN89, O43462, O54862, O75915, Q0III2, Q0IIK4, Q15041, Q1LZE6, Q28H54, Q3SWT5, Q4G019, Q4KLV1, Q4R4R4, Q502G2, Q56P28, Q5BJC1, Q5E978, Q5E9M1, Q5NV96, Q5R454, Q5R4X8, Q5RAC8, Q5ZLL0, Q66H21, Q66J05, Q66J44, Q68EQ9, Q6AXM5, Q6DFT6, Q6GPZ5, Q6IFY7, Q6INE8, Q7ZYQ3, Q80TA1, Q8BGS7, Q8C025, Q8CHX6, Q8LEQ4, Q8NFR3

Diamond homologs: O13901, O82567, O82568, P17898, P22140, Q1LZE6, Q28H54, Q4KLV1, Q54XM0, Q550W1, Q5NV96, Q5ZHQ5, Q5ZKD1, Q66H21, Q6AXM5, Q7ZW02, Q7ZYQ3, Q80TA1, Q8BGS7, Q8C025, Q8T2Q6, Q8WUD6, Q95ZE2, Q9C0D9, Q9Y6K0, Q17QM4, Q55AQ3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 17 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
endoplasmic reticulum to Golgi vesicle-mediated transport	5	42.5×	7e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	33
Likely benign	7
Benign	12

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
2576534	NM_033505.4(SELENOI):c.134C>T (p.Pro45Leu)	Pathogenic
2576535	NM_033505.4(SELENOI):c.126G>A (p.Lys42=)	Pathogenic
812574	NM_033505.4(SELENOI):c.335G>C (p.Arg112Pro)	Pathogenic
812575	NM_033505.4(SELENOI):c.732-2A>G	Pathogenic

SpliceAI

3718 predictions. Top by Δscore:

Variant	Effect	Δscore
2:26312937:TCTCA:T	donor_loss	1.0000
2:26312938:CTCAC:C	donor_loss	1.0000
2:26312939:TCA:T	donor_loss	1.0000
2:26312940:CACCT:C	donor_loss	1.0000
2:26312941:A:AT	donor_loss	1.0000
2:26312942:C:CA	donor_loss	1.0000
2:26313758:AC:A	donor_gain	1.0000
2:26313759:CC:C	donor_gain	1.0000
2:26314619:CTCAC:C	acceptor_gain	1.0000
2:26317494:ACC:A	donor_gain	1.0000
2:26317494:ACCC:A	donor_gain	1.0000
2:26317495:CCC:C	donor_gain	1.0000
2:26317495:CCCC:C	donor_gain	1.0000
2:26318964:A:AC	donor_gain	1.0000
2:26318965:C:CC	donor_gain	1.0000
2:26346279:A:AG	donor_gain	1.0000
2:26346279:A:G	donor_gain	1.0000
2:26364300:A:AG	acceptor_gain	1.0000
2:26364300:AG:A	acceptor_loss	1.0000
2:26364301:G:GT	acceptor_gain	1.0000
2:26364301:GT:G	acceptor_gain	1.0000
2:26364301:GTAC:G	acceptor_gain	1.0000
2:26364301:GTACA:G	acceptor_gain	1.0000
2:26364367:AAAG:A	donor_loss	1.0000
2:26364368:AAGG:A	donor_loss	1.0000
2:26364372:T:G	donor_loss	1.0000
2:26364824:A:AG	acceptor_gain	1.0000
2:26364825:A:G	acceptor_gain	1.0000
2:26364884:T:A	acceptor_gain	1.0000
2:26364941:G:C	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000155034 (2:26380352 T>C), RS1000159687 (2:26393160 G>A), RS1000201217 (2:26345974 C>T), RS1000227522 (2:26376532 A>G), RS1000250235 (2:26379269 A>G), RS1000346234 (2:26382953 C>G), RS1000499766 (2:26356123 T>C), RS1000529036 (2:26344219 A>C), RS1000538963 (2:26344434 G>A,T), RS1000546366 (2:26391833 T>G), RS1000636155 (2:26393443 T>C), RS1000712253 (2:26362855 A>G), RS1000786102 (2:26388409 A>G), RS1000863959 (2:26383329 G>A), RS1000938219 (2:26391536 C>G,T)

Disease associations

OMIM: gene MIM:607915 | disease phenotypes: MIM:618768

GenCC curated gene-disease

Disease	Classification	Inheritance
spastic paraplegia 81, autosomal recessive	Strong	Autosomal recessive
neurodevelopmental disorder	Moderate	Autosomal recessive

Mondo (2): spastic paraplegia 81, autosomal recessive (MONDO:0032905), neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

37 total (30 of 37 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000252	Microcephaly
HP:0000407	Sensorineural hearing impairment
HP:0000648	Optic atrophy
HP:0000750	Delayed speech and language development
HP:0001250	Seizure
HP:0001256	Mild intellectual disability
HP:0001260	Dysarthria
HP:0001270	Motor delay
HP:0001347	Hyperreflexia
HP:0002061	Lower limb spasticity
HP:0002191	Progressive spasticity
HP:0002194	Delayed gross motor development
HP:0002395	Lower limb hyperreflexia
HP:0002493	Upper motor neuron dysfunction
HP:0002540	Inability to walk
HP:0003487	Babinski sign
HP:0003623	Neonatal onset
HP:0004302	Functional motor deficit
HP:0006986	Upper limb spasticity
HP:0007020	Progressive spastic paraplegia
HP:0007199	Progressive spastic paraparesis
HP:0007220	Demyelinating motor neuropathy
HP:0007663	Reduced visual acuity
HP:0007768	Central retinal vessel vascular tortuosity
HP:0007814	Retinal pigment epithelial mottling
HP:0008376	Nasal dysarthria
HP:0008848	Moderately short stature

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005194_250	Coronary artery disease	2.000000e-07
GCST010241_320	Apolipoprotein A1 levels	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004614	apolipoprotein A 1 measurement

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): CHEMBL6067391 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.09	Kd	809.2	nM	CHEMBL5653589
6.09	ED50	809.2	nM	CHEMBL5653589
5.81	Kd	1535	nM	CHEMBL3752910
5.81	ED50	1535	nM	CHEMBL3752910

PubChem BioAssay actives

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

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148327: Binding affinity to human EPT1 incubated for 45 mins by Kinobead based pull down assay	kd	0.8092	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148327: Binding affinity to human EPT1 incubated for 45 mins by Kinobead based pull down assay	kd	1.5353	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, affects cotreatment, increases expression	6
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Cadmium	increases abundance, increases expression	2
Formaldehyde	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
titanium dioxide	decreases methylation	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
jinfukang	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Coumestrol	increases expression	1
Estradiol	increases expression	1
Fluoxetine	increases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Nickel	increases expression	1
Silicon Dioxide	decreases methylation	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651369	Binding	Binding affinity to human EPT1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9RE	Ubigene HEK293 SELENOI KO	Transformed cell line	Female
CVCL_E1W8	HAP1 EPT1 (-) 1	Cancer cell line	Male
CVCL_E1W9	HAP1 EPT1 (-) 2	Cancer cell line	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