DHPS

Summary

DHPS (deoxyhypusine synthase, HGNC:2869) is a protein-coding gene on chromosome 19p13.13, encoding Deoxyhypusine synthase (P49366). Catalyzes the NAD-dependent oxidative cleavage of spermidine and the subsequent transfer of the butylamine moiety of spermidine to the epsilon-amino group of a critical lysine residue of the eIF-5A precursor protein to form the intermediate deoxyhypusine residue. It is a selective cancer dependency (DepMap: 89.1% of cell lines).

This gene encodes a protein that is required for the formation of hypusine, a unique amino acid formed by the posttranslational modification of only one protein, eukaryotic translation initiation factor 5A. The encoded protein catalyzes the first step in hypusine formation by transferring the butylamine moiety of spermidine to a specific lysine residue of the eukaryotic translation initiation factor 5A precursor, forming an intermediate deoxyhypusine residue. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 1725 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with seizures and speech and walking impairment (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 119 total — 4 likely-pathogenic
• Phenotypes (HPO): 31
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 89.1% of screened cell lines
• MANE Select transcript: NM_001930

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2869
Approved symbol	DHPS
Name	deoxyhypusine synthase
Location	19p13.13
Locus type	gene with protein product
Status	Approved
Aliases	MIG13
Ensembl gene	ENSG00000095059
Ensembl biotype	protein_coding
OMIM	600944
Entrez	1725

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 20 protein_coding, 7 nonsense_mediated_decay, 6 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000210060, ENST00000351660, ENST00000593400, ENST00000593423, ENST00000593432, ENST00000593473, ENST00000594424, ENST00000595100, ENST00000595844, ENST00000595912, ENST00000596162, ENST00000596847, ENST00000597152, ENST00000598246, ENST00000598850, ENST00000599481, ENST00000600451, ENST00000600510, ENST00000600639, ENST00000600864, ENST00000601537, ENST00000601639, ENST00000862636, ENST00000862637, ENST00000862638, ENST00000862639, ENST00000862640, ENST00000917713, ENST00000917714, ENST00000917715, ENST00000917716, ENST00000917717, ENST00000949481, ENST00000949482

RefSeq mRNA: 6 — MANE Select: NM_001930 NM_001206974, NM_001369691, NM_001369692, NM_001369693, NM_001930, NM_013406

CCDS: CCDS12276, CCDS12277, CCDS59354

Canonical transcript exons

ENST00000210060 — 9 exons

Exon	Start	End
ENSE00002980445	12681560	12681880
ENSE00003198419	12675717	12675933
ENSE00003529524	12676017	12676142
ENSE00003542520	12677108	12677211
ENSE00003575774	12679623	12679719
ENSE00003598808	12679801	12679922
ENSE00003599470	12680161	12680325
ENSE00003659082	12679457	12679543
ENSE00003789308	12677291	12677396

Expression profiles

Bgee: expression breadth ubiquitous, 145 present calls, max score 98.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 59.1627 / max 320.5754, expressed in 1822 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179328	54.4123	1822
179327	2.3779	1335
179329	2.0336	1278
179326	0.3390	148

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	98.31	gold quality
cerebellum	UBERON:0002037	98.26	gold quality
cerebellar cortex	UBERON:0002129	98.26	gold quality
cerebellar hemisphere	UBERON:0002245	98.26	gold quality
cortical plate	UBERON:0005343	98.18	gold quality
ganglionic eminence	UBERON:0004023	98.06	gold quality
embryo	UBERON:0000922	98.05	gold quality
primary visual cortex	UBERON:0002436	97.72	gold quality
pituitary gland	UBERON:0000007	97.66	gold quality
adenohypophysis	UBERON:0002196	97.43	gold quality
right uterine tube	UBERON:0001302	97.42	gold quality
left ovary	UBERON:0002119	97.28	gold quality
prostate gland	UBERON:0002367	97.21	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.08	gold quality
prefrontal cortex	UBERON:0000451	97.07	gold quality
right ovary	UBERON:0002118	97.01	gold quality
skeletal muscle tissue	UBERON:0001134	96.98	gold quality
ovary	UBERON:0000992	96.97	gold quality
endocervix	UBERON:0000458	96.94	gold quality
body of uterus	UBERON:0009853	96.94	gold quality
frontal cortex	UBERON:0001870	96.91	gold quality
frontal lobe	UBERON:0016525	96.91	gold quality
fundus of stomach	UBERON:0001160	96.79	gold quality
right frontal lobe	UBERON:0002810	96.76	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.72	gold quality
left lobe of thyroid gland	UBERON:0001120	96.71	gold quality
body of stomach	UBERON:0001161	96.69	gold quality
right lobe of thyroid gland	UBERON:0001119	96.68	gold quality
uterine cervix	UBERON:0000002	96.67	gold quality
thyroid gland	UBERON:0002046	96.60	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.96

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF, E2F4, E2F6

miRNA regulators (miRDB)

18 targeting DHPS, 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-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4527	99.66	67.43	714
HSA-MIR-6503-5P	99.62	66.96	597
HSA-MIR-5197-3P	98.71	67.05	1905

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 89.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 16)

• deoxyhypusine synthase has a role in generating spermidine or homospermidine (PMID:12788913)
• deoxyhypusine synthase and its phosphorylation modification may have other independent cellular functions because of versatile roles of deoxyhypusine synthase (PMID:14749535)
• crystal structure of deoxyhypusine synthase reveals the configuration of the active enzyme and of an enzyme.NAD.inhibitor ternary complex (PMID:15100216)
• Dhps-437 and dhps-540 are strongly associated with SP treatment failure and should be evaluated further as a method for surveillance of SP-based therapy in DRC. (PMID:19055622)
• A novel series of cell movements that orient the polarity of Lrp12/Mig13a-expressing neurons and their axons just prior to cortical plate assembly do not occur in reeler mutant mice. (PMID:20439316)
• DHPS and WDR83 were capable of forming an RNA duplex at overlapping 3’ untranslated regions and this duplex increased their mutual stability, which was required for the bidirectional regulation. (PMID:22491477)
• eIF-5A as well as the hypusine-forming enzymes deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH) are highly overexpressed in glioblastoma patient sample (PMID:22927971)
• Whereas, dhps mutation study revealed that triple mutant haplotype AGEAA (S436A+A437G+K540E) associated with Sulphadoxine resistance was found among 26% of P. falciparum field isolates. (PMID:25511211)
• the use of N1-Guanyl-1,7-diaminoheptane, a DHPS inhibitor, resulted in a significant decrease in tumor formation in vivo. In patients with esophageal squamous cell carcinoma (ESCC), overexpression of DHPS in ESCC tumors was significantly associated with worse recurrence-free survival, and correlated with distant metastasis. (PMID:27041563)
• data suggest that rare biallelic variants in DHPS result in reduced enzyme activity that limits the hypusination of eIF5A and are associated with a neurodevelopmental disorder (PMID:30661771)
• DHPS-dependent hypusination of eIF5A1/2 is necessary for TGFbeta/fibronectin-induced breast cancer metastasis and associates with prognostically unfavorable genomic alterations in TP53 (PMID:31558321)
• Half Way to Hypusine-Structural Basis for Substrate Recognition by Human Deoxyhypusine Synthase. (PMID:32235505)
• eIF5A-Independent Role of DHPS in p21(CIP1) and Cell Fate Regulation. (PMID:34947982)
• Cryo-EM structure of human eIF5A-DHS complex reveals the molecular basis of hypusination-associated neurodegenerative disorders. (PMID:36973244)
• Deoxyhypusine synthase mutations alter the post-translational modification of eukaryotic initiation factor 5A resulting in impaired human and mouse neural homeostasis. (PMID:37333770)
• Clinical significance of mutations in dihydropteroate synthase in Pneumocystis jirovecii pneumonia among non-HIV-infected patients. (PMID:37925109)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dhps	ENSDARG00000003270
mus_musculus	Dhps	ENSMUSG00000060038
rattus_norvegicus	Dhps	ENSRNOG00000004219
drosophila_melanogaster	Dhps	FBGN0035854
caenorhabditis_elegans		WBGENE00012460

Protein

Protein identifiers

Deoxyhypusine synthase — P49366 (reviewed: P49366)

All UniProt accessions (13): P49366, B4E3M2, M0QX43, M0QXT2, M0QYZ7, M0QZT3, M0R0J4, M0R0V2, M0R1T2, M0R1T4, M0R253, M0R264, Q5J8M5

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the NAD-dependent oxidative cleavage of spermidine and the subsequent transfer of the butylamine moiety of spermidine to the epsilon-amino group of a critical lysine residue of the eIF-5A precursor protein to form the intermediate deoxyhypusine residue. This is the first step of the post-translational modification of that lysine into an unusual amino acid residue named hypusine. Hypusination is unique to mature eIF-5A factor and is essential for its function.

Subunit / interactions. Homotetramer formed by a dimer of dimers.

Disease relevance. Neurodevelopmental disorder with seizures and speech and walking impairment (NEDSSWI) [MIM:618480] An autosomal recessive disorder characterized by global developmental delay with intellectual disability and poor speech acquisition, and walking difficulties due to hypotonia, hypertonia, spasticity, or poor coordination. Additional features include seizures, mild dysmorphic features, and variable short stature. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Protein modification; eIF5A hypusination.

Miscellaneous. Inactive.

Similarity. Belongs to the deoxyhypusine synthase family.

Isoforms (3)

UniProt ID	Names	Canonical?
P49366-1	Long	yes
P49366-2	Short
P49366-3	3

RefSeq proteins (6): NP_001193903, NP_001356620, NP_001356621, NP_001356622, NP_001921, NP_037538 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002773	Deoxyhypusine_synthase	Family
IPR029035	DHS-like_NAD/FAD-binding_dom	Homologous_superfamily
IPR036982	Deoxyhypusine_synthase_sf	Homologous_superfamily

Pfam: PF01916

Enzyme classification (BRENDA):

• EC 2.5.1.46 — deoxyhypusine synthase (BRENDA: 37 organisms, 87 substrates, 98 inhibitors, 39 Km, 9 kcat entries)

Substrate kinetics (BRENDA)

10 substrates with measured Km, best-characterized 10. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
SPERMIDINE	0.0006–0.37	14
NAD+	0.0012–0.81	7
[EIF5A-PRECURSOR]-L-LYSINE	0.0001–1.12	5
[EIF5A-PRECURSOR]-LYSINE	0.0007–0.0018	3
1,3-DIAMINOPROPANE	0.0954–0.1058	2
PUTRESCINE	0.0015–0.203	2
[EIF5A-PRECURSOR]-DEOXYHYPUSINE	0.0066–0.0086	2
HOMOSPERMINE	0.0193	1
[EIF5A-1-PRECURSOR]-LYSINE	0.0015	1
[EIF5A-2-PRECURSOR]-LYSINE	0.0083	1

Catalyzed reactions (Rhea), 1 shown:

• [eIF5A protein]-L-lysine + spermidine = [eIF5A protein]-deoxyhypusine + propane-1,3-diamine (RHEA:33299)

UniProt features (76 total): helix 20, mutagenesis site 15, binding site 12, sequence conflict 9, strand 7, turn 5, sequence variant 3, splice variant 2, chain 1, active site 1, modified residue 1

Structure

Experimental structures (PDB)

89 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9IEG	X-RAY DIFFRACTION	1.27
9IE3	X-RAY DIFFRACTION	1.3
9IEA	X-RAY DIFFRACTION	1.3
9IDT	X-RAY DIFFRACTION	1.33
9IDV	X-RAY DIFFRACTION	1.33
9IDU	X-RAY DIFFRACTION	1.34
9IDW	X-RAY DIFFRACTION	1.34
9IE4	X-RAY DIFFRACTION	1.34
9IE1	X-RAY DIFFRACTION	1.35
9IDY	X-RAY DIFFRACTION	1.37
9IEN	X-RAY DIFFRACTION	1.37
9ID3	X-RAY DIFFRACTION	1.39
9IDO	X-RAY DIFFRACTION	1.39
9IDQ	X-RAY DIFFRACTION	1.39
9IE2	X-RAY DIFFRACTION	1.39
9IE9	X-RAY DIFFRACTION	1.39
9IEM	X-RAY DIFFRACTION	1.39
9IED	X-RAY DIFFRACTION	1.4
6XXJ	X-RAY DIFFRACTION	1.41
9IDA	X-RAY DIFFRACTION	1.41
9IEQ	X-RAY DIFFRACTION	1.41
9IE7	X-RAY DIFFRACTION	1.42
9IDF	X-RAY DIFFRACTION	1.43
9IDM	X-RAY DIFFRACTION	1.43
9IDN	X-RAY DIFFRACTION	1.43
9IE5	X-RAY DIFFRACTION	1.43
9ID6	X-RAY DIFFRACTION	1.44
9IDR	X-RAY DIFFRACTION	1.44
9IDZ	X-RAY DIFFRACTION	1.44
9IET	X-RAY DIFFRACTION	1.44

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49366-F1	93.95	0.89

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 329 (nucleophile)

Ligand- & substrate-binding residues (12): 308–309; 314–316; 323–329; 342–343; 105–109; 131–133; 136–137; 137; 238; 243; 283; 288

Post-translational modifications (1): 78

Mutagenesis-validated functional residues (15):

Position	Phenotype
106	strongly reduced nad and spermidine binding. reduced activity.
109	strongly reduced spermidine binding. reduced activity.
137	strongly reduced nad binding. strongly reduced formation of covalent intermediate.
238	strongly reduced nad binding. strongly reduced formation of covalent intermediate.
243	reduces spermidine binding by 98%. strongly reduced formation of covalent intermediate.
287	reduces covalent intermediate formation and deoxyhypusine synthesis by 99.5%. retains low spermidine cleavage activity.
288	reduces spermidine binding by 98%. strongly reduced nad binding. strongly reduced formation of covalent intermediate.
305	strongly reduced nad binding. no effect on enzyme activity.
313	strongly reduced nad binding.
316	reduces spermidine binding by 98%. loss of covalent intermediate formation and deoxyhypusine synthesis.
317	strongly reduced nad binding. no effect on enzyme activity.
323	reduces spermidine binding by 98%. strongly reduced formation of covalent intermediate.
327	reduces spermidine binding by 98%. loss of covalent intermediate formation and deoxyhypusine synthesis.
329	loss of covalent intermediate formation and deoxyhypusine synthesis.
342	strongly reduced nad binding. strongly reduced activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-204626	Hypusine synthesis from eIF5A-lysine

MSigDB gene sets: 263 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, HSIAO_HOUSEKEEPING_GENES, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_TRANSLATION, GCM_PRKCG, GOBP_CELL_CELL_ADHESION, GOBP_POLYAMINE_METABOLIC_PROCESS, GOBP_PROTEIN_MATURATION, GOBP_LEUKOCYTE_PROLIFERATION, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_POSITIVE_REGULATION_OF_CELL_ACTIVATION

GO Biological Process (8): translation (GO:0006412), spermidine metabolic process (GO:0008216), positive regulation of cell population proliferation (GO:0008284), positive regulation of T cell proliferation (GO:0042102), glucose homeostasis (GO:0042593), spermidine catabolic process (GO:0046203), protein maturation (GO:0051604), peptidyl-hypusine biosynthetic process (GO:0008612)

GO Molecular Function (4): deoxyhypusine synthase activity (GO:0034038), identical protein binding (GO:0042802), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	2
cellular anatomical structure	2
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein biosynthetic process	1
polyamine metabolic process	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
T cell proliferation	1
regulation of T cell proliferation	1
positive regulation of lymphocyte proliferation	1
positive regulation of T cell activation	1
carbohydrate homeostasis	1
polyamine catabolic process	1
spermidine metabolic process	1
gene expression	1
biosynthetic process	1
protein maturation	1
transferase activity, transferring alkyl or aryl (other than methyl) groups	1
protein binding	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1889 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DHPS	DOHH	Q9BU89	997
DHPS	EIF5A	P10159	994
DHPS	EIF5AL1	Q6IS14	837
DHPS	EIF5A2	Q9GZV4	793
DHPS	DHFR	P00374	789
DHPS	ODC1	P11926	698
DHPS	SRM	P19623	691
DHPS	SMS	P52788	667
DHPS	SH3BP5	O60239	637
DHPS	AGMAT	Q9BSE5	544
DHPS	XPO4	Q9C0E2	531
DHPS	PAOX	Q6QHF9	527
DHPS	ATP2B4	P23634	526
DHPS	SMOX	Q9NWM0	526
DHPS	WDR83	Q9BRX9	518

IntAct

160 interactions, top by confidence:

A	B	Type	Score
MAPK3	DHPS	psi-mi:“MI:0915”(physical association)	0.920
RPL9	DHPS	psi-mi:“MI:0915”(physical association)	0.870
DHPS	RPL9	psi-mi:“MI:0915”(physical association)	0.870
RPL9	DHPS	psi-mi:“MI:0914”(association)	0.870
EIF5A2	DHPS	psi-mi:“MI:0915”(physical association)	0.830
DHPS	EIF5A2	psi-mi:“MI:0915”(physical association)	0.830
EIF5A2	DHPS	psi-mi:“MI:0914”(association)	0.830
MAPK1	MAPK3	psi-mi:“MI:0914”(association)	0.770
MAPK3	MAPK1	psi-mi:“MI:0914”(association)	0.770
RAB27B	DHPS	psi-mi:“MI:0915”(physical association)	0.720
DHPS	EIF5A	psi-mi:“MI:0915”(physical association)	0.720
DHPS	RAB27B	psi-mi:“MI:0915”(physical association)	0.720
EIF5A	DHPS	psi-mi:“MI:0915”(physical association)	0.720
DHPS	DHPS	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (156): DHPS (Two-hybrid), EIF5A (Two-hybrid), PTPRH (Two-hybrid), RAB27B (Two-hybrid), REL (Two-hybrid), RPL9 (Two-hybrid), ZNF138 (Two-hybrid), VASH1 (Two-hybrid), WDYHV1 (Two-hybrid), EIF5A2 (Two-hybrid), BRCA1 (Two-hybrid), DHPS (Affinity Capture-MS), DHPS (Affinity Capture-MS), DHPS (Affinity Capture-MS), DHPS (Affinity Capture-MS)

ESM2 similar proteins: A2RRU1, A7MB78, A8XKV0, G3ISL7, J9VTK7, O06983, O08739, O09178, O31041, O34823, O34872, O93869, P05033, P0A1Z0, P0A1Z1, P0A9H3, P0A9H4, P0ABE9, P0ABF0, P0DUG1, P0DUM8, P10759, P13807, P13834, P17625, P23109, P23337, P27134, P27472, P28345, P45148, P49366, P52095, P54840, P61517, P61518, P9WEN1, Q01432, Q09580, Q22460

Diamond homologs: A3MVC9, A4YHK6, A6URC0, A8AA61, B0R5L2, B5APK2, B6YVB1, C3MPN8, C3MYN2, C3N5B4, C3NDW8, C3NHT5, C4KGY0, C5A5L0, O26230, O27984, O28088, O50105, O94337, P38791, P49365, P49366, P60038, Q38BX0, Q3TXU5, Q4J978, Q54MQ7, Q58224, Q5JEY0, Q6AY53, Q6CG56, Q6CNG7, Q6EWQ6, Q6FRN2, Q6KZL5, Q6RJS2, Q75EW4, Q8PV89, Q8Q051, Q8SQN2

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
ERK1/2	“up-regulates activity”	DHPS	phosphorylation
DHPS	“up-regulates activity”	EIF5A	“post translational modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	4
Uncertain significance	81
Likely benign	13
Benign	4

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1331656	NM_001930.4(DHPS):c.216_217dup (p.Lys73fs)	Likely pathogenic
2506774	NM_001930.4(DHPS):c.785-1G>C	Likely pathogenic
4526968	NM_001930.4(DHPS):c.709dup (p.Thr237fs)	Likely pathogenic
560195	NM_001930.4(DHPS):c.912_917del (p.Tyr305_Ile306del)	Likely pathogenic

SpliceAI

1514 predictions. Top by Δscore:

Variant	Effect	Δscore
19:12675513:C:CA	acceptor_gain	1.0000
19:12675521:A:AG	acceptor_gain	1.0000
19:12675521:AG:A	acceptor_gain	1.0000
19:12675522:G:GA	acceptor_loss	1.0000
19:12675522:G:GG	acceptor_gain	1.0000
19:12675522:GG:G	acceptor_gain	1.0000
19:12675522:GGGT:G	acceptor_gain	1.0000
19:12675895:C:CT	acceptor_gain	1.0000
19:12675929:TAGAC:T	acceptor_gain	1.0000
19:12675931:GACCT:G	acceptor_loss	1.0000
19:12675934:C:CC	acceptor_gain	1.0000
19:12676012:CTTA:C	donor_loss	1.0000
19:12676013:TTA:T	donor_loss	1.0000
19:12676014:TA:T	donor_loss	1.0000
19:12676015:A:AC	donor_gain	1.0000
19:12676015:AC:A	donor_gain	1.0000
19:12676016:C:CT	donor_gain	1.0000
19:12676016:CC:C	donor_gain	1.0000
19:12676138:TTCCG:T	acceptor_gain	1.0000
19:12676139:TCCG:T	acceptor_gain	1.0000
19:12676140:CCG:C	acceptor_gain	1.0000
19:12676140:CCGC:C	acceptor_gain	1.0000
19:12676141:CG:C	acceptor_gain	1.0000
19:12676141:CGC:C	acceptor_gain	1.0000
19:12676143:C:CC	acceptor_gain	1.0000
19:12676145:G:C	acceptor_gain	1.0000
19:12676154:C:CT	acceptor_gain	1.0000
19:12677102:ACTC:A	donor_loss	1.0000
19:12677103:CTCA:C	donor_loss	1.0000
19:12677104:TCACC:T	donor_loss	1.0000

AlphaMissense

2435 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:12676050:C:A	W327C	0.999
19:12676050:C:G	W327C	0.999
19:12676052:A:G	W327R	0.999
19:12676052:A:T	W327R	0.999
19:12677348:C:G	D243H	0.999
19:12677359:C:T	G239D	0.999
19:12677362:T:A	D238V	0.999
19:12677363:C:G	D238H	0.999
19:12679534:A:G	W201R	0.999
19:12679534:A:T	W201R	0.999
19:12679719:C:A	R165S	0.999
19:12679719:C:G	R165S	0.999
19:12679801:C:A	R165M	0.999
19:12679882:T:A	D138V	0.999
19:12679882:T:G	D138A	0.999
19:12679883:C:G	D138H	0.999
19:12679885:T:A	E137V	0.999
19:12680206:A:C	S109R	0.999
19:12680206:A:T	S109R	0.999
19:12680208:T:G	S109R	0.999
19:12676110:G:C	N307K	0.998
19:12676110:G:T	N307K	0.998
19:12677134:G:C	H288D	0.998
19:12677135:C:A	K287N	0.998
19:12677135:C:G	K287N	0.998
19:12677291:C:G	D262H	0.998
19:12677347:T:A	D243V	0.998
19:12677347:T:G	D243A	0.998
19:12677350:C:T	G242D	0.998
19:12677351:C:G	G242R	0.998

dbSNP variants (sampled 300 via entrez): RS1000133427 (19:12678027 T>A,C,G), RS1000217733 (19:12682860 C>G), RS1000308722 (19:12678753 A>G,T), RS1000433971 (19:12682965 A>C), RS1000465152 (19:12683124 T>C), RS1000624419 (19:12673587 T>C), RS1000718066 (19:12677654 T>C), RS1000730248 (19:12672374 T>C), RS1001158984 (19:12675208 C>G), RS1001400495 (19:12674983 G>A,T), RS1001847921 (19:12683797 C>T), RS1001871017 (19:12673542 T>A,C), RS1001883433 (19:12680288 T>C), RS1002165997 (19:12673912 C>G), RS1002400255 (19:12673711 C>T)

Disease associations

OMIM: gene MIM:600944 | disease phenotypes: MIM:618480

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with seizures and speech and walking impairment	Strong	Autosomal recessive

Mondo (1): neurodevelopmental disorder with seizures and speech and walking impairment (MONDO:0032775)

Orphanet (0):

HPO phenotypes

31 total (30 of 31 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000319	Smooth philtrum
HP:0000369	Low-set ears
HP:0000426	Prominent nasal bridge
HP:0000490	Deeply set eye
HP:0000750	Delayed speech and language development
HP:0000960	Sacral dimple
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001562	Oligohydramnios
HP:0001622	Premature birth
HP:0002019	Constipation
HP:0002317	Unsteady gait
HP:0002353	EEG abnormality
HP:0002509	Limb hypertonia
HP:0003593	Infantile onset
HP:0004209	Clinodactyly of the 5th finger
HP:0004322	Short stature
HP:0008936	Axial hypotonia
HP:0010880	Increased nuchal translucency
HP:0011856	Pica
HP:0031936	Delayed ability to walk
HP:0034210	Fetal intraventricular hemorrhage
HP:0100023	Recurrent hand flapping
HP:0100602	Preeclampsia
HP:0100876	Infra-orbital crease

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002401_250	Platelet distribution width	3.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4415 (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: 16,499 (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
CHEMBL957	BOSENTAN	4	16,499

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

ChEMBL bioactivities

51 potent at pChembl≥5 of 76 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.04	IC50	9.2	nM	CHEMBL5281395
7.96	IC50	11	nM	CHEMBL5265996
7.92	IC50	12	nM	CHEMBL5288132
7.85	IC50	14	nM	CHEMBL5091313
7.85	IC50	14	nM	CHEMBL5269564
7.75	IC50	18	nM	CHEMBL5274333
7.58	IC50	26	nM	CHEMBL5268272
7.54	IC50	29	nM	CHEMBL5267547
7.52	IC50	30	nM	CHEMBL5278471
7.40	IC50	40	nM	CHEMBL5079375
7.30	IC50	50	nM	CHEMBL5074971
7.21	IC50	62	nM	CHEMBL4555677
7.16	IC50	69	nM	CHEMBL5281395
7.04	IC50	92	nM	CHEMBL4543218
7.00	IC50	100	nM	CHEMBL5075342
6.96	IC50	110	nM	CHEMBL5282634
6.92	IC50	120	nM	CHEMBL4462702
6.85	IC50	140	nM	CHEMBL229457
6.82	IC50	150	nM	CHEMBL5281552
6.80	IC50	160	nM	CHEMBL5287156
6.77	IC50	170	nM	CHEMBL5288132
6.75	IC50	180	nM	CHEMBL5084409
6.75	IC50	180	nM	CHEMBL5091281
6.64	IC50	230	nM	CHEMBL5265996
6.50	IC50	320	nM	CHEMBL5090481
6.48	IC50	330	nM	CHEMBL5078063
6.39	IC50	410	nM	CHEMBL5269564
6.37	IC50	430	nM	CHEMBL4442298
6.36	IC50	440	nM	CHEMBL5283409
6.30	IC50	500	nM	CHEMBL229457
6.28	IC50	530	nM	CHEMBL5091279
6.25	IC50	560	nM	CHEMBL5070084
6.24	IC50	580	nM	CHEMBL5278471
6.20	IC50	630	nM	CHEMBL5267547
6.19	IC50	640	nM	CHEMBL5081296
6.10	IC50	790	nM	CHEMBL5268272
6.08	IC50	840	nM	CHEMBL4447948
5.93	IC50	1170	nM	CHEMBL5075319
5.76	IC50	1720	nM	CHEMBL229457
5.64	IC50	2300	nM	CHEMBL4470208
5.64	IC50	2290	nM	CHEMBL5089864
5.62	IC50	2380	nM	CHEMBL5080635
5.37	IC50	4310	nM	CHEMBL5080971
5.36	IC50	4420	nM	CHEMBL5073964
5.27	IC50	5400	nM	CHEMBL4572958
5.26	IC50	5430	nM	CHEMBL5078229
5.20	IC50	6300	nM	CHEMBL5269301
5.16	IC50	6900	nM	CHEMBL4555677
5.09	IC50	8200	nM	CHEMBL5281757
5.06	IC50	8700	nM	CHEMBL5274695

PubChem BioAssay actives

51 with measured affinity, of 184 total; 40 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
6-[(2R)-1-amino-4-methylpentan-2-yl]-3-pyridin-3-yl-4,5-dihydrothieno[2,3-c]pyridin-7-one	1943588: Displacement of [3H]spermidine trihydrochloride from N-terminal 6his tagged TEV fused human DHPS expressed in Escherichia coli BL21 (DE3) incubated for 120 mins in the presence of 14 uM NAD+ by radiometric assay	ic50	0.0092	uM
6-[(2R)-1-amino-3,3-dimethylbutan-2-yl]-3-pyridin-3-yl-4,5-dihydrothieno[2,3-c]pyridin-7-one	1943588: Displacement of [3H]spermidine trihydrochloride from N-terminal 6his tagged TEV fused human DHPS expressed in Escherichia coli BL21 (DE3) incubated for 120 mins in the presence of 14 uM NAD+ by radiometric assay	ic50	0.0110	uM
6-[(1R)-2-amino-1-cyclohexylethyl]-3-pyridin-3-yl-4,5-dihydrothieno[2,3-c]pyridin-7-one	1943588: Displacement of [3H]spermidine trihydrochloride from N-terminal 6his tagged TEV fused human DHPS expressed in Escherichia coli BL21 (DE3) incubated for 120 mins in the presence of 14 uM NAD+ by radiometric assay	ic50	0.0120	uM
6-[(1R)-2-amino-1-phenylethyl]-3-pyridin-3-yl-4,5-dihydrothieno[2,3-c]pyridin-7-one	1943588: Displacement of [3H]spermidine trihydrochloride from N-terminal 6his tagged TEV fused human DHPS expressed in Escherichia coli BL21 (DE3) incubated for 120 mins in the presence of 14 uM NAD+ by radiometric assay	ic50	0.0140	uM
2-(4-bromophenyl)-6-chloro-5-(2-methoxyphenoxy)pyrimidin-4-amine	1820366: Inhibition of DHPS (unknown origin ) incubated for 30 mins by NAD/NADH-Glow assay	ic50	0.0140	uM
6-(2-amino-1-phenylethyl)-3-pyridin-3-yl-4,5-dihydrothieno[2,3-c]pyridin-7-one	1943588: Displacement of [3H]spermidine trihydrochloride from N-terminal 6his tagged TEV fused human DHPS expressed in Escherichia coli BL21 (DE3) incubated for 120 mins in the presence of 14 uM NAD+ by radiometric assay	ic50	0.0180	uM
6-(1-aminopentan-2-yl)-3-pyridin-3-yl-4,5-dihydrothieno[2,3-c]pyridin-7-one	1943588: Displacement of [3H]spermidine trihydrochloride from N-terminal 6his tagged TEV fused human DHPS expressed in Escherichia coli BL21 (DE3) incubated for 120 mins in the presence of 14 uM NAD+ by radiometric assay	ic50	0.0260	uM
6-[2-amino-1-(1-benzothiophen-3-yl)ethyl]-3-pyridin-3-yl-4,5-dihydrothieno[2,3-c]pyridin-7-one	1943588: Displacement of [3H]spermidine trihydrochloride from N-terminal 6his tagged TEV fused human DHPS expressed in Escherichia coli BL21 (DE3) incubated for 120 mins in the presence of 14 uM NAD+ by radiometric assay	ic50	0.0290	uM
6-(1-aminooctan-2-yl)-3-pyridin-3-yl-4,5-dihydrothieno[2,3-c]pyridin-7-one	1943588: Displacement of [3H]spermidine trihydrochloride from N-terminal 6his tagged TEV fused human DHPS expressed in Escherichia coli BL21 (DE3) incubated for 120 mins in the presence of 14 uM NAD+ by radiometric assay	ic50	0.0300	uM
6-chloro-5-(2-methoxyphenoxy)-2-(3-methoxyphenyl)pyrimidin-4-amine	1820366: Inhibition of DHPS (unknown origin ) incubated for 30 mins by NAD/NADH-Glow assay	ic50	0.0400	uM
2-benzyl-6-chloro-5-(2-methoxyphenoxy)pyrimidin-4-amine	1820366: Inhibition of DHPS (unknown origin ) incubated for 30 mins by NAD/NADH-Glow assay	ic50	0.0500	uM
6-bromo-N-(1H-indol-4-yl)-1-benzothiophene-2-carboxamide	1561253: Inhibition of human N-terminal His6-tagged TEV protease site linked DHPS expressed in Escherichia coli BL21 (DE3) assessed as reduction in radiolabelled amino-butylidene incorporation in eIF5A using [3H]Spermidine trichloride as substrate after 90 to 120 mins in presence of eIF5A and 14 uM NAD+ by Topcount scintillation counting method	ic50	0.0620	uM
N-(1H-indol-4-yl)-6-iodo-1-benzothiophene-2-carboxamide	1561253: Inhibition of human N-terminal His6-tagged TEV protease site linked DHPS expressed in Escherichia coli BL21 (DE3) assessed as reduction in radiolabelled amino-butylidene incorporation in eIF5A using [3H]Spermidine trichloride as substrate after 90 to 120 mins in presence of eIF5A and 14 uM NAD+ by Topcount scintillation counting method	ic50	0.0920	uM
6-chloro-2-(4-chlorophenyl)-5-(2-methoxyphenoxy)pyrimidin-4-amine	1820366: Inhibition of DHPS (unknown origin ) incubated for 30 mins by NAD/NADH-Glow assay	ic50	0.1000	uM
6-[2-amino-1-(1H-indol-3-yl)ethyl]-3-pyridin-3-yl-4,5-dihydrothieno[2,3-c]pyridin-7-one	1943588: Displacement of [3H]spermidine trihydrochloride from N-terminal 6his tagged TEV fused human DHPS expressed in Escherichia coli BL21 (DE3) incubated for 120 mins in the presence of 14 uM NAD+ by radiometric assay	ic50	0.1100	uM
6-chloro-N-(1H-indol-4-yl)-1-benzothiophene-2-carboxamide	1561253: Inhibition of human N-terminal His6-tagged TEV protease site linked DHPS expressed in Escherichia coli BL21 (DE3) assessed as reduction in radiolabelled amino-butylidene incorporation in eIF5A using [3H]Spermidine trichloride as substrate after 90 to 120 mins in presence of eIF5A and 14 uM NAD+ by Topcount scintillation counting method	ic50	0.1200	uM
2-(7-aminoheptyl)guanidine	1561253: Inhibition of human N-terminal His6-tagged TEV protease site linked DHPS expressed in Escherichia coli BL21 (DE3) assessed as reduction in radiolabelled amino-butylidene incorporation in eIF5A using [3H]Spermidine trichloride as substrate after 90 to 120 mins in presence of eIF5A and 14 uM NAD+ by Topcount scintillation counting method	ic50	0.1400	uM
6-(2-hydroxy-1-phenylethyl)-3-pyridin-3-yl-4,5-dihydrothieno[2,3-c]pyridin-7-one	1943588: Displacement of [3H]spermidine trihydrochloride from N-terminal 6his tagged TEV fused human DHPS expressed in Escherichia coli BL21 (DE3) incubated for 120 mins in the presence of 14 uM NAD+ by radiometric assay	ic50	0.1500	uM
6-[(1S)-2-amino-1-phenylethyl]-3-pyridin-3-yl-4,5-dihydrothieno[2,3-c]pyridin-7-one	1943588: Displacement of [3H]spermidine trihydrochloride from N-terminal 6his tagged TEV fused human DHPS expressed in Escherichia coli BL21 (DE3) incubated for 120 mins in the presence of 14 uM NAD+ by radiometric assay	ic50	0.1600	uM
2-[6-amino-5-(2-methoxyphenoxy)-2-(4-methylphenyl)pyrimidin-4-yl]oxyethanol	1820366: Inhibition of DHPS (unknown origin ) incubated for 30 mins by NAD/NADH-Glow assay	ic50	0.1800	uM
6-chloro-2-(4-iodophenyl)-5-(2-methoxyphenoxy)pyrimidin-4-amine	1820366: Inhibition of DHPS (unknown origin ) incubated for 30 mins by NAD/NADH-Glow assay	ic50	0.1800	uM
2-[6-amino-2-benzyl-5-(2-methoxyphenoxy)pyrimidin-4-yl]oxyethanol	1820366: Inhibition of DHPS (unknown origin ) incubated for 30 mins by NAD/NADH-Glow assay	ic50	0.3200	uM
2-[6-amino-2-(3-fluorophenyl)-5-(2-methoxyphenoxy)pyrimidin-4-yl]oxyethanol	1820366: Inhibition of DHPS (unknown origin ) incubated for 30 mins by NAD/NADH-Glow assay	ic50	0.3300	uM
6-cyano-N-(1H-indol-4-yl)-1-benzothiophene-2-carboxamide	1561253: Inhibition of human N-terminal His6-tagged TEV protease site linked DHPS expressed in Escherichia coli BL21 (DE3) assessed as reduction in radiolabelled amino-butylidene incorporation in eIF5A using [3H]Spermidine trichloride as substrate after 90 to 120 mins in presence of eIF5A and 14 uM NAD+ by Topcount scintillation counting method	ic50	0.4300	uM
6-(3-amino-1-phenylpropyl)-3-pyridin-3-yl-4,5-dihydrothieno[2,3-c]pyridin-7-one	1943588: Displacement of [3H]spermidine trihydrochloride from N-terminal 6his tagged TEV fused human DHPS expressed in Escherichia coli BL21 (DE3) incubated for 120 mins in the presence of 14 uM NAD+ by radiometric assay	ic50	0.4400	uM
6-chloro-5-(2-methoxyphenoxy)-2-phenylpyrimidin-4-amine	1820366: Inhibition of DHPS (unknown origin ) incubated for 30 mins by NAD/NADH-Glow assay	ic50	0.5300	uM
2-[6-amino-2-(3-iodophenyl)-5-(2-methoxyphenoxy)pyrimidin-4-yl]oxyethanol	1820366: Inhibition of DHPS (unknown origin ) incubated for 30 mins by NAD/NADH-Glow assay	ic50	0.5600	uM
6-chloro-2-(4-fluorophenyl)-5-(2-methoxyphenoxy)pyrimidin-4-amine	1820366: Inhibition of DHPS (unknown origin ) incubated for 30 mins by NAD/NADH-Glow assay	ic50	0.6400	uM
4-tert-butyl-N-(1H-indol-4-yl)benzamide	1561253: Inhibition of human N-terminal His6-tagged TEV protease site linked DHPS expressed in Escherichia coli BL21 (DE3) assessed as reduction in radiolabelled amino-butylidene incorporation in eIF5A using [3H]Spermidine trichloride as substrate after 90 to 120 mins in presence of eIF5A and 14 uM NAD+ by Topcount scintillation counting method	ic50	0.8400	uM
2-[6-amino-5-(2-methoxyphenoxy)-2-(3-methylphenyl)pyrimidin-4-yl]oxyethanol	1820366: Inhibition of DHPS (unknown origin ) incubated for 30 mins by NAD/NADH-Glow assay	ic50	1.1700	uM
2-[6-amino-2-(4-iodophenyl)-5-(2-methoxyphenoxy)pyrimidin-4-yl]oxyethanol	1820366: Inhibition of DHPS (unknown origin ) incubated for 30 mins by NAD/NADH-Glow assay	ic50	2.2900	uM
N-(1H-indol-4-yl)-1-benzothiophene-2-carboxamide	1561253: Inhibition of human N-terminal His6-tagged TEV protease site linked DHPS expressed in Escherichia coli BL21 (DE3) assessed as reduction in radiolabelled amino-butylidene incorporation in eIF5A using [3H]Spermidine trichloride as substrate after 90 to 120 mins in presence of eIF5A and 14 uM NAD+ by Topcount scintillation counting method	ic50	2.3000	uM
2-[6-amino-2-(4-fluorophenyl)-5-(2-methoxyphenoxy)pyrimidin-4-yl]oxyethanol	1820366: Inhibition of DHPS (unknown origin ) incubated for 30 mins by NAD/NADH-Glow assay	ic50	2.3800	uM
2-[6-amino-2-(3-bromophenyl)-5-(2-methoxyphenoxy)pyrimidin-4-yl]oxyethanol	1820366: Inhibition of DHPS (unknown origin ) incubated for 30 mins by NAD/NADH-Glow assay	ic50	4.3100	uM
2-[6-amino-2-(3-chlorophenyl)-5-(2-methoxyphenoxy)pyrimidin-4-yl]oxyethanol	1820366: Inhibition of DHPS (unknown origin ) incubated for 30 mins by NAD/NADH-Glow assay	ic50	4.4200	uM
6-tert-butyl-N-(1H-indol-4-yl)-1-benzothiophene-2-carboxamide	1561253: Inhibition of human N-terminal His6-tagged TEV protease site linked DHPS expressed in Escherichia coli BL21 (DE3) assessed as reduction in radiolabelled amino-butylidene incorporation in eIF5A using [3H]Spermidine trichloride as substrate after 90 to 120 mins in presence of eIF5A and 14 uM NAD+ by Topcount scintillation counting method	ic50	5.4000	uM
2-[6-amino-2-(2-fluorophenyl)-5-(2-methoxyphenoxy)pyrimidin-4-yl]oxyethanol	1820366: Inhibition of DHPS (unknown origin ) incubated for 30 mins by NAD/NADH-Glow assay	ic50	5.4300	uM
6-benzyl-3-pyridin-3-yl-4,5-dihydrothieno[2,3-c]pyridin-7-one	1943588: Displacement of [3H]spermidine trihydrochloride from N-terminal 6his tagged TEV fused human DHPS expressed in Escherichia coli BL21 (DE3) incubated for 120 mins in the presence of 14 uM NAD+ by radiometric assay	ic50	6.3000	uM
2-benzyl-5-pyridin-3-yl-3,4-dihydroisoquinolin-1-one	1943588: Displacement of [3H]spermidine trihydrochloride from N-terminal 6his tagged TEV fused human DHPS expressed in Escherichia coli BL21 (DE3) incubated for 120 mins in the presence of 14 uM NAD+ by radiometric assay	ic50	8.2000	uM
2-benzyl-5-pyridin-3-ylisoquinolin-1-one	1943588: Displacement of [3H]spermidine trihydrochloride from N-terminal 6his tagged TEV fused human DHPS expressed in Escherichia coli BL21 (DE3) incubated for 120 mins in the presence of 14 uM NAD+ by radiometric assay	ic50	8.7000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
decabromobiphenyl ether	affects expression, increases expression	2
Tretinoin	decreases expression, increases expression	2
Valproic Acid	affects expression, decreases expression	2
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
bisphenol A	decreases expression	1
beta-lapachone	increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
corosolic acid	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Carbamazepine	affects expression	1
Dinitrochlorobenzene	affects binding	1
Doxorubicin	increases expression	1
Ivermectin	decreases expression	1
Lead	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Nicotine	decreases expression	1
Ozone	affects cotreatment, increases expression, increases abundance	1
Rotenone	increases expression	1

ChEMBL screening assays

12 unique, capped per target: 7 binding, 5 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4358945	Binding	Inhibition of human N-terminal His6-tagged TEV protease site linked DHPS expressed in Escherichia coli BL21 (DE3) assessed as reduction in radiolabelled amino-butylidene incorporation in eIF5A using [3H]Spermidine trichloride as substrate a	Discovery of Novel Allosteric Inhibitors of Deoxyhypusine Synthase. — J Med Chem
CHEMBL653163	Functional	Effect on hypusine synthesis in CHO cells at concentration 10 uM.	Diamine and triamine analogs and derivatives as inhibitors of deoxyhypusine synthase: synthesis and biological activity. — J Med Chem

Clinical trials (associated diseases)

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