DOHH

Summary

DOHH (deoxyhypusine hydroxylase, HGNC:28662) is a protein-coding gene on chromosome 19p13.3, encoding Deoxyhypusine hydroxylase (Q9BU89). Catalyzes the hydroxylation of the N(6)-(4-aminobutyl)-L-lysine intermediate produced by deoxyhypusine synthase/DHPS on a critical lysine of the eukaryotic translation initiation factor 5A/eIF-5A. It is a selective cancer dependency (DepMap: 59.9% of cell lines).

This gene encodes a metalloenzyme that catalyzes the last step in the conversion of lysine to the unique amino acid hypusine in eukaryotic initiation factor 5A. The encoded protein hydroxylates deoxyhypusine to form hypusine in the mature eukaryotic initiation factor 5A protein. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 83475 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment (Strong, GenCC)
• Clinical variants (ClinVar): 84 total — 5 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 39
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 59.9% of screened cell lines
• MANE Select transcript: NM_001145165

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28662
Approved symbol	DOHH
Name	deoxyhypusine hydroxylase
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC4293
Ensembl gene	ENSG00000129932
Ensembl biotype	protein_coding
OMIM	611262
Entrez	83475

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 retained_intron

ENST00000427575, ENST00000671696, ENST00000672935, ENST00000673168, ENST00000903391, ENST00000903392, ENST00000938386, ENST00000951774, ENST00000951775, ENST00000951776

RefSeq mRNA: 2 — MANE Select: NM_001145165 NM_001145165, NM_031304

CCDS: CCDS12108

Canonical transcript exons

ENST00000427575 — 5 exons

Exon	Start	End
ENSE00001056289	3494028	3494104
ENSE00001148660	3490824	3491811
ENSE00001148668	3496541	3496886
ENSE00003500861	3492262	3492499
ENSE00003893122	3500561	3500674

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 97.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.2124 / max 108.5483, expressed in 1769 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178284	3.7034	1654
178283	2.8484	1512
178282	1.0598	614
178281	0.6008	79

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
inferior vagus X ganglion	UBERON:0005363	97.49	gold quality
medial globus pallidus	UBERON:0002477	96.57	gold quality
pons	UBERON:0000988	96.43	gold quality
ventral tegmental area	UBERON:0002691	96.25	gold quality
globus pallidus	UBERON:0001875	95.72	gold quality
vena cava	UBERON:0004087	95.64	gold quality
superior vestibular nucleus	UBERON:0007227	95.46	gold quality
medulla oblongata	UBERON:0001896	95.29	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.29	gold quality
type B pancreatic cell	CL:0000169	95.13	gold quality
subthalamic nucleus	UBERON:0001906	95.05	gold quality
spinal cord	UBERON:0002240	94.90	gold quality
olfactory bulb	UBERON:0002264	94.83	gold quality
dorsal plus ventral thalamus	UBERON:0001897	94.55	gold quality
body of tongue	UBERON:0011876	93.35	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	93.03	gold quality
pylorus	UBERON:0001166	92.75	gold quality
nipple	UBERON:0002030	92.53	gold quality
tendon of biceps brachii	UBERON:0008188	92.52	gold quality
midbrain	UBERON:0001891	92.39	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.39	gold quality
substantia nigra	UBERON:0002038	91.98	gold quality
pharyngeal mucosa	UBERON:0000355	91.92	gold quality
tongue	UBERON:0001723	91.91	gold quality
inferior olivary complex	UBERON:0002127	91.72	gold quality
pericardium	UBERON:0002407	91.36	gold quality
cervix squamous epithelium	UBERON:0006922	91.36	gold quality
cardia of stomach	UBERON:0001162	91.31	gold quality
putamen	UBERON:0001874	91.04	gold quality
renal medulla	UBERON:0000362	91.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting DOHH, 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-3162-3P	100.00	65.37	363
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-331-3P	98.76	64.91	793
HSA-MIR-6801-3P	98.04	64.64	805
HSA-MIR-6810-3P	97.96	64.57	1023
HSA-MIR-3657	96.33	66.29	608
HSA-MIR-4746-5P	94.32	69.49	70
HSA-MIR-6803-3P	87.24	63.68	71
HSA-MIR-4655-3P	82.43	62.92	60

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 59.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 10)

• The structure and function of DOHH are reported. (PMID:16533814)
• analysis of the deoxyhypusine hydroxylase-eukaryotic translation initiation factor (eIF5A) interaction (PMID:17213197)
• Resonance Raman experiments show that its blue chromophore arises from a (mu-1,2-peroxo)diiron(III) center that forms in the reaction of the reduced enzyme with O2, so the peroxo form of hDOHH is unusually stable. (PMID:19706422)
• a novel role for miR-331-3p and miR-642-5p in the control of prostate cancer cell growth via the regulation of DOHH expression and eIF5A activity. (PMID:22908221)
• 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)
• Here, we show that PCBP1 and PCBP2 also deliver iron to deoxyhypusine hydroxylase (DOHH), the dinuclear iron enzyme required for hypusine modification of the translation factor eukaryotic initiation factor 5A. (PMID:24843120)
• Data describes 3-D structure of hDOHH in two states, hDOHHperoxo (POX) and a complex of the diiron core with glycerol (GLC) providing an explanation for the extreme longevity of POX and illustrate its substrate specificity for deoxyhypusine-eIF-5A. (PMID:25865244)
• Deoxyhypusine hydroxylase as a novel pharmacological target for ischemic stroke via inducing a unique post-translational hypusination modification. (PMID:35007708)
• Bi-allelic variants in DOHH, catalyzing the last step of hypusine biosynthesis, are associated with a neurodevelopmental disorder. (PMID:35858628)
• Deoxyhypusine hydroxylase: A novel therapeutic target differentially expressed in short-term vs long-term survivors of glioblastoma. (PMID:37141410)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dohh	ENSMUSG00000078440
rattus_norvegicus	Dohh	ENSRNOG00000004259

Protein

Protein identifiers

Deoxyhypusine hydroxylase — Q9BU89 (reviewed: Q9BU89)

Alternative names: Deoxyhypusine dioxygenase, Deoxyhypusine monooxygenase, HEAT-like repeat-containing protein 1

All UniProt accessions (2): Q9BU89, A0A5F9ZGM7

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the hydroxylation of the N(6)-(4-aminobutyl)-L-lysine intermediate produced by deoxyhypusine synthase/DHPS on a critical lysine of the eukaryotic translation initiation factor 5A/eIF-5A. This is the second 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.

Disease relevance. Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment (NEDMVIC) [MIM:620066] An autosomal recessive disorder characterized by global developmental delay, intellectual disability, facial dysmorphism, and microcephaly. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 2 Fe(2+) ions per subunit.

Pathway. Protein modification; eIF5A hypusination.

Similarity. Belongs to the deoxyhypusine hydroxylase family.

RefSeq proteins (2): NP_001138637, NP_112594 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004155	PBS_lyase_HEAT	Repeat
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR021133	HEAT_type_2	Repeat
IPR027517	Deoxyhypusine_hydroxylase	Family

Pfam: PF13646

Enzyme classification (BRENDA):

• EC 1.14.99.29 — deoxyhypusine monooxygenase (BRENDA: 14 organisms, 33 substrates, 96 inhibitors, 3 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

3 substrates with measured Km, best-characterized 3. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
6-N-[(R)-4-AMINO-2-HYDROXYBUTYL]-L-LYSINE OF HUM	0.0001	1
6-N-[(R)-4-AMINO-2-HYDROXYBUTYL]-L-LYSINE OF YEA	0.0004	1
DEOXYHYPUSINE	0.0001	1

Catalyzed reactions (Rhea), 1 shown:

• [eIF5A protein]-deoxyhypusine + AH2 + O2 = [eIF5A protein]-hypusine + A + H2O (RHEA:14101)

UniProt features (50 total): helix 21, mutagenesis site 11, binding site 6, repeat 5, sequence variant 5, chain 1, modified residue 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4D4Z	X-RAY DIFFRACTION	1.7
4D50	X-RAY DIFFRACTION	1.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BU89-F1	96.13	0.90

Functional residue map

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

Ligand- & substrate-binding residues (6): 240; 241; 56; 89; 90; 207

Post-translational modifications (1): 1

Mutagenesis-validated functional residues (11):

Position	Phenotype
56	loss of deoxyhypusine monooxygenase activity. loss of iron-binding.
57	loss of deoxyhypusine monooxygenase activity. no effect on iron-binding.
86	loss of iron-binding.
86	no effect on iron-binding. loss of iron-binding; when associated with l-237.
89	loss of deoxyhypusine monooxygenase activity. loss of iron-binding.
90	loss of deoxyhypusine monooxygenase activity. loss of iron-binding.
207	loss of deoxyhypusine monooxygenase activity. loss of iron-binding.
208	loss of deoxyhypusine monooxygenase activity. no effect on iron-binding.
237	decreased iron-binding. loss of iron-binding; when associated with l-86.
240	loss of deoxyhypusine monooxygenase activity. loss of iron-binding.
241	loss of deoxyhypusine monooxygenase activity. loss of iron-binding.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 204 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, BROWNE_HCMV_INFECTION_16HR_UP, GOBP_PEPTIDYL_LYSINE_MODIFICATION, GOBP_PROTEIN_MATURATION, USF_01, KIM_GASTRIC_CANCER_CHEMOSENSITIVITY, MARKEY_RB1_ACUTE_LOF_UP, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, chr19p13, GOMF_IRON_ION_BINDING, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOMF_MONOOXYGENASE_ACTIVITY, KRIGE_RESPONSE_TO_TOSEDOSTAT_6HR_DN, WAMUNYOKOLI_OVARIAN_CANCER_LMP_UP

GO Biological Process (1): peptidyl-hypusine biosynthetic process (GO:0008612)

GO Molecular Function (6): iron ion binding (GO:0005506), deoxyhypusine monooxygenase activity (GO:0019135), monooxygenase activity (GO:0004497), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), metal ion binding (GO:0046872)

GO Cellular Component (1): 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
biosynthetic process	1
protein maturation	1
transition metal ion binding	1
monooxygenase activity	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	1
catalytic activity, acting on a protein	1
oxidoreductase activity	1
binding	1
catalytic activity	1
cation binding	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2118 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DOHH	DHPS	P49366	997
DOHH	EIF5A	P10159	987
DOHH	EIF5AL1	Q6IS14	833
DOHH	EIF5A2	Q9GZV4	711
DOHH	SRM	P19623	665
DOHH	ODC1	P11926	644
DOHH	SMS	P52788	625
DOHH	AGMAT	Q9BSE5	563
DOHH	XPO4	Q9C0E2	558
DOHH	PEAK1	Q9H792	540
DOHH	AZIN1	O14977	491
DOHH	TPI1	P00938	484
DOHH	PAOX	Q6QHF9	475
DOHH	AZIN2	Q96A70	464
DOHH	SMOX	Q9NWM0	452

IntAct

15 interactions, top by confidence:

A	B	Type	Score
EIF5A2	DHPS	psi-mi:“MI:0914”(association)	0.830
ORF	EIF3F	psi-mi:“MI:0914”(association)	0.560
SCNM1	SNX3	psi-mi:“MI:0914”(association)	0.530
DOHH	IDE	psi-mi:“MI:0914”(association)	0.530
FN3KRP	LTF	psi-mi:“MI:0914”(association)	0.530
STARD7	TLE5	psi-mi:“MI:0914”(association)	0.530
DOHH	EIF5A	psi-mi:“MI:0915”(physical association)	0.500
FN3KRP	IGHA1	psi-mi:“MI:0914”(association)	0.350
STARD7	TLE3	psi-mi:“MI:0914”(association)	0.350
EIF5A2	PIK3C2A	psi-mi:“MI:0914”(association)	0.350
C14orf119	ERCC6L	psi-mi:“MI:0914”(association)	0.350
MTUS2	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350

BioGRID (31): IDE (Affinity Capture-MS), EIF5A2 (Affinity Capture-MS), EIF5A (Affinity Capture-MS), DOHH (Co-fractionation), DOHH (Co-fractionation), DOHH (Co-fractionation), SKIV2L2 (Co-fractionation), EIF5A2 (Affinity Capture-MS), EIF5A (Affinity Capture-MS), IDE (Affinity Capture-MS), DOHH (Affinity Capture-MS), DOHH (Affinity Capture-MS), DOHH (Affinity Capture-MS), DOHH (Affinity Capture-MS), DOHH (Affinity Capture-MS)

ESM2 similar proteins: A2QXL3, D9IFD5, P0CN10, P0CN11, P47120, P53602, Q06AU9, Q0P570, Q0UHL8, Q0VC53, Q14BV6, Q17949, Q1E9L2, Q297S2, Q2QLW3, Q2QXB3, Q2UMQ8, Q3SZV0, Q4HZ35, Q4PHU4, Q556G4, Q5AW32, Q5PPJ4, Q5RD03, Q5ZIP3, Q66H45, Q66KT3, Q68LP1, Q6AY79, Q6CHJ7, Q6CV81, Q6FUV3, Q6NXE6, Q6ZQ73, Q752Z8, Q75DX9, Q7S891, Q7ZUX6, Q8BNU0, Q8R307

Diamond homologs: A1CED0, A1DFW7, A2QXL3, D9IFD5, P0CN10, P0CN11, P47120, Q0UHL8, Q0VC53, Q17949, Q1E9L2, Q297S2, Q2H0C0, Q2QLW3, Q2QXB3, Q2UMQ8, Q4HZ35, Q4PHU4, Q4WHG5, Q556G4, Q59Z14, Q5AW32, Q5PPJ4, Q5ZIP3, Q66KT3, Q6BKA6, Q6CHJ7, Q6CV81, Q6FUV3, Q752Z8, Q7S891, Q7ZUX6, Q8SV71, Q94JW0, Q96WP5, Q99LN9, Q9BU89, Q9P6K9, Q9V9U4, A5JZ19

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	1
Uncertain significance	64
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
1285600	NM_001145165.2(DOHH):c.304del (p.Glu102fs)	Pathogenic
1285601	NM_001145165.2(DOHH):c.840T>A (p.Tyr280Ter)	Pathogenic
1285603	NM_001145165.2(DOHH):c.746T>C (p.Ile249Thr)	Pathogenic
1285605	NM_001145165.2(DOHH):c.552C>A (p.Asn184Lys)	Pathogenic
145080	GRCh38/hg38 19p13.3(chr19:3338024-4833139)x1	Pathogenic
4292397	NM_001145165.2(DOHH):c.898dup (p.Ala300fs)	Likely pathogenic

SpliceAI

708 predictions. Top by Δscore:

Variant	Effect	Δscore
19:3491807:CAGAC:C	acceptor_gain	1.0000
19:3491808:AGAC:A	acceptor_gain	1.0000
19:3491809:GAC:G	acceptor_gain	1.0000
19:3491810:ACCT:A	acceptor_loss	1.0000
19:3491812:C:CC	acceptor_gain	1.0000
19:3492256:CCTCA:C	donor_loss	1.0000
19:3492259:CA:C	donor_loss	1.0000
19:3492260:A:AC	donor_gain	1.0000
19:3492260:AC:A	donor_gain	1.0000
19:3492261:C:CA	donor_loss	1.0000
19:3492261:C:CC	donor_gain	1.0000
19:3492261:CC:C	donor_gain	1.0000
19:3492261:CCCT:C	donor_gain	1.0000
19:3492285:T:TA	donor_gain	1.0000
19:3492495:GCCAC:G	acceptor_gain	1.0000
19:3492496:CCAC:C	acceptor_gain	1.0000
19:3492496:CCACC:C	acceptor_gain	1.0000
19:3492497:CAC:C	acceptor_gain	1.0000
19:3492497:CACC:C	acceptor_gain	1.0000
19:3492498:AC:A	acceptor_gain	1.0000
19:3492498:ACC:A	acceptor_loss	1.0000
19:3492499:CC:C	acceptor_gain	1.0000
19:3492500:C:CC	acceptor_gain	1.0000
19:3492501:T:A	acceptor_loss	1.0000
19:3496537:TCA:T	donor_loss	1.0000
19:3496538:CACC:C	donor_loss	1.0000
19:3496540:CCTG:C	donor_gain	1.0000
19:3496894:A:T	acceptor_gain	1.0000
19:3500560:CCGAG:C	donor_gain	1.0000
19:3491810:AC:A	acceptor_gain	0.9900

AlphaMissense

1925 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:3496545:C:A	E90D	0.995
19:3496545:C:G	E90D	0.995
19:3492311:G:C	F180L	0.994
19:3492311:G:T	F180L	0.994
19:3492313:A:G	F180L	0.994
19:3496544:C:G	A91P	0.993
19:3491585:G:C	S272R	0.992
19:3491585:G:T	S272R	0.992
19:3491587:T:G	S272R	0.992
19:3496728:G:C	F29L	0.992
19:3496728:G:T	F29L	0.992
19:3496730:A:G	F29L	0.992
19:3491782:G:C	H207D	0.990
19:3494099:C:G	A94P	0.990
19:3496649:G:C	H56D	0.990
19:3496550:G:C	H89D	0.989
19:3496647:G:C	H56Q	0.989
19:3496647:G:T	H56Q	0.989
19:3496553:G:T	R88S	0.988
19:3491678:C:A	E241D	0.987
19:3491678:C:G	E241D	0.987
19:3491782:G:T	H207N	0.987
19:3491777:C:A	E208D	0.986
19:3491777:C:G	E208D	0.986
19:3496546:T:A	E90V	0.986
19:3496649:G:T	H56N	0.986
19:3492304:G:T	R183S	0.985
19:3491668:C:G	A245P	0.984
19:3496550:G:T	H89N	0.984
19:3496627:C:T	G63D	0.984

dbSNP variants (sampled 300 via entrez): RS1000117459 (19:3490724 G>A), RS1000287739 (19:3493479 A>G), RS1000504124 (19:3501736 A>G), RS1002030480 (19:3498406 A>T), RS1002221408 (19:3492366 C>A,G,T), RS1002271332 (19:3502606 T>C), RS1002329970 (19:3497081 C>T), RS1002567017 (19:3500122 G>A,C), RS1002999448 (19:3494864 G>A), RS1003150071 (19:3500283 G>A), RS1003279198 (19:3496306 C>T), RS1003332881 (19:3496080 T>C), RS1003436451 (19:3501533 G>A,T), RS1003507153 (19:3500491 G>A), RS1003633163 (19:3491095 T>C)

Disease associations

OMIM: gene MIM:611262 | disease phenotypes: MIM:620066

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment	Strong	Autosomal recessive

Mondo (2): neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment (MONDO:0859293), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (1): Non-specific syndromic intellectual disability (Orphanet:528084)

HPO phenotypes

39 total (30 of 39 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000486	Strabismus
HP:0000639	Nystagmus
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001344	Absent speech
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001635	Congestive heart failure
HP:0001640	Cardiomegaly
HP:0001647	Bicuspid aortic valve
HP:0001653	Mitral regurgitation
HP:0001659	Aortic regurgitation
HP:0001680	Coarctation of aorta
HP:0001684	Secundum atrial septal defect
HP:0002069	Bilateral tonic-clonic seizure
HP:0002078	Truncal ataxia
HP:0002119	Ventriculomegaly
HP:0002188	Delayed CNS myelination
HP:0002197	Generalized-onset seizure
HP:0002283	Global brain atrophy
HP:0002540	Inability to walk
HP:0002719	Recurrent infections
HP:0003577	Congenital onset
HP:0003623	Neonatal onset
HP:0005165	Shortened PR interval
HP:0005180	Tricuspid regurgitation

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523441 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 48,094 (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
CHEMBL1413	CICLOPIROX	4	14,782
CHEMBL556	DEFEROXAMINE	4	25,751
CHEMBL70927	DEFERIPRONE	4	7,561

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.30	IC50	5000	nM	DEFERIPRONE
5.30	IC50	5000	nM	DIPYRIDYL
5.30	IC50	5000	nM	DEFEROXAMINE
5.30	IC50	5000	nM	L-MIMOSINE
5.30	IC50	5000	nM	CICLOPIROX

PubChem BioAssay actives

5 with measured affinity, of 5 total; 5 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-pyridin-2-ylpyridine	1601772: Inhibition of DOHH (unknown origin)	ic50	5.0000	uM
Ciclopirox	1601772: Inhibition of DOHH (unknown origin)	ic50	5.0000	uM
Deferiprone	1601772: Inhibition of DOHH (unknown origin)	ic50	5.0000	uM
Deferoxamine	1601772: Inhibition of DOHH (unknown origin)	ic50	5.0000	uM
(2S)-2-amino-3-(3-hydroxy-4-oxo-1-pyridinyl)propanoic acid	1601772: Inhibition of DOHH (unknown origin)	ic50	5.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
Silicon Dioxide	increases expression	2
aristolochic acid I	increases expression	1
fluorene-9-bisphenol	decreases expression	1
bisphenol A	decreases methylation	1
lead acetate	increases expression	1
methylparaben	increases expression	1
cobaltous chloride	increases expression	1
cupric chloride	increases expression	1
cadmium sulfate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
eprenetapopt	affects expression, affects reaction	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Air Pollutants	increases expression, increases abundance	1
Cisplatin	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diazinon	increases methylation	1
Estradiol	increases expression	1
Selenium	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Testosterone	increases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation	1
Vitamin E	affects cotreatment, increases 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
CHEMBL4400854	Binding	Inhibition of DOHH (unknown origin)	Medicinal chemistry of metal chelating fragments in metalloenzyme active sites: A perspective. — Eur J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder