DHPS (deoxyhypusine synthase)

Gene

• Entrez ID: 1725
• Gene name: Deoxyhypusine synthase
• Gene symbol: DHPS
• Synonyms (NCBI Gene): DHS, DS, MIG13, NEDSSWI
• Chromosome: 19
• Chromosome location: 19p13.13
• Summary: 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

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs758100382	T>C	Uncertain-significance, pathogenic	5 prime UTR variant, coding sequence variant, non coding transcript variant, missense variant
rs1306390986	T>C	Pathogenic, uncertain-significance	5 prime UTR variant, initiator codon variant, non coding transcript variant, genic upstream transcript variant, upstream transcript variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT045190	hsa-miR-186-5p	CLASH	23622248

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005515	Function	Protein binding	IPI	14622290, 16189514, 19060904, 23602568, 24722188, 25416956, 25852190, 26496610, 28514442, 31980649, 32296183, 32707033, 33961781
GO:0005737	Component	Cytoplasm	IBA
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	TAS
GO:0006412	Process	Translation	TAS	7673224
GO:0008216	Process	Spermidine metabolic process	IBA
GO:0008216	Process	Spermidine metabolic process	IDA	23525104
GO:0008284	Process	Positive regulation of cell population proliferation	TAS	8549832
GO:0016740	Function	Transferase activity	IEA
GO:0034038	Function	Deoxyhypusine synthase activity	IBA
GO:0034038	Function	Deoxyhypusine synthase activity	IDA	8549832, 23525104, 30661771
GO:0034038	Function	Deoxyhypusine synthase activity	IEA
GO:0042102	Process	Positive regulation of T cell proliferation	IEA
GO:0042593	Process	Glucose homeostasis	IEA
GO:0042802	Function	Identical protein binding	IEA
GO:0042802	Function	Identical protein binding	IPI	25416956, 32296183
GO:0046203	Process	Spermidine catabolic process	IEA
GO:0051604	Process	Protein maturation	IDA	23525104

Other IDs

• MIM: 600944
• HGNC: 2869
• e!Ensembl: ENSG00000095059

Protein

• UniProt ID: P49366
• Protein name: Deoxyhypusine synthase (DHS) (EC 2.5.1.46)
• Protein 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 deox
• PDB: 1DHS, 1RLZ, 1ROZ, 1RQD, 6P4V, 6PGR, 6WKZ, 6WL6, 6XXH, 6XXI, 6XXJ, 6XXK, 6XXL, 6XXM, 7A6S, 7A6T, 8A0E, 8A0F, 8A0G, 8PVU, 8R3U
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01916	DS	44 → 354	Deoxyhypusine synthase	Domain

• Sequence:

  MEGSLEREAPAGALAAVLKHSSTLPPESTQVRGYDFNRGVNYRALLEAFGTTGFQATNFG
  RAVQQVNAMIEKKLEPLSQDEDQHADLTQSRRPLTSCTIFLGYTSNLISSGIRETIRYLV
  QHNMVDVLVTTAGGVEEDLIKCLAPTYLGEFSLRGKELRENGINRIGNLLVPNENYCKFE
  DWLMPILDQMVMEQNTEGVKWTPSKMIARLGKEINNPESVYYWAQKNHIPVFSPALTDGS
  LGDMIFFHSYKNPGLVLDIVEDLRLINTQAIFAKCTGMIILGGGVVKHHIANANLMRNGA
  DYAVYINTAQEFDGSDSGARPDEAVSWGKIRVDAQPVKVYADASLVFPLLVAETFAQKMD
  AFMHEKNED

• Sequence length: 369

Pathways

Reactome:

Hypusine synthesis from eIF5A-lysine

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
DHPS-related disorder	Likely pathogenic; Pathogenic	rs1568317152, rs758100382	RCV003420196 RCV003403569	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Neurodevelopmental disorder with seizures and speech and walking impairment	Likely pathogenic; Pathogenic	rs1568317152, rs758100382	RCV000786002 RCV000786000	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Clear cell carcinoma of kidney	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Breast Neoplasms	Breast neoplasm	Pubtator	31558321	Associate	★☆☆☆☆ Found in Text Mining only
Bronchiolitis	Bronchiolitis	BEFREE	14736212		★☆☆☆☆ Found in Text Mining only
Byzanthine arch palate	High palate	HPO_DG			★☆☆☆☆ Found in Text Mining only
Clinodactyly of the 5th finger	Camptodactyly of fingers	HPO_DG			★☆☆☆☆ Found in Text Mining only
Crohn Disease	Crohn Disease	BEFREE	22694849		★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	30661771, 36973244	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes	Diabetes	BEFREE	24496311, 25218134		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	BEFREE	24496311, 25218134		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Insulin-Dependent	Diabetes Mellitus	BEFREE	24496311		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	BEFREE	22927971		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	22927971	Associate	★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	22927971		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	GENOMICS_ENGLAND_DG	21850436		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Growth Disorders	Growth disorder	Pubtator	30661771	Associate	★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	GENOMICS_ENGLAND_DG	21850436		★☆☆☆☆ Found in Text Mining only
Lung diseases	Lung Diseases	BEFREE	15175932		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	31558321		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of stomach	Stomach Neoplasms	BEFREE	22491477		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	25218134, 29295892		★☆☆☆☆ Found in Text Mining only
Melanoma	Melanoma	Pubtator	34947982	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	22491477, 27041563, 29295892		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	BEFREE	29295892		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Diseases	Neurodegenerative disorder	Pubtator	32235505, 36973244	Associate	★☆☆☆☆ Found in Text Mining only
Neurodevelopmental Disorders	Neurodevelopmental Disorders	BEFREE	30257869, 30661771		★☆☆☆☆ Found in Text Mining only
Papillary craniopharyngioma	Papillary Craniopharyngioma	BEFREE	10915088, 10970350		★☆☆☆☆ Found in Text Mining only
Pica Disease	Pica	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sarcoma Kaposi	Sarcoma	Pubtator	35486659	Associate	★☆☆☆☆ Found in Text Mining only
Seizures	Seizures	Pubtator	30661771	Associate	★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of esophagus	Esophagus Neoplasm	BEFREE	27041563		★☆☆☆☆ Found in Text Mining only
Stomach Carcinoma	Stomach Carcinoma	BEFREE	22491477		★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	22491477	Associate	★☆☆☆☆ Found in Text Mining only