DPH1 (diphthamide biosynthesis 1)

Gene

• Entrez ID: 1801
• Gene name: Diphthamide biosynthesis 1
• Gene symbol: DPH1
• Synonyms (NCBI Gene): DEDSSH, DPH2L, DPH2L1, OVCA1
• Chromosome: 17
• Chromosome location: 17p13.3
• Summary: The protein encoded by this gene is an enzyme involved in the biosynthesis of diphthamide, a modified histidine found only in elongation factor-2 (EEF2). Diphthamide residues in EEF2 are targeted for ADP-ribosylation by diphtheria toxin and Pseudomonas ex

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs200530055	T>C	Likely-pathogenic, uncertain-significance	Non coding transcript variant, intron variant, coding sequence variant, missense variant
rs730882250	T>C,G	Pathogenic, likely-pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs756128712	G>-	Pathogenic	Coding sequence variant, frameshift variant, 5 prime UTR variant, non coding transcript variant
rs757167361	T>A,C,G	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant, 5 prime UTR variant, initiator codon variant, non coding transcript variant
rs763506909	->T	Likely-pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT004180	hsa-miR-197-3p	Microarray	16822819
MIRT041212	hsa-miR-193b-3p	CLASH	23622248
MIRT038600	hsa-miR-106b-3p	CLASH	23622248
MIRT943845	hsa-miR-4649-3p	CLIP-seq
MIRT1979507	hsa-miR-374a	CLIP-seq
MIRT1979508	hsa-miR-374b	CLIP-seq
MIRT2518866	hsa-miR-1255a	CLIP-seq
MIRT2518867	hsa-miR-1255b	CLIP-seq
MIRT2518868	hsa-miR-1343	CLIP-seq
MIRT2518869	hsa-miR-1913	CLIP-seq
MIRT2518870	hsa-miR-3125	CLIP-seq
MIRT2518871	hsa-miR-3174	CLIP-seq
MIRT2518872	hsa-miR-3192	CLIP-seq
MIRT2518873	hsa-miR-3197	CLIP-seq
MIRT2518874	hsa-miR-324-3p	CLIP-seq
MIRT2518875	hsa-miR-3616-3p	CLIP-seq
MIRT2518876	hsa-miR-3622b-5p	CLIP-seq
MIRT2518877	hsa-miR-3689a-3p	CLIP-seq
MIRT2518878	hsa-miR-3689c	CLIP-seq
MIRT2518879	hsa-miR-3916	CLIP-seq
MIRT2518880	hsa-miR-4253	CLIP-seq
MIRT2518881	hsa-miR-4299	CLIP-seq
MIRT2518882	hsa-miR-4316	CLIP-seq
MIRT2518883	hsa-miR-4456	CLIP-seq
MIRT2518884	hsa-miR-4481	CLIP-seq
MIRT2518885	hsa-miR-4519	CLIP-seq
MIRT2518886	hsa-miR-4710	CLIP-seq
MIRT2518887	hsa-miR-4728-5p	CLIP-seq
MIRT2518888	hsa-miR-4745-5p	CLIP-seq
MIRT2518889	hsa-miR-4749-3p	CLIP-seq
MIRT2518890	hsa-miR-4758-5p	CLIP-seq
MIRT2518891	hsa-miR-4761-3p	CLIP-seq
MIRT2518892	hsa-miR-4792	CLIP-seq
MIRT2518893	hsa-miR-485-5p	CLIP-seq
MIRT2518894	hsa-miR-490-5p	CLIP-seq
MIRT2518895	hsa-miR-548q	CLIP-seq
MIRT2518896	hsa-miR-582-3p	CLIP-seq
MIRT2518897	hsa-miR-877	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005515	Function	Protein binding	IPI	25416956
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	TAS
GO:0016740	Function	Transferase activity	IEA
GO:0017183	Process	Protein histidyl modification to diphthamide	IBA
GO:0017183	Process	Protein histidyl modification to diphthamide	IEA
GO:0017183	Process	Protein histidyl modification to diphthamide	ISS
GO:0030054	Component	Cell junction	IDA
GO:0032991	Component	Protein-containing complex	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0048144	Process	Fibroblast proliferation	IEA
GO:0051536	Function	Iron-sulfur cluster binding	IEA
GO:0051539	Function	4 iron, 4 sulfur cluster binding	ISS
GO:0090560	Function	2-(3-amino-3-carboxypropyl)histidine synthase activity	IEA
GO:0090560	Function	2-(3-amino-3-carboxypropyl)histidine synthase activity	ISS
GO:0120513	Component	2-(3-amino-3-carboxypropyl)histidine synthase complex	IEA
GO:0120513	Component	2-(3-amino-3-carboxypropyl)histidine synthase complex	ISS

Other IDs

• MIM: 603527
• HGNC: 3003
• e!Ensembl: ENSG00000108963

Protein

• UniProt ID: Q9BZG8
• Protein name: 2-(3-amino-3-carboxypropyl)histidine synthase subunit 1 (EC 2.5.1.108) (Diphthamide biosynthesis protein 1) (Diphtheria toxin resistance protein 1) (Ovarian cancer-associated gene 1 protein) (S-adenosyl-L-methionine:L-histidine 3-amino-3-carboxypropyltran
• Protein function: Catalyzes the first step of diphthamide biosynthesis, a post-translational modification of histidine which occurs in elongation factor 2 (PubMed:30877278). DPH1 and DPH2 transfer a 3-amino-3-carboxypropyl (ACP) group from S-adenosyl-L-methionine
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01866	Diphthamide_syn	81 → 382	Putative diphthamide synthesis protein	Family

• Tissue specificity: TISSUE SPECIFICITY: Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thymus, mammary gland, colon, small intestine, testis and ovary. Reduced expression in primary breast and ovarian tumors. {ECO:0000269|PubMed:
• Sequence:

  MRRQVMAALVVSGAAEQGGRDGPGRGRAPRGRVANQIPPEILKNPQLQAAIRVLPSNYNF
  EIPKTIWRIQQAQAKKVALQMPEGLLLFACTIVDILERFTEAEVMVMGDVTYGACCVDDF
  TARALGADFLVHYGHSCLIPMDTSAQDFRVLYVFVDIRIDTTHLLDSLRLTFPPATALAL
  VSTIQFVSTLQAAAQELKAEYRVSVPQCKPLSPGEILGCTSPRLSKEVEAVVYLGDGRFH
  LESVMIANPNVPAYRYDPYSKVLSREHYDHQRMQAARQEAIATARSAKSWGLILGTLGRQ
  GSPKILEHLESRLRALGLSFVRLLLSEIFPSKLSLLPEVDVWVQVACPRLSIDWGTAFPK
  PLLTPYEAAVALRDISWQQPYPMDFYAGSSLGPWTVNHGQDRRPHAPGRPARGKVQEGSA
  RPPSAVACEDCSCRDEKVAPLAP

• Sequence length: 443

Pathways

Reactome:

Synthesis of diphthamide-EEF2

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
Cerebellar vermis hypoplasia	Likely pathogenic; Pathogenic	rs730882250	RCV000162191	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Dandy-Walker syndrome	Likely pathogenic; Pathogenic	rs730882250	RCV000162191	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Developmental delay with short stature, dysmorphic facial features, and sparse hair	Likely pathogenic; Pathogenic	rs2151346853, rs2151347730, rs730882250	RCV001594434 RCV001594435 RCV000210874	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Developmental delay with short stature, dysmorphic facial features, and sparse hair 1	Likely pathogenic; Pathogenic	rs1185902827, rs730882250, rs757167361, rs2151341681, rs756128712, rs2067429826, rs772969956	RCV003147670 RCV003147374 RCV004567447 RCV003479657 RCV004569770 RCV004570672 RCV004570673	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
DPH1-related disorder	Likely pathogenic	rs1185902827	RCV004758196	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Global developmental delay	Likely pathogenic; Pathogenic	rs730882250	RCV000162191	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hydrocephalus	Likely pathogenic; Pathogenic	rs730882250	RCV000162191	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ASTHMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CRANIOFACIAL DYSPLASIA, SHORT STATURE, ECTODERMAL ANOMALIES, INTELLECTUAL DISABILITY SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CRANIOFACIAL DYSPLASIA-SHORT STATURE-ECTODERMAL ANOMALIES-INTELLECTUAL DISABILITY SYNDROME	—	GenCC, Orphanet GenCC, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INTRACEREBRAL HEMORRHAGE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
3C syndrome	3C syndrome	BEFREE	26220823		★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	GWASCAT_DG	25918132		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Carcinoma, Ovarian Epithelial	Ovarian Epithelial carcinoma	BEFREE	15661533, 21487939, 28521400		★☆☆☆☆ Found in Text Mining only
cervical cancer	Cervical Cancer	BEFREE	28521400		★☆☆☆☆ Found in Text Mining only
Cervical Intraepithelial Neoplasia	Cervical Intraepithelial Neoplasia	BEFREE	28521400		★☆☆☆☆ Found in Text Mining only
Cervix carcinoma	Cervix carcinoma	BEFREE	28521400		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	29145210		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	29145210	Associate	★☆☆☆☆ Found in Text Mining only
Congenital Abnormalities	Congenital abnormalities	Pubtator	30877278	Associate	★☆☆☆☆ Found in Text Mining only
Congenital Epicanthus	Congenital Epicanthus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cranioectodermal dysplasia	Cranioectodermal Dysplasia	BEFREE	26220823		★☆☆☆☆ Found in Text Mining only
Cranioectodermal Dysplasia	Craniodiaphyseal dysplasia	Pubtator	26220823	Associate	★☆☆☆☆ Found in Text Mining only
CRANIOECTODERMAL DYSPLASIA 1	Cranioectodermal Dysplasia	BEFREE	26220823		★☆☆☆☆ Found in Text Mining only
Craniofacial Abnormalities	Craniofacial abnormalities	Pubtator	26220823	Associate	★☆☆☆☆ Found in Text Mining only
Craniofacial dysplasia-short stature-ectodermal anomalies-intellectual disability syndrome	Developmental Delay With Short Stature, Dysmorphic Features, And Sparse Hair	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Craniosynostosis	Craniosynostosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dandy-Walker Syndrome	Dandy-Walker Syndrome	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
DEVELOPMENTAL DELAY WITH SHORT STATURE, DYSMORPHIC FEATURES, AND SPARSE HAIR	Developmental Delay With Short Stature, Dysmorphic Features, And Sparse Hair	UNIPROT_DG	25558065, 26220823		★☆☆☆☆ Found in Text Mining only
DEVELOPMENTAL DELAY WITH SHORT STATURE, DYSMORPHIC FEATURES, AND SPARSE HAIR	Developmental Delay With Short Stature, Dysmorphic Features, And Sparse Hair	GENOMICS_ENGLAND_DG	25558065		★☆☆☆☆ Found in Text Mining only
DEVELOPMENTAL DELAY WITH SHORT STATURE, DYSMORPHIC FEATURES, AND SPARSE HAIR	Developmental Delay With Short Stature, Dysmorphic Features, And Sparse Hair	ORPHANET_DG	26220823		★☆☆☆☆ Found in Text Mining only
DEVELOPMENTAL DELAY WITH SHORT STATURE, DYSMORPHIC FEATURES, AND SPARSE HAIR	Developmental Delay With Short Stature, Dysmorphic Features, And Sparse Hair	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
DEVELOPMENTAL DELAY WITH SHORT STATURE, DYSMORPHIC FEATURES, AND SPARSE HAIR	Developmental Delay With Short Stature, Dysmorphic Features, And Sparse Hair	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	30877278	Associate	★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	BEFREE	26220823, 29362492, 29410513		★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Epithelial ovarian cancer	Ovarian cancer	BEFREE	21487939		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	BEFREE	15661533, 29362492, 29410513, 30877278		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Global developmental delay	Developmental Delay	HPO_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Global developmental delay	Developmental Delay	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Growth Disorders	Growth disorder	Pubtator	26220823, 30877278	Associate	★☆☆☆☆ Found in Text Mining only
Hydrocephalus	Hydrocephalus	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Intellectual Disability	Mental retardation	BEFREE	26220823, 29362492, 29410513		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Intellectual developmental disorder	Pubtator	26220823	Associate	★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intraepithelial Neoplasia	Intraepithelial Neoplasia	BEFREE	28521400		★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	GWASCAT_DG	27903959		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of ovary	Ovarian cancer	BEFREE	10519411, 15661533, 21487939, 28521400		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of ovary	Ovarian cancer	UNIPROT_DG			★☆☆☆☆ Found in Text Mining only
Malignant tumor of cervix	Cervical Tumor	BEFREE	28521400		★☆☆☆☆ Found in Text Mining only
Micrognathism	Micrognathism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	10519411, 11979432, 15661533, 16759848, 21487939, 30675298		★☆☆☆☆ Found in Text Mining only
Neurodevelopmental Disorders	Neurodevelopmental Disorders	BEFREE	30877278		★☆☆☆☆ Found in Text Mining only
Ovarian Carcinoma	Ovarian Carcinoma	BEFREE	15661533		★☆☆☆☆ Found in Text Mining only
ovarian neoplasm	Ovarian neoplasm	BEFREE	15661533, 21487939, 28521400		★☆☆☆☆ Found in Text Mining only
Scaphycephaly	Scaphocephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Trigonocephaly	Trigonocephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ventricular Septal Defects	Ventricular septal defect	HPO_DG			★☆☆☆☆ Found in Text Mining only