DPH5

diphthamide biosynthesis 5, the group of Diphthamide biosynthesis pathway genes

Basic information

Region (hg38): 1:100989623-101026088

Links

ENSG00000117543 ∙ NCBI:51611 ∙ OMIM:611075 ∙ HGNC:24270 ∙ Uniprot:Q9H2P9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with short stature, prominent forehead, and feeding difficulties (Limited), mode of inheritance: AR
• neurodevelopmental disorder with short stature, prominent forehead, and feeding difficulties (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with short stature, prominent forehead, and feeding difficulties	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	35482014

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DPH5 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DPH5 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense		1	14			15
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	1	14	0	0

Variants in DPH5

This is a list of pathogenic ClinVar variants found in the DPH5 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-100990449-G-T		not specified	Uncertain significance (Oct 06, 2023)
1-100990469-A-G		not specified	Uncertain significance (May 24, 2023)
1-100990475-A-C		not specified	Uncertain significance (Oct 07, 2024)
1-100990486-A-T		not specified	Uncertain significance (Dec 10, 2024)
1-100990487-T-C		Neurodevelopmental disorder with short stature, prominent forehead, and feeding difficulties	Pathogenic/Likely pathogenic (Jul 31, 2023)
1-100990497-C-T		not specified	Uncertain significance (Jul 25, 2023)
1-100990560-T-G		not specified	Uncertain significance (Nov 18, 2022)
1-100990566-C-G		not specified	Uncertain significance (Nov 22, 2024)
1-100990580-T-G		not specified	Uncertain significance (Jun 29, 2022)
1-100990581-C-T		not specified	Uncertain significance (Oct 27, 2023)
1-100990584-C-T		not specified	Uncertain significance (Oct 19, 2024)
1-100992652-G-A		Neurodevelopmental disorder with short stature, prominent forehead, and feeding difficulties • DPH5-related diphthamide-deficiency syndrome	Pathogenic (Dec 02, 2022)
1-100992660-T-A		not specified	Uncertain significance (Aug 28, 2024)
1-100992720-G-A		Neurodevelopmental disorder with short stature, prominent forehead, and feeding difficulties	Uncertain significance (Dec 18, 2024)
1-100992721-G-C		not specified	Uncertain significance (Aug 04, 2024)
1-100992731-C-A		not specified	Uncertain significance (Oct 16, 2023)
1-100995147-T-C		not specified	Uncertain significance (Sep 09, 2024)
1-101013750-T-C		Neurodevelopmental disorder with short stature, prominent forehead, and feeding difficulties • DPH5-related diphthamide-deficiency syndrome	Pathogenic (Dec 02, 2022)
1-101013769-G-T		not specified	Uncertain significance (Jul 15, 2021)
1-101013780-T-A		not specified	Uncertain significance (Nov 18, 2023)
1-101021721-T-A		not specified	Uncertain significance (Oct 05, 2023)
1-101021729-T-C			Uncertain significance (Dec 18, 2023)
1-101025347-C-A		not specified	Uncertain significance (Oct 25, 2023)
1-101025404-C-T		not specified	Uncertain significance (Feb 13, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DPH5	protein_coding	protein_coding	ENST00000370109	7	36466

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.11e-7	0.513	124756	0	41	124797	0.000164

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.481	131	147	0.888	0.00000662	1855
Missense in Polyphen		37	49.095	0.75364		636
Synonymous	-0.358	56	52.7	1.06	0.00000253	547
Loss of Function	0.817	11	14.3	0.767	7.07e-7	184

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000187	0.000187
Ashkenazi Jewish	0.00	0.00
East Asian	0.000111	0.000111
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000197	0.000194
Middle Eastern	0.000111	0.000111
South Asian	0.000203	0.000196
Other	0.000663	0.000660

dbNSFP

Source: dbNSFP

• Function: FUNCTION: S-adenosyl-L-methionine-dependent methyltransferase that catalyzes four methylations of the modified target histidine residue in translation elongation factor 2 (EF-2), to form an intermediate called diphthine methyl ester. The four successive methylation reactions represent the second step of diphthamide biosynthesis. {ECO:0000250|UniProtKB:P32469, ECO:0000269|PubMed:23486472}.
• Pathway: Post-translational protein modification;Metabolism of proteins;Synthesis of diphthamide-EEF2;Gamma carboxylation, hypusine formation and arylsulfatase activation;diphthamide biosynthesis (Consensus)

Recessive Scores

• pRec: 0.102

Intolerance Scores

• loftool: 0.437
• rvis_EVS: 0.3
• rvis_percentile_EVS: 72.01

Haploinsufficiency Scores

• pHI: 0.548
• hipred: Y
• hipred_score: 0.731
• ghis: 0.536

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.292

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Dph5

Gene ontology

• Biological process: peptidyl-diphthamide biosynthetic process from peptidyl-histidine;methylation
• Cellular component: cellular_component;cytosol
• Molecular function: diphthine synthase activity