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
neurodevelopmental disorder with short stature, prominent forehead, and feeding difficulties (Moderate), 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.

not_specified (24 variants)
Neurodevelopmental_disorder_with_short_stature,_prominent_forehead,_and_feeding_difficulties (9 variants)
DPH5-related_diphthamide-deficiency_syndrome (2 variants)
not_provided (1 variants)

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. These statistics are base on transcript: NM_000015958.3. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous						0
missense	1 clinvar	1 clinvar	29 clinvar			31
nonsense	1 clinvar					1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	2	1	30	0	0

Highest pathogenic variant AF is 0.000033472388

Loading clinvar variants...

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
Phenotype

Gene ontology

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