DPH3

diphthamide biosynthesis 3, the group of Diphthamide biosynthesis pathway genes

Basic information

Region (hg38): 3:16257060-16264969

Previous symbols: [ "ZCSL2" ]

Links

ENSG00000154813

∙ NCBI:285381 ∙ OMIM:608959 ∙ HGNC:27717 ∙ Uniprot:Q96FX2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DPH3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DPH3 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			3 clinvar			3
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	3	0	0

Variants in DPH3

This is a list of pathogenic ClinVar variants found in the DPH3 region.

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

Position	Phenotype	Significance	ClinVar
3-16264198-G-T	not specified	Uncertain significance (Aug 12, 2022)	2355757
3-16264795-A-G	not specified	Uncertain significance (Sep 22, 2022)	2205135
3-16264806-T-C	not specified	Uncertain significance (Oct 06, 2021)	2227746
3-16264816-T-A	not specified	Uncertain significance (Mar 21, 2024)	3273594

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DPH3	protein_coding	protein_coding	ENST00000488423	3	6995

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0663	0.746	125710	0	7	125717	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0913	44	42.3	1.04	0.00000184	545
Missense in Polyphen		11	13.301	0.82698		184
Synonymous	-0.0529	16	15.7	1.02	7.40e-7	135
Loss of Function	0.891	2	3.90	0.513	1.63e-7	55

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000560	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000441	0.0000440
Middle Eastern	0.0000560	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Essential for the first step in the synthesis of diphthamide, a post-translational modification of histidine which occurs in elongation factor 2 (EEF2) and which can be ADP- ribosylated by diphtheria toxin and by Pseudomonas exotoxin A (Eta). {ECO:0000250}.;
Pathway: Post-translational protein modification;Metabolism of proteins;Synthesis of diphthamide-EEF2;Gamma carboxylation, hypusine formation and arylsulfatase activation (Consensus)

Recessive Scores

pRec: 0.130

Intolerance Scores

loftool: 0.509
rvis_EVS: 0.1
rvis_percentile_EVS: 60.96

Haploinsufficiency Scores

pHI: 0.405
hipred: Y
hipred_score: 0.860
ghis: 0.621

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.617

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Dph3
Phenotype: growth/size/body region phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype;

Gene ontology

Biological process: tRNA wobble uridine modification;peptidyl-diphthamide biosynthetic process from peptidyl-histidine;negative regulation of protein secretion;positive regulation of binding
Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol
Molecular function: protein binding;metal ion binding