DPH2

diphthamide biosynthesis 2, the group of Diphthamide biosynthesis pathway genes

Basic information

Region (hg38): 1:43970000-43973369

Previous symbols: [ "DPH2L2" ]

Links

ENSG00000132768 ∙ NCBI:1802 ∙ OMIM:603456 ∙ HGNC:3004 ∙ Uniprot:Q9BQC3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental delay with short stature, dysmorphic features, and sparse hair 2	AR	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic	27421267; 32576952

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DPH2 gene.

• not_specified (74 variants)
• Developmental_delay_with_short_stature,_dysmorphic_facial_features,_and_sparse_hair_2 (5 variants)
• Global_developmental_delay (3 variants)
• Short_stature (2 variants)
• Ventricular_septal_defect (2 variants)
• not_provided (1 variants)
• diphthamide-deficiency_syndrome (1 variants)
• Intellectual_disability (1 variants)
• Macrocephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DPH2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001384.5. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2		2
missense		1	71	3		75
nonsense		3				3
start loss						0
frameshift		1				1
splice donor/acceptor (+/-2bp)						0
Total	0	5	71	5	0

Highest pathogenic variant AF is 0.000030355783

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DPH2	protein_coding	protein_coding	ENST00000255108	6	3370

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000909	0.935	125709	0	38	125747	0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.759	261	298	0.876	0.0000178	3038
Missense in Polyphen		51	60.031	0.84956		718
Synonymous	0.218	120	123	0.975	0.00000657	1143
Loss of Function	1.73	11	19.2	0.573	0.00000112	193

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000216	0.000216
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000194	0.000193
Middle Eastern	0.000218	0.000217
South Asian	0.000163	0.000163
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for the first step in the synthesis of diphthamide, a post-translational modification of histidine which occurs in translation elongation factor 2 (EEF2). {ECO:0000250|UniProtKB:Q9CR25}.
• Pathway: Post-translational protein modification;Metabolism of proteins;Synthesis of diphthamide-EEF2;Gamma carboxylation, hypusine formation and arylsulfatase activation (Consensus)

Recessive Scores

• pRec: 0.0902

Intolerance Scores

• loftool: 0.300
• rvis_EVS: -0.14
• rvis_percentile_EVS: 43.77

Haploinsufficiency Scores

• pHI: 0.0691
• hipred: Y
• hipred_score: 0.520
• ghis: 0.485

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.231

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dph2
• Phenotype: 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); immune system phenotype; skeleton phenotype; hematopoietic system phenotype

Gene ontology

• Biological process: peptidyl-diphthamide biosynthetic process from peptidyl-histidine
• Cellular component: cytosol
• Molecular function: protein binding;2-(3-amino-3-carboxypropyl)histidine synthase activity