DPH1

diphthamide biosynthesis 1, the group of Minor histocompatibility antigens|Diphthamide biosynthesis pathway genes

Basic information

Region (hg38): 17:2030136-2043898

Previous symbols: [ "DPH2L", "DPH2L1" ]

Links

ENSG00000108963 ∙ NCBI:1801 ∙ OMIM:603527 ∙ HGNC:3003 ∙ Uniprot:Q9BZG8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• craniofacial dysplasia-short stature-ectodermal anomalies-intellectual disability syndrome (Strong), mode of inheritance: AR
• craniofacial dysplasia-short stature-ectodermal anomalies-intellectual disability syndrome (Moderate), mode of inheritance: AR
• developmental delay with short stature, dysmorphic facial features, and sparse hair 1 (Strong), mode of inheritance: AR
• craniofacial dysplasia-short stature-ectodermal anomalies-intellectual disability syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental delay with short stature, dysmorphic features, and sparse hair 1	AR	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic	25558065; 26220823

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DPH1 gene.

• Inborn genetic diseases (45 variants)
• not provided (32 variants)
• Developmental delay with short stature, dysmorphic facial features, and sparse hair (14 variants)
• Developmental delay with short stature, dysmorphic facial features, and sparse hair 1 (9 variants)
• not specified (3 variants)
• Global developmental delay;Dandy-Walker syndrome;Hydrocephalus;Cerebellar vermis hypoplasia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DPH1 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				7	1	8
missense		3	33	9		45
nonsense	1	1				2
start loss						0
frameshift	3	1	1			5
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region			4	2		6
non coding			19	2	6	27
Total	4	5	55	18	7

Highest pathogenic variant AF is 0.0000328

Variants in DPH1

This is a list of pathogenic ClinVar variants found in the DPH1 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-2030155-A-G			Uncertain significance (Oct 01, 2018)
17-2030157-G-A		Developmental delay with short stature, dysmorphic facial features, and sparse hair 1	Uncertain significance (Mar 29, 2024)
17-2030158-C-T		Inborn genetic diseases	Uncertain significance (May 18, 2022)
17-2030168-T-A		Inborn genetic diseases	Uncertain significance (Aug 02, 2022)
17-2030171-T-A		Developmental delay with short stature, dysmorphic facial features, and sparse hair	Pathogenic/Likely pathogenic (Oct 01, 2015)
17-2030179-C-A		Inborn genetic diseases	Uncertain significance (Oct 27, 2022)
17-2030180-T-C		Inborn genetic diseases	Uncertain significance (Oct 05, 2023)
17-2030203-C-A		Developmental delay with short stature, dysmorphic facial features, and sparse hair	Uncertain significance (Sep 05, 2019)
17-2033508-G-A		Developmental delay with short stature, dysmorphic facial features, and sparse hair 1 • Inborn genetic diseases	Uncertain significance (Mar 02, 2023)
17-2033509-G-T			Likely benign (Dec 31, 2019)
17-2033517-G-A		Inborn genetic diseases	Uncertain significance (Mar 22, 2023)
17-2033523-G-A		Developmental delay with short stature, dysmorphic facial features, and sparse hair	Uncertain significance (Jan 29, 2018)
17-2033525-G-A		Inborn genetic diseases	Uncertain significance (Aug 08, 2022)
17-2033545-T-G			Likely benign (Dec 31, 2019)
17-2033546-G-T		Developmental delay with short stature, dysmorphic facial features, and sparse hair 1	Pathogenic (Nov 03, 2023)
17-2033556-A-C			Likely benign (Dec 31, 2019)
17-2033557-G-A		DPH1-related disorder	Likely benign (Jan 29, 2024)
17-2033579-A-G		Inborn genetic diseases	Likely benign (Oct 26, 2021)
17-2033582-C-T		Developmental delay with short stature, dysmorphic facial features, and sparse hair 1 • Inborn genetic diseases	Uncertain significance (Jul 19, 2022)
17-2033583-G-A		Inborn genetic diseases	Likely benign (Jan 16, 2024)
17-2033598-A-G		Developmental delay with short stature, dysmorphic facial features, and sparse hair 1	Uncertain significance (Jan 20, 2021)
17-2033642-G-A		Inborn genetic diseases	Uncertain significance (Jan 06, 2021)
17-2033769-C-T			Likely benign (Jul 31, 2018)
17-2033792-G-T		Inborn genetic diseases	Uncertain significance (Jan 22, 2024)
17-2033832-A-G		Inborn genetic diseases	Uncertain significance (Dec 20, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DPH1	protein_coding	protein_coding	ENST00000263083	12	13321

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.02e-17	0.00847	124709	0	98	124807	0.000393

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.178	278	270	1.03	0.0000158	2809
Missense in Polyphen		110	119.7	0.91899		1331
Synonymous	-0.0235	110	110	1.00	0.00000614	936
Loss of Function	0.0818	25	25.4	0.983	0.00000133	258

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00113	0.00109
Ashkenazi Jewish	0.00	0.00
East Asian	0.000561	0.000556
Finnish	0.0000464	0.0000464
European (Non-Finnish)	0.000436	0.000424
Middle Eastern	0.000561	0.000556
South Asian	0.000399	0.000392
Other	0.000675	0.000660

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). When overexpressed, suppresses colony formation ability and growth rate of ovarian cancer cells. Acts also as a tumor suppressor in lung and breast cancers (By similarity). Plays a role in embryonic growth, organogenesis and postnatal survival (By similarity). {ECO:0000250|UniProtKB:Q5NCQ5, ECO:0000269|PubMed:10519411}.
• Pathway: Post-translational protein modification;Metabolism of proteins;Synthesis of diphthamide-EEF2;Gamma carboxylation, hypusine formation and arylsulfatase activation (Consensus)

Recessive Scores

• pRec: 0.133

Intolerance Scores

• loftool: 0.818
• rvis_EVS: 0.4
• rvis_percentile_EVS: 76.36

Haploinsufficiency Scores

• pHI: 0.602
• hipred: N
• hipred_score: 0.498
• ghis: 0.499

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.815

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dph1
• Phenotype: growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; liver/biliary system phenotype; respiratory system phenotype; embryo phenotype; pigmentation phenotype; neoplasm; hematopoietic system 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); vision/eye phenotype; digestive/alimentary phenotype; limbs/digits/tail 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); skeleton phenotype

Gene ontology

• Biological process: cell population proliferation;peptidyl-diphthamide biosynthetic process from peptidyl-histidine
• Cellular component: nucleoplasm;cytosol;cell junction
• Molecular function: protein binding;transferase activity