DPH1
Basic information
Region (hg38): 17:2030137-2043898
Previous symbols: [ "DPH2L", "DPH2L1" ]
Links
Phenotypes
GenCC
Source:
- 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:
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
- not provided (3 variants)
- Developmental delay with short stature, dysmorphic facial features, and sparse hair 1 (2 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 | 10 | 12 | ||||
missense | 44 | 10 | 57 | |||
nonsense | 2 | |||||
start loss | 0 | |||||
frameshift | 5 | |||||
inframe indel | 2 | |||||
splice donor/acceptor (+/-2bp) | 1 | |||||
splice region | 3 | 2 | 5 | |||
non coding | 24 | 33 | ||||
Total | 4 | 5 | 72 | 23 | 8 |
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 1 | 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) | ||
17-2030204-A-G | Inborn genetic diseases | Uncertain significance (Jun 05, 2024) | ||
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 | Inborn genetic diseases | Likely benign (Mar 25, 2024) | ||
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) |
GnomAD
Source:
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:
- 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