DSTYK
dual serine/threonine and tyrosine protein kinase
Basic information
Region (hg38): 1:205142504-205211702
Previous symbols: [ "RIPK5", "SPG23" ]
Links
Phenotypes
GenCC
Source:
- congenital anomalies of kidney and urinary tract 1 (Definitive), mode of inheritance: AD
- congenital anomalies of kidney and urinary tract 1 (Limited), mode of inheritance: AR
- renal agenesis, unilateral (Supportive), mode of inheritance: AD
- hereditary spastic paraplegia 23 (Supportive), mode of inheritance: AR
- congenital anomalies of kidney and urinary tract 1 (Limited), mode of inheritance: AD
- complex hereditary spastic paraplegia (Moderate), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Congenital anomalies of the kidney and urinary tract, 1 | AD | Renal | Monitoring and intervention related to vesicoureteral reflux may be beneficial in terms of helping to preserve renal function | Craniofacial; Dermatologic; Neurologic; Renal | 17273976; 28157540; 23862974 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (129 variants)
- Inborn genetic diseases (25 variants)
- Congenital anomalies of kidney and urinary tract 1 (14 variants)
- Hereditary spastic paraplegia 23 (7 variants)
- not specified (4 variants)
- DSTYK-related condition (2 variants)
- Chronic kidney disease (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the DSTYK 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 | 22 | 30 | ||||
| missense | 76 | 85 | ||||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 3 | |||||
| inframe indel | 1 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 5 | 5 | ||||
| non coding ? | 18 | 24 | ||||
| Total | 0 | 2 | 80 | 34 | 28 |
Variants in DSTYK
This is a list of pathogenic ClinVar variants found in the DSTYK region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| DSTYK | protein_coding | protein_coding | ENST00000367162 | 13 | 69096 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.513 | 0.487 | 125660 | 0 | 87 | 125747 | 0.000346 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.59 | 434 | 537 | 0.807 | 0.0000304 | 6046 |
| Missense in Polyphen | 113 | 173.4 | 0.65166 | 1878 | ||
| Synonymous | -0.174 | 212 | 209 | 1.02 | 0.0000111 | 1847 |
| Loss of Function | 4.90 | 10 | 45.8 | 0.218 | 0.00000266 | 486 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00111 | 0.00110 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000163 | 0.000163 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000432 | 0.000422 |
| Middle Eastern | 0.000163 | 0.000163 |
| South Asian | 0.00 | 0.00 |
| Other | 0.000500 | 0.000489 |
dbNSFP
Source:
- Function
- FUNCTION: Acts as a positive regulator of ERK phosphorylation downstream of fibroblast growth factor-receptor activation (PubMed:23862974, PubMed:28157540). Involved in the regulation of both caspase-dependent apoptosis and caspase-independent cell death (PubMed:15178406). In the skin, it plays a predominant role in suppressing caspase-dependent apoptosis in response to UV stress in a range of dermal cell types (PubMed:28157540). {ECO:0000269|PubMed:15178406, ECO:0000269|PubMed:23862974, ECO:0000269|PubMed:28157540}.;
- Disease
- DISEASE: Spastic paraplegia 23 (SPG23) [MIM:270750]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG23 is an autosomal recessive form characterized by childhood-onset of gait difficulties and pigmentary abnormalities, including premature graying of the hair and vitiligo-like or hyperpigmented skin lesions. {ECO:0000269|PubMed:28157540}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.102
Intolerance Scores
- loftool
- 0.340
- rvis_EVS
- 0.09
- rvis_percentile_EVS
- 60.68
Haploinsufficiency Scores
- pHI
- 0.204
- hipred
- Y
- hipred_score
- 0.515
- ghis
- 0.556
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.774
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Dstyk
- Phenotype
- behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);
Zebrafish Information Network
- Gene name
- dstyk
- Affected structure
- cloaca
- Phenotype tag
- abnormal
- Phenotype quality
- malformed
Gene ontology
- Biological process
- peptidyl-tyrosine phosphorylation;positive regulation of kinase activity;negative regulation of apoptotic process;cellular response to fibroblast growth factor stimulus;positive regulation of fibroblast growth factor receptor signaling pathway;positive regulation of ERK1 and ERK2 cascade
- Cellular component
- cytoplasm;basolateral plasma membrane;apical plasma membrane;cell junction
- Molecular function
- protein serine/threonine kinase activity;protein serine/threonine/tyrosine kinase activity;protein tyrosine kinase activity;ATP binding