PRKD2
protein kinase D2, the group of Pleckstrin homology domain containing|MicroRNA protein coding host genes
Basic information
Region (hg38): 19:46674275-46717127
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRKD2 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 | 3 | |||||
| missense | 37 | 40 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | ||||
| non coding | 1 | |||||
| Total | 0 | 0 | 38 | 3 | 4 |
Variants in PRKD2
This is a list of pathogenic ClinVar variants found in the PRKD2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 19-46674539-C-T | not specified | Uncertain significance (Dec 16, 2023) | ||
| 19-46674540-G-A | not specified | Uncertain significance (Aug 17, 2022) | ||
| 19-46674576-G-A | not specified | Uncertain significance (Nov 09, 2023) | ||
| 19-46674666-T-C | not specified | Uncertain significance (Apr 28, 2022) | ||
| 19-46674672-G-A | not specified | Uncertain significance (Jan 24, 2024) | ||
| 19-46675096-C-T | Likely benign (Sep 01, 2022) | |||
| 19-46675103-T-C | not specified | Uncertain significance (Feb 03, 2022) | ||
| 19-46675115-A-G | not specified | Uncertain significance (May 11, 2022) | ||
| 19-46678401-G-A | not specified | Uncertain significance (Nov 18, 2022) | ||
| 19-46678446-T-C | not specified | Uncertain significance (Jun 11, 2021) | ||
| 19-46678543-A-T | not specified | Uncertain significance (Feb 11, 2022) | ||
| 19-46678631-G-C | not specified | Uncertain significance (Feb 03, 2022) | ||
| 19-46678636-G-A | not specified | Uncertain significance (May 26, 2024) | ||
| 19-46689574-C-T | not specified | Uncertain significance (Mar 29, 2022) | ||
| 19-46689684-G-C | Benign (Jan 19, 2018) | |||
| 19-46689691-C-T | not specified | Uncertain significance (Jun 24, 2022) | ||
| 19-46689692-G-C | PRKD2-related disorder | Uncertain significance (Mar 11, 2024) | ||
| 19-46691973-A-G | not specified | Uncertain significance (Mar 20, 2023) | ||
| 19-46691979-G-A | not specified | Uncertain significance (Jan 08, 2024) | ||
| 19-46693958-C-T | not specified | Uncertain significance (Apr 18, 2023) | ||
| 19-46693971-C-T | PRKD2-related disorder | Likely benign (May 31, 2022) | ||
| 19-46693973-C-G | Benign (Jan 19, 2018) | |||
| 19-46694033-T-C | not specified | Uncertain significance (Sep 17, 2021) | ||
| 19-46694054-C-A | not specified | Uncertain significance (Mar 13, 2023) | ||
| 19-46694063-T-C | not specified | Uncertain significance (Jan 26, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PRKD2 | protein_coding | protein_coding | ENST00000433867 | 18 | 42853 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.0000540 | 125737 | 0 | 10 | 125747 | 0.0000398 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.68 | 320 | 566 | 0.565 | 0.0000366 | 5672 |
| Missense in Polyphen | 74 | 190.23 | 0.38901 | 1833 | ||
| Synonymous | -0.399 | 260 | 252 | 1.03 | 0.0000176 | 1804 |
| Loss of Function | 5.50 | 3 | 41.1 | 0.0731 | 0.00000196 | 464 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000588 | 0.0000588 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000272 | 0.000217 |
| Finnish | 0.0000533 | 0.0000462 |
| European (Non-Finnish) | 0.0000269 | 0.0000264 |
| Middle Eastern | 0.000272 | 0.000217 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of cell proliferation via MAPK1/3 (ERK1/2) signaling, oxidative stress- induced NF-kappa-B activation, inhibition of HDAC7 transcriptional repression, signaling downstream of T-cell antigen receptor (TCR) and cytokine production, and plays a role in Golgi membrane trafficking, angiogenesis, secretory granule release and cell adhesion (PubMed:15604256, PubMed:14743217, PubMed:17077180, PubMed:16928771, PubMed:17962809, PubMed:17951978, PubMed:18262756, PubMed:19192391, PubMed:19001381, PubMed:23503467, PubMed:28428613). May potentiate mitogenesis induced by the neuropeptide bombesin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression (By similarity). In response to oxidative stress, is phosphorylated at Tyr-438 and Tyr-717 by ABL1, which leads to the activation of PRKD2 without increasing its catalytic activity, and mediates activation of NF-kappa-B (PubMed:15604256, PubMed:28428613). In response to the activation of the gastrin receptor CCKBR, is phosphorylated at Ser-244 by CSNK1D and CSNK1E, translocates to the nucleus, phosphorylates HDAC7, leading to nuclear export of HDAC7 and inhibition of HDAC7 transcriptional repression of NR4A1/NUR77 (PubMed:17962809). Upon TCR stimulation, is activated independently of ZAP70, translocates from the cytoplasm to the nucleus and is required for interleukin- 2 (IL2) promoter up-regulation (PubMed:17077180). During adaptive immune responses, is required in peripheral T-lymphocytes for the production of the effector cytokines IL2 and IFNG after TCR engagement and for optimal induction of antibody responses to antigens (By similarity). In epithelial cells stimulated with lysophosphatidic acid (LPA), is activated through a PKC-dependent pathway and mediates LPA-stimulated interleukin-8 (IL8) secretion via a NF-kappa-B-dependent pathway (PubMed:16928771). During TCR- induced T-cell activation, interacts with and is activated by the tyrosine kinase LCK, which results in the activation of the NFAT transcription factors (PubMed:19192391). In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane and in polarized cells is involved in the transport of proteins from the TGN to the basolateral membrane (PubMed:14743217). Plays an important role in endothelial cell proliferation and migration prior to angiogenesis, partly through modulation of the expression of KDR/VEGFR2 and FGFR1, two key growth factor receptors involved in angiogenesis (PubMed:19001381). In secretory pathway, is required for the release of chromogranin-A (CHGA)-containing secretory granules from the TGN (PubMed:18262756). Downstream of PRKCA, plays important roles in angiotensin-2-induced monocyte adhesion to endothelial cells (PubMed:17951978). Plays a regulatory role in angiogenesis and tumor growth by phosphorylating a downstream mediator CIB1 isoform 2, resulting in vascular endothelial growth factor A (VEGFA) secretion (PubMed:23503467). {ECO:0000250|UniProtKB:Q8BZ03, ECO:0000269|PubMed:14743217, ECO:0000269|PubMed:15604256, ECO:0000269|PubMed:16928771, ECO:0000269|PubMed:17077180, ECO:0000269|PubMed:17951978, ECO:0000269|PubMed:17962809, ECO:0000269|PubMed:18262756, ECO:0000269|PubMed:19001381, ECO:0000269|PubMed:19192391, ECO:0000269|PubMed:23503467, ECO:0000269|PubMed:28428613}.;
- Pathway
- Aldosterone synthesis and secretion - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);VEGFA-VEGFR2 Signaling Pathway;Metabolism of lipids;TCR;Metabolism;Gastrin;Sphingolipid de novo biosynthesis;Sphingolipid metabolism
(Consensus)
Recessive Scores
- pRec
- 0.266
Intolerance Scores
- loftool
- rvis_EVS
- -0.73
- rvis_percentile_EVS
- 14.14
Haploinsufficiency Scores
- pHI
- 0.0950
- hipred
- Y
- hipred_score
- 0.775
- ghis
- 0.582
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.992
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Prkd2
- Phenotype
- hematopoietic system phenotype; immune system phenotype; endocrine/exocrine gland phenotype;
Zebrafish Information Network
- Gene name
- prkd2
- Affected structure
- heart
- Phenotype tag
- abnormal
- Phenotype quality
- physical object quality
Gene ontology
- Biological process
- angiogenesis;positive regulation of endothelial cell proliferation;adaptive immune response;protein phosphorylation;cell adhesion;cell death;positive regulation of endothelial cell migration;peptidyl-serine phosphorylation;peptidyl-threonine phosphorylation;sphingolipid biosynthetic process;positive regulation of vascular endothelial growth factor receptor signaling pathway;positive regulation of interleukin-2 production;positive regulation of interleukin-8 production;positive regulation of CREB transcription factor activity;positive regulation of peptidyl-serine phosphorylation;intracellular signal transduction;cellular response to vascular endothelial growth factor stimulus;positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway;positive regulation of blood vessel endothelial cell migration;positive regulation of fibroblast growth factor receptor signaling pathway;positive regulation of angiogenesis;positive regulation of cell adhesion;positive regulation of transcription by RNA polymerase II;protein autophosphorylation;vascular endothelial growth factor receptor signaling pathway;T cell receptor signaling pathway;positive regulation of T cell receptor signaling pathway;positive regulation of DNA-binding transcription factor activity;positive regulation of NF-kappaB transcription factor activity;endothelial tube morphogenesis;positive regulation of ERK1 and ERK2 cascade;protein kinase D signaling;positive regulation of histone deacetylase activity;positive regulation of intracellular signal transduction;positive regulation of DNA biosynthetic process;positive regulation of endothelial cell chemotaxis
- Cellular component
- nucleus;nucleoplasm;cytoplasm;Golgi apparatus;cytosol;plasma membrane
- Molecular function
- protein kinase activity;protein serine/threonine kinase activity;protein kinase C activity;protein kinase C binding;protein binding;ATP binding;metal ion binding