PKN1
protein kinase N1, the group of AGC family kinases|C2 domain containing protein kinases
Basic information
Region (hg38): 19:14433053-14471867
Previous symbols: [ "PRKCL1" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (151 variants)
- not_provided (7 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PKN1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002741.5. 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 | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | |||||
| missense | 146 | 150 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 146 | 6 | 3 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PKN1 | protein_coding | protein_coding | ENST00000342216 | 22 | 38815 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.204 | 0.796 | 124783 | 0 | 32 | 124815 | 0.000128 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.34 | 496 | 588 | 0.844 | 0.0000410 | 5994 |
| Missense in Polyphen | 134 | 201.07 | 0.66644 | 2083 | ||
| Synonymous | 0.111 | 259 | 261 | 0.991 | 0.0000190 | 1988 |
| Loss of Function | 4.82 | 11 | 46.4 | 0.237 | 0.00000256 | 504 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000202 | 0.000193 |
| Ashkenazi Jewish | 0.000100 | 0.0000993 |
| East Asian | 0.000117 | 0.000111 |
| Finnish | 0.0000994 | 0.0000928 |
| European (Non-Finnish) | 0.000182 | 0.000177 |
| Middle Eastern | 0.000117 | 0.000111 |
| South Asian | 0.0000709 | 0.0000654 |
| Other | 0.000165 | 0.000165 |
dbNSFP
Source:
- Function
- FUNCTION: PKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. Regulates the cytoskeletal network by phosphorylating proteins such as VIM and neurofilament proteins NEFH, NEFL and NEFM, leading to inhibit their polymerization. Phosphorylates 'Ser-575', 'Ser-637' and 'Ser-669' of MAPT/Tau, lowering its ability to bind to microtubules, resulting in disruption of tubulin assembly. Acts as a key coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and specifically mediating phosphorylation of 'Thr-11' of histone H3 (H3T11ph), a specific tag for epigenetic transcriptional activation that promotes demethylation of histone H3 'Lys-9' (H3K9me) by KDM4C/JMJD2C. Phosphorylates HDAC5, HDAC7 and HDAC9, leading to impair their import in the nucleus. Phosphorylates 'Thr-38' of PPP1R14A, 'Ser- 159', 'Ser-163' and 'Ser-170' of MARCKS, and GFAP. Able to phosphorylate RPS6 in vitro. {ECO:0000269|PubMed:11104762, ECO:0000269|PubMed:12514133, ECO:0000269|PubMed:17332740, ECO:0000269|PubMed:18066052, ECO:0000269|PubMed:20188095, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:21754995, ECO:0000269|PubMed:24248594, ECO:0000269|PubMed:8557118, ECO:0000269|PubMed:8621664, ECO:0000269|PubMed:9175763}.;
- Pathway
- PI3K-Akt signaling pathway - Homo sapiens (human);Salmonella infection - Homo sapiens (human);Apoptosis-related network due to altered Notch3 in ovarian cancer;PI3K-Akt Signaling Pathway;G13 Signaling Pathway;Signal Transduction;pkc-catalyzed phosphorylation of inhibitory phosphoprotein of myosin phosphatase;protein kinase a at the centrosome;Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3;RHO GTPases activate PKNs;RHO GTPase Effectors;Signaling by Rho GTPases;TNFalpha;PAR1-mediated thrombin signaling events;Regulation of Androgen receptor activity;Signaling mediated by p38-gamma and p38-delta;RhoA signaling pathway
(Consensus)
Recessive Scores
- pRec
- 0.490
Intolerance Scores
- loftool
- 0.588
- rvis_EVS
- -0.97
- rvis_percentile_EVS
- 8.96
Haploinsufficiency Scores
- pHI
- 0.318
- hipred
- Y
- hipred_score
- 0.611
- ghis
- 0.518
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.989
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Pkn1
- Phenotype
- cellular phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); immune system phenotype; renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); normal phenotype; hematopoietic system phenotype;
Gene ontology
- Biological process
- B cell homeostasis;B cell apoptotic process;regulation of germinal center formation;regulation of immunoglobulin production;renal system process;regulation of transcription by RNA polymerase II;protein phosphorylation;negative regulation of protein kinase activity;hyperosmotic response;signal transduction;activation of JUN kinase activity;epithelial cell migration;peptidyl-serine phosphorylation;negative regulation of B cell proliferation;histone H3-T11 phosphorylation;intracellular signal transduction;spleen development;positive regulation of nucleic acid-templated transcription;regulation of cell motility
- Cellular component
- nucleus;nucleoplasm;cytoplasm;endosome;cytosol;midbody;cleavage furrow;protein-containing complex
- Molecular function
- chromatin binding;protein kinase activity;protein serine/threonine kinase activity;protein kinase C activity;protein kinase C binding;protein binding;ATP binding;GTP-Rho binding;nuclear receptor transcription coactivator activity;histone kinase activity (H3-T11 specific);histone binding;histone deacetylase binding;Rac GTPase binding;androgen receptor binding