PKN1

protein kinase N1, the group of AGC family kinases|C2 domain containing protein kinases

Basic information

Region (hg38): 19:14433052-14471867

Previous symbols: [ "PRKCL1" ]

Links

ENSG00000123143 ∙ NCBI:5585 ∙ OMIM:601032 ∙ HGNC:9405 ∙ Uniprot:Q16512 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PKN1 gene.

• Inborn genetic diseases (38 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.

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	2	5
missense			37	1	1	39
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	37	4	3

Variants in PKN1

This is a list of pathogenic ClinVar variants found in the PKN1 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-14433525-G-A		not specified	Uncertain significance (Sep 13, 2023)
19-14441188-G-A		not specified	Uncertain significance (Sep 17, 2021)
19-14441204-C-T		not specified	Uncertain significance (Jun 10, 2022)
19-14441299-C-T		not specified	Uncertain significance (Jul 08, 2022)
19-14441368-C-T		not specified	Uncertain significance (Sep 29, 2023)
19-14441384-A-G		not specified	Uncertain significance (Mar 02, 2023)
19-14441413-G-A		not specified	Uncertain significance (Nov 07, 2022)
19-14443509-C-T		not specified	Uncertain significance (Aug 21, 2023)
19-14443525-C-A		not specified	Uncertain significance (Jun 13, 2022)
19-14443527-G-A		not specified	Uncertain significance (Oct 14, 2023)
19-14443582-G-A			Benign (Jul 06, 2018)
19-14446429-C-G		not specified	Uncertain significance (May 27, 2022)
19-14446429-C-T		not specified	Uncertain significance (Jul 11, 2022)
19-14446500-A-C		not specified	Uncertain significance (Mar 11, 2024)
19-14446511-C-T		not specified	Uncertain significance (Apr 22, 2022)
19-14446519-G-A		not specified	Uncertain significance (Dec 14, 2023)
19-14450321-G-C		not specified	Uncertain significance (Jun 16, 2022)
19-14450338-G-C		not specified	Uncertain significance (Feb 26, 2024)
19-14450371-T-A		not specified	Uncertain significance (Sep 20, 2023)
19-14450400-T-C			Likely benign (May 08, 2018)
19-14450450-A-G		not specified	Uncertain significance (Dec 06, 2021)
19-14450910-A-A			Likely benign (Oct 01, 2018)
19-14450916-A-C		not specified	Uncertain significance (Jun 01, 2023)
19-14451044-C-A		not specified	Uncertain significance (Mar 07, 2024)
19-14451088-T-A		not specified	Uncertain significance (May 05, 2023)

GnomAD

Source: gnomAD

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: dbNSFP

• 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