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PKN3

Chr 9

protein kinase N3

Also known as: UTDP4-1

NCBI Gene: 29941 ENSG00000160447 UniProt: Q6P5Z2

Predicted to enable protein serine/threonine kinase activity. Involved in epithelial cell migration. Predicted to be located in Golgi apparatus; cytosol; and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

262

ClinVar variants

34

Pathogenic / LP

0.00

pLI score

0

Active trials

Clinical Summary— PKN3

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

34 Pathogenic / Likely Pathogenic· 193 VUS of 262 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.95LOEUF

pLI 0.000

Z-score 1.84

OE 0.72 (0.55–0.95)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

1.30Z-score

OE missense 0.85 (0.78–0.91)

475 obs / 561.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.72 (0.55–0.95)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.78–0.91)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.94

0≤1.21.6

LoF obs/exp: 36 / 50.0Missense obs/exp: 475 / 561.8Syn Z: 0.74

ClinVar Variant Classifications

262 submitted variants in ClinVar

Classification Summary

Pathogenic33

Likely Pathogenic1

VUS193

Likely Benign8

33

Pathogenic

1

Likely Pathogenic

193

VUS

8

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	33	0	33
Likely Pathogenic	0	0	1	0	1
VUS	1	185	7	0	193
Likely Benign	0	7	0	1	8
Benign	0	0	0	0	0
Total	1	192	41	1	235

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PKN3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

PROTEIN KINASE N3; PKN3

MIM #610714 · *

External Resources

Links to major genomics databases and tools

Variant Interpretation

Variant interpretation & classification platform

Franklin by Genoox

AI-powered variant curation and clinical analysis

Genomic literature search for variants and genes

ACMG/AMP variant classification tool

Population Databases

Population allele frequencies & constraint metrics

Genomic variants and phenotypes in rare disease patients

Clinical variant interpretations from submitters worldwide

Short genetic variation database

Gene Resources

Gene annotation, transcripts & comparative genomics

Comprehensive gene information and references

Protein sequence, structure and function

Online Mendelian Inheritance in Man

Human gene compendium

Gene expression across human tissues

Expert Curation

Expert-curated gene-disease validity

Gene Curation Coalition — multi-curator classifications

Rare disease encyclopedia and gene-disease associations

Autism-gene association scoring (SFARI)

Gene panels for rare disease diagnostics (Genomics England)

Leiden Open Variation Database — variant listings

Expert-authored summaries of heritable conditions (NCBI)

Clinical Literature

Landmark / reviewRecent case evidence

Key Publications

Landmark & review papers · by relevance

PubMed

A Chemoproteomic Strategy for Direct and Proteome-Wide Covalent Inhibitor Target-Site Identification.

Browne CM et al.·J Am Chem Soc

2019

The Race of 10 Synthetic RNAi-Based Drugs to the Pharmaceutical Market.

Titze-de-Almeida R et al.·Pharm Res

2017Review

Enzyme kinetics and distinct modulation of the protein kinase N family of kinases by lipid activators and small molecule inhibitors.

Falk MD et al.·Biosci Rep

2014

DNA methylation patterns of LINE-1 and Alu for pre-symptomatic dementia in type 2 diabetes.

Sae-Lee C et al.·PLoS One

2020

Phase I clinical development of Atu027, a siRNA formulation targeting PKN3 in patients with advanced solid tumors.

Strumberg D et al.·Int J Clin Pharmacol Ther

2012Clinical trial

Top 10 resultsSearch PubMed ↗

Recent Gene-Specific Literature

Gene in title · MEDLINE · newest first

Europe PMC

Selective Inhibitor of Protein Kinase PKN3 Generated by Conjugation of a Structurally Optimized Bumped N-(2-Aminoethyl)-8-anilinoisoquinoline-5-sulfonamide (H-9) with d-Arginine-Rich Chain.

Smorodina V et al.·Molecules

2026

PKN3 as a key regulator in cancer - From signaling pathways to targeted therapies.

Wang ZX et al.·Bioorg Chem

2025

Efficient delivery of PKN3 shRNA for the treatment of breast cancer via lipid nanoparticles.

Liu C et al.·Bioorg Med Chem

2022

Identification of 4-Anilinoquin(az)oline as a Cell-Active Protein Kinase Novel 3 (PKN3) Inhibitor Chemotype.

Asquith CRM et al.·ChemMedChem

2022

A Screen for PKN3 Substrates Reveals an Activating Phosphorylation of ARHGAP18.

Dibus M et al.·Int J Mol Sci

2020🔓 Open Access

Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Variant Interpretation

Variant interpretation & classification platform

Franklin by Genoox

AI-powered variant curation and clinical analysis

Genomic literature search for variants and genes

ACMG/AMP variant classification tool

Population Databases

Population allele frequencies & constraint metrics

Genomic variants and phenotypes in rare disease patients

Clinical variant interpretations from submitters worldwide

Short genetic variation database

Gene Resources

Gene annotation, transcripts & comparative genomics

Comprehensive gene information and references

Protein sequence, structure and function

Online Mendelian Inheritance in Man

Human gene compendium

Gene expression across human tissues

Expert Curation

Expert-curated gene-disease validity

Gene Curation Coalition — multi-curator classifications

Rare disease encyclopedia and gene-disease associations

Autism-gene association scoring (SFARI)

Gene panels for rare disease diagnostics (Genomics England)

Leiden Open Variation Database — variant listings

Expert-authored summaries of heritable conditions (NCBI)