PAK2

Chr 3AD

p21 (RAC1) activated kinase 2

Also known as: KNO2, PAK65, PAKgamma

NCBI Gene: 5062ENSG00000180370UniProt: Q13177

PAK2 encodes a serine/threonine protein kinase that regulates cytoskeleton organization, cell motility, cell cycle progression, and apoptosis by acting as a downstream effector of the small GTPases CDC42 and RAC1. Mutations cause Knobloch syndrome 2, which follows autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants, indicating that proper PAK2 function is essential for normal development.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

?Knobloch syndrome 2MIM #618458
AD
0
Active trials
53
Pubs (1 yr)
91
P/LP submissions
3%
P/LP missense
0.32
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical Summary— PAK2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
90 unique Pathogenic / Likely Pathogenic· 64 VUS of 186 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.32LOEUF
pLI 0.972
Z-score 4.27
OE 0.14 (0.07–0.32)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
3.40Z-score
OE missense 0.43 (0.37–0.50)
122 obs / 283.0 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.14 (0.07–0.32)
0≤0.351.4
Missense OE0.43 (0.37–0.50)
0≤0.61.4
Synonymous OE1.01
0≤1.21.6
LoF obs/exp: 4 / 28.6Missense obs/exp: 122 / 283.0Syn Z: -0.06
DN
0.4785th %ile
GOF
0.5954th %ile
LOF
0.67top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.32

Literature Evidence

LOF3q29 microdeletion syndrome: clinical and molecular characterization of a new syndromePMID:15918153

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

186 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic85
Likely Pathogenic5
VUS64
Likely Benign5
Benign1
Conflicting1
85
Pathogenic
5
Likely Pathogenic
64
VUS
5
Likely Benign
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
84
0
85
Likely Pathogenic
0
2
3
0
5
VUS
1
45
18
0
64
Likely Benign
0
2
2
1
5
Benign
0
0
1
0
1
Conflicting
—1
Total1501081161

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

View in ClinVar →

Protein Context — Lollipop Plot

PAK2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients