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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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PRKG2
protein kinase cGMP-dependent 2
Chromosome 4 Β· 4q21.21
NCBI Gene: 5593Ensembl: ENSG00000138669.12HGNC: HGNC:9416UniProt: A0A140VJM3
64PubMed Papers
22Diseases
0Drugs
9Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneKinase
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein serine kinase activitymitogen-activated protein kinase bindingintracellular signal transductioncGMP-dependent protein kinase activityacromesomelic dysplasiaspondylometaphyseal dysplasia, pagnamenta typeAbnormality of the skeletal systematrial fibrillation
✦AI Summary

PRKG2 encodes cGMP-dependent protein kinase II (cGKII), a serine/threonine kinase that serves as a crucial regulator of bone growth and intestinal secretion 1. The kinase is prominently expressed in secretory epithelium of the small intestine, juxtaglomerular cells, adrenal cortex, and chondrocytes 2. PRKG2 functions as a major downstream effector in the NO/cGMP and ANP/cGMP signaling pathways, specifically inhibiting renin secretion, chloride/water secretion in the small intestine, and regulating endochondral bone growth 1. In chondrogenic differentiation, PRKG2 acts downstream of the CNP/NPR-B/cGMP pathway, phosphorylating c-Raf 1 at Ser43 and subsequently activating ERK1/2 signaling in response to growth factors 3. Loss-of-function mutations in PRKG2 cause acromesomelic dysplasia, characterized by severe short stature, limb shortening, and disrupted endochondral ossification 3. Similar skeletal dysplasias have been documented in Dalmatian dogs carrying PRKG2 nonsense mutations 4. Additionally, PRKG2 polymorphisms have been associated with gout susceptibility in some populations 5 and vertebral traits in livestock 6. Notably, PRKG2 fusion proteins with PDGFRB have been identified in atypical myeloproliferative disorders, which respond to imatinib therapy 7.

Sources cited
1
PRKG2 encodes cGKII, a serine/threonine kinase that inhibits intestinal secretion and endochondral bone growth
PMID: 23709024
2
PRKG2 is expressed in secretory epithelium, juxtaglomerular cells, adrenal cortex, and chondrocytes
PMID: 19089329
3
PRKG2 functions in CNP/NPR-B/cGMP pathway, phosphorylates c-Raf 1, and mutations cause acromesomelic dysplasia
PMID: 33106379
4
PRKG2 nonsense mutations cause skeletal dysplasia in Dalmatian dogs
PMID: 41296694
5
PRKG2 polymorphisms associated with gout susceptibility
PMID: 25688884
6
PRKG2 polymorphisms associated with vertebral traits in donkeys
PMID: 36600198
7
PRKG2 fusion with PDGFRB found in atypical myeloproliferative disorders responsive to imatinib
PMID: 18262053
Disease Associationsβ“˜22
acromesomelic dysplasiaOpen Targets
0.67Moderate
spondylometaphyseal dysplasia, pagnamenta typeOpen Targets
0.55Moderate
Abnormality of the skeletal systemOpen Targets
0.50Moderate
atrial fibrillationOpen Targets
0.43Moderate
osteoarthritis, hipOpen Targets
0.41Moderate
dengue diseaseOpen Targets
0.37Weak
smoking behaviorOpen Targets
0.37Weak
alcohol drinkingOpen Targets
0.34Weak
osteoarthritis, kneeOpen Targets
0.30Weak
insomniaOpen Targets
0.30Weak
adolescent idiopathic scoliosisOpen Targets
0.29Weak
mathematical abilityOpen Targets
0.27Weak
osteoarthritisOpen Targets
0.26Weak
total hip arthroplastyOpen Targets
0.26Weak
Hammer Toe SyndromeOpen Targets
0.24Weak
schizophreniaOpen Targets
0.23Weak
joint diseaseOpen Targets
0.21Weak
genetic disorderOpen Targets
0.19Weak
temporomandibular joint disorderOpen Targets
0.17Weak
type 2 diabetes mellitusOpen Targets
0.08Suggestive
Acromesomelic dysplasia 4UniProt
Spondylometaphyseal dysplasia, Pagnamenta typeUniProt
Pathogenic Variants9
NM_006259.3(PRKG2):c.1074del (p.Ala359fs)Likely pathogenic
Acromesomelic dysplasia 4
β˜…β˜†β˜†β˜†2024β†’ Residue 359
NM_006259.3(PRKG2):c.1154+1G>APathogenic
Acromesomelic dysplasia 4
β˜…β˜†β˜†β˜†2023
NM_006259.3(PRKG2):c.1901_1902insCAGCCACCTCTTCAGAGAAATGCAAAAATAACCTAACTAGTGATAAAGTGTATATACTTTAAGAGC (p.Trp634delinsCysSerHisLeuPheArgGluMetGlnLysTer)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 634
NM_006259.3(PRKG2):c.1904_1905insCACCTCTTCAGAGAAATGCAAAAATAACCTAACTAGTGATAAAGTGTATATACTTTAAGAGCGTA (p.Ser635_Leu636insThrSerSerGluLysCysLysAsnAsnLeuThrSerAspLysValTyrIleLeuTer)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 635
NM_006259.3(PRKG2):c.1409T>G (p.Val470Gly)Likely pathogenic
Acromesomelic dysplasia 4
β˜…β˜†β˜†β˜†β†’ Residue 470
NM_006259.3(PRKG2):c.1630G>T (p.Asp544Tyr)Likely pathogenic
Acromesomelic dysplasia 4
β˜…β˜†β˜†β˜†β†’ Residue 544
NM_006259.3(PRKG2):c.2282dup (p.Asp761fs)Pathogenic
Spondylometaphyseal dysplasia, pagnamenta type
β˜†β˜†β˜†β˜†2022β†’ Residue 761
NM_006259.3(PRKG2):c.1705C>T (p.Arg569Ter)Pathogenic
Acromesomelic dysplasia 4
β˜†β˜†β˜†β˜†2022β†’ Residue 569
NM_006259.3(PRKG2):c.491dup (p.Asn164fs)Pathogenic
Acromesomelic dysplasia 4
β˜†β˜†β˜†β˜†2022β†’ Residue 164
View on ClinVar β†—
Related Genes
KCNU1Protein interaction98%SLC8A3Protein interaction96%GUCY1A2Protein interaction95%GUCY1B1Protein interaction95%GUCY1A1Protein interaction95%VASPProtein interaction94%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
16%
Lung
12%
Heart
4%
Liver
2%
Ovary
1%
Gene Interaction Network
Click a node to explore
PRKG2KCNU1SLC8A3GUCY1A2GUCY1B1GUCY1A1VASP
PROTEIN STRUCTURE
Preparing viewer…
PDB5JIX Β· 1.47 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.48Moderately Constrained
pLIβ“˜
0.99Intolerant
Observed/Expected LoF0.34 [0.24–0.48]
RankingsWhere PRKG2 stands among ~20K protein-coding genes
  • #7,307of 20,598
    Most Researched64
  • #2,957of 5,498
    Most Pathogenic Variants9
  • #2,790of 17,882
    Most Constrained (LOEUF)0.48 Β· top quartile
Genes detectedPRKG2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Polymorphism detection of PRKG2 gene and its association with the number of thoracolumbar vertebrae and carcass traits in Dezhou donkey.
PMID: 36600198
BMC Genom Data Β· 2023
1.00
2
cGMP-dependent protein kinases (cGK).
PMID: 23709024
Methods Mol Biol Β· 2013
0.90
3
Polymorphism of rs7688672 and rs10033237 in cGKII/PRKG2 and gout susceptibility of Han population in northern China.
PMID: 25688884
Gene Β· 2015
0.80
4
cGK substrates.
PMID: 19089330
Handb Exp Pharmacol Β· 2009
0.70
5
Biallelic cGMP-dependent type II protein kinase gene (
PMID: 33106379
J Med Genet Β· 2022
0.60