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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PNRC2
proline rich nuclear receptor coactivator 2
Chromosome 1 · 1p36.11
NCBI Gene: 55629Ensembl: ENSG00000189266.14HGNC: HGNC:23158UniProt: Q9NPJ4
31PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingnuclear-transcribed mRNA catabolic process, nonsense-mediated decayP-bodynucleusprostate carcinomaAbnormality of the skeletal systemsmoking initiationinfection
✦AI Summary

PNRC2 (proline-rich nuclear receptor coactivator 2) functions primarily as a molecular adaptor linking mRNA surveillance and decapping machinery. It acts as a bridge between the mRNA decaying complex and UPF1, a key component of nonsense-mediated mRNA decay (NMD) 1. Structurally, PNRC2's proline-rich region binds the EVH1 domain of decapping enzyme Dcp1a, while its NR-box interacts with hyperphosphorylated UPF1, enabling PNRC2 to recruit decapping machinery to aberrant mRNAs and facilitate their degradation 2. PNRC2 also localizes to P-bodies and is required for UPF1 P-body localization 1. Beyond NMD, PNRC2 participates in ligand-dependent glucocorticoid receptor-mediated mRNA degradation by recruiting UPF1 and DCP1A to target transcripts 3. It regulates cyclic gene transcripts during vertebrate somitogenesis through cooperation with Pumilio proteins and AU-rich element-binding proteins 4. Additionally, PNRC2 serves as a nuclear receptor coactivator 5. Clinically, PNRC2 dysregulation associates with malignant meningioma progression 6 and hepatocellular carcinoma, particularly in Mongolian populations with hepatitis D viral infection 7. PNRC2 also functions in adipogenesis where it facilitates Staufen1-mediated mRNA decay of antiadipogenic factors 8.

Sources cited
1
PNRC2 acts as a bridge between mRNA decapping complex and NMD machinery, required for UPF1 localization to P-bodies
PMID: 19150429
2
Crystal structure showing PNRC2's proline-rich region binds Dcp1a's EVH1 domain and NR-box binds hyperphosphorylated UPF1; PNRC2 is a decapping coactivator
PMID: 23085078
3
PNRC2 participates in glucocorticoid receptor-mediated mRNA degradation by recruiting UPF1 and DCP1A
PMID: 25775514
4
PNRC2 functions as a nuclear receptor coactivator
PMID: 11574675
5
PNRC2 cooperates with Pumilio proteins and ARE-binding proteins to promote rapid turnover of cyclic gene transcripts during somitogenesis
PMID: 32246943
6
PNRC2 is associated with malignant progression of meningioma
PMID: 37024523
7
PNRC2 is a unique driver gene in Mongolian hepatocellular carcinoma associated with hepatitis D viral infection
PMID: 32873799
8
PNRC2 functions in Staufen1-mediated mRNA decay during adipogenesis by facilitating degradation of antiadipogenic factors
PMID: 22503102
Disease Associationsⓘ20
prostate carcinomaOpen Targets
0.19Weak
Abnormality of the skeletal systemOpen Targets
0.04Suggestive
smoking initiationOpen Targets
0.04Suggestive
infectionOpen Targets
0.02Suggestive
ovarian carcinomaOpen Targets
0.01Suggestive
viral diseaseOpen Targets
0.01Suggestive
colorectal carcinomaOpen Targets
0.01Suggestive
colorectal cancerOpen Targets
0.00Suggestive
obesityOpen Targets
0.00Suggestive
acute lymphoblastic leukemiaOpen Targets
0.00Suggestive
acute monocytic leukemiaOpen Targets
0.00Suggestive
cancerOpen Targets
0.00Suggestive
glioblastoma multiformeOpen Targets
0.00Suggestive
gliomaOpen Targets
0.00Suggestive
hepatocellular carcinomaOpen Targets
0.00Suggestive
liver and intrahepatic bile duct neoplasmOpen Targets
0.00Suggestive
Neoplasm of the liverOpen Targets
0.00Suggestive
renal cell carcinomaOpen Targets
0.00Suggestive
multiple myelomaOpen Targets
0.00Suggestive
Other metabolic diseaseOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
EDC3Protein interaction100%UPF3AProtein interaction99%SMG9Protein interaction94%ESRRGProtein interaction91%TLE1Protein interaction91%UPF1Protein interaction85%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
73%
Ovary
71%
Brain
56%
Heart
51%
Liver
41%
Gene Interaction Network
Click a node to explore
PNRC2EDC3UPF3ASMG9ESRRGTLE1UPF1
PROTEIN STRUCTURE
Preparing viewer…
PDB5KQ4 · 2.56 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.45Moderately Constrained
pLIⓘ
0.97Intolerant
Observed/Expected LoF0.10 [0.03–0.45]
RankingsWhere PNRC2 stands among ~20K protein-coding genes
  • #11,775of 20,598
    Most Researched31
  • #2,521of 17,882
    Most Constrained (LOEUF)0.45 · top quartile
Genes detectedPNRC2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Pumilio response and AU-rich elements drive rapid decay of Pnrc2-regulated cyclic gene transcripts.
PMID: 32246943
Dev Biol · 2020
1.00
2
Dissecting the functions of SMG5, SMG7, and PNRC2 in nonsense-mediated mRNA decay of human cells.
PMID: 29348139
RNA · 2018
0.90
3
Structural basis of the PNRC2-mediated link between mrna surveillance and decapping.
PMID: 23085078
Structure · 2012
0.80
4
SMG5-PNRC2 is functionally dominant compared with SMG5-SMG7 in mammalian nonsense-mediated mRNA decay.
PMID: 23234702
Nucleic Acids Res · 2013
0.70
5
Prognostic factors and Doxorubicin involved in malignant progression of meningioma.
PMID: 37024523
Sci Rep · 2023
0.60