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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PNMA2
PNMA family member 2
Chromosome 8 · 8p21.2
NCBI Gene: 10687Ensembl: ENSG00000240694.10HGNC: HGNC:9159UniProt: Q5U5Z3
54PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingpositive regulation of apoptotic processnucleolusneurodegenerative diseasehypertensionfungal infectious diseaseSjogren syndrome
✦AI Summary

PNMA2 (paraneoplastic Ma antigen 2) is a gag-like protein predominantly expressed in the central nervous system that functions as a regulator of cell proliferation, apoptosis, and immune responses 1. Structurally, PNMA2 is derived from a domesticated Ty3 retrotransposon and forms icosahedral non-enveloped virus-like capsids that are released from cells as extracellular antigens 23. Mechanistically, PNMA2 promotes anti-apoptotic signaling and inhibits autophagy through protein-protein interactions; knockdown of PNMA2 enhances apoptosis and reduces cell proliferation and migration 1. PNMA2 antagonizes pro-apoptotic functions of other PNMA family members (PNMA1 and MOAP-1) through heterodimeric interactions 4. Additionally, PNMA2 mediates apoptosis resistance in neural stem cells and may contribute to effects of prenatal alcohol exposure 5. Clinically, PNMA2 is associated with paraneoplastic neurological syndromes, where its capsid structure triggers autoimmune responses with autoantibodies preferentially binding spike epitopes, resulting in neurological deficits 2. PNMA2 is upregulated in endometriosis and achalasia and serves as a potential diagnostic biomarker and therapeutic target 16. The engineered PNMA2 capsids show promise as mRNA delivery vehicles for therapeutic applications 3.

Sources cited
1
PNMA2 is upregulated in endometriosis, promotes anti-apoptosis and proliferation, inhibits autophagy, and associates with immune cell infiltration
PMID: 40323214
2
PNMA2 forms immunogenic non-enveloped virus-like capsids that trigger autoimmune responses and neurological deficits in paraneoplastic disease
PMID: 38301645
3
PNMA2 forms icosahedral capsids with resolved cryo-EM structure and can be engineered for mRNA delivery
PMID: 38437549
4
PNMA2 antagonizes pro-apoptotic functions of PNMA1 and MOAP-1 through heterodimeric interactions
PMID: 27003254
5
PNMA2 mediates apoptosis resistance in neural stem cells and is transferred in extracellular vesicles
PMID: 35187673
6
PNMA2 is ectopically expressed in lower esophageal sphincter muscle of achalasia patients with associated autoantibodies
PMID: 35254715
7
PNMA2 is a candidate gene for somatic signs of nicotine withdrawal
PMID: 36781202
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.43Moderate
hypertensionOpen Targets
0.17Weak
fungal infectious diseaseOpen Targets
0.12Weak
Sjogren syndromeOpen Targets
0.11Weak
cardiovascular diseaseOpen Targets
0.09Suggestive
neuroendocrine neoplasmOpen Targets
0.07Suggestive
ovarian neoplasmOpen Targets
0.07Suggestive
glomerulonephritisOpen Targets
0.07Suggestive
Abruptio PlacentaeOpen Targets
0.06Suggestive
neoplasmOpen Targets
0.06Suggestive
metabolic diseaseOpen Targets
0.05Suggestive
Barrett's esophagusOpen Targets
0.05Suggestive
esophageal adenocarcinomaOpen Targets
0.04Suggestive
encephalitisOpen Targets
0.04Suggestive
clear cell renal carcinomaOpen Targets
0.04Suggestive
paraneoplastic neurologic syndromeOpen Targets
0.03Suggestive
secondary malignant neoplasmOpen Targets
0.02Suggestive
cerebellar ataxiaOpen Targets
0.02Suggestive
endometriosisOpen Targets
0.02Suggestive
breast cancerOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
BLIDShared pathway100%C3orf38Shared pathway100%PNMA5Shared pathway100%STPG1Shared pathway100%CSRNP3Shared pathway100%PNMA3Shared pathway100%
Tissue Expression6 tissues
Brain
100%
Heart
4%
Lung
3%
Ovary
1%
Liver
1%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
PNMA2BLIDC3orf38PNMA5STPG1CSRNP3PNMA3
PROTEIN STRUCTURE
Preparing viewer…
PDB8UYO · 3.30 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.21LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.73 [0.46–1.21]
RankingsWhere PNMA2 stands among ~20K protein-coding genes
  • #8,356of 20,598
    Most Researched54
  • #12,756of 17,882
    Most Constrained (LOEUF)1.21
Genes detectedPNMA2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Unveiling the Role of PNMA2 in Endometriosis: From Proliferation and Apoptosis to Immunomodulation.
PMID: 40323214
J Cell Mol Med · 2025
1.00
2
PNMA2 forms immunogenic non-enveloped virus-like capsids associated with paraneoplastic neurological syndrome.
PMID: 38301645
Cell · 2024
0.90
3
Gag-like proteins: Novel mediators of prenatal alcohol exposure in neural development.
PMID: 35187673
Alcohol Clin Exp Res · 2022
0.80
4
PNMA2 mediates heterodimeric interactions and antagonizes chemo-sensitizing activities mediated by members of PNMA family.
PMID: 27003254
Biochem Biophys Res Commun · 2016
0.70
5
Human paraneoplastic antigen Ma2 (PNMA2) forms icosahedral capsids that can be engineered for mRNA delivery.
PMID: 38437549
Proc Natl Acad Sci U S A · 2024
0.60