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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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DPPA2
developmental pluripotency associated 2
Chromosome 3 · 3q13.13
NCBI Gene: 151871Ensembl: ENSG00000163530.5HGNC: HGNC:19197UniProt: Q7Z7J5
27PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingchromatin bindingsystem developmentnucleusprimary ovarian insufficiencyretinopathyosteonecrosisretinoschisis
✦AI Summary

DPPA2 (Developmental Pluripotency Associated 2) is a chr3-binding transcription factor that serves as a key epigenetic priming factor regulating cell fate transitions and maintaining developmental competency 1. The protein functions by binding to target gene promoters and maintaining the active epigenetic status of developmental genes through regulation of bivalent chr3 domains containing both H3K4me3 and H3K27me3 modifications 12. DPPA2 works in partnership with DPPA4 as a heterodimer to facilitate chr3 remodeling during somatic cell reprogramming to induced pluripotency, achieving reprogramming efficiencies exceeding 80% when co-expressed with standard pluripotency factors 3. The protein directly regulates zygotic genome activation by upregulating DUX expression, with its activity negatively controlled by SUMO E3 ligase PIAS4 through sumoylation 4. DPPA2 promotes cell proliferation and pluripotency maintenance through activation of the PI3K/AKT/GSK3β/β-catenin signaling pathway and subsequent LEF1 upregulation 5. Clinically, DPPA2 functions as a cancer/testis antigen, being normally expressed in germ cells and trophoblasts but aberrantly reactivated in various malignancies 6. Its expression pattern during human preimplantation development suggests distinct roles in late-stage embryonic reprogramming processes, particularly in blastocysts and primordial germ cells 7.

Sources cited
1
DPPA2 functions as epigenetic priming factor regulating bivalent chromatin domains with H3K4me3 and H3K27me3 modifications
PMID: 34767751
2
DPPA2 is a novel regulator of bivalent chromatin domains that maintains developmental competency
PMID: 38385532
3
DPPA2/4 heterodimer facilitates chromatin remodeling during reprogramming to pluripotency with >80% efficiency
PMID: 30146411
4
DPPA2 directly regulates zygotic genome activation by upregulating DUX and is negatively regulated by PIAS4 sumoylation
PMID: 31226106
5
DPPA2/4 promote pluripotency and proliferation through PI3K/AKT/GSK3β/β-catenin pathway and LEF1 activation
PMID: 38474345
6
DPPA2 functions as cancer/testis antigen aberrantly expressed in malignancies
PMID: 29849983
7
DPPA2 shows distinct expression pattern in human preimplantation development, particularly in blastocysts and primordial germ cells
PMID: 18467432
Disease Associationsⓘ20
primary ovarian insufficiencyOpen Targets
0.27Weak
osteonecrosisOpen Targets
0.09Suggestive
retinopathyOpen Targets
0.09Suggestive
retinoschisisOpen Targets
0.09Suggestive
anemia (phenotype)Open Targets
0.09Suggestive
Abnormality of the skeletal systemOpen Targets
0.09Suggestive
schizophreniaOpen Targets
0.08Suggestive
gastric cancerOpen Targets
0.07Suggestive
lagophthalmosOpen Targets
0.06Suggestive
cholelithiasisOpen Targets
0.06Suggestive
cancerOpen Targets
0.03Suggestive
Down syndromeOpen Targets
0.03Suggestive
non-small cell lung carcinomaOpen Targets
0.03Suggestive
adolescent idiopathic scoliosisOpen Targets
0.02Suggestive
joint diseaseOpen Targets
0.02Suggestive
placental retentionOpen Targets
0.02Suggestive
occlusion precerebral arteryOpen Targets
0.02Suggestive
strokeOpen Targets
0.02Suggestive
colorectal cancerOpen Targets
0.02Suggestive
neoplasmOpen Targets
0.02Suggestive
Pathogenic Variants1
NM_138815.4(DPPA2):c.833T>C (p.Leu278Ser)Likely pathogenic
Premature ovarian failure
★☆☆☆2020→ Residue 278
View on ClinVar ↗
Related Genes
DPPA4Protein interaction83%DPPA5Protein interaction70%KIF26BShared pathway50%SIM2Shared pathway50%SALL2Shared pathway50%SIM1Shared pathway33%
Tissue Expression6 tissues
Lung
0%
Bone Marrow
0%
Heart
0%
Ovary
0%
Liver
0%
Brain
0%
Gene Interaction Network
Click a node to explore
DPPA2DPPA4DPPA5KIF26BSIM2SALL2SIM1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q7Z7J5
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.00LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.72 [0.53–1.00]
RankingsWhere DPPA2 stands among ~20K protein-coding genes
  • #12,550of 20,598
    Most Researched27
  • #5,284of 5,498
    Most Pathogenic Variants1
  • #9,736of 17,882
    Most Constrained (LOEUF)1.00
Genes detectedDPPA2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
DPPA2, DPPA4, and other DPPA factor epigenomic functions in cell fate and cancer.
PMID: 34767751
Stem Cell Reports · 2021
1.00
2
Ectopic Expression of Human
PMID: 29849983
Avicenna J Med Biotechnol · 2018
0.90
3
Keeping your options open: insights from Dppa2/4 into how epigenetic priming factors promote cell plasticity.
PMID: 33336687
Biochem Soc Trans · 2020
0.80
4
Bivalent chromatin: a developmental balancing act tipped in cancer.
PMID: 38385532
Biochem Soc Trans · 2024
0.70
5
DPPA2/4 and SUMO E3 ligase PIAS4 opposingly regulate zygotic transcriptional program.
PMID: 31226106
PLoS Biol · 2019
0.60