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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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PRRX1
paired related homeobox 1
Chromosome 1 Β· 1q24.2
NCBI Gene: 5396Ensembl: ENSG00000116132.12HGNC: HGNC:9142UniProt: P54821
75PubMed Papers
21Diseases
0Drugs
6Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingpositive regulation of transcription by RNA polymerase IInucleoplasmRNA polymerase II-specific DNA-binding transcription factor bindingagnathia-otocephaly complexatrial fibrillationAgnathia - holoprosencephaly - situs inversuscardiac arrhythmia
✦AI Summary

PRRX1 (paired related homeobox 1) is a transcription factor that functions as both a transcriptional repressor and activator, depending on cellular context. As a repressor, PRRX1 regulates cell fate determination and lineage differentiation across multiple tissue types 1. In neuroblastoma, PRRX1 acts as a key driver of mesenchymal cell identity by reprogramming super-enhancer landscapes, enabling cellular interconversion between undifferentiated mesenchymal and committed adrenergic states 1. Similarly, in triple-negative breast cancer, PRRX1 drives mesenchymal features by reprogramming super-enhancer landscapes in basal cells 2. PRRX1 also marks skeletal stem cells involved in bone fracture healing, with lineage-tracing studies showing that Prrx1+ cells generate spatially distinct subsets of chondrocytes and osteoblasts during repair 3. In pathological contexts, PRRX1 contributes to cancer progression as part of NUP98 fusion oncoproteins in pediatric leukemias 4 and regulates immunosuppressive pericyte function in esophageal cancer metastasis 5. Additionally, PRRX1 plays roles in tissue homeostasis, including cartilage maintenance 6, hematopoietic regulation 7, and kidney fibrosis through downstream TNC signaling 8. These diverse functions highlight PRRX1's critical role in developmental programs, tissue repair, and disease pathogenesis.

Sources cited
1
PRRX1 reprograms super-enhancer landscapes to drive mesenchymal cell identity in neuroblastoma
PMID: 28650485
2
PRRX1 is a key driver of mesenchymal features in triple-negative breast cancer through super-enhancer reprogramming
PMID: 38100350
3
Prrx1+ cells generate spatially distinct chondrocytes and osteoblasts during bone fracture healing
PMID: 39225088
4
NUP98-PRRX1 fusion oncoprotein contributes to leukemic transformation in pediatric leukemias
PMID: 34903620
5
PRRX1 transcriptionally regulates GPR116+ pericytes that promote tumor metastasis in esophageal cancer
PMID: 41073785
6
PRRX1 is involved in cartilage homeostasis and osteoarthritis pathogenesis
PMID: 38012390
7
PRRX1 marks leptin-receptor-positive stromal bone marrow cells involved in hematopoietic regulation
PMID: 31700184
8
PRRX1 mediates kidney fibrosis as a downstream target of Twist1, promoting TNC expression
PMID: 39181396
Disease Associationsβ“˜21
agnathia-otocephaly complexOpen Targets
0.69Moderate
atrial fibrillationOpen Targets
0.58Moderate
Agnathia - holoprosencephaly - situs inversusOpen Targets
0.55Moderate
cardiac arrhythmiaOpen Targets
0.51Moderate
atrial flutterOpen Targets
0.49Moderate
Abnormality of the skeletal systemOpen Targets
0.49Moderate
craniosynostosisOpen Targets
0.49Moderate
aortic stenosisOpen Targets
0.47Moderate
eyelid diseaseOpen Targets
0.41Moderate
cardioembolic strokeOpen Targets
0.40Moderate
aortic valve diseaseOpen Targets
0.40Weak
heart failureOpen Targets
0.39Weak
blood coagulation diseaseOpen Targets
0.38Weak
aortic valve calcificationOpen Targets
0.33Weak
Alzheimer diseaseOpen Targets
0.33Weak
pancreatic carcinomaOpen Targets
0.32Weak
lung cancerOpen Targets
0.32Weak
chronic obstructive pulmonary diseaseOpen Targets
0.31Weak
heart valve prosthesisOpen Targets
0.31Weak
androgenetic alopeciaOpen Targets
0.29Weak
Agnathia-otocephaly complexUniProt
Pathogenic Variants6
NM_022716.4(PRRX1):c.370C>T (p.Arg124Ter)Pathogenic
Craniosynostosis syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 124
NM_022716.4(PRRX1):c.317T>C (p.Leu106Pro)Likely pathogenic
Agnathia-otocephaly complex
β˜†β˜†β˜†β˜†2020β†’ Residue 106
NM_022716.4(PRRX1):c.266_269dup (p.Arg92fs)Pathogenic
Agnathia-otocephaly complex
β˜†β˜†β˜†β˜†2013β†’ Residue 92
NM_022716.4(PRRX1):c.269del (p.Lys90fs)Pathogenic
Agnathia-otocephaly complex
β˜†β˜†β˜†β˜†2012β†’ Residue 90
NM_022716.4(PRRX1):c.691G>C (p.Ala231Pro)Pathogenic
Agnathia-otocephaly complex
β˜†β˜†β˜†β˜†2012β†’ Residue 231
NM_022716.4(PRRX1):c.338T>C (p.Phe113Ser)Pathogenic
Agnathia-otocephaly complex
β˜†β˜†β˜†β˜†2011β†’ Residue 113
View on ClinVar β†—
Related Genes
MNTShared pathway100%NFICShared pathway100%NFIXShared pathway100%NFYAShared pathway100%GLIS3Shared pathway100%CCDC124Shared pathway100%
Tissue Expression6 tissues
Heart
100%
Ovary
48%
Lung
35%
Brain
10%
Liver
1%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
PRRX1MNTNFICNFIXNFYAGLIS3CCDC124
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt P54821
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.57Moderately Constrained
pLIβ“˜
0.89Intermediate
Observed/Expected LoF0.32 [0.18–0.57]
RankingsWhere PRRX1 stands among ~20K protein-coding genes
  • #6,357of 20,598
    Most Researched75
  • #3,365of 5,498
    Most Pathogenic Variants6
  • #3,762of 17,882
    Most Constrained (LOEUF)0.57 Β· top quartile
Genes detectedPRRX1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Neuroblastoma is composed of two super-enhancer-associated differentiation states.
PMID: 28650485
Nat Genet Β· 2017
1.00
2
Heterogeneity and transcriptional drivers of triple-negative breast cancer.
PMID: 38100350
Cell Rep Β· 2023
0.90
3
Itm2a expression marks periosteal skeletal stem cells that contribute to bone fracture healing.
PMID: 39225088
J Clin Invest Β· 2024
0.80
4
Phase Separation Mediates NUP98 Fusion Oncoprotein Leukemic Transformation.
PMID: 34903620
Cancer Discov Β· 2022
0.70
5
Single-cell multi-omic and spatial profiling of esophageal squamous cell carcinoma reveals the immunosuppressive role of GPR116
PMID: 41073785
Nat Genet Β· 2025
0.60