PRRX2

Chr 9

paired related homeobox 2

Also known as: PMX2, PRX2

NCBI Gene: 51450ENSG00000167157UniProt: Q99811

The DNA-associated protein encoded by this gene is a member of the paired family of homeobox proteins. Expression is localized to proliferating fetal fibroblasts and the developing dermal layer, with downregulated expression in adult skin. Increases in expression of this gene during fetal but not adult wound healing suggest a possible role in mechanisms that control mammalian dermal regeneration and prevent formation of scar response to wounding. The expression patterns provide evidence consistent with a role in fetal skin development and a possible role in cellular proliferation. [provided by RefSeq, Jul 2008]

0
Active trials
34
Pathogenic / LP
100
ClinVar variants
6
Pubs (1 yr)
0.5
Missense Z
1.09
LOEUF
Clinical Summary— PRRX2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.35) despite low pLI — interpret in context.
📋
ClinVar Variants
34 Pathogenic / Likely Pathogenic· 66 VUS of 100 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.09LOEUF
pLI 0.140
Z-score 1.45
OE 0.35 (0.14–1.09)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.48Z-score
OE missense 0.88 (0.74–1.03)
102 obs / 116.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.35 (0.14–1.09)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.74–1.03)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.14
0≤1.21.6
LoF obs/exp: 2 / 5.7Missense obs/exp: 102 / 116.5Syn Z: -0.78
DN
0.7228th %ile
GOF
0.4777th %ile
LOF
0.54top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

100 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic2
VUS66
32
Pathogenic
2
Likely Pathogenic
66
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
32
0
32
Likely Pathogenic
0
0
2
0
2
VUS
0
52
14
0
66
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total052480100

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PRRX2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Transcriptional regulation of ATOX1 by PRRX2 impacts the progression and cuproptosis of hepatocellular carcinoma.
Tang L et al.·Cell Signal
2025
Silencing of Prrx2 Inhibits the Invasion and Metastasis of Breast Cancer both In Vitro and In Vivo by Reversing Epithelial-Mesenchymal Transition.
Lv ZD et al.·Cell Physiol Biochem
2017
Inhibition of PRRX2 suppressed colon cancer liver metastasis via inactivation of Wnt/β-catenin signaling pathway.
Chai WX et al.·Pathol Res Pract
2019
Cystathionine β-synthase mediated PRRX2/IL-6/STAT3 inactivation suppresses Tregs infiltration and induces apoptosis to inhibit HCC carcinogenesis.
Zhou YF et al.·J Immunother Cancer
2021
MiR-212-5p Suppresses the Epithelial-Mesenchymal Transition in Triple-Negative Breast Cancer by Targeting Prrx2.
Lv ZD et al.·Cell Physiol Biochem
2017
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Clinicopathological Characteristics of PRRX1 and PRRX2 Genes Expressions in Colorectal Cancer Patients.
Zaman Nezhad S et al.·Cell Mol Biol (Noisy-le-grand)
2026Cohort
Single-cell and spatial transcriptomics reveal the interaction between PRRX2-driven epithelial cells and SPP1+ macrophages in mediating gemcitabine resistance in pancreatic ductal adenocarcinoma.
Liu J et al.·Chin Med J (Engl)
2025
Single-cell and bulk RNA-sequencing reveal PRRX2-driven cancer-associated fibroblast-mediated perineural invasion for predicting the immunotherapy outcome in colorectal cancer.
Chen M et al.·Front Cell Dev Biol
2025Open Access
3D-printed scaffold loaded with baicalin exosomes promotes bone defect repair via mediating PRRX2 to alleviate inflammation.
Zhu H et al.·iScience
2026Open Access
PRRX2 Regulates GLI2 to Promote Proliferation, Invasion, and Metastasis by Inhibiting Senescence via Hedgehog Signaling.
Huang W et al.·Cancer Sci
2025Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients