PAX2

Chr 10AD

paired box 2

Also known as: FSGS7, PAPRS, PAX-2

NCBI Gene: 5076ENSG00000075891UniProt: Q02962

PAX2 encodes paired box gene 2, one of many human homologues of the Drosophila melanogaster gene prd. The central feature of this transcription factor gene family is the conserved DNA-binding paired box domain. PAX2 is believed to be a target of transcriptional supression by the tumor suppressor gene WT1. Mutations within PAX2 have been shown to result in optic nerve colobomas and renal hypoplasia. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2014]

Primary Disease Associations & Inheritance

Glomerulosclerosis, focal segmental, 7MIM #616002
AD
Papillorenal syndromeMIM #120330
AD
UniProtFocal segmental glomerulosclerosis 7
544
ClinVar variants
139
Pathogenic / LP
0.67
pLI score
0
Active trials
Clinical Summary— PAX2
🧬
Gene-Disease Validity (ClinGen)
focal segmental glomerulosclerosis 7 · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.67) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
139 Pathogenic / Likely Pathogenic· 237 VUS of 544 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.43LOEUF
pLI 0.670
Z-score 3.45
OE 0.19 (0.09–0.43)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
1.49Z-score
OE missense 0.73 (0.65–0.83)
178 obs / 243.4 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.0.19 (0.09–0.43)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.73 (0.65–0.83)
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: 4 / 21.1Missense obs/exp: 178 / 243.4Syn Z: -1.09

ClinVar Variant Classifications

544 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic69
Likely Pathogenic70
VUS237
Likely Benign121
Benign33
Conflicting14
69
Pathogenic
70
Likely Pathogenic
237
VUS
121
Likely Benign
33
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
33
6
30
0
69
Likely Pathogenic
28
26
16
0
70
VUS
4
204
24
5
237
Likely Benign
0
3
56
62
121
Benign
0
0
31
2
33
Conflicting
—14
Total6523915769544

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

View in ClinVar →

Protein Context — Lollipop Plot

PAX2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

PAX2-related papillorenal syndrome

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
PAIRED BOX GENE 2; PAX2
MIM #167409 · *

Glomerulosclerosis, focal segmental, 7

MIM #616002

Molecular basis of disorder known

Autosomal dominant

Papillorenal syndrome

MIM #120330

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — PAX2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Autophagy in the physiological endometrium and cancer.
Devis-Jauregui L et al.·Autophagy
2021Review
PATZ1 fusions define a novel molecularly distinct neuroepithelial tumor entity with a broad histological spectrum.
Alhalabi KT et al.·Acta Neuropathol
2021
Genetic Characterization of Kidney Failure of Unknown Etiology in Spain: Findings From the GENSEN Study.
Blasco M et al.·Am J Kidney Dis
2024
Kidney Organoid Modeling of WT1 Mutations Reveals Key Regulatory Paths Underlying Podocyte Development.
Wang G et al.·Adv Sci (Weinh)
2024Functional
Renal coloboma syndrome.
Schimmenti LA·Eur J Hum Genet
2011Review
Primary renal osteosarcoma.
Lopez-Beltran A et al.·Am J Clin Pathol
2014Case report
Molecular basis of proteinuria.
Akhtar M et al.·Adv Anat Pathol
2004Review
Renal coloboma syndrome.
Dureau P et al.·Ophthalmology
2001
Genotype of PAX2-related disorders correlates with kidney and ocular manifestations.
Kim JH et al.·Eur J Hum Genet
2025
Ocular manifestations of the genetic causes of focal and segmental glomerulosclerosis.
Zhu V et al.·Pediatr Nephrol
2024Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Expanded Phenotype of PAX2-Related Papillorenal Syndrome: A Case Featuring FSGS, Atypical Retinopathy, Cerebellar Hypoplasia, and ADHD.
Sultana N et al.·Clin Case Rep
2026🔓 Open Access
Betulin, an active component from Chinese herb birch bark, suppresses tumor angiogenesis and tumor growth by inhibiting the PAX2/VEGF-A/VEGR2 signaling pathway in non-small cell lung cancer.
Li Z et al.·Phytomedicine
2025
Genotype-phenotype correlations and functional characterization of novel PAX2 variants in a 10-patient pediatric cohort.
Fu M et al.·Ren Fail
2025🔓 Open AccessCohort
Presentation of Patients With Congenital Anomalies of the Kidney and Urinary Tract and PAX2 Loss-of-Function Variants and Implications for Clinical Management.
Greipel L et al.·Kidney Int Rep
2025🔓 Open AccessCohort
A distinct mechanism of epigenetic reprogramming silences PAX2 and initiates endometrial carcinogenesis.
Sahoo SS et al.·J Clin Invest
2025🔓 Open AccessFunctional
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools