PAX2

Chr 10AD

paired box 2

Also known as: FSGS7, PAPRS, PAX-2

PAX2 encodes a transcription factor containing a conserved DNA-binding paired box domain that regulates gene expression in the nucleus. Mutations cause autosomal dominant papillorenal syndrome and focal segmental glomerulosclerosis type 7, characterized by optic nerve colobomas and renal hypoplasia. The pathogenic mechanism involves loss of function of this critical transcriptional regulator.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.432 OMIM phenotypes
Clinical SummaryPAX2
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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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.43LOEUF
pLI 0.670
Z-score 3.45
OE 0.19 (0.090.43)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.49Z-score
OE missense 0.73 (0.650.83)
178 obs / 243.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.19 (0.090.43)
00.351.4
Missense OE0.73 (0.650.83)
00.61.4
Synonymous OE1.14
01.21.6
LoF obs/exp: 4 / 21.1Missense obs/exp: 178 / 243.4Syn Z: -1.09
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePAX2-related papillorenal syndromeLOFAD
DN
0.6552th %ile
GOF
0.4085th %ile
LOF
0.72top 10%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · 1 literature citation · LOEUF 0.43
DNprediction above median · 1 literature citation

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.

Literature Evidence

DNMoreover, these results indicate PAX2 mutations can cause disease through haploinsufficiency and dominant negative effects, which could have implications for tailoring individualized drug therapy in the future.PMID:24676634
LOFArray comparative genomic hybridization analysis in patients with anophthalmia, microphthalmia, and colobomaPMID:21285886

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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