PITX3

Chr 10ADAR

paired like homeodomain 3

Also known as: ASGD1, ASMD, ASOD, CTPP4, CTRCT11

This gene encodes a transcription factor essential for lens development and the differentiation and maintenance of dopaminergic neurons in the brain. Mutations cause congenital cataracts and anterior segment dysgenesis affecting eye development, with inheritance patterns that can be either autosomal dominant or autosomal recessive depending on the specific mutation. The gene is highly constrained against loss-of-function variants (pLI 0.81, LOEUF 0.48), indicating that complete loss of protein function is likely not tolerated.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/ARLOEUF 0.483 OMIM phenotypes
Clinical SummaryPITX3
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.81) — some intolerance to loss-of-function variants.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.48LOEUF
pLI 0.813
Z-score 2.62
OE 0.10 (0.040.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.50Z-score
OE missense 0.68 (0.580.79)
115 obs / 170.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.10 (0.040.48)
00.351.4
Missense OE0.68 (0.580.79)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 1 / 9.9Missense obs/exp: 115 / 170.0Syn Z: 0.54
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePITX3-related cataract with or without ocular developmental defectsLOFAD
DN
0.5868th %ile
GOF
0.3590th %ile
LOF
0.74top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.48

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

PITX3 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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