CUX2

Chr 12AD

cut like homeobox 2

Also known as: CDP2, CUTL2, DEE67, EIEE67

This gene encodes a transcription factor that regulates neuronal proliferation, differentiation, dendrite development, and synaptogenesis in cortical layers II-III through sequence-specific DNA binding. Mutations cause developmental and epileptic encephalopathy 67 with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to cause severe developmental consequences.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.191 OMIM phenotype
Clinical SummaryCUX2
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Gene-Disease Validity (ClinGen)
developmental and epileptic encephalopathy · ADModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.19LOEUF
pLI 1.000
Z-score 6.67
OE 0.09 (0.050.19)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
3.18Z-score
OE missense 0.70 (0.650.75)
615 obs / 880.7 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.09 (0.050.19)
00.351.4
Missense OE0.70 (0.650.75)
00.61.4
Synonymous OE0.90
01.21.6
LoF obs/exp: 6 / 63.2Missense obs/exp: 615 / 880.7Syn Z: 1.62
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongCUX2-related developmental epileptic encephalopathyOTHERAD
DN
0.3395th %ile
GOF
0.3590th %ile
LOF
0.76top 10%

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

LOFprediction above median · LOEUF 0.19

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

CUX2 · 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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